Science.gov

Sample records for observed highly-active antiretroviral

  1. Birth outcomes in South African women receiving highly active antiretroviral therapy: a retrospective observational study

    PubMed Central

    2011-01-01

    Background Use of highly active antiretroviral therapy (HAART), a triple-drug combination, in HIV-infected pregnant women markedly reduces mother to child transmission of HIV and decreases maternal morbidity. However, there remains uncertainty about the effects of in utero exposure to HAART on foetal development. Methods Our objectives were to investigate whether in utero exposure to HAART is associated with low birth weight and/or preterm birth in a population of South African women with advanced HIV disease. A retrospective observational study was performed on women with CD4 counts ≤250 cells/mm3 attending antenatal antiretroviral clinics in Johannesburg between October 2004 and March 2007. Low birth weight (<2.5 kg) and preterm birth rates (<37 weeks) were compared between those exposed and unexposed to HAART during pregnancy. Effects of different HAART regimen and duration were assessed. Results Among HAART-unexposed infants, 27% (60/224) were low birth weight compared with 23% (90/388) of early HAART-exposed (exposed <28 weeks gestation) and 19% (76/407) of late HAART-exposed (exposed ≥28 weeks) infants (p = 0.05). In the early HAART group, a higher CD4 cell count was protective against low birth weight (AOR 0.57 per 50 cells/mm3 increase, 95% CI 0.45-0.71, p < 0.001) and preterm birth (AOR 0.68 per 50 cells/mm3 increase, 95% CI 0.55-0.85, p = 0.001). HAART exposure was associated with an increased preterm birth rate (15%, or 138 of 946, versus 5%, or seven of 147, in unexposed infants, p = 0.001), with early nevirapine and efavirenz-based regimens having the strongest associations with preterm birth (AOR 5.4, 95% CI 2.1-13.7, p < 0.001, and AOR 5.6, 95% CI 2.1-15.2, p = 0.001, respectively). Conclusions In this immunocompromised cohort, in utero HAART exposure was not associated with low birth weight. An association between NNRTI-based HAART and preterm birth was detected, but residual confounding is plausible. More advanced immunosuppression was a risk

  2. Community-based treatment of advanced HIV disease: introducing DOT-HAART (directly observed therapy with highly active antiretroviral therapy).

    PubMed Central

    Farmer, P.; Léandre, F.; Mukherjee, J.; Gupta, R.; Tarter, L.; Kim, J. Y.

    2001-01-01

    In 2000, acquired immunodeficiency syndrome (AIDS) overtook tuberculosis (TB) as the world's leading infectious cause of adult deaths. In affluent countries, however, AIDS mortality has dropped sharply, largely because of the use of highly active antiretroviral therapy (HAART). Antiretroviral agents are not yet considered essential medications by international public health experts and are not widely used in the poor countries where human immunodeficiency virus (HIV) takes its greatest toll. Arguments against the use of HAART have mainly been based on the high cost of medications and the lack of the infrastructure necessary for using them wisely. We re- examine these arguments in the setting of rising AIDS mortality in developing countries and falling drug prices, and describe a small community-based treatment programme based on lessons gained in TB control. With the collaboration of Haitian community health workers experienced in the delivery of home-based and directly observed treatment for TB, an AIDS-prevention project was expanded to deliver HAART to a subset of HIV patients deemed most likely to benefit. The inclusion criteria and preliminary results are presented. We conclude that directly observed therapy (DOT) with HAART, "DOT-HAART", can be delivered effectively in poor settings if there is an uninterrupted supply of high-quality drugs. PMID:11799447

  3. Measures of site resourcing predict virologic suppression, immunologic response and HIV disease progression following highly active antiretroviral therapy (HAART) in the TREAT Asia HIV Observational Database (TAHOD)

    PubMed Central

    Oyomopito, R; Lee, MP; Phanuphak, P; Lim, PL; Ditangco, R; Zhou, J; Sirisanthana, T; Chen, YMA; Pujari, S; Kumarasamy, N; Sungkanuparph, S; Lee, CKC; Kamarulzaman, A; Oka, S; Zhang, FJ; Mean, CV; Merati, T; Tau, G; Smith, J; Li, PCK

    2010-01-01

    Objectives Surrogate markers of HIV disease progression are HIV RNA in plasma viral load (VL) and CD4 cell count (immune function). Despite improved international access to antiretrovirals, surrogate marker diagnostics are not routinely available in resource-limited settings. Therefore, the objective was to assess effects of economic and diagnostic resourcing on patient treatment outcomes. Methods Analyses were based on 2333 patients initiating highly active antiretroviral therapy (HAART) from 2000 onwards. Sites were categorized by World Bank country income criteria (high/low) and annual frequency of VL (≥ 3, 1–2 or <1) or CD4 (≥ 3 or <3) testing. Endpoints were time to AIDS/death and change in CD4 cell count and VL suppression (<400 HIV-1 RNA copies/mL) at 12 months. Demographics, Centers for Disease Control and Prevention (CDC) classification, baseline VL/CD4 cell counts, hepatitis B/C coinfections and HAART regimen were covariates. Time to AIDS/death was analysed by proportional hazards models. CD4 and VL endpoints were analysed using linear and logistic regression, respectively. Results Increased disease progression was associated with site-reported VL testing less than once per year [hazard ratio (HR)=1.4; P=0.032], severely symptomatic HIV infection (HR=1.4; P=0.003) and hepatitis C virus coinfection (HR=1.8; P=0.011). A total of 1120 patients (48.2%) had change in CD4 cell count data. Smaller increases were associated with older age (P<0.001) and `Other' HIV source exposures, including injecting drug use and blood products (P=0.043). A total of 785 patients (33.7%) contributed to the VL suppression analyses. Patients from sites with VL testing less than once per year [odds ratio (OR)=0.30; P<0.001] and reporting `Other' HIV exposures experienced reduced suppression (OR=0.28; P<0.001). Conclusion Low measures of site resourcing were associated with less favourable patient outcomes, including a 35% increase in disease progression in patients from sites

  4. Highly active antiretroviral treatment for the prevention of HIV transmission

    PubMed Central

    2010-01-01

    In 2007 an estimated 33 million people were living with HIV; 67% resided in sub-Saharan Africa, with 35% in eight countries alone. In 2007, there were about 1.4 million HIV-positive tuberculosis cases. Globally, approximately 4 million people had been given highly active antiretroviral therapy (HAART) by the end of 2008, but in 2007, an estimated 6.7 million were still in need of HAART and 2.7 million more became infected with HIV. Although there has been unprecedented investment in confronting HIV/AIDS - the Joint United Nations Programme on HIV/AIDS estimates $13.8 billion was spent in 2008 - a key challenge is how to address the HIV/AIDS epidemic given limited and potentially shrinking resources. Economic disparities may further exacerbate human rights issues and widen the increasingly divergent approaches to HIV prevention, care and treatment. HIV transmission only occurs from people with HIV, and viral load is the single greatest risk factor for all modes of transmission. HAART can lower viral load to nearly undetectable levels. Prevention of mother to child transmission offers proof of the concept of HAART interrupting transmission, and observational studies and previous modelling work support using HAART for prevention. Although knowing one's HIV status is key for prevention efforts, it is not known with certainty when to start HAART. Building on previous modelling work, we used an HIV/AIDS epidemic of South African intensity to explore the impact of testing all adults annually and starting persons on HAART immediately after they are diagnosed as HIV positive. This theoretical strategy would reduce annual HIV incidence and mortality to less than one case per 1000 people within 10 years and it would reduce the prevalence of HIV to less than 1% within 50 years. To explore HAART as a prevention strategy, we recommend further discussions to explore human rights and ethical considerations, clarify research priorities and review feasibility and acceptability

  5. [Highly Active AntiRetroviral Therapy and opportunistic protozoan infections].

    PubMed

    Pozio, E

    2004-06-01

    Opportunistic parasite infections (OPIs) are an important cause of morbidity and mortality in persons infected with HIV. In industrialised countries, the use of Highly Active AntiRetroviral Therapy (HAART) results to be effective in suppressing the HIV viral load, with a quantitative and qualitative improvement in the CD4+ T-cell count followed by a strong reduction of opportunistic infections including those caused by parasites. These successes have been mainly attributed to the reconstitution of the cell immunity, which play the most important role in controlling OPIs. However, there are many clinical reports and several laboratory results, which suggest that the control of OPIs in HIV-positive persons under HAART is also induced by the anti-HIV protease inhibitors (PIs), which inhibit the aspartyl proteases of the parasites. The non-conventional use of HIV-PIs seems to be an alternative way for the treatment of parasitic infections, which should be deeply investigated. Of five longitudinal studies carried out before and after the introduction of HAART, four studies showed a strong reduction of toxoplasmic encephalitis (TE) in HIV-positive persons under HAART, whereas in another study, no difference was observed in the incidence rate of TE before and after the introduction of HAART. The influence of HAART in reducing TE has been also confirmed in a randomised, controlled clinical trial, which showed that there is no increase in the risk of developing TE after beginning HAART, even though HIV-infected persons with TE had a discontinuing prophylaxis for Toxoplasma gondii. Four HIV protease inhibitors were tested against the T. gondii virulent RH strain in vitro, alone or in association with pyrimethamine or sulfadiazine. Ritonavir and nelfinavir were highly inhibitory for the parasite growth. Furthermore, none of the antiviral drugs negatively affected the anti-Toxoplasma activity of pyrimethamine or sulfadiazine. In HIV-Leishmania co-infections, a changing pattern

  6. [Ergotism due to simultaneous use of ergot alkaloids and high activity antiretroviral therapy].

    PubMed

    Cifuentes M, Daniel; Blanco L, Sergio; Ramírez F, Camila

    2016-06-01

    High activity antiretroviral therapy may exacerbate the activity of ergot alkaloids due to an inhibition of cytochrome P450. We report a 57 years old female with AIDS treated with lamivudine, zidovudine, atazanavir, ritonavir and cotrimoxazole presenting with ischemic signs in the four limbs. There was acrocyanosis and weak radial and ulnar pulses. A family member referred that the patient used ergot alkaloids for headaches. An ergotism due to the simultaneous use of ergot alkaloids and antiretroviral therapy was suspected. The latter was discontinued and intravenous nitroglycerin, nifedipine and pentoxifyline were started with good results. PMID:27598502

  7. Identifying risk factors of immune reconstitution inflammatory syndrome in AIDS patients receiving highly active anti-retroviral therapy.

    PubMed

    He, Bo; Zheng, Yuhuang; Liu, Meng; Zhou, Guoqiang; Chen, Xia; Mamadou, Diallo; He, Yan; Zhou, Huaying; Chen, Zi

    2013-01-01

    Immune reconstitution inflammation syndrome typically occurs within days after patients undergo highly active anti-retroviral therapy and is a big hurdle for effective treatment of AIDS patients. In this study, we monitored immune reconstitution inflammation syndrome occurrence in 238 AIDS patients treated with highly active anti-retroviral therapy. Among them, immune reconstitution inflammation syndrome occurred in 47 cases (19.7%). Immune reconstitution inflammation syndrome patients had significantly higher rate of opportunistic infection (p<0.001) and persistently lower CD4(+) cell count (p<0.001) compared to the non-immune reconstitution inflammation syndrome patients. In contrast, no significant differences in HIV RNA loads were observed between the immune reconstitution inflammation syndrome group and non-immune reconstitution inflammation syndrome group. These data suggest that a history of opportunistic infection and CD4(+) cell counts at baseline may function as risk factors for immune reconstitution inflammation syndrome occurrence in AIDS patients as well as potential prognostic markers. These findings will improve the management of AIDS with highly active anti-retroviral therapy. PMID:23434049

  8. CLEFT PALATE IN HIV-EXPOSED NEWBORNS OF MOTHERS ON HIGHLY ACTIVE ANTIRETROVIRAL THERAPY

    PubMed Central

    James, Ayotunde; Oluwatosin, Babatunde; Njideka, Georgina; Babafemi; Benjamin, Onyekwere George; Olufemi, David; Leo, Robert; Folorunso, Isaac; Phylis; Olusina, Olusegun

    2014-01-01

    Aims Cleft lip/palate, though rare, is the commonest head and neck congenital malformation. Both genetic and environmental factors have been implicated in the aetiopathogenesis but the role of in-utero exposure to human immunodeficiency virus (HIV) and highly active antiretroviral therapy (HAART) is still being investigated. This short communication reports the occurrence of cleft palate in three newborns exposed in-utero to HIV and HAART. Material and methods This is a case series of HIV-exposed newborns observed to have cleft palate among a larger cohort of HIV-exposed and unexposed newborns in a study evaluating the effect of HIV infection and HAART on newborn hearing. The Risk Ratio (RR) was calculated to detect a potential association between in-utero exposure to Efavirenz containing ART and cleft palate. Results Three HIV-exposed newborns with cleft palate were identified during hearing screening performed on 126 HIV-exposed and 121 HIV unexposed newborns. Two had exposure to tenofovir+lamivudine+efavirenz (TDF+3TC+EFV) while the third had exposure to zidovudine+lamivudine+nevirapine (ZDV+3TC+NVP) during the first trimester. There was no statistically significant association between presence of cleft palate and exposure to an EFV containing HAART regimen (p=0.07, RR=10.95 [0.94-126.84]). Conclusions This communication highlights the possible aetiologic role of HAART in cleft palate, the need for further prospective follow-up studies and establishment of antiretroviral pregnancy, birth and neonatal registries. PMID:25653715

  9. HIV-infected patients' adherence to highly active antiretroviral therapy: a phenomenological study.

    PubMed

    Mohammadpour, Ali; Yekta, Zohre Parsa; Nikbakht Nasrabadi, Ali R

    2010-12-01

    Adherence to the treatment regimen is essential to the success of highly active antiretroviral therapy for patients who are infected with HIV. The evidence suggests that poor adherence to antiretroviral drug therapy is a major problem that has the potential to diminish effective viral suppression, promote viral resistance, and place patients at risk for hospitalization, opportunistic infections, and an increased risk of HIV transmission. The primary aim of this study was to understand patients' experiences regarding their adherence to antiretroviral drug therapy. Thus, 19 participants were recruited for in-depth interviews regarding their adherence to drug regimens. All the interviews were transcribed verbatim and analyzed by using Benner's phenomenological analysis approach. Four main themes emerged from the data: (i) choosing to live and the decision to start taking medications; (ii) strategies for adhering to the regimen and managing the side-effects; (iii) relationships with healthcare providers; and (iv) advantages of the medications as a motivator to continue one's adherence to the regimen. Studying and understanding the experiences of patients can provide new insights and strategies in order to enhance patients' adherence to highly active antiretroviral therapy. PMID:21210925

  10. Vitamin E Concentrations in Adults with HIV/AIDS on Highly Active Antiretroviral Therapy

    PubMed Central

    Kaio, Daniella J. Itinoseki; Rondó, Patricia Helen C.; Luzia, Liania Alves; Souza, José Maria P.; Firmino, Aline Vale; Santos, Sigrid Sousa

    2014-01-01

    HIV/AIDS patients are probably more predisposed to vitamin E deficiency, considering that they are more exposed to oxidative stress. Additionally, there are an extensive number of drugs in the highly active antiretroviral therapy (HAART) regimens that may interfere with vitamin E concentrations. The objective of this study was to compare serum concentrations of alpha-tocopherol in 182 HIV/AIDS patients receiving different HAART regimens. The patients were divided into three groups according to regimen: nucleoside analog reverse-transcriptase inhibitors (NRTIs) + non-nucleoside analog reverse-transcriptase inhibitors (NNRTIs); NRTIs + protease inhibitors + ritonavir; NRTIs + other classes. Alpha-tocopherol was assessed by high-performance liquid chromatography. Multiple linear regression analysis was used to evaluate the effects of HAART regimen, time of use, and compliance with the regimen on alpha-tocopherol concentrations. Alpha-tocopherol concentrations were on average 4.12 μmol/L lower for the NRTIs + other classes regimen when compared to the NRTIs + NNRTIs regimen (p = 0.037). A positive association (p < 0.001) was observed between alpha-tocopherol and cholesterol concentrations, a finding due, in part, to the relationship between liposoluble vitamins and lipid profile. This study demonstrated differences in alpha-tocopherol concentrations between patients using different HAART regimens, especially regimens involving the use of new drugs. Long-term prospective cohort studies are needed to monitor vitamin E status in HIV/AIDS patients since the beginning of treatment. PMID:25225815

  11. Effect of Highly Active Antiretroviral Therapy on Incident AIDS Using Calendar Period as an Instrumental Variable

    PubMed Central

    Cole, Stephen R.; Greenland, Sander; Brown, Todd T.; Chmiel, Joan S.; Kingsley, Lawrence; Detels, Roger

    2009-01-01

    Human immunodeficiency virus (HIV) researchers often use calendar periods as an imperfect proxy for highly active antiretroviral therapy (HAART) when estimating the effect of HAART on HIV disease progression. The authors report on 614 HIV-positive homosexual men followed from 1984 to 2007 in 4 US cities. During 5,321 person-years, 268 of 614 men incurred acquired immunodeficiency syndrome, 49 died, and 90 were lost to follow-up. Comparing the pre-HAART calendar period (<1996) with the HAART calendar period (≥1996) resulted in a naive rate ratio of 3.62 (95% confidence limits: 2.67, 4.92). However, this estimate is likely biased because of misclassification of HAART use by calendar period. Simple calendar period approaches may circumvent confounding by indication at the cost of inducing exposure misclassification. To correct this misclassification, the authors propose an instrumental-variable estimator analogous to ones previously used for noncompliance corrections in randomized clinical trials. When the pre-HAART calendar period was compared with the HAART calendar period, the instrumental-variable rate ratio was 5.02 (95% confidence limits: 3.45, 7.31), 39% higher than the naive result. Weighting by the inverse probability of calendar period given age at seroconversion, race/ethnicity, and time since seroconversion did not appreciably alter the results. These methods may help resolve discrepancies between observational and randomized evidence. PMID:19318615

  12. Hybrid data capture for monitoring patients on highly active antiretroviral therapy (HAART) in urban Botswana.

    PubMed Central

    Bussmann, Hermann; Wester, C. William; Ndwapi, Ndwapi; Vanderwarker, Chris; Gaolathe, Tendani; Tirelo, Geoffrey; Avalos, Ava; Moffat, Howard; Marlink, Richard G.

    2006-01-01

    Individual patient care and programme evaluation are pivotal for the success of antiretroviral treatment programmes in resource-limited countries. While computer-aided documentation and data storage are indispensable for any large programme, several important issues need to be addressed including which data are to be collected, who collects it and how it is entered into an electronic database. We describe a patient-monitoring approach, which uses patient encounter forms (in hybrid paper + electronic format) based on optical character recognition, piloted at Princess Marina Hospital in Gaborone, Botswana's first public highly active antiretroviral therapy (HAART) outpatient clinic. Our novel data capture approach collects "key" data for tracking patient and programme outcomes. It saves physician time and does not detract from clinical care. PMID:16501730

  13. Sex Differences in HIV Outcomes in the Highly Active Antiretroviral Therapy Era: A Systematic Review

    PubMed Central

    Melekhin, Vlada V.; Sterling, Timothy R.

    2014-01-01

    Abstract To assess sex disparities in AIDS clinical and laboratory outcomes in the highly active antiretroviral therapy (HAART) era we conducted a systematic review of the published literature on mortality, disease progression, and laboratory outcomes among persons living with HIV and starting HAART. We performed systematic PubMed and targeted bibliographic searches of observational studies published between January, 1998, and November, 2013, that included persons starting HAART and reported analyses of mortality, progression to AIDS, or virologic or immunologic treatment outcomes by sex. Risk ratios (relative risks, odd ratios, and hazard ratios) and 95% confidence intervals were obtained. Sixty-five articles were included in this review. Thirty-nine studies were from North America and Europe and 26 were from Latin America, Asia, and Africa. Forty-four studies (68%) showed no statistically significant difference in risk of mortality, progression to AIDS, or virologic or immunologic treatment outcomes by sex. Decreased risk of death among females compared to males was observed in 24 of the 25 articles that included mortality analyses [pooled risk ratio 0.72 (95% confidence interval=0.69–0.75)], and decreased risk of death or AIDS was observed in 9 of the 13 articles that examined the composite outcome [pooled risk ratio=0.91 (0.84–0.98)]. There was no significant effect of sex on the risk of progression to AIDS [pooled risk ratio=1.15 (0.99–1.31)]. In this systematic review, females starting HAART appeared to have improved survival compared to males. However, this benefit was not associated with decreased progression to either AIDS or to differences in virologic or immunologic treatment outcomes. PMID:24401107

  14. Enteric parasitic infections in HIV/AIDS patients before and after the highly active antiretroviral therapy.

    PubMed

    Bachur, Tatiana Paschoalette Rodrigues; Vale, Josias Martins; Coêlho, Ivo Castelo Branco; Queiroz, Telma Régia Bezerra Sales de; Chaves, Cristina de Souza

    2008-04-01

    Enteroparasites are related to gastrointestinal alterations among patients with HIV/AIDS, some causing severe manifestations in the period before the institution of the highly active antiretroviral therapy (HAART). The prevalence of enteroparasitoses in patients with HIV/AIDS seen at two hospitals in Ceará , Brazil, was compared in the pre-HAART (Group 1; n = 482) and HAART (Group 2; n = 100) eras. Fecal parasitologic examinations (FPE) were performed using the direct, Lutz, Baermann-Moraes and modified Ziehl-Neelsen methods. The following parasites were detected in Groups 1 and 2, respectively: Strongyloides stercoralis--30.1% and 11% (p<0.0001), Ascaris lumbricoides--15.6% and 2% (p<0.0001), hookworms--3.7% and 2% (p<0.0001), Trichuris trichiura--13.1% and 1% (p<0.0001), Hymenolepis nana--0 and 1% (p = 0.1718), Giardia duodenalis--7.9% and 1% (p = 0.0076), Entamoeba histolytica/dispar--3.3% and 1% (p = 0.3301), Isospora belli--4.8% and 1% (p = 0.0993), Cryptosporidium sp.--8.1% and 0 (p = 0.0007), and non-pathogenic protozoans as well. There was a significant reduction in the prevalence of enteroparasites between the eras (63.9% to 24%; p<0.0001). In the HAART era, the following observations were made: greater frequency of enteroparasites in patients without antiretroviral therapy (p = 0.0575), as in those with AIDS (p = 0.08), and diarrhea (36% of the patients); lack of association with positive FPE (p = 0.626); and non-detection of Cryptosporidium sp. Strongyloides stercoralis showed an elevated prevalence in the two eras and was more frequent in men (32.41%) than women (19.04%) of Group 1 (p = 0.018), a finding suggesting the transmission of the helminth through sodomy. The advent of the HAART modified the profile of opportunistic infections, including parasites, probably due to the reconstitution of cellular immunity and the direct action of HAART on the parasites. PMID:18641847

  15. Adherence to highly active antiretroviral therapy in Hyderabad, India: barriers, facilitators and identification of target groups.

    PubMed

    Dworkin, Mark S; Douglas, G W; Sabitha Rani, G P; Chakraborty, Apurba

    2016-03-01

    We assessed the barriers and facilitators to highly active antiretroviral therapy adherence and determined their prevalence among HIV/AIDS patients in Hyderabad, India. We conducted a cross-sectional study among HIV-infected adults prescribed highly active antiretroviral therapy and receiving care from nine clinics. Depression was screened using Patient Health Questionnaire 9 and facilitators of HIV medication adherence were assessed using an 11-item scale which yielded a total positive attitude to disease score. Prevalence ratios of non-adherence between different categories of potential risk factors were calculated. We compared mean 'facilitators to adherence' scores between the adherent and non-adherent population. Multivariable Poisson regression with robust variance was used to identify independent risk factors. Among the 211 respondents, nearly 20% were non-adherent, approximately 8% had either moderately severe or severe depression and mean score for combined facilitators to medication adherence was 33.35 (±7.88) out of a possible 44 points. Factors significantly associated with non-adherence included older age, female sex worker, moderate-to-severe depression and the combined facilitators to medication adherence score. These data from a broad range of clinical settings in Hyderabad reveal that key groups to focus on for adherence intervention are female sex workers, older persons and those with depression. PMID:25801316

  16. Brief Report: Highly Active Antiretroviral Therapy Mitigates Liver Disease in HIV Infection

    PubMed Central

    Seaberg, Eric C.; Phair, John P.; Witt, Mallory D.; Koletar, Susan L.; Thio, Chloe L.

    2016-01-01

    Abstract: To determine the impact of highly active antiretroviral therapy (HAART) on liver disease, we analyzed changes in the aspartate aminotransferase to platelet ratio index (APRI) pre- and post-HAART initiation among 441 HIV-monoinfected and 53 HIV-viral hepatitis–coinfected men. Before HAART, APRI increased 17% and 34% among the HIV-monoinfected and coinfected men, respectively. With HAART initiation, APRI decreased significantly in men who achieved HIV RNA of <500 copies per milliliter: 16% for HIV-monoinfected and 22% for coinfected men. Decreases in APRI were dependent on HIV suppression. This protective effect of HAART decreased after 2 years, particularly in the HIV-monoinfected men. PMID:26945179

  17. A case of atypical progressive outer retinal necrosis after highly active antiretroviral therapy.

    PubMed

    Woo, Se Joon; Yu, Hyeong Gon; Chung, Hum

    2004-06-01

    This is a report of an atypical case of progressive outer retinal necrosis (PORN) and the effect of highly active antiretroviral therapy (HAART) on the clinical course of viral retinitis in an acquired immunodeficiency syndrome (AIDS) patient. A 22-year-old male patient infected with human immunodeficiency virus (HIV) presented with unilaterally reduced visual acuity and a dense cataract. After cataract extraction, retinal lesions involving the peripheral and macular areas were found with perivascular sparing and the mud-cracked, characteristic appearance of PORN. He was diagnosed as having PORN based on clinical features and was given combined antiviral treatment. With concurrent HAART, the retinal lesions regressed, with the regression being accelerated by further treatment with intravenous acyclovir and ganciclovir. This case suggests that HAART may change the clinical course of PORN in AIDS patients by improving host immunity. PORN should be included in the differential diagnosis of acute unilateral cataract in AIDS patients. PMID:15255240

  18. Brief Report: Highly Active Antiretroviral Therapy Mitigates Liver Disease in HIV Infection.

    PubMed

    Price, Jennifer C; Seaberg, Eric C; Phair, John P; Witt, Mallory D; Koletar, Susan L; Thio, Chloe L

    2016-07-01

    To determine the impact of highly active antiretroviral therapy (HAART) on liver disease, we analyzed changes in the aspartate aminotransferase to platelet ratio index (APRI) pre- and post-HAART initiation among 441 HIV-monoinfected and 53 HIV-viral hepatitis-coinfected men. Before HAART, APRI increased 17% and 34% among the HIV-monoinfected and coinfected men, respectively. With HAART initiation, APRI decreased significantly in men who achieved HIV RNA of <500 copies per milliliter: 16% for HIV-monoinfected and 22% for coinfected men. Decreases in APRI were dependent on HIV suppression. This protective effect of HAART decreased after 2 years, particularly in the HIV-monoinfected men. PMID:26945179

  19. Highly active antiretroviral therapy-related mechanisms of endothelial and platelet function alterations.

    PubMed

    Gresele, Paolo; Falcinelli, Emanuela; Momi, Stefania; Francisci, Daniela; Baldelli, Franco

    2014-01-01

    Highly active antiretroviral therapy (HAART) has transformed human immunodeficiency virus (HIV) infection into a chronic condition, which has allowed the infected population to age and become prone to chronic degenerative diseases common to the general population, including atherosclerotic cardiovascular disease, and coronary artery disease (CAD). Possible causative mechanisms of HIV-associated CAD are related to classic cardiovascular risk factors, such as dyslipidemia, insulin resistance, and fat redistribution, which may be due to either HIV infection or to HAART-associated toxicity. However, other mechanisms are emerging as crucial for the cardiovascular complication of HIV and HAART. This article analyzes the effects of HIV and HAART on endothelial function, endothelium-leukocyte interactions, and platelets as possible mechanisms of enhanced cardiovascular risk. PMID:24987863

  20. Ophthalmic manifestations of HIV in the highly active anti-retroviral therapy era.

    PubMed

    Mowatt, L

    2013-01-01

    HIV-related eye disease can be classified as retinal HIV microangiopathy, opportunistic infections, neuro-ophthalmic manifestations and unusual malignancies. There is a 52-100% lifetime accumulative risk of HIV patients developing eye problems. Seventy-seven per cent of patients with ocular manifestations of HIV had CD4 counts < 200 cells/μL. Cytomegalovirus (CMV) is the most prevalent opportunistic infection, however, Africa has a low incidence of this, and more commonly squamous cell carcinoma, compared to the western hemisphere. Due to highly active antiretroviral therapy (HAART), the anti-CMV therapy may be discontinued if the CD4+ T cell count is > 100 cells/μL for a minimum of three months. Despite HAART, patients with a CD4 count < 50 cells/μL have a similar risk of developing CMV retinitis as compared to the pre-HAART era. Opportunistic infections include CMV, herpetic retinopathy (progressive outer retinal necrosis - PORN), less commonly toxoplasmosis, pneumocystis and cryptococcus. Malignancies associated with HIV include Kaposi's sarcoma and conjunctival squamous cell carcinoma. Cranial nerve palsies, optic disc swelling and atrophy are characteristic neuro-ophthalmic features. They usually occur secondary to meningitis/encephalitis (from cryptococcus and tuberculosis). With the advent of HAART, new complications have developed in CMV retinitis: immune recovery uveitis (IRU) and cystoid macula oedema (CMO). Immune recovery uveitis occurs in 71% of patients if HAART is started before the induction of the anti-CMV treatment. However, this is reduced to 31% if HAART is started after the induction treatment. Molluscum contagiosum and Kaposi's sarcoma can spontaneously resolve on HAART. Highly active anti-retroviral therapy has reduced the frequencies of opportunistic infections and improved the remission duration in HIV patients. PMID:24756590

  1. Highly active antiretroviral therapy and tuberculosis control in Africa: synergies and potential.

    PubMed Central

    Harries, Anthony D.; Hargreaves, Nicola J.; Chimzizi, Rehab; Salaniponi, Felix M.

    2002-01-01

    HIV/AIDS (human immunodeficiency virus/acquired immunodeficiency syndrome) and TB (tuberculosis) are two of the world's major pandemics, the brunt of which falls on sub-Saharan Africa. Efforts aimed at controlling HIV/AIDS have largely focused on prevention, little attention having been paid to care. Work on TB control has concentrated on case detection and treatment. HIV infection has complicated the control of tuberculosis. There is unlikely to be a decline in the number of cases of TB unless additional strategies are developed to control both this disease and HIV simultaneously. Such strategies would include active case-finding in situations where TB transmission is high, the provision of a package of care for HIV-related illness, and the application of highly active antiretroviral therapy. The latter is likely to have the greatest impact, but for this therapy to become more accessible in Africa the drugs would have to be made available through international support and a programme structure would have to be developed for its administration. It could be delivered by means of a structure based on the five-point strategy called DOTS, which has been adopted for TB control. However, it may be unrealistic to give TB control programmes the responsibility for running such a programme. A better approach might be to deliver highly active antiretroviral therapy within a comprehensive HIV/AIDS management strategy complementing the preventive work already being undertaken by AIDS control programmes. TB programmes could contribute towards the development and implementation of this strategy. PMID:12132003

  2. HIV-Associated Lung Cancer in the Era of Highly Active Antiretroviral Therapy (HAART)

    PubMed Central

    Pakkala, Suchita; Chen, Zhengjia; Rimland, David; Owonikoko, Taofeek K.; Gunthel, Clifford; Brandes, Johann R.; Saba, Nabil R.; Shin, Dong M.; Curran, Walter J.; Khuri, Fadlo R.; Ramalingam, Suresh S.

    2011-01-01

    Background Lung cancer is the leading cause of death among non-acquired immunodeficiency syndrome (AIDS) defining malignancies. Since highly active anti-retroviral therapy (HAART) has improved survival for human immunodeficiency virus (HIV) patients, we evaluated lung cancer outcomes in the HAART era. Methods HIV-positive patients diagnosed with lung cancer in our institution during the HAART era (1995-2008) were analyzed. Patient charts were reviewed for clinical and laboratory data. CD4 count at diagnosis was treated as a continuous variable and subcategorized into distinct variables with 3 cut-off points (50, 200, & 500 μl). Pearson’s correlation coefficients were estimated for each covariate studied. Survival was determined by the Kaplan-Meier method. Results Out of 80 patients, 73 had non-small cell lung cancer. Baseline characteristics were: median age-52 yrs; male-80%; African American-84%; injection drug use-25%; smokers-100%; and prior exposure to antiretroviral agents-55%. Mean CD4 count and viral load were 304 μL and 82,420 copies/ml, respectively at cancer diagnosis. The latency between diagnosis of HIV and lung cancer was significantly shorter in women (4.1 yrs vs. 7.7 yrs, P=0.02) and 71% of the patients received anti-cancer therapy. The 1- and 3-year survival rates were 31% and 4% overall. Grade 3/4 toxicities occurred in 60% with chemo-radiation vs. 36% with chemotherapy. Cancer-related survival was better for patients with CD4 count >200 (P=0.0298) and >500 (P=0.0076). Conclusions The latency from diagnosis of HIV to lung cancer was significantly shorter for women. Although outcomes for lung cancer patients with HIV remain poor, high CD4 count is associated with an improved lung cancer-related survival. PMID:21713759

  3. Highly Active Antiretroviral Therapy and Adverse Birth Outcomes Among HIV-Infected Women in Botswana

    PubMed Central

    Chen, Jennifer Y.; Ribaudo, Heather J.; Souda, Sajini; Parekh, Natasha; Ogwu, Anthony; Lockman, Shahin; Powis, Kathleen; Dryden-Peterson, Scott; Creek, Tracy; Jimbo, William; Madidimalo, Tebogo; Makhema, Joseph; Essex, Max; Shapiro, Roger L

    2012-01-01

    Background. It is unknown whether adverse birth outcomes are associated with maternal highly active antiretroviral therapy (HAART) in pregnancy, particularly in resource-limited settings. Methods. We abstracted obstetrical records at 6 sites in Botswana for 24 months. Outcomes included stillbirths (SBs), preterm delivery (PTD), small for gestational age (SGA), and neonatal death (NND). Among human immunodeficiency virus (HIV)–infected women, comparisons were limited to HAART exposure status at conception, and those with similar opportunities for outcomes. Comparisons were adjusted for CD4+ lymphocyte cell count. Results. Of 33 148 women, 32 113 (97%) were tested for HIV, of whom 9504 (30%) were HIV infected. Maternal HIV was significantly associated with SB, PTD, SGA, and NND. Compared with all other HIV-infected women, those continuing HAART from before pregnancy had higher odds of PTD (adjusted odds ratio [AOR], 1.2; 95% confidence interval [CI], 1.1, 1.4), SGA (AOR, 1.8; 95% CI, 1.6, 2.1) and SB (AOR, 1.5; 95% CI, 1.2, 1.8). Among women initiating antiretroviral therapy in pregnancy, HAART use (vs zidovudine) was associated with higher odds of PTD (AOR, 1.4; 95% CI, 1.2, 1.8), SGA (AOR, 1.5; 95% CI, 1.2, 1.9), and SB (AOR, 2.5; 95% CI, 1.6, 3.9). Low CD4+ was independently associated with SB and SGA, and maternal hypertension during pregnancy with PTD, SGA, and SB. Conclusions. HAART receipt during pregnancy was associated with increased PTD, SGA, and SB. PMID:23066160

  4. Adverse Drug Reaction Profile in Patients on Anti-tubercular Treatment Alone and in Combination with Highly Active Antiretroviral Therapy

    PubMed Central

    Sadiq, Shamiya; Khajuria, Vijay; Mahajan, Annil; Singh, Jang B.

    2015-01-01

    Background and Objectives Adverse drug reactions are very common among patients on anti-tubercular treatment alone or in combination with highly active antiretroviral therapy but comparatively studied very less. Hence, the current study was done to evalaute the adverse drug reaction (ADR) profile in patients receiving anti-tubercular treatment (ATT) and ATT with highly active antiretroviral therapy (HAART). Materials and Methods A one year prospective, cross-sectional observational study was undertaken using suspected adverse drug data collection form available under Pharmacovigilance Programme of India. Results Seventy four patients receiving ATT & 32 patients on both ATT & HAART presented with 74 and 45 adverse drug events (ADE) respectively. Males were more affected than females in both the groups. DOTS category- 1 regimen was mostly responsible for ADE in both the groups. Epigastric pain was the most common ADE in TB patients, while anaemia was the most common presentation in TB with HIV group. On comparison, ADE rate of TB with HIV co-morbid patients was more (55.8%) than TB patients (0.36%) (p < 0.001). Urban population presented more with ADR in TB/HIV group unlike rural population in TB group (p<0.0001). Whereas, illiterate were more involved in TB group unlike literate in TB/HIV group (p<0.05). Type A reactions were more common in TB group (p < 0.001). Addition of drugs for the management of ADR events was more in TB/HIV group (p < 0.001) as compared to TB group. Rest all the parameters were comparable. Conclusion The study underscores that concomitant HAART and ATT, result in more ADRs in comparison to ATT alone demanding collaboration & integration of National AIDS Control programme and PvPI to enhance drug safety in this field. PMID:26557538

  5. Hypertension among HIV-Infected Adults Receiving Highly Active Antiretroviral Therapy (HAART) in Malaysia

    PubMed Central

    Hejazi, Nazisa; MSL, Huang; Lin, Khor Geok; Choong, Lee Christopher Kwok

    2014-01-01

    There are increasing researches about non-communicable disease such as elevated blood pressure among people living with HIV before and after initiation of highly active antiretroviral therapy (HAART). This cross-sectional study was designed to determine the prevalence of hypertension and associated risk factors among 340 HIV-infected patients on antiretroviral therapy at a Malaysian public hospital providing HIV-related treatment. Data on socioeconomic background, anthropometry, medical history and dietary intake of the patients were collected. Hypertension is defined as blood pressure ≥130/85 (mm Hg). Prevalence of hypertension was 45.60% (n=155) of which 86.5% of the hypertensive group were male (n=134). The results showed that increase in age (OR 1.051, 95% confidence interval (CI) 1.024-1.078), higher body mass index (OR 1.18, 95% CI 1.106-2.71), bigger waist circumference (OR 1.18, 95%CI 1.106-2.71), higher waist-hip ratio (OR 1.070, 95%CI 1.034-1.106), higher fasting plasma glucose (OR 1.332, 95% CI 0.845-2.100) and percentage energy intake from protein >15 (OR 2.519, 95%CI 1.391-4.561) were significant risk factors for hypertension (p<0.001). After adjusting for other variables, increasing age (adjusted odds ratio (aOR) 1.069 95%CI 1.016-1.124, p=0.010), being male (aOR 3.026, 95%CI 1.175-7.794, p=0.022) and higher body mass index (aOR 1.26, 95%CI 1.032-1.551, p=0.024) were independently associated with hypertension. None of the antiretroviral therapy and immunologic factors was linked to hypertension. In conclusion hypertension among PLHIV was linked to the well-known risk factors such as age, gender and body mass index. With HAART, people can live longer by making monitoring and control of some reversible factors, especially excessive weight gain for maintaining quality of life. PMID:24576366

  6. Viral Tropism and Antiretroviral Drug Resistance in HIV-1 Subtype C-Infected Patients Failing Highly Active Antiretroviral Therapy in Johannesburg, South Africa

    PubMed Central

    Ketseoglou, Irene; Lukhwareni, Azwidowi; Steegen, Kim; Carmona, Sergio; Stevens, Wendy S.

    2014-01-01

    Abstract Reports show that up to 30% of antiretroviral drug-naive patients in Johannesburg have CXCR4-utilizing HIV-1 subtype C. We assessed whether HIV-1 subtype C-infected individuals failing highly active antiretroviral therapy (HAART) have a higher proportion of CXCR4-utilizing viruses compared to antiretroviral drug-naive patients. The V3 loop was sequenced from plasma from 100 randomly selected HAART-failing patients, and tropism was established using predictive algorithms. All patients harbored HIV-1 subtype C with at least one antiretroviral drug resistance mutation. Viral tropism prediction in individuals failing HAART revealed similar proportions (29%) of X4-utilizing viruses compared to antiretroviral drug-naive patients (30%). Findings are in contrast to reports from Durban in which 60% of HAART-failing subjects harbored X4/dual/mixed-tropic viruses. Despite differences in proportions of X4-tropism within South Africa, the high proportion of thymidine analogue mutations (TAMs) and CXCR4-utilizing HIV-1 highlights the need for intensified monitoring of HAART patients and the predicament of diminishing drug options, including CCR5 antagonists, for patients failing therapy. PMID:24224886

  7. Adherence to highly active antiretroviral therapy in HIV-infected inmates.

    PubMed

    Inés, Sandra M; Moralejo, Leticia; Marcos, Miguel; Fuertes, Aurelio; Luna, Guillermo

    2008-03-01

    Adherence to highly active antiretroviral therapy (HAART) has been scarcely studied in correctional settings. Our study aims to evaluate the relationship between adherence and virological outcome and to determine factors related to adherence in correctional settings. A cross-sectional retrospective study was performed in Topas prison (Salamanca, Spain). 50 inmates starting HAART were studied. Adherence was estimated through a self-report questionnaire and variables related to adherence (covering individual factors, the illness itself and the therapeutic regimen) were recorded. HIV-RNA levels and CD4 lymphocyte count were measured before starting therapy and six months after. Statistical analysis was performed using univariate and multivariate methods. 21 inmates (42%) were considered adherent and 29 (58%) were non-adherent. Adherence to treatment, as measured by our questionnaire, was the only significant and independent factor associated with an undetectable viral load at six months of therapy. Five variables were significantly associated with adherence to treatment, four of them as predictor factors for good adherence: an active occupation inside prison, the absence of HIV-related symptoms, a good or average acceptance of treatment, and a higher academic background; previous injection drug use as a risk factor for HIV transmission was associated with non-adherence. A simple self-report questionnaire may be useful for assessing adherence in prison inmates. Recognizing variables associated with adherence is essential to identify prisoners at high risk of being non-adherents in order to develop strategies for improving compliance. PMID:18336264

  8. Disseminated rhodococcus equi infection in HIV infection despite highly active antiretroviral therapy

    PubMed Central

    2011-01-01

    Background Rhodococcus equi (R.equi) is an acid fast, GRAM + coccobacillus, which is widespread in the soil and causes pulmonary and extrapulmonary infections in immunocompromised people. In the context of HIV infection, R.equi infection (rhodococcosis) is regarded as an opportunistic disease, and its outcome is influenced by highly active antiretroviral therapy (HAART). Case presentation We report two cases of HIV-related rhodococcosis that disseminated despite suppressive HAART and anti-rhodococcal treatment; in both cases there was no immunological recovery, with CD4+ cells count below 200/μL. In the first case, pulmonary rhodococcosis presented 6 months after initiation of HAART, and was followed by an extracerebral intracranial and a cerebral rhodococcal abscess 1 and 8 months, respectively, after onset of pulmonary infection. The second case was characterized by a protracted course with spread of infection to various organs, including subcutaneous tissue, skin, colon and other intra-abdominal tissues, and central nervous system; the spread started 4 years after clinical resolution of a first pulmonary manifestation and progressed over a period of 2 years. Conclusions Our report highlights the importance of an effective immune recovery, despite fully suppressive HAART, along with anti-rhodococcal therapy, in order to clear rhodococcal infection. PMID:22168333

  9. Erectile Dysfunction Among HIV Patients Undergoing Highly Active Antiretroviral Therapy: Dyslipidemia as a Main Risk Factor

    PubMed Central

    Romero-Velez, Gustavo; Lisker-Cervantes, Andrés; Villeda-Sandoval, Christian I; Sotomayor de Zavaleta, Mariano; Olvera-Posada, Daniel; Sierra-Madero, Juan Gerardo; Arreguin-Camacho, Lucrecia O; Castillejos-Molina, Ricardo A

    2014-01-01

    Objective To assess the prevalence and risk factors of erectile dysfunction (ED) in HIV patients from the HIV clinic of a tertiary referral center in Mexico City. Design Prevalence was obtained from cross-sectional studies, and the International Index of Erectile Function (IIEF), a standardized method, was used to assess ED. Methods A cross-sectional study was performed in the HIV clinic. Participants completed the IIEF to allow ED assessment. Information on demographics, clinical and HIV-related variables was retrieved from their medical records. Results One hundred and nine patients were included, with a mean age of 39.9 ± 8.8 years. ED was present in 65.1% of the individuals. Patients had been diagnosed with HIV for a mean of 92.7 ± 70.3 months and had undergone a mean 56.4 ± 45.5 months of HAART. The only variable associated with ED in the univariate analysis was dyslipidemia, and this association was also found in the multivariate analysis (P = 0.01). Conclusions ED is highly prevalent in HIV patients. Dyslipidemia should be considered as a risk factor for ED in HIV patients. Romero-Velez G, Lisker-Cervantes A, Villeda-Sandoval CI, Sotomayor de Zavaleta M, Olvera-Posada D, Sierra-Madero JG, Arreguin-Camacho LO, and Castillejos-Molina RA. Erectile dysfunction among HIV patients undergoing highly active antiretroviral therapy: Dyslipidemia as a main risk factor. Sex Med 2014;2:24–30. PMID:25356298

  10. Glycaemic profile changes by highly active antiretroviral therapy in human immunodeficiency virus-infected patients.

    PubMed

    Duro, M; Rebelo, I; Barreira, S; Sarmento-Castro, R; Medeiros, R; Almeida, C

    2015-10-01

    To study dysglycaemia in human immunodeficiency virus (HIV)-infected patients we conducted a retrospective cohort study of the glucose profile in HIV-infected patients. The fasting blood glucose was analysed taking into consideration conventional risk factors as well as HIV infection and highly active antiretroviral therapy (HAART). One hundred seventy-three cases were selected for this study. Five risk factors had significant effects (p < 0.05) on glucose levels: age, body mass index (BMI), hepatitis C virus/hepatitis B virus (HCV/HBV) co-infection, viral load (VL), and CD4(+) T-lymphocyte count. Fasting blood glucose levels increased with age (0.59 mg/dL/year), decreased with the VL (-4.1 × 10(-6 )mg/dL/number of viral RNA copies) and the CD4(+) T-lymphocyte count (-0.016 mg/dL/cell count). Furthermore, obese patients and those co-infected with HCV/HBV were more prone to develop dysglycaemia having, on average, 15.4 mg/dL and 13.8 mg/dL higher levels, respectively, of fasting blood glucose. Despite an increase of 1.0% and 8.4% in the glucose levels noticed among HIV patients treated with non-nucleotide inhibitors of reverse transcriptase and protease inhibitors, respectively, HAART did not prove to be a significant predictor of fasting glucose levels as well as lipodystrophy and male gender. Age, BMI, HCV/HBV co-infection and HIV-related (VL and CD4(+) T-lymphocyte count) factors seem to be the most influential on fasting blood glucose levels in HIV-infected individuals. PMID:25281540

  11. Importance of Baseline Prognostic Factors With Increasing Time Since Initiation of Highly Active Antiretroviral Therapy

    PubMed Central

    2012-01-01

    Background The extent to which the prognosis for AIDS and death of patients initiating highly active antiretroviral therapy (HAART) continues to be affected by their characteristics at the time of initiation (baseline) is unclear. Methods We analyzed data on 20,379 treatment-naive HIV-1–infected adults who started HAART in 1 of 12 cohort studies in Europe and North America (61,798 person-years of follow-up, 1844 AIDS events, and 1005 deaths). Results Although baseline CD4 cell count became less prognostic with time, individuals with a baseline CD4 count <25 cells/µL had persistently higher progression rates than individuals with a baseline CD4 count >350 cells/µL (hazard ratio for AIDS = 2.3, 95% confidence interval [CI]: 1.0 to 2.3; mortality hazard ratio = 2.5, 95% CI: 1.2 to 5.5, 4 to 6 years after starting HAART). Rates of AIDS were persistently higher in individuals who had experienced an AIDS event before starting HAART. Individuals with presumed transmission by means of injection drug use experienced substantially higher rates of AIDS and death than other individuals throughout follow-up (AIDS hazard ratio = 1.6, 95% CI: 0.8 to 3.0; mortality hazard ratio = 3.5, 95% CI: 2.2 to 5.5, 4 to 6 years after starting HAART). Conclusions Compared with other patient groups, injection drug users and patients with advanced immunodeficiency at baseline experience substantially increased rates of AIDS and death up to 6 years after starting HAART. PMID:18043315

  12. The Influence of Different Types of Alcoholic Beverages on Disrupting Highly Active Antiretroviral Treatment (HAART) Outcome

    PubMed Central

    Míguez-Burbano, María José; Lewis, John E.; Fishman, Joel; Asthana, Deshratn; Malow, Robert M.

    2009-01-01

    Aims: Studies have yielded conflicting results regarding alcohol's influence on HIV outcomes, particularly after highly active antiretroviral treatment (HAART). Discrepant findings may be related to confounding variables, including gender, patterns of alcohol abuse and type of alcohol beverage beyond the amount consumed. Methods: Using a cohort study, differences in HAART effectiveness after 24 weeks of therapy were compared as a function of amount and preference for alcohol, drinking only liquor (LI, n = 55) or only wine or beer (BW, n = 110). Given the critical role of thymus on HAART response, changes in thymus size, CD4s, naïve lymphocytes and viral loads were assessed. Results: After HAART, positive increases in both CD4s (+12 cell counts/mm3) and thymus size (+0.7 mm3) were evident in the BW group. In contrast, the LI subgroup exhibited a decline in both parameters (−4 CD4 cells/mm3 and −0.6 mm3 in thymus size). Women in the LI group exhibited significantly lower CD4 (163.4 ± 46.2) and naïve counts (178 ± 69.5) than LI men (CD4: 281.6 ± 203, P = 0.05; lymphocytes: 301.4 ± 198, P = 0.04). In adjusted regression models, the LI compared to the BW subgroup had greater odds of maintaining detectable viral loads (RR = 1.35, 95% CI 1.04–1.75; P = 0.03), increased thymus volumes (RR = 3.8, P = 0.04) and replenished naïve cells (RR = 13, P = 0.02). Conclusions: Liquor was associated with thymus deterioration and thus with poorer viro-immune outcomes after HAART. Subtyping participants by alcohol consumption patterns seems to be clinically relevant and needs to be accounted for in future studies. PMID:19454401

  13. The immune pathogenesis of immune reconstitution inflammatory syndrome associated with highly active antiretroviral therapy in AIDS.

    PubMed

    Zheng, Yuhuang; Zhou, Huaying; He, Yan; Chen, Zi; He, Bo; He, Mei

    2014-12-01

    The present study investigated the immunological pathogenesis of immune reconstitution inflammatory syndrome (IRIS) in acquired immunodeficiency syndrome (AIDS) patients undergoing highly active antiretroviral therapy (HAART). A total of 238 patients with AIDS who received initial HAART were included in this prospective cohort study. Blood samples were collected immediately, at baseline, at week 12, and at week 24 after initial HAART and at the onset of IRIS. Lymphocyte subsets, Th1 and Th2 cytokines, and interleukin (IL)-7 levels were measured by flow cytometry or ELISA. Among the 238 patients with AIDS who received HAART, 47 patients developed IRIS. The percentages of CD4(+) and CD8(+) naive, memory, and activated cells exhibited no significant differences between AIDS patients with and without IRIS 24 weeks after initial HAART. The percentage of CD4(+)CD25(+)Foxp3(+) regulatory T cells was lower in IRIS patients than in non-IRIS patients before HAART, 12 weeks after HAART, 24 weeks after HAART, and at the onset of IRIS. IL-2 and interferon (IFN)-γ levels were significantly higher at week 4 and at the onset of IRIS in IRIS patients than in non-IRIS patients. In contrast, IL-4 and IL-10 levels were significantly lower at week 4 and at the onset of IRIS in IRIS patients than in non-IRIS patients. Plasma IL-7 decreased gradually with the progression of HAART. The level of IL-7 was higher in IRIS patients than in non-IRIS patients at all follow-up time points. An imbalance of Th1/Th2 cytokines, a consistently low CD(+)CD25(+)Fox3(+) percentage, and a high IL-7 level may be crucial in the pathogenesis of IRIS in AIDS patients who had received HAART. PMID:25131160

  14. Polyomavirus JCV excretion and genotype analysis in HIV-infected patients receiving highly active antiretroviral therapy

    NASA Technical Reports Server (NTRS)

    Lednicky, John A.; Vilchez, Regis A.; Keitel, Wendy A.; Visnegarwala, Fehmida; White, Zoe S.; Kozinetz, Claudia A.; Lewis, Dorothy E.; Butel, Janet S.

    2003-01-01

    OBJECTIVE: To assess the frequency of shedding of polyomavirus JC virus (JCV) genotypes in urine of HIV-infected patients receiving highly active antiretroviral therapy (HAART). METHODS: Single samples of urine and blood were collected prospectively from 70 adult HIV-infected patients and 68 uninfected volunteers. Inclusion criteria for HIV-infected patients included an HIV RNA viral load < 1000 copies, CD4 cell count of 200-700 x 106 cells/l, and stable HAART regimen. PCR assays and sequence analysis were carried out using JCV-specific primers against different regions of the virus genome. RESULTS: JCV excretion in urine was more common in HIV-positive patients but not significantly different from that of the HIV-negative group [22/70 (31%) versus 13/68 (19%); P = 0.09]. HIV-positive patients lost the age-related pattern of JCV shedding (P = 0.13) displayed by uninfected subjects (P = 0.01). Among HIV-infected patients significant differences in JCV shedding were related to CD4 cell counts (P = 0.03). Sequence analysis of the JCV regulatory region from both HIV-infected patients and uninfected volunteers revealed all to be JCV archetypal strains. JCV genotypes 1 (36%) and 4 (36%) were the most common among HIV-infected patients, whereas type 2 (77%) was the most frequently detected among HIV-uninfected volunteers. CONCLUSION: These results suggest that JCV shedding is enhanced by modest depressions in immune function during HIV infection. JCV shedding occurred in younger HIV-positive persons than in the healthy controls. As the common types of JCV excreted varied among ethnic groups, JCV genotypes associated with progressive multifocal leukoencephalopathy may reflect demographics of those infected patient populations.

  15. Oral manifestations of human immunodeficiency virus in children: An institutional study at highly active antiretroviral therapy centre in India

    PubMed Central

    Ponnam, Srinivas Rao; Srivastava, Gautam; Theruru, Kotaih

    2012-01-01

    Context: More than 1000 children are newly infected with Human immunodefi ciency virus (HIV) every day, and of these more than half will die as a result of AIDS due to lack of access to HIV treatment. HIV disease varies considerably in children. Among those infected prenatally, some experience few or no symptoms for years, whereas in others the disease progresses rapidly. The risk factors that influence the development of such oral manifestations include, low CD4+ T cell count, xerostomia and lack of highly active antiretroviral therapy (HAART). Aims: To identify the oral manifestations of HIV in children receiving HAART. Materials and Methods: The study comprised 95 children receiving HAART. 95 HIV +ve children not receiving HAART and 95 HIV –ve children were also included for comparing the manifestations of HIV. Statistical Analysis Used: Statistical analysis was done using Fisher's Chi-square test. Probability value (P value) was obtained for the three groups. Results: The manifestations of HIV that were observed in children receiving HAART include dental caries (26%), periodontal diseases (23%), candidiasis (19%), hyperpigmentation (17%), ulcerative stomatitis (9%) and one case of mucocele. These manifestations were compared with HIV +ve children not receiving HAART and HIV –ve children to find manifestations with statistical significance. Conclusions: We conclude that HAART had increased the disease-free states in HIV +ve children on HAART promising them better life span. The incidence of oral lesions can further come down with adequate oral hygiene measures in HIV-infected children. PMID:22923890

  16. Epstein-Barr virus DNA loads in adult human immunodeficiency virus type 1-infected patients receiving highly active antiretroviral therapy

    NASA Technical Reports Server (NTRS)

    Ling, Paul D.; Vilchez, Regis A.; Keitel, Wendy A.; Poston, David G.; Peng, Rong Sheng; White, Zoe S.; Visnegarwala, Fehmida; Lewis, Dorothy E.; Butel, Janet S.

    2003-01-01

    Patients with human immunodeficiency virus type 1 (HIV-1) infection are at high risk of developing Epstein-Barr virus (EBV)-associated lymphoma. However, little is known of the EBV DNA loads in patients receiving highly active antiretroviral therapy (HAART). Using a real-time quantitative polymerase chain reaction assay, we demonstrated that significantly more HIV-1-infected patients receiving HAART than HIV-1-uninfected volunteers had detectable EBV DNA in blood (57 [81%] of 70 vs. 11 [16%] of 68 patients; P=.001) and saliva (55 [79%] of 68 vs. 37 [54%] of 68 patients; P=.002). The mean EBV loads in blood and saliva samples were also higher in HIV-1-infected patients than in HIV-1-uninfected volunteers (P=.001). The frequency of EBV detection in blood was associated with lower CD4+ cell counts (P=.03) among HIV-1-infected individuals, although no differences were observed in the EBV DNA loads in blood or saliva samples in the HIV-1-infected group. Additional studies are needed to determine whether EBV-specific CD4+ and CD8+ cells play a role in the pathogenesis of EBV in HIV-1-infected patients receiving HAART.

  17. Lipodystrophy in Human Immunodeficiency Virus (HIV) Patients on Highly Active Antiretroviral Therapy (HAART)

    PubMed Central

    Kumar, N. Sunil; Shashibhushan, J.; Venugopal, K.; Vishwanatha, Huggi; Menon, Mahesh

    2015-01-01

    Background In recent years, abnormal lipid deposition (both lipoatrophy and fat redistribution) and its related complications have changed from an anecdotal issue into a major problem for HIV (Human Immunodeficiency Virus) infected patients on HAART (Highly Active Anti-Retroviral Therapy). Lipoatrophy and fat redistribution are potentially stigmatizing complications of HAART and leads to poor adherence among patients. Hence we conducted this study to determine the pattern and to assess various risk factors for maldeposition of lipids in HIV patients. Materials and Methods A cross-sectional case series study was conducted in ART PLUS centre, Bellary over a period of 8 months from January to August 2014 in HIV patients on ART to determine risk factors associated with and epidemiological pattern of fat redistribution or atrophy. Results A total of 50 patients with LD {lipodystrophy} (26 with fat redestribution and 24 with lipoatrophy {LA} were diagnosed in this period. Most of them belonged to younger age and was commonly seen in females (76%). Patients with LA had a significantly lower BMI (18.73 ± 7.4), {the p-value being 0.19} compared to LH group (21.54 ± 7.62). The duration of disease was comparable among both groups (6.96 years in LH and 5.79 years in LA group) {p-value is 0.29}. There was a relatively good immunity among these patients with mean CD4 count was 509.23 in LH and 545.91 in LA group {single CD4 count was taken and the p-value was 0.001}. Most of the patients were in TLN (Tenofovir, Lamivudine, Nevirapine) regimen (58%).The duration that patient was on ART before commencement of study varied from patient to patient, but the mean duration was approximately five years in fat redistribution group and 4.5 years in LA group. There were no derangements in lipid and sugar levels among them. Conclusion This study shows the need to identify and impact of LD with respect to treatment adherence in young patients especially female patients. Early community

  18. Detection of Simian Immunodeficiency Virus in Semen, Urethra, and Male Reproductive Organs during Efficient Highly Active Antiretroviral Therapy

    PubMed Central

    Matusali, G.; Dereuddre-Bosquet, N.; Le Tortorec, A.; Moreau, M.; Satie, A.-P.; Mahé, D.; Roumaud, P.; Bourry, O.; Sylla, N.; Bernard-Stoecklin, S.; Pruvost, A.; Le Grand, R.

    2015-01-01

    ABSTRACT A number of men receiving prolonged suppressive highly active antiretroviral therapy (HAART) still shed human immunodeficiency virus (HIV) in semen. To investigate whether this seminal shedding may be due to poor drug penetration and/or viral production by long-lived cells within male genital tissues, we analyzed semen and reproductive tissues from macaques chronically infected with simian immunodeficiency virus mac251 (SIVmac251) who were treated for 4 months with HAART, which was intensified over the last 7 weeks with an integrase inhibitor. We showed that a subset of treated animals continued shedding SIV in semen despite efficient HAART. This shedding was not associated with low antiretroviral drug concentrations in semen or in testis, epididymis, seminal vesicles, and prostate. HAART had no significant impact on SIV RNA in the urethra, whereas it drastically reduced SIV RNA levels in the prostate and vas deferens and to a lesser extent in the epididymis and seminal vesicle. The only detectable SIV RNA-positive cells within the male genital tract after HAART were urethral macrophages. SIV DNA levels in genital tissues were not decreased by HAART, suggesting the presence throughout the male genital tract of nonproductively infected cells. In conclusion, our results demonstrate that 4 months of HAART induced variable and limited control of viral infection in the male reproductive organs, particularly in the urethra, and suggest that infected long-lived cells in the male genital tract may be involved in persistent seminal shedding during HAART. These results pave the way for further investigations of male genital organ infection in long-term-treated infected individuals. IMPORTANCE A substantial subset of men receiving prolonged HAART suppressing viral loads in the blood still harbor HIV in semen, and cases of sexual transmission have been reported. To understand the origin of this persistence, we analyzed the semen and male reproductive tissues from SIV

  19. Incidence of adverse drug reactions in human immune deficiency virus-positive patients using highly active antiretroviral therapy.

    PubMed

    Srikanth, B Akshaya; Babu, S Chandra; Yadav, Harlokesh Narayan; Jain, Sunil Kumar

    2012-01-01

    To estimate the incidence of adverse drug reactions (ADRs) in Human immune deficiency virus (HIV) patients on highly active antiretroviral therapy (HAART). To identify the risk factors associated with ADRs in HIV patients. To analyze reported ADRs based on various parameters like causality, severity, predictability, and preventability. Retrospective case-control study. An 18-month retrospective case-control study of 208 patients newly registered in ART center, RIMS hospital, Kadapa, were intensively monitored for ADRs to HAART. Predictability was calculated based on the history of previous exposure to drug. Multivariate logistic regressions were used to identify the risk factors for ADRs. Data were analyzed using the chi-square test for estimating the correlation between ADRs and different variables. All statistical calculations were performed using EpiInfo version 3.5.3. Monitoring of 208 retrospective patients by active Pharmacovigilance identified 105 ADRs that were identified in 71 patients. Skin rash and anemia were the most commonly observed ADRs. The organ system commonly affected by ADR was skin and appendages (31.57%). The ADRs that were moderate were 90.14% of cases. The incidence of ADRs (53.52%) was higher with Zidovudine + Lamivudine + Nevirapine combination. CD4 cell count less than <250 cells/μl were 80.28%, male gender were observed to be the risk factors for ADRs. Our study finding showed that there is a need of active pharmaceutical care with intensive monitoring for ADRs in Indian HIV-positive patients who are illiterate, of male and female gender, with CD4 count ≤250 cells/mm(3) with comorbid conditions. PMID:22470896

  20. Predictors of impaired renal function among HIV infected patients commencing highly active antiretroviral therapy in Jos, Nigeria

    PubMed Central

    Agbaji, Oche O.; Onu, Adamu; Agaba, Patricia E.; Muazu, Muhammad A.; Falang, Kakjing D.; Idoko, John A.

    2011-01-01

    Background: Kidney disease is a common complication of human immunodeficiency virus (HIV) infection even in the era of antiretroviral therapy, with kidney function being abnormal in up to 30% of HIV-infected patients. We determined the predictors of impaired renal function in HIV-infected adults initiating highly active antiretroviral therapy (HAART) in Nigeria. Materials and Methods: This was a retrospective study among HIV-1 infected patients attending the antiretroviral clinic at the Jos University Teaching Hospital (JUTH), between November 2005 and November 2007. Data were analysed for age, gender, weight, WHO clinical stage, CD4 count, HIV-1 RNA viral load, HBsAg and anti-HCV antibody status. Estimated glomerular filtration rate (eGFR) was calculated using the Cockcroft-Gault equation. Statistical analysis was done using Epi Info 3.5.1. Results: Data for 491 (294 females and 197 males) eligible patients were abstracted. The mean age of this population was 38.8±8.87 years. One hundred and seventeen patients (23.8%; 95% CI, 20.2-27.9%) had a reduced eGFR (defined as <60 mL/min), with more females than males (28.6% vs. 16.8%; P=0.02) having reduced eGFR. Age and female sex were found to have significant associations with reduced eGFR. Adjusted odds ratios were 1.07 (95% CI, 1.04, 1.10) and 1.96 (95% CI, 1.23, 3.12) for age and female sex, respectively. Conclusions: Older age and female sex are independently associated with a higher likelihood of having lower eGFRs at initiation of HAART among our study population. We recommend assessment of renal function of HIV-infected patients prior to initiation of HAART to guide the choice and dosing of antiretroviral drugs. PMID:22083208

  1. The Reason for Regimen Change Among HIV/AIDS Patients Initiated on First Line Highly Active Antiretroviral Therapy in Southern Ethiopia

    PubMed Central

    Woldemedhin, Beharu; Wabe, Nasir Tajure

    2012-01-01

    Background: Highly active antiretroviral therapy (HAART) has markedly decreased the morbidity and mortality due to HIV disease. However, toxicities, comorbidity, pregnancy, and treatment failure, among others, would result in frequent initial HAART regimen change. Aim: The study was designed to assess the causes of initial highly active antiretroviral therapeutic regimen changes among patients on HAART. Materials and Methods: The study was conducted using a retrospective institution-based study, by reviewing the patient information sheet and physician diagnosis cards. Patient cards that showed a change in the initial treatment regimen were assessed and analyzed, to identify the common reason that resulted in a change from the initial treatment regimen. The data was analyzed using SPSS version 16.0. Results: A total of 340 patient cards were assessed. The majority of the patients (69.29%) were females. The most common first regimen, before the first switch, was stavudine / lamivudine / nevirapine (D4T/3TC/NVP) (54.70%) and stavudine / lamivudine / Efavirenz (D4T/3TC/EFV) (20.88%). The main reasons for modification were toxicity, comorbidity, pregnancy, and treatment failure. The main types of toxicities observed were peripheral neuropathy (36.52%), rash (17.83%), and anemia (17.39%). Conclusion: Toxicity was the main reason for the modification of initial HAART among the study population. Efavirenz-based regimens had the lowest hazard for change relatively, except in pregnancy-related cases. PMID:22393543

  2. Usefulness of highly active antiretroviral therapy on health-related quality of life of adult recipients in Tanzania.

    PubMed

    Magafu, Mgaywa G M D; Moji, Kazuhiko; Igumbor, Ehimario U; Hashizume, Masahiro; Mizota, Tsutomu; Komazawa, Osuke; Cai, Guoxi; Yamamoto, Taro

    2009-07-01

    This study assessed health-related quality of life (HRQOL) of highly active antiretroviral therapy (HAART) recipients aged 18 or older and associated factors, 2 years after HAART administration had started in Kagera, Tanzania. Using the 36-Item Short Form Health Survey (SF-36), 329 HAART recipients were interviewed in May 2007. Questions on sociodemographic characteristics, chronic diseases (besides HIV/AIDS), HAART side effects and adherence to antiretroviral drugs were added. Treatment data, the first and latest available CD4 counts were retrieved from patients' records. Gender and age-adjusted mean scale scores of the sample were compared to those of the general Tanzanian population of the late 1990 s using t test. Logistic regression was used to explore the effect of sex, age, education level, income, chronic diseases, CD4 count, HAART side effects and adherence to antiretroviral drugs on recipients' physical functioning and mental health scale scores. The mean scale scores of HAART recipients were generally lower than those of the general population except for general health perceptions (p = 0.191) and mental health (p = 0.161). HAART recipients with chronic disease comorbidity were more likely to score below the general population's mean score for mental health (p = 0.007). While the effect of chronic disease comorbidity on physical functioning among those who recorded a CD4 count increase was negative (odds ratio [OR] = 13.6, 95% confidence interval [CI] = 3.7, 49.9), there was no effect on those who did not have such an increase. The control of chronic diseases among recipients should be given priority to improve their HRQOL. PMID:19534603

  3. Prevalence and factors associated with traditional herbal medicine use among patients on highly active antiretroviral therapy in Uganda

    PubMed Central

    2011-01-01

    Background In Africa, herbal medicines are often used as primary treatment for Human immunodeficiency virus (HIV) related problems. Concurrent use of traditional herbal medicines (THM) with antiretroviral drugs (ARVs) is widespread among HIV infected patients. However, the extent of THM use is not known in most settings in Sub-Saharan Africa. This study aimed at determining the prevalence and factors associated with THM use among HIV infected patients on highly active antiretroviral therapy (HAART) attending The AIDS Support Organization (TASO) in Uganda. TASO is a non-governmental organization devoted to offering HIV/AIDS care and treatment services in the population. Methods This was a cross-sectional study carried out in two TASO treatment centres in Uganda among 401 randomly selected eligible participants. We included participants who were 18 years and above, were enrolled on HAART, and consented to participate in the study. Data was collected using an interviewer-administered semi-structured questionnaire. THM use referred to someone who had ever used or was currently using herbal medicine while on highly active antiretroviral therapy (HAART) by the time of the study. Data was captured in Epi-data version 3.1 and exported to STATA version 9.0 for analysis. Results The prevalence of THM use was 33.7%. Patients on HAART for < 4 years were more likely to use THM (OR = 5.98, 95% CI 1.13 - 31.73) as well as those who experienced HAART side effects (OR = 3.66, 95% CI: 1.15 - 11.68). Older patients (≥39 years) were less likely to use THM (OR = 0.26 95% CI: 0.08 - 0.83). Participants with HAART adherence levels > 95% were less likely to use THM (OR = 0.09, 95% CI 0.01 - 0.65). Conclusion The prevalence of THM use among participants on HAART was high. This raises clinical and pharmacological concerns that need attention by the health care service providers. PMID:22074367

  4. Rehabilitation Program for the Quality of Life for Individuals on Highly Active Antiretroviral Therapy in KwaZulu-Natal, South Africa: A Short Report

    ERIC Educational Resources Information Center

    Maharaj, Sonill S.; Chetty, Verusia

    2011-01-01

    Patients on highly active antiretroviral therapy (HAART) spend less time on vigorous activities due to lower aerobic capacity with functional limitations that can be attributed to a detraining effect, resulting in a poor quality of life (QoL). The overall aims of rehabilitation are to restore, to maintain, and to enhance the QoL and this…

  5. Immunoglobulin G kappa [IgG kappa] and IgG lambda paraproteinemia in a child with AIDS and response to highly active antiretroviral therapy.

    PubMed

    Seeborg, Filiz Odabasi; Gay, Hannah; Schmiege, Lorenz M; Bernard, David; Shearer, William T

    2005-11-01

    We report an 8-year-old boy with AIDS, extremely elevated serum immunoglobulin G (IgG) concentration and IgG kappa [IgG(kappa)] and IgG lambda [IgG(lambda)] paraproteinemia. This paraproteinemia partially responded to highly active antiretroviral therapy. This case emphasizes the importance of controlling B-cell activation. PMID:16275950

  6. Mitochondrial DNA Haplogroups influence lipoatrophy after Highly Active Anti-retroviral Therapy

    PubMed Central

    Hendrickson, Sher L.; Kingsley, Lawrence A.; Ruiz-Pesini, Eduardo; Poole, Jason C.; Jacobson, Lisa P.; Palella, Frank J.; Bream, Jay H.; Wallace, Douglas C.; O’Brien, Stephen J.

    2009-01-01

    Although highly active retroviral therapy (HAART) has been extremely effective in lowering AIDS incidence among patients infected with HIV, certain drugs included in HAART can cause serious mitochondrial toxicities. One of the most frequent adverse events is lipoatrophy, which is the loss of subcutaneous fat in the face, arms, buttocks and/or legs as an adverse reaction to nucleoside reverse transcriptase inhibitors (NRTIs). The clinical symptoms of lipoatrophy resemble those of inherited mitochondrial diseases, which suggests that host mitochondrial genotype may play a role in susceptibility. We analyzed the association between mitochondrial haplogroup and severity of lipoatrophy in HIV-infected European American patients on HAART in the Multicenter AIDS cohort Study (MACS) and found that mitochondrial haplogroup H was strongly associated with increased atrophy (arms: p = 0.007, OR = 1.77, 95% CI = 1.17–2.69 legs: p = 0.037, OR = 1.54 95% CI = 1.03–2.31, and buttocks: p = 0.10, OR = 1.41 95% CI = 0.94–2.12). We also saw borderline significance for haplogroup T as protective against lipoatrophy (p = 0.05, OR = 0.52, 95% CI = 0.20–1.00). These data suggest that mitochondrial DNA haplogroup may influence the propensity for lipoatrophy in patients receiving NRTIs. PMID:19339895

  7. [Pontine reversible leucopathy in an AIDS patient associated with highly active antiretroviral therapy (HAART): Report of one case].

    PubMed

    Cartier, Luis; Matamala, José Manuel; Yáñez, Alonso

    2016-05-01

    Posterior reversible encephalopathy (PRES) is a condition characterized by T2 and FLAIR hyperintensities in magnetic resonance imaging (MRI) studies, localized preferentially in the occipital-parietal white matter regions. Pathological MRI images located in midbrain, pons, medulla and spinal cord, that could be asymptomatic, were recently included in this entity. These images are interpreted as vasogenic edema, which is caused by arterial hypertension or eclampsia, neurotoxicity related to immunosuppressive agents or chemotherapy, among other causes. We report a 25 years old asymptomatic male with AIDS, with normal blood pressure who after initiating highly active antiretroviral therapy (HAART) reported vertigo. The MRI showed a central pontine T2 hyperintensity with diffusion restriction, which was interpreted as a central pontine myelinolysis (CPM), but the lack of motor symptoms made improbable a real demyelination of the pons. The follow-up MRI revealed complete regression of the images. To our knowledge, this case could be the second report of a reversible leucopathy of the pons in a patient with AIDS, were the MRI images also simulated a CPM. This report extends the knowledge around the variability of the pathogenic interpretation of CPM images and their association with HAART. PMID:27552021

  8. Immunogenicity, Immunologic Memory, and Safety Following Measles Revaccination in HIV-Infected Children Receiving Highly Active Antiretroviral Therapy

    PubMed Central

    Abzug, Mark J.; Qin, Min; Levin, Myron J.; Fenton, Terence; Beeler, Judy A.; Bellini, William J.; Audet, Susette; Sowers, Sun Bae; Borkowsky, William; Nachman, Sharon A.; Pelton, Stephen I.; Rosenblatt, Howard M.

    2012-01-01

    Background. Response rates and immunologic memory following measles vaccination are reduced in human immunodeficiency virus (HIV)–infected children in the absence of highly active antiretroviral therapy (HAART). Methods. HIV-infected children 2 to <19 years old receiving HAART and with HIV loads <30 000 copies/mL, CD4% ≥15, and ≥1 prior measles-mumps-rubella vaccination (MMR) were given another MMR. Measles antibody concentrations before and 8, 32, and 80 weeks postvaccination were determined by plaque reduction neutralization (PRN). A subset was given another MMR 4–5 years later, and PRN antibody was measured before and 7 and 28 days later. Results. At entry, 52% of 193 subjects were seroprotected (PRN ≥120 mIU/mL). Seroprotection increased to 89% 8 weeks postvaccination, and remained at 80% 80 weeks postvaccination. Of 65 subjects revaccinated 4–5 years later, 85% demonstrated memory based on seroprotection before or 7 days after vaccination. HIV load ≤400 copies/mL at initial study vaccination was associated with higher seroprotection rates, greater antibody concentrations, and memory. Grade 3 fever or fatigue occurred in 2% of subjects. Conclusions. Measles revaccination induced high rates of seroprotection and memory in children receiving HAART. Both endpoints were associated with HIV viral load suppression. Clinical Trials Registration: NCT00013871 (www.clinicaltrials.gov). PMID:22693229

  9. Safety, tolerability, pharmacokinetics, and efficacy of an interleukin-2 agonist among HIV-infected patients receiving highly active antiretroviral therapy.

    PubMed

    Davey, Richard T; Pertel, Peter E; Benson, Alice; Cassell, Delanie J; Gazzard, Brian G; Holodniy, Mark; Lalezari, Jacob P; Levy, Yves; Mitsuyasu, Ronald T; Palella, Frank J; Pollard, Richard B; Rajagopalan, Prabhu; Saag, Michael S; Salata, Robert A; Sha, Beverly E; Choudhri, Shurjeel

    2008-02-01

    We sought to determine the safety, maximum tolerated dose, optimal dose, and preliminary dose efficacy of intermittent subcutaneously (s.c.) administered BAY 50-4798 among patients with HIV infection receiving highly active antiretroviral therapy (HAART) compared with patients receiving HAART alone. A phase I/II randomized, double-blind, dose-escalation study was conducted of the safety, tolerability, pharmacokinetics, and efficacy of s.c. BAY 50-4798 administered to HIV-infected patients already receiving stable HAART. There were no unexpected safety findings in a population of HIV-infected patients receiving HAART plus SC BAY 50-4798 as adjunctive therapy. BAY 50-4798 exhibited nearly dose-proportional pharmacokinetics, and accumulation was minimal during multiple-dose treatment. Limited efficacy data indicated that treatment with BAY 50-4798 caused at least a transient increase in CD4(+) T cell counts in some recipients, particularly at the early time points. In general, this effect appeared to increase with increasing dose. Bay 50-4798 was generally well tolerated across the dose range tested, but a lack of potent, sustained immunologic activity suggests that further optimization of dose and schedule will be necessary. PMID:18279104

  10. [Poor quality of sleep associated with low adherence to highly active antiretroviral therapy in Peruvian patients with HIV/AIDS].

    PubMed

    Tello-Velásquez, Jorge Renzo; Díaz-Llanes, Bruno Eduardo; Mezones-Holguín, Edward; Rodríguez-Morales, Alfonso J; Huamaní, Charles; Hernández, Adrián V; Arévalo-Abanto, Jorge

    2015-05-01

    This cross-sectional study analyzed the association between poor quality of sleep and adherence to highly active antiretroviral therapy (HAART) in 389 Peruvian patients with HIV/AIDS. Poor quality of sleep was measured with the Pittsburgh Sleep Quality Index (PSQI) and adherence with the CEAT-VIH (Peruvian adaptation). A Poisson generalized linear model with robust standard errors was used to estimate prevalence ratios and 95%CI. A crude model showed that mild, moderate, and severe poor quality of sleep were associated with inadequate treatment adherence. In the adjusted model for variables associated in the bivariate analysis or variables theoretically associated with adherence, only moderate/severe poor quality of sleep remained associated (PR = 1.34, 95%CI: 1.17-1.54; and PR = 1.34, 95%CI: 1.16-1.57, respectively). The study concluded that moderate/severe poor quality of sleep was independently associated with adherence to HAART. Assessing quality of sleep may be helpful in the comprehensive evaluation of HIV patients. PMID:26083174

  11. Factors associated with adherence to highly active antiretroviral therapy in homeless or unstably housed adults living with HIV.

    PubMed

    Royal, Scott W; Kidder, Daniel P; Patrabansh, Satyendra; Wolitski, Richard J; Holtgrave, David R; Aidala, Angela; Pals, Sherri; Stall, Ron

    2009-04-01

    The aim of this study is to investigate adherence to highly active antiretroviral therapy (HAART) in persons living with HIV/AIDS (PLWHA) who are homeless or unstably housed. We evaluated homeless or unstably housed PLWHA (n=644) in three US cities were enrolled in the Housing and Health Study. Using baseline data and controlling for gender, race, age, and education, we examined associations between self-reported two- and Seven-day adherence and access to healthcare, mental health, substance use, and attitudes toward HIV medical therapy. Of the 644 participants, 358 (55%) were currently on HAART. For two-day adherence, 280 (78%) reported missing no prescribed doses (100% adherence), and for seven-day adherence, 291 (81%) reported > or =90% adherence. Logistic regression analyses indicated being younger, not having health insurance, and drug use were associated with missing > or =1 dose over the past two days. Scoring lower on SF-36 mental component summary scale and having greater risk of depression (CES-D) and stress (Perceived Stress Scale) were associated with poorer adherence for both two- and seven-day outcomes. Negative attitudes toward HIV treatment were also associated with lower adherence. Adherence to HIV medications in this population is similar to other groups. Coexisting problems of access to healthcare, higher risk of mental health problems, along with poorer attitudes toward treatment are associated with increased likelihood of missing doses. Comprehensive models of HIV care that include a continuum of medical and social services are essential for treating this population. PMID:19401865

  12. Unusual Enterocytozoon bieneusi genotypes and Cryptosporidium hominis subtypes in HIV-infected patients on highly active antiretroviral therapy.

    PubMed

    Akinbo, Frederick O; Okaka, Christopher E; Omoregie, Richard; Adamu, Haileeyesus; Xiao, Lihua

    2013-07-01

    Human immunodeficiency virus (HIV)-infected persons are commonly infected with Cryptosporidium species and Enterocytozoon bieneusi in both developed and developing countries, particularly patients with CD4+ cell counts below 200 cells/μL; 285 HIV-infected patients on highly active antiretroviral therapy (HAART) were enrolled in this study, and both stool and blood specimens were collected from participants. The stool specimens were analyzed and typed for E. bieneusi and Cryptosporidium spp. by polymerase chain reaction (PCR) and DNA sequencing. CD4 count was analyzed using flow cytometry. E. bieneusi and Cryptosporidium were detected in 18 (6.3%) and 4 (1.4%) patients, respectively. The E. bieneusi detected mostly belonged to a new genotype group that, thus far, has only been found in a few humans: genotype Nig4 in 2 patients and two new genotypes related to Nig4 in 12 patients. The Cryptosporidium detected included C. hominis (two patients), C. parvum (one patient), and C. felis (one patient), with the two C. hominis infections belonging to an unusual subtype family. Additional studies are required to determine whether some E. bieneusi genotypes and C. hominis subtypes are more prevalent in HIV patients on HAART. PMID:23629938

  13. [Long term survival after Rhodococcus equi pneumonia in a patient with human immunodeficiency virus infection in the era of highly active antiretroviral therapy: case report and review].

    PubMed

    Vladusić, Ivona; Krajinović, Vladimir; Begovac, Josip

    2006-06-01

    Before highly active antiretroviral therapy (HAART) has become available, antibiotic treatment was usually unable to eradicate Rhodococcus (R.) equi infection in HIV-infected patients, although some clinical improvement could be observed in most cases. There are limited data on the outcome of treatment of R. equi pneumonia in the HAART era. We report on a 52-year-old HIV-infected man who presented in poor general condition with an extensive lung cavitation lesion caused by R. equi. The patient recalled exposure to horses on several occasions. R. equi was cultured from the sputum and the isolate was sensitive to imipenem vancomycin, co-trimoxazole, erythromycin, azithromycin, ciprofloxacin and rifampicin. The CD4+ lymphocyte count was 5 cells/mm3 (0.9%) and his plasma HIV-1 RNA viral load was 101000 copies/mL. The patient was successfully treated with a combination of antibiotics that included azithromycin both as part of an initial and suppressive regimen together with antiretroviral treatment. Surgery was not needed and the patient had no relapse for more than five years after the diagnosis and for more than 3 years of suppressive therapy discontinuation. Our literature search revealed 27 patients treated for R. equi infection in the HAART era. However, details on antimicrobial treatment were given in only 3 cases. The optimal drug regimen and duration of treatment for R. equi pneumonia have not yet been established. Because drug resistance may occur during single agent therapy, it has been suggested that at least two antibiotics to which R. equi is susceptible be given. The recommended choices usually include imipenem, antipseudomonal aminoglycosides, erythromycin or azithromycin, vancomycin, rifampin, and levofloxacin. To our knowledge this is the first documented case of long term remission of R. equi pneumonia in an HIV-infected man treated with azithromycin as part of his antibiotic regimen and HAART. PMID:16933840

  14. Hypofibrinolytic state in HIV-1-infected patients treated with protease inhibitor-containing highly active antiretroviral therapy.

    PubMed

    Koppel, Kristina; Bratt, Göran; Schulman, Sam; Bylund, Håkan; Sandström, Eric

    2002-04-15

    Decreased insulin sensitivity, hyperlipidemia, and body fat changes are considered as risk factors for coronary heart disease (CHD). A clustering of such factors (metabolic syndrome [MSDR]) exponentially increases the risk. Impaired fibrinolysis and increased coagulation are additional independent risk factors for CHD. We studied the effects of protease inhibitor (PI)-containing highly active antiretroviral therapy (HAART) on metabolic and hemostatic parameters in 363 HIV-infected individuals, of whom 266 were receiving PI-containing HAART and 97 were treatment naive. The fasting plasma levels of insulin, glucose, triglycerides, cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, plasminogen activator inhibitor type 1 (PAI-1), and fibrinogen were evaluated together with the areas of visceral adipose tissue and the visceral adipose tissue/subcutaneous adipose tissue area ratio. The levels of insulin, triglycerides, cholesterol, and low-density lipoprotein cholesterol; visceral adipose tissue area; low-density lipoprotein/high-density lipoprotein ratio; and visceral adipose tissue/subcutaneous adipose tissue area ratio were significantly increased in patients receiving PI-containing HAART compared with treatment-naive patients. The levels of PAI-1 and fibrinogen were significantly higher in patients receiving PI-containing HAART. PAI-1 levels were higher in individuals with MSDR but also in patients without MSDR who were receiving PI-containing HAART. PAI-1 was independently correlated to use of PI-containing HAART, triglyceride level, insulin level, and body mass index (p <.001). These findings suggest that patients receiving PI-containing HAART have decreased fibrinolysis and increased coagulability, which may thus represent additional risk factors for cardiovascular disease in this patient group. PMID:11981359

  15. Immunogenicity and Immunologic Memory after Hepatitis B Virus Booster Vaccination in HIV-Infected Children Receiving Highly Active Antiretroviral Therapy

    PubMed Central

    Abzug, Mark J.; Warshaw, Meredith; Rosenblatt, Howard M.; Levin, Myron J.; Nachman, Sharon A.; Pelton, Stephen I.; Borkowsky, William; Fenton, Terence

    2010-01-01

    Background Hepatitis B virus (HBV) is an important cause of comorbidity in human immunodeficiency virus (HIV)–infected individuals. The immunogenicity of HBV vaccination in children receiving highly active antiretroviral therapy (HAART) was investigated. Methods HIV-infected children receiving HAART who had low to moderate HIV loads and who had previously received ≥3 doses of HBV vaccine were given an HBV vaccine booster. Concentrations of antibody to hepatitis B surface antigen (anti-HBs) were determined before vaccination and at weeks 8, 48, and 96. A subset of subjects was administered a subsequent dose, and anti-HBs was measured before and 1 and 4 weeks later. Results At entry, 24% of 204 subjects were seropositive. Vaccine response occurred in 46% on the basis of seropositivity 8 weeks after vaccination and in 37% on the basis of a ≥4-fold rise in antibody concentration. Of 69 subjects given another vaccination 4–5 years later, immunologic memory was exhibited by 45% on the basis of seropositivity 1 week after vaccination and by 29% on the basis of a ≥4-fold rise in antibody concentration at 1 week. Predictors of response and memory included higher nadir and current CD4 cell percentage, higher CD19 cell percentage, and undetectable HIV load. Conclusions HIV-infected children frequently lack protective levels of anti-HBs after previous HBV vaccination, and a significant proportion of them do not respond to booster vaccination or demonstrate memory despite receiving HAART, leaving this population insufficiently protected from infection with HBV. PMID:19663708

  16. Excess mortality in patients with AIDS in the era of highly active antiretroviral therapy: Temporal changes and risk factors

    PubMed Central

    Puhan, Milo A.; Van Natta, Mark L.; Palella, Frank J.; Addessi, Adrienne; Meinert, Curtis

    2010-01-01

    Background Excess mortality has declined among HIV infected patients but without evidence of a decline in patients with AIDS. We assessed temporal changes in excess mortality and elucidated risk factors for excess mortality in patients with AIDS diagnosed in the era of highly active antiretroviral therapy (HAART). Methods We included 1,188 patients of the Longitudinal Study of Ocular Complications in AIDS who were between 25-64 years old at enrollment and diagnosed with AIDS after 1995. We calculated excess mortality as the age-, year- and sex-adjusted difference in mortality rates between patients with AIDS and persons in the US general population, between 1999 and 2007, and used a relative survival model to identify risk factors for excess mortality. Results There were an average of 50 excess deaths (95% CI 44-57) per 1,000 person years between 1999 and 2007. Excess mortality almost halved with an annual decline of 8.0% per year (3.0-12.7 p=0.002) but remained high at 36 excess deaths per 1,000 person years in 2007. Viral load >400 vs. ≤400 copies/mL (risk ratio 3.4 [2.3-5.0]), CD4+ count <200 vs. ≥200 cells/μL (2.7 [1.9-3.9]) and cytomegalovirus retinitis (1.6 [1.2-2.1]) were the strongest risk factors for excess mortality. Conclusions Excess mortality among patients with AIDS was nearly halved in the HAART era and most strongly linked to stage of HIV disease. These results reflect the continuing improvements in AIDS management but also highlight that excess mortality remains about five times higher in patients with AIDS than in patients with HIV-infection but no AIDS. PMID:20825306

  17. Association of cervical biopsy with HIV type 1 genital shedding among women on highly active antiretroviral therapy.

    PubMed

    Woo, Victoria G; Liegler, Teri; Cohen, Craig R; Sawaya, George F; Smith-McCune, Karen; Bukusi, Elizabeth A; Huchko, Megan J

    2013-07-01

    HIV-1 genital shedding is associated with increased HIV-1 transmission risk. Inflammation and ulceration are associated with increased shedding, while highly active antiretroviral therapy (HAART) has been shown to have a protective effect. We sought to examine the impact of cervical biopsies, a routine component of cervical cancer screening, on HIV-1 genital RNA levels in HIV-infected women on HAART. We enrolled HIV-1-infected women undergoing cervical biopsy for diagnosis of cervical intraepithelial neoplasia (CIN) 2/3 in this prospective cohort study. All were stable on HAART for at least 3 months. Clinical and demographic information as well as plasma HIV-1 viral load were collected at the baseline visit. Specimens for cervical HIV-1 RNA were collected immediately prior to biopsy, and 2 and 7 days afterward. Quantitative PCR determined HIV-1 concentration in cervical specimens at each time point to a lower limit of detection of 40 copies/specimen. Among the 30 participants, five (16.6%) women had detectable cervical HIV-1 RNA at baseline, of whom four (80%) had detectable HIV-1 RNA after cervical biopsy, with no significant increase in viral load in the follow-up specimens. Only one woman (3.3%) with undetectable baseline cervical HIV-1 RNA had detection postbiopsy. Detectable plasma HIV-1 RNA was the only factor associated with baseline cervical HIV-1 RNA. In women on HAART, an increase in cervical HIV-1 RNA detection or concentration was not associated with cervical biopsy. These findings help provide safety data regarding cervical cancer screening and diagnosis in HIV-infected women and inform postprocedure counseling. PMID:23594240

  18. Effect of highly active antiretroviral therapy on vaginal Candida spp. isolation in HIV-infected compared to HIV-uninfected women.

    PubMed

    Alczuk, Silvia de Souza Dantas; Bonfim-Mendonça, Patrícia de Souza; Rocha-Brischiliari, Sheila Cristina; Shinobu-Mesquita, Cristiane Suemi; Martins, Helen Priscilla Rodrigues; Gimenes, Fabrícia; Abreu, André Luelsdorf Pimenta de; Carvalho, Maria Dalva de Barros; Pelloso, Sandra Marisa; Svidzinski, Terezinha Inez Estivalet; Consolaro, Marcia Edilaine Lopes

    2015-01-01

    Vulvovaginal candidiasis (VVC) in HIV-infected women contributed to the impairment of their quality of life. The aim of this study was to evaluate the effect of highly active antiretroviral therapy (HAART) use on the vaginal Candida spp. isolation in HIV-infected compared to HIV-uninfected women. This cross-sectional study included 178 HIV-infected (HIV group) and 200 HIV-uninfected women (control) that were studied at the Specialized Assistance Service (SAE) for sexually transmitted diseases (STD)/AIDS of the city of Maringá, Brazil, from April 1 to October 30, 2011. The yeasts were isolated and identified by phenotypic and molecular methods. The in vitro antifungal susceptibility to fluconazole, itraconazole, nystatin and amphotericin B was tested by the reference microdilution method. Higher frequencies of total vaginal Candida spp. isolation were found in the HIV-infected group than in the control group. However, both groups showed a similar frequency of colonization and VVC. Although C. albicans was the most frequent and sensitive to azolics and polyenes in both HIV-infected and uninfected women, the emerging resistance of C. glabrata to amphotericin B in the HIV-infected women was observed. Although higher frequency of vaginal Candida spp. isolation had been observed in the HIV-infected than in HIV-uninfected women, colonization and VVC showed similar frequency in both groups, indicating that HAART appears to protect against vaginal colonization and VVC. PMID:25923898

  19. EFFECT OF HIGHLY ACTIVE ANTIRETROVIRAL THERAPY ON VAGINAL Candida spp. ISOLATION IN HIV-INFECTED COMPARED TO HIV-UNINFECTED WOMEN

    PubMed Central

    ALCZUK, Silvia de Souza Dantas; BONFIM-MENDONÇA, Patrícia de Souza; ROCHA-BRISCHILIARI, Sheila Cristina; SHINOBU-MESQUITA, Cristiane Suemi; MARTINS, Helen Priscilla Rodrigues; GIMENES, Fabrícia; de ABREU, André Luelsdorf Pimenta; CARVALHO, Maria Dalva de Barros; PELLOSO, Sandra Marisa; SVIDZINSKI, Terezinha Inez Estivalet; CONSOLARO, Marcia Edilaine Lopes

    2015-01-01

     Vulvovaginal candidiasis (VVC) in HIV-infected women contributed to the impairment of their quality of life. The aim of this study was to evaluate the effect of highly active antiretroviral therapy (HAART) use on the vaginal Candida spp. isolation in HIV-infected compared to HIV-uninfected women. This cross-sectional study included 178 HIV-infected (HIV group) and 200 HIV-uninfected women (control) that were studied at the Specialized Assistance Service (SAE) for sexually transmitted diseases (STD)/AIDS of the city of Maringá, Brazil, from April 1 to October 30, 2011. The yeasts were isolated and identified by phenotypic and molecular methods. The in vitro antifungal susceptibility to fluconazole, itraconazole, nystatin and amphotericin B was tested by the reference microdilution method. Higher frequencies of total vaginal Candida spp. isolation were found in the HIV-infected group than in the control group. However, both groups showed a similar frequency of colonization and VVC. Although C. albicans was the most frequent and sensitive to azolics and polyenes in both HIV-infected and uninfected women, the emerging resistance of C. glabrata to amphotericin B in the HIV-infected women was observed. Although higher frequency of vaginal Candida spp. isolation had been observed in the HIV-infected than in HIV-uninfected women, colonization and VVC showed similar frequency in both groups, indicating that HAART appears to protect against vaginal colonization and VVC. PMID:25923898

  20. Factors Associated with Prevalent Tuberculosis Among Patients Receiving Highly Active Antiretroviral Therapy in a Nigerian Tertiary Hospital

    PubMed Central

    Iroezindu, MO; Ofondu, EO; Mbata, GC; van Wyk, B; Hausler, HP; DH, Au; Lynen, L; Hopewell, PC

    2016-01-01

    Background: Tuberculosis (TB) causes significant morbidity/mortality among human immunodeficiency virus-infected individuals in Africa. Reducing TB burden in the era of highly active antiretroviral therapy (HAART) is a public health priority. Aim: We determined the factors associated with prevalent TB among patients receiving HAART. Subjects and Methods: We conducted a cross-sectional study of adult patients who had received HAART for ≥12 weeks in a Nigerian tertiary hospital. Patients whose TB diagnosis predated HAART were excluded from the study. Pre-HAART data were collected from the clinic records, whereas post-HAART data were obtained through medical history, physical examination, and laboratory investigations. Standard TB screening/diagnostic algorithms as applicable in Nigeria were used. Logistic regression analysis was used to determine factors independently associated with prevalent TB. Results: about 65.8% (222/339) were women. The mean age was 41.1 (10.0) years and 23.6% (73/339) had past history of TB. The prevalence of active TB was 7.7% (26/339). Among these patients, 42.3% (11/26) had pulmonary TB, 34.6% (9/26) had disseminated TB, whereas 23.1% (6/26) had only extra-pulmonary disease. Only 45% (9/20) of patients with pulmonary involvement had positive sputum smear. Factors independently associated with prevalent TB were lower social class (adjusted odds ratio [aOR]: 31.7; 95% confidence interval [CI]: 1.1–1417.3), HAART non-adherence (aOR125.5; 95% CI: 9.6–1636.3), baseline CD4 <200cells/μl (aOR31.0; 95%CI: 1.6–590.6), previous TB (aOR13.8; 95% CI: 2.0–94.1), and current hemoglobin <10 g/dl (aOR10.3; 95% CI: 1.1–99.2). Conclusion: Factors associated with prevalent TB were a lower social class, HAART non-adherence, severe immunosuppression before HAART initiation, previous TB, and anemia post-HAART. TB case finding should be intensified in these high-risk groups. PMID:27213096

  1. Trends and Predictors of Mortality Among HIV Positive Patients in the Era of Highly Active Antiretroviral Therapy in Uganda

    PubMed Central

    Rubaihayo, John; Tumwesigye, Nazarius M.; Konde-Lule, Joseph; Makumbi, Fredrick; Nakku, Edith J.; Wamani, Henry; Etukoit, Michael B.

    2015-01-01

    Knowledge of mortality trends and predictors among HIV-positive patients in the era of highly active antiretroviral therapy (HAART) in resource poor settings is still limited. The aim of this study was to describe trends and predictors of mortality among HIV-positive patients in the era of HAART in Uganda. Data from 2004 to 2013 for adult HIV-positive patients (≥15 years) obtaining care and treatment from the AIDS Support Organization in Uganda were reviewed for mortality. Descriptive statistics were analyzed by frequencies and cross tabulations. Calendar period was used as a proxy measure for HAART exposure and a time plot of the proportion of HIV-positive patients reporting dead per year was used to describe the trends. Logistic regression was used to determine the predictors of mortality at bivariate and multivariate levels, respectively. We included in the analysis 95,857 HIV positive patients; 64% were female with median age of 33 years (interquartile range 27-40). Of these 36,133 (38%) were initiated on ART and a total of 4279 (4.5%) died; 19.5% (835/4279) of those who died had an opportunistic infection. Overall, mortality first increased between 2004 and 2006 and thereafter substantially declined (X2trend=211.9, P<0.001). Mortality was relatively higher in Eastern Uganda compared to other geographical areas. Male gender, older age (>45 years), being from Eastern or Northern Uganda, having none or primary education, being unemployed, advanced immunodeficiency (CD4 count <100 cell/µL or WHO stage III or IV) and underweight (<45 kg weight) at HAART initiation and calendar period 2004-2008 were significant predictors of mortality (P<0.001). Overall, the expanding coverage of HAART is associated with a declining trend in mortality among HIV positive patients in Uganda. However, mortality trends differed significantly by geographical area and men remain potentially at higher risk of death probably because of delayed initiation on ART. There is urgent need for

  2. Gender Differences in Health Related Quality of Life among People Living with HIV on Highly Active Antiretroviral Therapy in Mekelle Town, Northern Ethiopia

    PubMed Central

    Tesfay, Amanuel; Gebremariam, Abebe; Abrha, Hailay

    2015-01-01

    Background. Health related quality of life (HRQOL) is an important outcome measure for highly active antiretroviral treatment program. In Ethiopia, studies revealed that there are improved qualities of life among adults living with the viruses taking antiretroviral therapy but there is no explicit data showing gender differences in health related quality of life. Aim. To assess gender differences in HRQOL and its associated factors among people living with HIV and on highly active antiretroviral therapy in public health institutions of Mekelle town, Northern Ethiopia. Methods. A comparative cross-sectional study was conducted among 494 adult people living with HIV taking ART services. Quality of life was measured using WHOQOL-HIV BREF. Result. There was a statistically significant gender difference (P < 0.05) in HRQOL among PLHIV on HAART. Females had low score in all HRQOL domains. High perceived stigma was strongly associated with poor psychological quality of domain among both female and male groups with [AOR = 2.89(1.69,4.96)] and [AOR = 2.5(1.4,4.4)], respectively. Conclusion. There was statistically significant gender difference in all quality of life domains. Public health interventions to improve HRQOL of PLHIV should take in to account the physical, psychological, social, environmental, and spiritual health of PLHIV during treatment, care, and support. PMID:25632393

  3. Human immunodeficiency virus infection and autoimmune hepatitis during highly active anti-retroviral treatment: a case report and review of the literature

    PubMed Central

    2011-01-01

    Introduction The emergence of hepatic injury in patients with human immunodeficiency virus infection during highly active therapy presents a diagnostic dilemma. It may represent treatment side effects or autoimmune disorders, such as autoimmune hepatitis, emerging during immune restoration. Case presentation We present the case of a 42-year-old African-American woman with human immunodeficiency virus infection who presented to our emergency department with severe abdominal pain and was found to have autoimmune hepatitis. A review of the literature revealed 12 reported cases of autoimmune hepatitis in adults with human immunodeficiency virus infection, only three of whom were diagnosed after highly active anti-retroviral treatment was initiated. All four cases (including our patient) were women, and one had a history of other autoimmune disorders. In our patient (the one patient case we are reporting), a liver biopsy revealed interface hepatitis, necrosis with lymphocytes and plasma cell infiltrates and variable degrees of fibrosis. All four cases required treatment with corticosteroids and/or other immune modulating agents and responded well. Conclusion Our review suggests that autoimmune hepatitis is a rare disorder which usually develops in women about six to eight months after commencing highly active anti-retroviral treatment during the recovery of CD4 lymphocytes. It represents either re-emergence of a pre-existing condition that was unrecognized or a de novo manifestation during immune reconstitution. PMID:21702972

  4. Virologic and Immunologic Correlates With the Magnitude of Antibody Responses to the Hepatitis A Vaccine in HIV-Infected Children on Highly Active Antiretroviral Treatment

    PubMed Central

    Weinberg, Adriana; Huang, Sharon; Fenton, Terence; Patterson-Bartlett, Julie; Gona, Philimon; Read, Jennifer S.; Dankner, Wayne M.; Nachman, Sharon

    2010-01-01

    Background HIV-infected individuals mount poor antibody responses to vaccines. We sought to identify the immunologic and virologic factors associated with a robust response to hepatitis Avirus (HAV) vaccine in children on highly active antiretroviral treatment. Methods One hundred fifty-two pediatric highly active antiretroviral treatment recipients immunized against HAV at weeks 0 and 24 had anti-HAV antibodies, CD4+, CD8+, and CD19+ cell percent assessed at weeks 0 and 32. Subgroups had HIV viremia, B- and T-cell subpopulations, and cell-mediated immunity (CMI) to HAV and other stimulants measured. Results Anti-HAV antibodies after complete vaccination correlated positively with CD4+ percent and CD19+ percent and negatively with viremia and CD8+ percent at baseline, but not at 32 weeks. There were no significant correlations between anti-HAV antibodies and B- or T-cell-naïve, memory, or activated subpopulations or non-HAV CMI. Compared with children who remained HAV-CMI-negative, those who mounted HAV-CMI in response to vaccination had higher anti-HAV antibody titers and CD19+ CD21+ CD27+ memory B cell percent at 32 weeks, but no other differences. Conclusions In HIV-infected children on highly active antiretroviral treatment, control of viral replication and conserved or reconstituted CD19+ and CD4+ cell numbers and function determine a robust antibody response to anti-HAV primary immunization. Our data support a bidirectional B- and T-cell cooperation in the response to the HAV vaccine. PMID:19617848

  5. Prevalence and impact of body physical changes in HIV patients treated with highly active antiretroviral therapy: results from a study on patient and physician perceptions.

    PubMed

    Cabrero, Esther; Griffa, Laura; Burgos, Angel

    2010-01-01

    Patients infected with HIV treated with highly active antiretroviral therapy (HAART) frequently develop body physical changes (BPC) that have an important psychosocial burden. The purpose of this study was to determine the prevalence of BPC observed by HIV-infected patients and their attending physicians and to assess the impact BPC had on daily life. In this epidemiologic multicenter study, patients with HIV infection and their treating physicians filled out parallel questionnaires about their perceptions of specific BPC and their impact on daily activities. A total of 965 patient-physician questionnaires were collected across 98 health centers. Patient's mean age was 43.7 +/- 8.5 years and 72.6% were men. Adjusted prevalence of perceived BPC by patients and physicians was 55.1% (95% confidence interval [CI]: 52.0-58.1) and 55.2% (95% CI: 52.1-58.2), respectively (p = 1.000). Overall patient-physician agreement concerning perception of BPC was 83% (p < 0.0005). The most common BPC was lipoatrophy, described by 46.8% (95% CI: 43.7-49.8) of patients and 49.4% (95% CI: 46.3-52.5) of physicians (p = 0.033) followed by lipohypertrophy. No gender differences were observed in the global prevalence of BPC (p = 0.649). However, significantly more women reported lipoatrophy of the lower limbs (p = 0.009) and buttocks (p = 0.007), as well as lipohypertrophy (p = 0.007), than men; 58.2% (95% CI: 54.0-62.4) patients noted that BPC negatively affected their daily activities. This study reflects the high prevalence of patient and physician-perceived BPC in the HIV population, and the adverse impact on daily life. Physicians should be aware of the psychosocial consequences of BPC in HIV patients in order to improve patient well-being. PMID:20095903

  6. Long-Term Effects of Highly Active Antiretroviral Therapy on CD4+ Cell Evolution among Children and Adolescents Infected with HIV: 5 Years and Counting

    PubMed Central

    Patel, Kunjal; Hernán, Miguel A.; Williams, Paige L.; Seeger, John D.; McIntosh, Kenneth; Van Dyke, Russell B.; Seage, George R.

    2011-01-01

    Background Lower percentages of CD4+ T lymphocytes are associated with adverse clinical outcomes among children and adolescents infected with human immunodeficiency virus (HIV). CD4+ lymphocyte percentage generally increases with receipt of highly active antiretroviral therapy (HAART), but long-term follow-up is required to assess whether these increases in CD4+ cell percentage are maintained and whether they lead to normal CD4+ cell percentages in children with severe immunosuppression. Methods The study population included 1236 children and adolescents perinatally infected with HIV who were enrolled in a US-based multicenter prospective cohort study (Pediatric AIDS Clinical Trials Group 219/219C) and who were not receiving HAART at study initiation. We estimated the effects of HAART, HAART with protease inhibitors, and HAART with nonnucleoside reverse-transcriptase inhibitors on CD4+ cell percentage, using marginal structural models to account for confounding by severity. Results Initiation of any type of HAART increased CD4+ cell percentage by 2.34% (95% confidence interval, 1.35%–3.33%) in the first year, relative to noninitiation of HAART. The substantial increases in CD4+ cell percentage observed after the first year of experience with these combination therapies were followed by relatively smaller increases that continued for 5 years after initiation. Although larger increases in CD4+ cell percentage were observed among children with a greater degree of immunosuppression at baseline, the mean CD4+ cell percentage after 5 years of HAART did not reach normal levels. Conclusions Our study supports the initiation of HAART in children before severe immunosuppression occurs for long-term maintenance of normal CD4+ cell percentages. This beneficial result must be weighed against the evidence of potential adverse events associated with the prolonged use of such therapy. PMID:18426371

  7. Liver ultrastructural morphology and mitochondrial DNA levels in HIV/hepatitis C virus coinfection: no evidence of mitochondrial damage with highly active antiretroviral therapy.

    PubMed

    Matsukura, Motoi; Chu, Fanny F S; Au, May; Lu, Helen; Chen, Jennifer; Rietkerk, Sonja; Barrios, Rolando; Farley, John D; Montaner, Julio S; Montessori, Valentina C; Walker, David C; Côté, Hélène C F

    2008-06-19

    Liver mitochondrial toxicity is a concern, particularly in HIV/hepatitis C virus (HCV) coinfection. Liver biopsies from HIV/HCV co-infected patients, 14 ON-highly active antiretroviral therapy (HAART) and nine OFF-HAART, were assessed by electron microscopy quantitative morphometric analyses. Hepatocytes tended to be larger ON-HAART than OFF-HAART (P = 0.05), but mitochondrial volume, cristae density, lipid volume, mitochondrial DNA and RNA levels were similar. We found no evidence of increased mitochondrial toxicity in individuals currently on HAART, suggesting that concomitant HAART should not delay HCV therapy. PMID:18525271

  8. Suboptimal adherence associated with virological failure and resistance mutations to first-line highly active antiretroviral therapy (HAART) in Bangalore, India

    PubMed Central

    Ekstrand, Maria L.; Shet, Anita; Chandy, Sara; Singh, Girija; Shamsundar, Ranjani; Madhavan, Vidya; Saravanan, Shanmugam; Heylen, Elsa; Kumarasamy, Nagalingeswaran

    2010-01-01

    This study was conducted to examine the relationship between adherence, viral load (VL) and resistance among outpatients receiving highly active antiretroviral therapy (HAART) in Bangalore, India. In total, 552 outpatients were recruited and VL testing was conducted for all study participants. HIV-1 genotypic resistance testing was performed for 92 participants with a VL ≥ 1000 copies/ml. Interpretation of resistance mutations was performed according to the Stanford database. Past-month adherence and treatment interruptions for >48 h were assessed via self-report. At baseline, 34 participants (6%) reported <95% past-month adherence and 110 (20%) reported a history of >48 h treatment interruptions. Combining the two adherence measures, 22% of participants were classified as ‘suboptimally adherent’. In total, 24% of study participants (n = 132) had a detectable VL. Among the 92 samples sent for resistance testing, 68% had at least one nucleoside reverse transcriptase inhibitor (NRTI) mutation, with M184V being the most common (62%) and with 48% having thymidine analogue mutations. Moreover, 72% had at least one non-nucleoside reverse transcriptase inhibitor (NNRTI) mutation and 23% had three or more NNRTI mutations. Both adherence measures were significantly associated with VL (P < 0.001). Suboptimal adherence was significantly associated with resistance mutations (P < 0.02). The findings illustrate for the first time the strong association between suboptimal adherence, treatment failure and drug resistance to first-line HAART in India. The predictive value of standard adherence measures was improved by including treatment interruption data. The observed mutations can jeopardise future treatment options, especially in light of limited access to second-line treatments. To develop effective adherence interventions, research is needed to examine culturally-specific reasons for treatment interruptions. PMID:21516199

  9. Quantitation of cytomegalovirus (CMV) DNA by real-time PCR for occurrence of CMV disease in HIV-infected patients receiving highly active antiretroviral therapy.

    PubMed

    Gourlain, Karine; Salmon, Dominique; Gault, Elyanne; Leport, Catherine; Katlama, Christine; Matheron, Sophie; Costagliola, Dominique; Mazeron, Marie-Christine; Fillet, Anne-Marie

    2003-03-01

    In HIV-infected patients treated with highly active antiretroviral therapy (HAART) included in the Predivir cohort, we have evaluated the usefulness of CMV DNA quantitation by a TaqMan PCR assay from peripheral blood leukocytes (PBLs) to predict CMV disease occurrence. In parallel with the immune restoration after treatment by HAART, the percentage of positive samples decreased progressively from 7.3% at Day 0 to 3.5% at Month 12. Among the CMV markers, the smallest concordance with PBL CMV TaqMan PCR, as evaluated by kappa, was observed with pp65 antigenemia, whereas concordance with all other CMV markers was high. Among the 16 patients with CMV DNA copies at least once >100/150,000 cells, CMV disease occurred in six during follow-up, whereas among the 159 patients with CMV DNA copies always <10/150,000 cells, CMV disease occurred in three and among the seven patients with CMV DNA copies >10 and <100 occurred in only one. In univariate Cox models, all the CMV markers including PBL CMV TaqMan PCR >10/150,000 cells (RR: 27.6, IC95: 7.1-107.2), the CD4 cell count <75 cells/mm(3) and the HIV viral load >100,000 copies/ml were predictive for CMV disease. In a stepwise multivariate analysis, which should be interpreted with caution due to the small number of events (n = 10), three covariates were associated independently with CMV disease: pp65 antigenemia >100 nuclei/200,000, PBL CMV TaqMan PCR >10 copies/150,000 cells and HIV viral load remaining or increasing >100,000 copies/ml. PMID:12526052

  10. Immune activation and IL-12 production during acute/early HIV infection in the absence and presence of highly active, antiretroviral therapy.

    PubMed

    Byrnes, Adriana A; Harris, David M; Atabani, Sowsan F; Sabundayo, Beulah P; Langan, Susan J; Margolick, Joseph B; Karp, Christopher L

    2008-12-01

    Suppressed IL-12 production and maladaptive immune activation, both of which are ameliorated by successful highly active antiretroviral therapy (HAART), are thought to play important roles in the immunopathogenesis of chronic HIV infection. Despite the important effects of the immunological and virological events of early HIV infection on subsequent disease progression, IL-12 production and immune activation in early infection remain under-defined. To quantify IL-12 production and immune activation during acute/early HIV infection, in the presence and absence of HAART, we performed a prospective, longitudinal study of participants in the Baltimore site of the Acute Infection and Early Disease Research Program, with cross-sectional comparison to healthy control subjects. PBMC cytokine productive capacity and plasma immune activation markers [soluble CD8 (sCD8), sCD4, granzyme B, neopterin, beta2-microglobulin, sIL-2R, sTNFRI, sTNFRII, and IL-12p70] were quantified by ELISA. Notably, PBMC from patients with acute/early HIV infection exhibited in vivo IL-12p70 production along with increased, maximal in vitro IL-12 production. Further, despite evidence from plasma markers of generalized immune activation, no elevation in plasma levels of sCD4 was observed, suggesting relative blunting of in vivo CD4+ T cell activation from the beginning of HIV infection. Finally, despite successful virological responses to HAART, heightened in vivo CD8+ T cell activation, IL-12 production, and IFN activity were sustained for at least 6 months during primary HIV infection. These data underscore the need for comparative mechanistic analysis of the immunobiology of early and chronic HIV infection. PMID:18806124

  11. Association of immune recovery with hyperlipidaemia and apolipoprotein gene polymorphisms following highly active antiretroviral therapy in a cohort of Chinese HIV patients

    PubMed Central

    Chan, Denise Pui-Chung; Lee, Man-Po; Wong, Ngai-Sze; Leung, Ross Ka-Kit; Naftalin, Claire Melinda; Lee, Shui-Shan

    2016-01-01

    Objective To examine the associations between CD4 recovery, dyslipidaemia and apolipoprotein (APO) gene single nucleotide polymorphisms (SNPs) following highly active antiretroviral therapy (HAART). Design Retrospective observational cohort study. Setting A major HIV care clinic in Hong Kong. Participants 197 Chinese treatment-naïve HIV patients. Outcome measures Maximum CD4 count and its rise 2–3 years after HAART initiation and their association with abnormal total cholesterol (TC), triglyceride (TG) and 8 selected APO SNP at multiple time points. Results Before HAART, abnormal levels of TC, TG, high-density lipoprotein cholesterol and low-density lipoprotein cholesterol were detected in 13%, 26%, 59% and 19% of the recruited patients, respectively. APOA5 −1131T>C and c.553G>T were significantly associated with high pre-HAART TG while APOE 2198C>T was correlated with high TG at baseline and/or a rise 2–3 years following HAART initiation. Poor CD4 achievement, defined as the highest CD4 count <350/μL and a net gain of <100/μL, was associated with a low CD4 count ≤200/μL at baseline and a rise of TC beyond 5.17 mmol/L following HAART with or without the use of antilipid agents. Conversely, satisfactory CD4 achievement was associated with APOC3 3238GG genotype. Applying a linear generalised estimating equation, APOA5 −1131T>C was shown to be a predictor of a weaker temporal trend for CD4 response in the presence of a low baseline CD4≤200/μL. Conclusions Dyslipidaemia plays a predictive role in impacting immunological recovery following HAART, which could be partly explained by the APO gene SNP. PMID:27067897

  12. Concurrent Chemoradiotherapy With 5-Fluorouracil and Mitomycin C for Invasive Anal Carcinoma in Human Immunodeficiency Virus-Positive Patients Receiving Highly Active Antiretroviral Therapy

    SciTech Connect

    Fraunholz, Ingeborg

    2010-04-15

    Purpose: To report the clinical outcomes of chemoradiotherapy (CRT) for anal carcinoma in human immunodeficiency virus (HIV)-infected patients receiving highly active antiretroviral therapy. Patients and Methods: Between 1997 and 2008, 21 HIV-positive patients who were receiving highly active antiretroviral therapy were treated with CRT (50.4 Gy at 1.8 Gy/fraction plus a 5.4-10.8-Gy external boost; 5-fluorouracil, 1,000 mg/m{sup 2}, Days 1-4 and 29-32; and mitomycin C, 10 mg/m{sup 2}, Days 1 and 29). A retrospective analysis was performed with respect to the tumor response, local control, cancer-specific and overall survival, and toxicity. The immunologic parameters, including pre- and post-treatment CD4 count, viral load, and acquired immunodeficiency syndrome-specific morbidity was recorded during follow-up (median, 53 months; range, 10-99). Results: CRT could be completed in all 21 patients with a reduction in the chemotherapy dose and/or interruption of radiotherapy in 5 and 5 cases, respectively. Acute Grade 3 toxicity occurred in 8 (38%) of the 21 patients. A complete response was achieved in 17 patients (81%), and tumor persistence or early progression was noted in 4 (19%). Six patients (29%) died, 5 of cancer progression and 1 of treatment-related toxicity. The 5-year local control, cancer-specific, and overall survival rate was 59%, 75%, and 67%, respectively. The median CD4 count significantly decreased from 347.5 cells/muL before CRT to 125 cells/muL 3-7 weeks after CRT completion (p <.001). In 6 (32%) of 19 patients, an increase of the HIV viral load was noted. Both parameters returned to the pretreatment values with additional follow-up. Conclusion: Our data have confirmed that in the highly active antiretroviral therapy era, HIV-related anal cancer can be treated with standard CRT without dose reductions. Close surveillance of the immunologic parameters is necessary.

  13. Plasma Mitochondrial DNA Levels as a Biomarker of Lipodystrophy Among HIV-infected Patients Treated with Highly Active Antiretroviral Therapy (HAART).

    PubMed

    Dai, Z; Cai, W; Hu, F; Lan, Y; Li, L; Chung, C; Caughey, B; Zhang, K; Tang, X

    2015-01-01

    Lipodystrophy is a common complication in HIV-infected patients taking highly active antiretroviral therapy. Its early diagnosis is crucial for timely modification of antiretroviral therapy. We hypothesize that mitochondrial DNA in plasma may be a potential marker of LD in HIV-infected individuals. In this study, we compared plasma mitochondrial DNA levels in HIV-infected individuals and non-HIV-infected individuals to investigate its potential diagnostic value. Total plasma DNA was extracted from 67 HIV-infected patients at baseline and 12, 24 and 30 months after initiating antiretroviral therapy. Real-time quantitative PCR was used to determine the mitochondrial DNA levels in plasma. Lipodystrophy was defined by the physician-assessed presence of lipoatrophy or lipohypertrophy in one or more body regions. The mitochondrial DNA levels in plasma were significantly higher at baseline in HIV-infected individuals than in non-HIV-infected individuals (p<0.05). At month 30, 33 out of 67 patients (49.2%) showed at least one sign of lipodystrophy. The mean plasma mitochondrial DNA levels in lipodystrophy patients were significantly higher compared to those without lipodystrophy at month 24 (p<0.001). The receiver operating curve analysis demonstrated that using plasma mitochondrial DNA level (with cut-off value <5.09 log10 copies/ml) as a molecular marker allowed identification of patients with lipodystrophy with a sensitivity of 64.2% and a specificity of 73.0%. Our data suggest that mitochondrial DNA levels may help to guide therapy selection with regards to HIV lipodystrophy risk. PMID:26592244

  14. Drug-Drug Interactions Based on Pharmacogenetic Profile between Highly Active Antiretroviral Therapy and Antiblastic Chemotherapy in Cancer Patients with HIV Infection.

    PubMed

    Berretta, Massimiliano; Caraglia, Michele; Martellotta, Ferdinando; Zappavigna, Silvia; Lombardi, Angela; Fierro, Carla; Atripaldi, Luigi; Muto, Tommaso; Valente, Daniela; De Paoli, Paolo; Tirelli, Umberto; Di Francia, Raffaele

    2016-01-01

    The introduction of Highly Active Antiretroviral Therapy (HAART) into clinical practice has dramatically changed the natural approach of HIV-related cancers. Several studies have shown that intensive antiblastic chemotherapy (AC) is feasible in HIV-infected patients with cancer, and that the outcome is similar to that of HIV-negative patients receiving the same AC regimens. However, the concomitant use of HAART and AC can result in drug accumulation or possible toxicity with consequent decreased efficacy of one or both classes of drugs. In fact, many AC agents are preferentially metabolized by CYP450 and drug-drug interactions (DDIs) with HAART are common. Therefore, it is important that HIV patients with cancer in HAART receiving AC treatment at the same time receive an individualized cancer management plan based on their liver and renal functions, their level of bone marrow suppression, their mitochondrial dysfunction, and their genotype profile. The rationale of this review is to summarize the existing data on the impact of HAART on the clinical management of cancer patients with HIV/AIDS and DDIs between antiretrovirals and AC. In addition, in order to maximize the efficacy of antiblastic therapy and minimize the risk of drug-drug interaction, a useful list of pharmacogenomic markers is provided. PMID:27065862

  15. Failure to Restore the Vγ2-Jγ1.2 Repertoire in HIV-infected Men Receiving Highly Active Antiretroviral Therapy (HAART)

    PubMed Central

    Hebbeler, Andrew M.; Propp, Nadia; Cairo, Cristiana; Li, Haishan; Cummings, Jean Saville; Jacobson, Lisa P.; Margolick, Joseph B.; Pauza, C. David

    2008-01-01

    Gammadelta (γδ) T cells expressing the Vγ2-Jγ1.2Vδ2 (Vγ9-JPVδ2, alternate nomenclature) T cell receptor (TCR) constitute the major peripheral blood population of γδ T cells in adult humans and are specifically depleted during human immunodeficiency virus (HIV) disease. Vγ2-Jγ1.2Vδ2 T cells provide a convenient model for assessing the impact of antiretroviral therapy on cell populations that are not susceptible to direct infection because they do not express CD4 and depletion occurs by indirect mechanisms. We obtained longitudinal PBMC samples from 16 HIV-infected individuals who were enrolled in the Multicenter AIDS Cohort Study (MACS) and starting highly active antiretroviral therapy (HAART). Vγ2-Jγ1.2Vδ2 T cells were depleted in these individuals as a result of HIV infection. Despite evidence for clinical benefits of HAART, the Vγ2-Jγ1.2Vδ2 T cell repertoire did not recover after HAART initiation irrespective of treatment duration. These studies highlight important defects among cell subsets lost due to indirect effects of HIV. PMID:18606571

  16. Drug–Drug Interactions Based on Pharmacogenetic Profile between Highly Active Antiretroviral Therapy and Antiblastic Chemotherapy in Cancer Patients with HIV Infection

    PubMed Central

    Berretta, Massimiliano; Caraglia, Michele; Martellotta, Ferdinando; Zappavigna, Silvia; Lombardi, Angela; Fierro, Carla; Atripaldi, Luigi; Muto, Tommaso; Valente, Daniela; De Paoli, Paolo; Tirelli, Umberto; Di Francia, Raffaele

    2016-01-01

    The introduction of Highly Active Antiretroviral Therapy (HAART) into clinical practice has dramatically changed the natural approach of HIV-related cancers. Several studies have shown that intensive antiblastic chemotherapy (AC) is feasible in HIV-infected patients with cancer, and that the outcome is similar to that of HIV-negative patients receiving the same AC regimens. However, the concomitant use of HAART and AC can result in drug accumulation or possible toxicity with consequent decreased efficacy of one or both classes of drugs. In fact, many AC agents are preferentially metabolized by CYP450 and drug–drug interactions (DDIs) with HAART are common. Therefore, it is important that HIV patients with cancer in HAART receiving AC treatment at the same time receive an individualized cancer management plan based on their liver and renal functions, their level of bone marrow suppression, their mitochondrial dysfunction, and their genotype profile. The rationale of this review is to summarize the existing data on the impact of HAART on the clinical management of cancer patients with HIV/AIDS and DDIs between antiretrovirals and AC. In addition, in order to maximize the efficacy of antiblastic therapy and minimize the risk of drug–drug interaction, a useful list of pharmacogenomic markers is provided. PMID:27065862

  17. Alcohol and Race/Ethnicity Elicit Different Changes in Lipid Profiles in HIV-Infected Individuals Receiving Highly Active Antiretroviral Therapy

    PubMed Central

    Míguez-Burbano, Maria J.; Lewis, John E.; Malow, Robert

    2015-01-01

    This longitudinal study examined the impact of alcohol consumption (88 hazardous and 76 nonhazardous drinkers) and race/ethnicity on lipid profiles in individuals starting highly active antiretroviral therapy (HAART). At baseline, Whites and Hispanics had the most adverse lipid profiles, whereas Blacks had the least atherogenic. Whites and Hispanics showed higher increases in cholesterol (W = 11%; H = 6%), triglycerides (W = 40%; H = 24%), and low-density lipoprotein (10%) than Blacks (cholesterol = 4%; triglycerides = 9%; low-density lipoprotein = 4%). Hazardous alcohol consumption was correlated with increased lipids in each group. Hispanics had a clear trait risk for hypertriglyceridemia with HAART (1.9-fold) and with hazardous drinking (3.2-fold; p = .04). The highest risk for hypertriglyceridemia was found in heavy drinkers (3.75-fold; p = .05). Results underscore the importance of an alcohol/race interactive effect on HAART-associated dyslipidemia and the need for assessment and treatment of alcohol disorders. PMID:19427595

  18. Second-line protease inhibitor-based highly active antiretroviral therapy after failing non-nucleoside reverse transcriptase inhibitors-based regimens in Asian HIV-infected children

    PubMed Central

    Bunupuradah, Torsak; Puthanakit, Thanyawee; Fahey, Paul; Kariminia, Azar; Yusoff, Nik Khairulddin Nik; Khanh, Truong Huu; Sohn, Annette H.; Chokephaibulkit, Kulkanya; Lumbiganon, Pagakrong; Hansudewechakul, Rawiwan; Razali, Kamarul; Kurniati, Nia; Huy, Bui Vu; Sudjaritruk, Tavitiya; Kumarasamy, Nagalingeswaran; Fong, Siew Moy; Saphonn, Vonthanak; Ananworanich, Jintanat

    2013-01-01

    Background The WHO recommends boosted protease inhibitor (bPI)-based highly active antiretroviral therapy (HAART) after failing non-nucleoside reverse transcriptase inhibitor (NNRTI) treatment. We examined outcomes of this regimen in Asian HIV-infected children. Methods Children from five Asian countries in the TREAT Asia Pediatric HIV Observational Database (TApHOD) with ≥24 weeks of NNRTI-based HAART followed by ≥24 weeks of bPI-based HAART were eligible. Primary outcomes were the proportions with virologic suppression (HIV-RNA <400 copies/ml) and immune recovery (CD4% ≥25% if age <5 years and CD4 count ≥500 cells/mm3 if age ≥5 years) at 48 and 96 weeks. Results Of 3422 children, 153 were eligible; 52% were female. At switch, median age was 10 years, 26% were in WHO stage 4. Median weight-for-age z-score (WAZ) was −1.9 (n=121), CD4% was 12.5% (n=106), CD4 count was 237 (n=112) cells/mm3, and HIV-RNA was 4.6 log10copies/ml (n=61). The most common PI was lopinavir/ritonavir (83%). At 48 weeks, 61% (79/129) had immune recovery, 60% (26/43) had undetectable HIV-RNA and 73% (58/79) had fasting triglycerides ≥130mg/dl. By 96 weeks, 70% (57/82) achieved immune recovery, 65% (17/26) virologic suppression, and hypertriglyceridemia occurred in 66% (33/50). Predictors for virologic suppression at week 48 were longer duration of NNRTI-based HAART (p=0.006), younger age (p=0.007), higher WAZ (p=0.020), and HIV-RNA at switch <10,000 copies/ml (p=0.049). Conclusion In this regional cohort of Asian children on bPI-based second-line HAART, 60% of children tested had immune recovery by one year, and two-thirds had hyperlipidemia, highlighting difficulties in optimizing second-line HAART with limited drug options. PMID:23296119

  19. Insulin resistance predicts endothelial dysfunction and cardiovascular risk in HIV-infected persons on long-term highly active antiretroviral therapy

    PubMed Central

    Mondy, Kristin E.; de las Fuentes, Lisa; Waggoner, Alan; Önen, Nur F.; Bopp, Coco S.; Lassa-Claxton, Sherry; Powderly, William G.; Dávila-Román, Victor; Yarasheski, Kevin E.

    2011-01-01

    Objective Cardiovascular disease risk among persons with HIV is likely multifactorial, thus testing a variety of available noninvasive vascular ultrasound and other surrogate tests may yield differing results. To address this issue, we assessed multiple metabolic and clinical predictors of endothelial function and carotid intima–media thickness in HIV-infected subjects and compared results with HIV-negative controls. Design Prospective, cross-sectional study of 50 HIV-infected, healthy adults on stable highly active antiretroviral therapy matched to 50 HIV-negative controls by age, sex, race, and body mass index. Methods Flow-mediated vasodilation of the brachial artery, carotid intima–media thickness, dual energy X-ray absorptiometry (HIV-infected subjects), and fasting insulin, lipids, and oral glucose tolerance tests were performed. Results were compared between HIV-infected and control groups. Results Fifty percent of subjects were African–American with 34% women. Among HIV-infected, mean CD4 cell count was 547 cells/ µl; 90% had HIV RNA less than 50 copies/ml. There were no significant differences between HIV-infected and control subjects with regard to brachial artery flow-mediated vasodilation or carotid intima–media thickness. In multivariate analyses of the HIV cohort, independent predictors of endothelial dysfunction (lower flow-mediated vasodilation) were increasing insulin resistance, greater alcohol consumption, and higher baseline brachial artery diameter (P < 0.05); predictors of increased carotid intima–media thickness were hypertension, higher trunk/limb fat ratio, and insulin resistance (P < 0.05). Conclusion In this HIV cohort on modern highly active antiretroviral therapy with well controlled HIV, there were no significant differences with regard to preclinical markers of cardiovascular disease. Insulin resistance was a strong predictor of impaired brachial artery flow-mediated vasodilation and increased carotid intima

  20. Effects of highly active antiretroviral therapy on the survival of HIV-infected adult patients in urban slums of Kenya.

    PubMed

    Muhula, Samuel Opondo; Peter, Memiah; Sibhatu, Biadgilign; Meshack, Ndirangu; Lennie, Kyomuhangi

    2015-01-01

    Recent improvements in access to Anti-Retroviral Therapy (ART) have radically reduced hospitalizations and deaths associated with HIV infection in both developed countries and sub-Saharan Africa. Not much is known about survival of patients on ART in slums. The objective of this study was to identify factors associated with mortality among adult patients on ART in resource poor, urban, sub-Saharan African setting. A prospective open cohort study was conducted with adult patients on ART at a clinic in Kibera slums, Nairobi, Kenya. The patients' enrollment to care was between March 2005 and November 2011. Descriptive statistics were computed and Kaplan-Meier (KM) methods used to estimate survival time while Cox's proportional hazards (CPH) model fitted to determine mortality predictors. A total of 2,011 adult patients were studied, 69% being female. Female gender (p=0.0016), zidovudine-based regimen patients (p<0.0001), CD4 count>351 patients (p<0.0001), WHO stage I patients (p<0.0001) and "Working" functional status patients recorded better survival probability on ART. In CPH analysis, the hazard of dying was higher in patients on Stavudine-based regimen(hazard ratio (HR)=.8; 95% CI, 1.5-2.2; p<0.0001),CD4 count<50 cells/µl (HR=1.6; 95% CI, 1.5-1.7;p<0.0001), WHO Stage IV at ART initiation (HR=1.3; 95% CI, 1.1-1.6; p=0.016) and bedridden patients (HR=2.7; 95% CI, 1.7-4.4;p<0.0001). There was increased mortality among the males, those with advanced Immunosuppression, late WHO stage and bedridden patients. The findings further justify the need to switch patients on Stavudine-based regimen as per the WHO recommendations. PMID:26090021

  1. Is long-term virological response related to CCR5 Δ32 deletion in HIV-1-infected patients started on highly active antiretroviral therapy?

    PubMed Central

    Laurichesse, Jean-Jacques; Taieb, Audrey; Capoulade-Metay, Corinne; Katlama, Christine; Villes, Virginie; Drobacheff-Thiebaud, Marie-Christine; Raffi, François; Chêne, Genevieve; Theodorou, Ioannis; Leport, Catherine

    2010-01-01

    Objective To examine whether CCR5 Δ32 deletion is associated with long-term response to combination antiretroviral treatment (cART) in HIV-1 infected patients. Methods The genetic sub-study of ANRS CO8 APROCO-COPILOTE cohort included 609 patients who started a protease inhibitor-containing cART in 1997–99. Patients were considered to have a sustained virological response if all plasma HIV-RNA measurements between month 4 and years 3–5 were <500 copies/ml, allowing for a single blip. Virological response was compared between patients heterozygous for CCR5 Δ32 (Δ32/wt) and wild-type patients (wt/wt) from month 4 to year 3 and month 4 to year 5. Logistic regression analysis was used to adjust for baseline demographical data, HIV-RNA, CD4 cell counts, antiretroviral naive status, time spent on antiretroviral therapy at year 3 and 5 and adherence to treatment (month 4 to year 3 and 5). Results Sustained virological response was better in Δ32/wt than in wt/wt patients: 66% versus 52% up to year 3 (p=0.02), nearly significant after adjustment to potential cofounders (p=0.07). Δ32/wt patients had a better virological response, up to year 5, 48% versus 35% (p=0.01), and remained significantly better, after adjustment, associated with a better virological response up to 5 years post initiation of cART (p=0.04). There was no association with CD4 response. Conclusion Δ32/wt deletion is associated with a beneficial virological response to cART on the long-term. Whether this association can be a direct effect of Δ32/wt deletion remains questionable and needs confirmation in other observational studies. PMID:20050936

  2. Isoniazid-resistant Mycobacterium kansasii in an HIV-positive patient, and possible development of immune reconstitution inflammatory syndrome after initiation of highly active antiretroviral therapy: case report.

    PubMed

    Despotovic, A; Savic, B; Salemovic, D; Ranin, J; Jevtovic, Dj

    2016-01-01

    Non-tuberculous mycobacteria are rare but important causes of infection in HIV-positive individuals. A 28-year-old HIV-positive male presented with a high fever, non-productive cough, right subcostal pain, splenomegaly, a very low CD4 count, elevated C-reactive protein and erythrocyte sedimentation rate, and a normal white blood cell count. The suspicion of tuberculosis (TB) was very high, and sputum samples were positive for acid-fast bacilli. Standard quadruple anti-TB therapy was initiated, but once culture of the sample revealed Mycobacterium kansasii, pyrazinamide was withdrawn. Highly active antiretroviral therapy (HAART) was initiated soon after, consisting of abacavir/lamivudine and efavirenz. The patient's general condition deteriorated 2 weeks after HAART initiation, which could have been due to the development of immune reconstitution inflammatory syndrome (IRIS). The patient recovered and was discharged in good condition. However, the results of resistance testing of the isolated organism arrived after discharge, and showed isoniazid and streptomycin resistance. This is the first case report of M. kansasii infection from Serbia and shows the difficulties encountered during the course of treatment. PMID:26603644

  3. Preventive measures to prevent loss to follow-up in highly active antiretroviral therapy (HAART): implementing a strategy in Ziguinchor (Casamance, Senegal) in 2014.

    PubMed

    Randé, H; Rouffy, D

    2016-05-01

    Since 2010, the Pharmacie et Aide Humanitaire (PAH) in Casamance (Senegal) has been maintaining a software package (Tacojo) that allows monthly monitoring of the distribution of treatment to every patient with HIV infection receiving highly active antiretroviral therapy (HAART). We used this program to set up measures to prevent the loss to follow-up of patients receiving HAART. Our involvement focused on two main areas. First, each patient is routinely contacted after inclusion, to help us to understand the patient's experience of the disease and the treatment. This process aims to improve adherence to the treatment. Then, all patients who miss an appointment are routinely contacted by telephone within seven days of that appointment. The goal is to understand the reasons for the absence and to encourage patients to continue their treatment. Despite the lack of distance due to the relative newness of this program, these preventive measures have shown hopeful results (80% of the patients came back after a call). It would be interesting to apply it in a sustainable manner and in more medical facilities. PMID:27412981

  4. Effect of highly active antiretroviral therapy on the serological response to additional measles vaccinations in human immunodeficiency virus-infected children.

    PubMed

    Berkelhamer, S; Borock, E; Elsen, C; Englund, J; Johnson, D

    2001-04-01

    Children infected with human immunodeficiency virus (HIV) often lose their vaccine-induced antibody to measles virus. Before highly active antiretroviral therapy (HAART), an additional immunization against measles infrequently resulted in protective antibodies. The antibody response to an additional measles-mumps-rubella (MMR) vaccination was compared in 28 HIV-infected children who lacked protective antibody to measles virus and were undergoing HAART or non-HAART regimens. Serostatus was measured by automated enzyme-linked immunoassay. Nine (64.3%) of 14 children undergoing HAART, compared with 3 (21.4%) of 14 in the non-HAART group, had antibody to measles virus after the additional vaccination with MMR (P=.027). The groups showed no significant difference in CD4 cell values. Ten of 14 HAART patients had undetectable levels of HIV. The mean HIV load for the HAART group was 27,700 copies/mL (median, <400 copies/mL); for the non-HAART group, it was 86,000 copies/mL (median, 9000 copies/mL). Thus, HAART improves the response to an additional MMR vaccination, which is consistent with immune system reconstitution. PMID:11264038

  5. Impact of highly active antiretroviral therapy on oral manifestations of patients with human immunodeficiency virus/acquired immuno deficiency syndrome in South India

    PubMed Central

    Rao, K. V. S. Eswara; Chitturi, Ravi Teja; Kattappagari, Kiran Kumar; Kantheti, Lalith Prakash Chandra; Poosarla, Chandrasekhar; Baddam, Venkat Ramana Reddy

    2015-01-01

    Background: Human immunodeficiency virus (HIV) infection remains a global health problem, although the development of highly active antiretroviral therapy (HAART) has significantly modified the course of HIV disease into a manageable disease with improved quality-of-life mainly in the developed countries. Very few studies are available regarding effect of HAART on oral lesions in developing countries like India. Aims and Objectives: The aim was to document and compare oral lesions in HIV-seropositive patients before and after HAART. Materials and Methods: Oral manifestations were recorded in 320 HIV seropositive patients attending to the Voluntary Counseling and Confidential Testing Centre at the Government General Hospital, Guntur, before and after treating with HAART and the results were statistically analyzed using Student's t-test and Chi-square test. Results: Oral Candidiasis was significantly reduced in patients under HAART after 3 months. Furthermore, there was decreased incidence of periodontal diseases, but increased hyperpigmentation in patients undergoing HAART. Conclusion: The oral manifestations of HIV infection have changed due to the advent of HAART. Many opportunistic infections have resolved as a result of an improved immune system. Though the risk of hyperpigmentation in those with HAART has increased the prevalence of oral candidiasis and periodontal diseases were less in patients who had access to HAART. PMID:26392652

  6. Antiretroviral drugs.

    PubMed

    De Clercq, Erik

    2010-10-01

    In October 2010, it will be exactly 25 years ago that the first antiretroviral drug, AZT (zidovudine, 3'-azido-2',3'-dideoxythymidine), was described. It was the first of 25 antiretroviral drugs that in the past 25 years have been formally licensed for clinical use. These antiretroviral drugs fall into seven categories [nucleoside reverse transcriptase inhibitors (NRTIs), nucleotide reverse transcriptase inhibitors (NtRTIs), non-nucleoside reverse transcriptase inhibitors (NNRTIs), protease inhibitors (PIs), fusion inhibitors (FIs), co-receptor inhibitors (CRIs) and integrase inhibitors (INIs). The INIs (i.e. raltegravir) represent the most recent advance in the search for effective and selective anti-HIV agents. Combination of several anti-HIV drugs [often referred to as highly active antiretroviral therapy (HAART)] has drastically altered AIDS from an almost uniformly fatal disease to a chronic manageable one. PMID:20471318

  7. Adherence to directly observed antiretroviral therapy among human immunodeficiency virus-infected prison inmates.

    PubMed

    Wohl, David A; Stephenson, Becky L; Golin, Carol E; Kiziah, C Nichole; Rosen, David; Ngo, Bich; Liu, Honghu; Kaplan, Andrew H

    2003-06-15

    Directly observed therapy (DOT) for human immunodeficiency virus (HIV) infection is commonly used in correctional settings; however, the efficacy of DOT for treating HIV infection has not been determined. We prospectively assessed adherence to antiretroviral therapy regimens among 31 HIV-infected prison inmates who were receiving >or=1 antiretrovirals via DOT. Adherence was measured by self-report, pill count, electronic monitoring caps, and, for DOT only, medication administration records. Overall, median adherence was 90%, as measured by pill count; 86%, by electronic monitoring caps; and 100%, by self-report. Adherence, as measured by electronic monitoring caps, was >90% in 32% of the subjects. In 91% of cases, adherence, as measured by medication administration records, was greater than that recorded by electronic monitoring caps for the same medications administered by DOT. Objective methods of measurement revealed that adherence to antiretroviral regimens administered wholly or in part by DOT was antiretroviral therapy. PMID:12802758

  8. Selected micronutrient levels and response to highly active antiretroviral therapy (HAART) among HIV/AIDS patients attending a teaching Hospital in Addis Ababa, Ethiopia.

    PubMed

    Eshetu, Amare; Tsegaye, Aster; Petros, Beyene

    2014-12-01

    Poor micronutrient levels are associated with an increased risk of progression to AIDS and are also suggested to influence outcome of highly active antiretroviral therapy (HAART), though existing data are inconclusive to support the latter. Few published data are available on micronutrient levels in Ethiopian HIV/AIDS patients taking HAART. The objective of the study was to determine the association of micronutrient levels and response to HAART (CD4(+) T cell count) among adult HIV/AIDS patients attending a teaching Hospital in Addis Ababa. CD4(+) T cell counts and micronutrient (retinol, zinc, and iron) levels for 171 subjects were determined using standard procedures. Some proportions of the study participants were found deficient for retinol (14.03 %), zinc (47.3 %), and iron (2.8 %). Patients who were deficient in retinol had a significantly lower median CD4(+) T cell counts (P = 0.002) compared to non-deficient subjects. Association of micronutrient quartiles with CD4+ T cell count was assessed using adjusted multivariate regression by taking quartile 4 as a reference category. Accordingly, patients who had retinol levels in quartile 4 had a significantly lower mean CD4(+) T cell count compared to quartile 3 (P = 0.02). The significantly higher CD4(+) T cell counts in patients who were non-deficient in retinol imply the role of retinol in improving the production of CD4(+) T cells. However, both lower and higher retinol levels were associated with suppressed immunity (CD4 < 200 cells/mm(3)), suggesting an adverse effect of higher retinol levels. Thus, retinol may be potentially harmful depending on the dose, emphasizing the need for optimized level of retinol in nutrient supplements in patients taking HAART. PMID:25256923

  9. Nutrition and disease progression pre–highly active antiretroviral therapy (HAART) and post-HAART: can good nutrition delay time to HAART and affect response to HAART?1234

    PubMed Central

    Chandrasekhar, Aditya; Gupta, Amita

    2011-01-01

    Several studies have investigated a variety of nutritional supplementation interventions in adults with HIV. In this narrative review, we summarize the evidence from 31 clinical trials that explore clinical benefits of macronutrient and micronutrient supplementation in this population while attempting to answer the question of whether good nutrition can delay the time to highly active antiretroviral therapy (HAART) initiation and response. We focused on trials published in English between 1990 and 2010 that reported on CD4 count, viral load, and disease progression or survival. Among 9 macronutrient and 22 micronutrient trials, we found that evidence for improved CD4 count and HIV viral load with nutritional supplementation was limited; only 11.1% and 36.8% of macronutrient and micronutrient supplementation trials, respectively, reported improved CD4 count; and 33.3% and 12.5% of macronutrient and micronutrient trials, respectively, reported decreased viral load. Given their utility as surrogate markers of HIV disease progression, this suggests limited evidence for nutritional interventions having an impact on delaying HAART initiation or on improving HAART response. However, there are challenges in evaluating the effects of nutritional supplementation on clinical disease in that comparisons are difficult due to heterogeneity in study design, patient population, nutrient doses and combinations, baseline levels of deficiency, and study endpoints, including lack of clarity in defining and reporting HAART status. Future studies need to adopt a more rigorous standard design with adequate power and follow-up and require a consensus on composition and dose of nutrient interventions to be tested to more specifically answer the question on the impact of nutritional interventions on HIV disease progression and HAART response. PMID:22089439

  10. New Subtypes and Genetic Recombination in HIV Type 1-Infecting Patients with Highly Active Antiretroviral Therapy in Peru (2008–2010)

    PubMed Central

    Acuña, Maribel; Gazzo, Cecilia; Salinas, Gabriela; Cárdenas, Fanny; Valverde, Ada; Romero, Soledad

    2012-01-01

    Abstract HIV-1 subtype B is the most frequent strain in Peru. However, there is no available data about the genetic diversity of HIV-infected patients receiving highly active antiretroviral therapy (HAART) here. A group of 267 patients in the Peruvian National Treatment Program with virologic failure were tested for genotypic evidence of HIV drug resistance at the Instituto Nacional de Salud (INS) of Peru between March 2008 and December 2010. Viral RNA was extracted from plasma and the segments of the protease (PR) and reverse transcriptase (RT) genes were amplified by reverse transcriptase polymerase chain reaction (RT-PCR), purified, and fully sequenced. Consensus sequences were submitted to the HIVdb Genotypic Resistance Interpretation Algorithm Database from Stanford University, and then aligned using Clustal X v.2.0 to generate a phylogenetic tree using the maximum likelihood method. Intrasubtype and intersubtype recombination analyses were performed using the SCUEAL program (Subtype Classification by Evolutionary ALgo-rithms). A total of 245 samples (91%) were successfully genotyped. The analysis obtained from the HIVdb program showed 81.5% resistance cases (n=198). The phylogenetic analysis revealed that subtype B was predominant in the population (98.8%), except for new cases of A, C, and H subtypes (n=4). Of these cases, only subtype C was imported. Likewise, recombination analysis revealed nine intersubtype and 20 intrasubtype recombinant cases. This is the first report of the presence of HIV-1 subtypes C and H in Peru. The introduction of new subtypes and circulating recombinants forms can make it difficult to distinguish resistance profiles in patients and consequently affect future treatment strategies against HIV in this country. PMID:22559065

  11. Disparities in the Magnitude of Human Immunodeficiency Virus-related Opportunistic Infections Between High and Low/Middle-income Countries: Is Highly Active Antiretroviral Therapy Changing the Trend?

    PubMed

    Iroezindu, M O

    2016-01-01

    Opportunistic infections (OIs) cause significant morbidity/mortality in human immunodeficiency virus (HIV)-infected individuals globally. Disparities between high-income countries (HICs) and low/middle-income countries (LMICs) in the magnitude of HIV-related OIs in pre-highly active antiretroviral therapy (HAART) populations was reviewed, and HAART-induced decline in OIs was further compared between the two settings. Studies published in English from onset of HIV epidemic up to December 2013 were searched in PubMed, Google, Google Scholar, and African Journal online. An article was included if (a) the study was conducted in HIC or LMIC, (b) the age of the participants was ≥12 years, (c) the HAART status of the participants was stated, and (d) various types of OIs were investigated. In predominantly pre-HAART populations, the incidence and prevalence of overall HIV-related OIs in HIC ranged from 5.5 to 50.0 per 100 person-years (PY) and 27.4-56.7%, respectively. In LMIC, the respective overall incidence and prevalence of OIs were 12.2-93.9 per 100 PY and 32.0-77.7%. Pneumocystis jirovecii pneumonia, candidiasis, Cytomegalovirus disease, Mycobacterium avium complex disease, and Kaposi's sarcoma were the most frequent OIs in HICs while tuberculosis, candidiasis, chronic diarrhea, and cryptococcosis were predominant in LMICs. The introduction of HAART led to substantial reduction in the incidence of OIs with more impressive percentage decline in HICs (43-97%) compared to 30-79% in LMICs. Disparities in the magnitude of HIV-related OIs between HICs and LMICs are evident both in the pre-HAART and post-HAART era. Efforts to optimize HAART-induced decline in HIV-related OIs should become a global health priority irrespective of prevailing socioeconomic circumstances. PMID:27144071

  12. Serum lipid levels associated with increased risk for cardiovascular disease is associated with highly active antiretroviral therapy (HAART) in HIV-1 infection.

    PubMed

    Koppel, K; Bratt, G; Eriksson, M; Sandström, E

    2000-07-01

    The long-term effects of fat metabolism, storage and utilization in HIV-1 infected patients on highly active antiretroviral therapy (HAART) including a protease inhibitor are profound and cause increasing concern. The main importance of these lipid/metabolic disorders lies in their assumed contribution to an increased risk of coronary heart disease (CHD). In the general population increased levels of lipoprotein(a) [Lp(a)] constitute an independent risk factor for CHD by itself as well as in combination with increased levels of cholesterol and low density lipoprotein (LDL)-cholesterol, respectively. Two hundred and fifty-six patients with 27 +/- 7 months HAART and 84 treatment-naive HIV-1 positive patients were screened for cardiovascular risk factors. The subjective perception of fat wasting and/or accumulation in different sites of the body, which was possible to evaluate in 235 patients on HAART and 73 treatment-naive patients, the levels of plasma triglycerides (TG), cholesterol, LDL and high-density lipoproteins (HDL)-cholesterol, LDL/HDL ratio and Lp(a) were measured. Of the patients on HAART, 42% (98/235) reported abnormal fat distribution as compared with 4% (3/73) of the treatment-naive patients (P<0.0001). The levels of TG, cholesterol and LDL-cholesterol, but not HDL-cholesterol or Lp(a) were higher (P<0.0001) in the HAART group as compared with the naive group. Very high Lp(a) levels (> 700 mg/l) were more common among HAART patients as compared with naive, 14% (36/256) vs 2% (2/83); P=0.0022. The Lp(a) levels correlated to the levels of LDL-cholesterol, but not to total cholesterol, HDL-cholesterol or TG, and did not differ between patients with and without subjective perception of abnormal fat distribution. A significant number of the HAART patients had very high levels of Lp(a) and various combinations of increased lipid values associated with considerably increased risk for CHD. The elevation of Lp(a) did not relate to any other clinical or

  13. Prevalence of Hypertension in HIV/AIDS Patients on Highly Active Antiretroviral Therapy (HAART) Compared with HAART-Naïve Patients at the Limbe Regional Hospital, Cameroon

    PubMed Central

    Dimala, Christian Akem; Atashili, Julius; Mbuagbaw, Josephine C.; Wilfred, Akam; Monekosso, Gottlieb L.

    2016-01-01

    Background Highly active antiretroviral therapy (HAART) has greatly reduced the morbidity and mortality of HIV/AIDS patients but has also been associated with increased metabolic complications and cardiovascular diseases. Data on the association between HAART and hypertension (HTN) in Africa are scarce. Objectives Primarily to compare the prevalence of HTN in HIV/AIDS patients on HAART and HAART-naïve patients in Limbe, Cameroon; and secondarily to assess other socio-demographic and clinical factors associated with HTN in this population. Methods A cross-sectional study was conducted at the Limbe Regional Hospital HIV treatment center between April and June 2013, involving 200 HIV/AIDS patients (100 on first-line HAART regimens for at least 12 months matched by age and sex to 100 HAART-naïve patients). HTN was defined as a systolic blood pressure (BP) ≥ 140 mmHg and/or diastolic BP ≥ 90 mmHg. Results The prevalence of HTN in patients on HAART was twice (38%; 95% CI: 28.5–48.3) that of the HAART-naïve patients (19%; 95% CI, 11.8–28.1), p = 0.003. In multivariate analyses adjusted for age, gender, smoking, family history of HTN, and BMI-defined overweight, HAART was associated with HTN, the adjusted odds ratio of the HAART-treated versus HAART-naïve group was 2.20 (95% CI: 1.07–4.52), p = 0.032. HTN was associated with older age and male gender, in the HAART group and with BMI-defined overweight in the HAART-naïve group. Conclusion The prevalence of hypertension in HIV/AIDS patients in Limbe stands out to be elevated, higher in patients on HAART compared to those not on treatment. Blood pressure and cardiovascular risk factors should be routinely monitored. Other factors such as diet, weight control and physical exercise should also be considered. PMID:26862763

  14. Preparing for highly active antiretroviral therapy rollout in rural South Africa: an assessment using the information, motivation, and behavioral skills model.

    PubMed

    Simon, Margo D; Altice, Frederick L; Moll, Anthony P; Shange, Mbuso; Friedland, Gerald H

    2010-04-01

    Following a controversial history and before South Africa started the world's largest highly active antiretroviral therapy (HAART) rollout, little was known about community-level information, motivation, and behavioral skills (IMB) regarding HAART in high-HIV-prevalence rural communities. The IMB model has been shown to predict behaviors that are associated with desirable HAART outcomes. We conducted an anonymous, cross-sectional "HAART-Felt Prospects" survey among HIV-serostatus-unknown young adults in Tugela Ferry, KwaZulu-Natal. We aimed to identify behavioral aspects of HAART preparedness that could be targeted by local interventions to enhance HAART outcomes. Data analysis included: percent correct, thematic means based on a four-point Likert-scale, and composite quotients. Subjects (N=176) were Zulu (99%), young (mean 19 years), and severely impoverished (55%). Relatively high levels of information were reported: overall correct score was 46%, secondary-transmission-of-resistance information was highest (81%), and only 15% reported traditional or government-advocated folk remedies cure or treat HIV/AIDS. Motivation quotient was "consistent" with favorable HAART behaviors; attitudes toward medication-taking behaviors (3.48) and condom use during HAART (3.43) ranked the highest. Desire for HIV testing (71%) was associated with HIV treatment optimism [adjusted odds ratio (AOR)=4.0, p=0.0004] and previous experience with good treatment outcome [AOR=3.2, p=0.01]. Acceptance of HAART (93%) was associated with HIV optimism [AOR=18.0, p=0.001] and not believing government-advocated folk remedies cure or treat HIV/AIDS [AOR=10.0, p=0.04]. Behavioral skills quotient was "neutral" for favorable HAART behaviors; side effects self-efficacy was the highest (3.16); and medication-taking self-efficacy the lowest (2.51). Only 47% believed disclosing HIV-serostatus would be easy. Despite controversy surrounding HAART initiation, these results suggest that local South African

  15. 2B4 expression on natural killer cells increases in HIV-1 infected patients followed prospectively during highly active antiretroviral therapy.

    PubMed

    Ostrowski, S R; Ullum, H; Pedersen, B K; Gerstoft, J; Katzenstein, T L

    2005-09-01

    Human immunodeficiency virus (HIV)-1 infection influences natural killer (NK) cell expression of inhibitory NK receptors and activating natural cytotoxicity receptors. It is unknown whether expression of the co-stimulatory NK cell receptor 2B4 (CD244) on NK cells and CD3+ CD8+ cells are affected by highly active antiretroviral therapy (HAART), low-level viraemia, proviral-DNA or immune activation in HIV-1 infected patients. A total of 101 HAART-treated HIV-1 infected patients with < or = 200 HIV-RNA copies/ml were followed prospectively for 24 months. HIV-RNA was investigated 3-monthly and 2B4 expression on CD3- CD16+ NK cells and CD3+ CD8+ cells, proviral-DNA and plasma soluble tumour necrosis factor receptor (sTNFr)-II were investigated 6-monthly. For comparison, 2B4 expression was investigated in 20 healthy individuals. The concentration of 2B4+ NK cells was initially reduced in HIV-1 infected patients (P < 0.001) but increased to a normal level during the 24 months' follow-up. The concentration of CD3+ CD8+ 2B4+ cells in HIV-1 infected patients was normal and did not change during follow-up. The relative fluorescence intensity (RFI) of 2B4 increased on both NK cells and CD3+ CD8+ cells during follow-up (both P < 0.001). Higher levels of proviral-DNA carrying cells and plasma sTNFrII were associated with reductions in the concentration of 2B4+ NK cells (all P < 0.05). HIV-RNA had no effect on 2B4 expression on NK cells or CD3+ CD8+ cells. These findings demonstrate that the concentration of 2B4+ NK cells normalizes during long-term HAART in HIV-1 infected patients. The finding that proviral-DNA and sTNFrII were associated negatively with the concentration of 2B4+ NK cells suggests that immune activation in HIV-1 infected patients receiving HAART influences the target cell recognition by NK cells. PMID:16045743

  16. Inhibition of CYP2B6 by Medicinal Plant Extracts: Implication for Use of Efavirenz and Nevirapine-Based Highly Active Anti-Retroviral Therapy (HAART) in Resource-Limited Settings.

    PubMed

    Thomford, Nicholas E; Awortwe, Charles; Dzobo, Kevin; Adu, Faustina; Chopera, Denis; Wonkam, Ambroise; Skelton, Michelle; Blackhurst, Dee; Dandara, Collet

    2016-01-01

    Highly active antiretroviral therapy (HAART) has greatly improved health parameters of HIV infected individuals. However, there are several challenges associated with the chronic nature of HAART administration. For populations in health transition, dual use of medicinal plant extracts and conventional medicine poses a significant challenge. There is need to evaluate interactions between commonly used medicinal plant extracts and antiretroviral drugs used against HIV/AIDS. Efavirenz (EFV) and nevirapine (NVP) are the major components of HAART both metabolized by CYP2B6, an enzyme that can potentially be inhibited or induced by compounds found in medicinal plant extracts. The purpose of this study was to evaluate the effects of extracts of selected commonly used medicinal plants on CYP2B6 enzyme activity. Recombinant human CYP2B6 was used to evaluate inhibition, allowing the assessment of herb-drug interactions (HDI) of medicinal plants Hyptis suaveolens, Myrothamnus flabellifolius, Launaea taraxacifolia, Boerhavia diffusa and Newbouldia laevis. The potential of these medicinal extracts to cause HDI was ranked accordingly for reversible inhibition and also classified as potential time-dependent inhibitor (TDI) candidates. The most potent inhibitor for CYP2B6 was Hyptis suaveolens extract (IC50 = 19.09 ± 1.16 µg/mL), followed by Myrothamnus flabellifolius extract (IC50 = 23.66 ± 4.86 µg/mL), Launaea taraxacifolia extract (IC50 = 33.87 ± 1.54 µg/mL), and Boerhavia diffusa extract (IC50 = 34.93 ± 1.06 µg/mL). Newbouldia laevis extract, however, exhibited weak inhibitory effects (IC50 = 100 ± 8.71 µg/mL) on CYP2B6. Launaea taraxacifolia exhibited a TDI (3.17) effect on CYP2B6 and showed a high concentration of known CYP450 inhibitory phenolic compounds, chlorogenic acid and caffeic acid. The implication for these observations is that drugs that are metabolized by CYP2B6 when co-administered with these herbal medicines and when adequate amounts of the extracts

  17. Adherence to highly active antiretroviral therapy impact on clinical and economic outcomes for Medicaid enrollees with HIV and hepatitis C co-infection

    PubMed Central

    Zhang, Shun; Rust, George; Cardarelli, Kathryn; Felizzola, Jesus; Fransua, Mesfin; Stringer, Harold G.

    2016-01-01

    We examined the impact of antiretroviral treatment adherence among Hepatitis C co-infected HIV patients on survival and clinical outcomes. We analyzed Medicaid claims data from fourteen southern states from 2005-2007, comparing survival and clinical outcomes and cost of treatment for HIV and hepatitis-C co-infected patients (N=4,115) at different levels of adherence to antiretroviral therapy.More than one in five patients (20.5%) showed less than 50% adherence to antiretroviral treatment, but there were no racial-ethnic or gender disparities. Significant survival benefit was demonstrated at each incremental level of adherence to antiretroviral therapy (one-year mortality ranging from 3.5% in the highest adherence group to 26.0% in the lowest). Low adherence patients also had higher rates of hospitalization and emergency department visits. Relative to patients with high (>95%) ART-adherence, those with less than 25% treatment adherence had four-fold greater risk of death (adjusted odds ratio 4.22 [95% CI, 3.03,5.87]). Non-drug Medicaid expenditures were lower for high adherence patients, but cost of medications drove total Medicaid expenditures higher for high-adherence patients. Cost per quality-adjusted life year (QALY) saved (relative to the <25% low-adherence group) ranged from $21,874 for increasing adherence to 25-50% to $37,229 for increasing adherence to 75-95%. Adherence to antiretroviral therapy for patients with HIV and hepatitis C co-infection is associated with lower adverse clinical outcomes at a Medicaid cost per QALY commensurate with other well-accepted treatment and prevention strategies. Further research is needed to identify interventions which can best achieve optimal ART adherence at a population scale. PMID:25814041

  18. Effect of Rosiglitazone and Metformin on Insulin Resistance in Patients Infected with Human Immunodeficiency Virus Receiving Highly Active Antiretroviral Therapy Containing Protease Inhibitor: Randomized Prospective Controlled Clinical Trial

    PubMed Central

    Silič, Anja; Janež, Andrej; Tomažič, Janez; Karner, Primož; Vidmar, Ludvik; Sharma, Prem; Matičič, Mojca

    2007-01-01

    Aim To evaluate and compare effects of 48-week treatment with rosiglitazone and metformin on insulin resistance in patients infected with Human Immunodeficiency Virus (HIV) receiving highly active antiretroviral therapy (HAART), containing a protease inhibitor. Methods Randomized prospective controlled clinical trial enrolled 90 male patients infected with HIV and having impaired glucose tolerance and insulin resistance (fasting insulin concentration >20 mIU/L). The patients were randomly assigned into three groups (each 30 patients); the first group receiving 4 mg rosiglitazone once a day, the second group receiving 500 mg metformin two times a day, and the third group serving as control without hypoglycemic treatment. The primary efficacy parameters were fasting plasma glucose and insulin levels compared between baseline and week. Data on insulin resistance and beta cell function were analyzed by the Homeostasis Model Assessment (HOMA). Results After 48 weeks of treatment, the fasting insulin concentration (±standard deviation) in rosiglitazone group significantly declined from 39.0 ± 3.35 to 19.7 ± 3.99 mIU/L (P<0.001; 49% decrease) and in metformin group from 40.3 ± 2.29 to 29.2 ± 2.82 mIU/L (P<0.001; 27% decrease). HOMA indicated that rosiglitazone significantly reduced insulin resistance from 11.3 ± 1.03 to 4.0 ± 0.95 (P<0.001), compared with metformin which reduced it from 11.9 ± 0.73 to 5.7 ± 0.62 (P<0.001). Insulin resistance was significantly lower in the rosiglitazone group after 48 weeks (P<0.001). Metformin significantly improved beta cell function (from 257.3 ± 21.91 to 707.4 ± 207.32; P<0.001), as did rosiglitazone (from 261.3 ± 27.98 to 403.3 ± 162.50; P<0.001), but the improvement in the metformin group was significantly better (P<0.001). However, metformin was more efficient in improving beta cell function (from 257.3 ± 21.91 to 707.4 ± 207.32) than rosiglitazone (from 261.3

  19. The pricing and procurement of antiretroviral drugs: an observational study of data from the Global Fund.

    PubMed

    Vasan, Ashwin; Hoos, David; Mukherjee, Joia S; Farmer, Paul E; Rosenfield, Allan G; Perriëns, Joseph H

    2006-05-01

    The Purchase price report released in August 2004 by the Global Fund to Fight AIDS, Tuberculosis, and Malaria (Global Fund) was the first publication of a significant amount of real transaction purchase data for antiretrovirals (ARVs). We did an observational study of the ARV transaction data in the Purchase price report to examine the procurement behaviour of principal recipients of Global Fund grants in developing countries. We found that, with a few exceptions for specific products (e.g. lamivudine) and regions (e.g. eastern Europe), prices in low-income countries were broadly consistent or lower than the lowest differential prices quoted by the research and development sector of the pharmaceutical industry. In lower middle-income countries, prices were more varied and in several instances (lopinavir/ritonavir, didanosine, and zidovudine/lamivudine) were very high compared with the per capita income of the country. In all low- and lower middle-income countries, ARV prices were still significantly high given limited local purchasing power and economic strength, thus reaffirming the need for donor support to achieve rapid scale-up of antiretroviral therapy. However, the price of ARVs will have to decrease to render scale-up financially sustainable for donors and eventually for governments themselves. An important first step in reducing prices will be to make available in the public domain as much ARV transaction data as possible to provide a factual basis for discussions on pricing. The price of ARVs has considerable implications for the sustainability of human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS) treatment in the developing world. PMID:16710550

  20. Video observations of treatment administration to children on antiretroviral therapy in rural KwaZulu-Natal.

    PubMed

    Coetzee, Bronwyne; Kagee, Ashraf; Bland, Ruth

    2016-03-01

    For children younger than five years, caregivers are responsible for the measurement and administration of antiretroviral medication doses to children. Failure to adhere to the regimen as prescribed may lead to high viral loads (VLs), immune suppression and ultimately drug resistance. In the content of this study, adherence refers to adequate dosing of the medication by a caregiver. Acquired drug resistance to antiretroviral therapy (ART) is prevalent amongst children in South Africa, and poor adherence to the dosing regimen by caregivers may be associated with this problem. In this qualitative study, we purposively recruited 33 caregiver-child dyads from the Hlabisa HIV Treatment and Care Programme database. Children were divided into three groups based on their VL at the time of recruitment. Children with a VL ≥ 400 cps/ml were grouped as unsuppressed (n = 11); children with a VL ≤ 400 cps/ml were grouped as suppressed (n = 12); and children with no VL data were grouped as newly initiated (n = 10). Caregiver-child dyads were visited at their households twice to document, by means of video recording, how treatment was administered to the child. Observational notes and video recordings were entered into ATLAS.ti v 7 and analysed thematically. Results were interpreted through the lens of Ecological Systems Theory and the information-motivation-behavioural skills model was used to understand and reflect on several of the factors influencing adherence within the child's immediate environment as identified in this study. Thematic video analysis indicated context- and medication-related factors influencing ART adherence. Although the majority of children in this sample took their medicine successfully, caregivers experienced several challenges with the preparation and administration of the medications. In the context of emerging drug resistance, efforts are needed to carefully monitor caregiver knowledge of treatment administration by

  1. Video observations of treatment administration to children on antiretroviral therapy in rural KwaZulu-Natal

    PubMed Central

    Coetzee, Bronwyne; Kagee, Ashraf; Bland, Ruth

    2016-01-01

    ABSTRACT For children younger than five years, caregivers are responsible for the measurement and administration of antiretroviral medication doses to children. Failure to adhere to the regimen as prescribed may lead to high viral loads (VLs), immune suppression and ultimately drug resistance. In the content of this study, adherence refers to adequate dosing of the medication by a caregiver. Acquired drug resistance to antiretroviral therapy (ART) is prevalent amongst children in South Africa, and poor adherence to the dosing regimen by caregivers may be associated with this problem. In this qualitative study, we purposively recruited 33 caregiver–child dyads from the Hlabisa HIV Treatment and Care Programme database. Children were divided into three groups based on their VL at the time of recruitment. Children with a VL ≥ 400 cps/ml were grouped as unsuppressed (n = 11); children with a VL ≤ 400 cps/ml were grouped as suppressed (n = 12); and children with no VL data were grouped as newly initiated (n = 10). Caregiver–child dyads were visited at their households twice to document, by means of video recording, how treatment was administered to the child. Observational notes and video recordings were entered into ATLAS.ti v 7 and analysed thematically. Results were interpreted through the lens of Ecological Systems Theory and the information–motivation–behavioural skills model was used to understand and reflect on several of the factors influencing adherence within the child’s immediate environment as identified in this study. Thematic video analysis indicated context- and medication-related factors influencing ART adherence. Although the majority of children in this sample took their medicine successfully, caregivers experienced several challenges with the preparation and administration of the medications. In the context of emerging drug resistance, efforts are needed to carefully monitor caregiver knowledge of treatment

  2. The pricing and procurement of antiretroviral drugs: an observational study of data from the Global Fund.

    PubMed Central

    Vasan, Ashwin; Hoos, David; Mukherjee, Joia S.; Farmer, Paul E.; Rosenfield, Allan G.; Perriëns, Joseph H.

    2006-01-01

    The Purchase price report released in August 2004 by the Global Fund to Fight AIDS, Tuberculosis, and Malaria (Global Fund) was the first publication of a significant amount of real transaction purchase data for antiretrovirals (ARVs). We did an observational study of the ARV transaction data in the Purchase price report to examine the procurement behaviour of principal recipients of Global Fund grants in developing countries. We found that, with a few exceptions for specific products (e.g. lamivudine) and regions (e.g. eastern Europe), prices in low-income countries were broadly consistent or lower than the lowest differential prices quoted by the research and development sector of the pharmaceutical industry. In lower middle-income countries, prices were more varied and in several instances (lopinavir/ritonavir, didanosine, and zidovudine/lamivudine) were very high compared with the per capita income of the country. In all low- and lower middle-income countries, ARV prices were still significantly high given limited local purchasing power and economic strength, thus reaffirming the need for donor support to achieve rapid scale-up of antiretroviral therapy. However, the price of ARVs will have to decrease to render scale-up financially sustainable for donors and eventually for governments themselves. An important first step in reducing prices will be to make available in the public domain as much ARV transaction data as possible to provide a factual basis for discussions on pricing. The price of ARVs has considerable implications for the sustainability of human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS) treatment in the developing world. PMID:16710550

  3. Impact of Antiretroviral Therapy on Opportunistic Infections of HIV-Infected Children in the TREAT Asia Pediatric HIV Observational Database

    PubMed Central

    Prasitsuebsai, Wasana; Kariminia, Azar; Puthanakit, Thanyawee; Lumbiganon, Pagakrong; Hansudewechakul, Rawiwan; Moy, Fong Siew; Law, Matthew; Kumarasamy, Nagalingeswaran; Razali, Kamarul; Sirisanthana, Virat; Sohn, Annette H.; Chokephaibulkit, Kulkanya

    2014-01-01

    Background There are limited data on opportunistic infections (OI) and factors associated with their occurrence after highly active antiretroviral therapy (HAART) in Asian children. The use of HAART in Asia started much later than in developed countries and therefore reported findings may not be fully applicable to the pediatric HIV epidemic in Asia. Methods Retrospective and prospectively collected data from the TREAT Asia Pediatric HIV Observational Database cohort study from March 1993 to March 2009 were analyzed. OIs were defined according to WHO clinical staging criteria, and incidence rates calculated. Factors associated with the incidence of severe OIs were analyzed using random effects Poisson regression modeling. Results Of 2280 children in the cohort, 1752 were ever reported to have received ART, of whom 1480 (84%) started on HAART. Before commencing any ART, OIs occurred at a rate of 89.5 per 100 person-years. The incidence rate was 28.8 infections per 100 person-years during mono- or dual-therapy, and 10.5 infections per 100 person-years during HAART. The most common OIs both before and after ART initiation were recurrent upper respiratory tract infections, persistent oral candidiasis, and pulmonary tuberculosis. The incidence rates of WHO clinical stage 3 or 4 OIs after HAART were highest among children <18 months of age and those with low weight-for-age z scores, CD4 cell percentage <15%, and WHO stage 3 at HAART initiation. Conclusions Despite dramatic declines in their incidence, OIs remained important causes of morbidity after HAART initiation in this regional cohort of HIV-infected children in Asia. PMID:24378942

  4. The impact of integrating food supplementation, nutritional education and HAART (Highly Active Antiretroviral Therapy) on the nutritional status of patients living with HIV/AIDS in Mozambique: results from the DREAM Programme.

    PubMed

    Scarcella, P; Buonomo, E; Zimba, I; Doro Altan, A M; Germano, P; Palombi, L; Marazzi, M C

    2011-01-01

    DREAM (Drug Resources Enhancement against AIDS and Malnutrition) is a multiregional health program active in Mozambique since 2002 and provides free of charge an integrating package of care consisting of peer to peer nutritional and health education, food supplementation, voluntary counseling and testing, immunological, virological, clinical assessment and HAART (Highly Active AntiRetroviral Treatment). The main goals of this paper are to describe the state of health and nutrition and the adequacy of the diet of a sample of HIV/AIDS patients in Mozambique on HAART and not. A single-arm retrospective cohort study was conducted. 106 HIV/AIDS adult patients (84 in HAART), all receiving food supplementation and peer-to-peer nutritional education, were randomly recruited in Mozambique in two public health centres where DREAM is running. The programme is characterized by: provision of HAART, clinical and laboratory monitoring, peer to peer health and nutritional education and food supplementation. We measured BMI, haemoglobin, viral load, CD4 count at baseline (T0) and after at least 1 year (T1). Dietary intake was estimated using 24h food recall and dietary diversity was assessed by using the Dietary Diversity Score (DDS) at T1. Overall, the patients'diet appeared to be quite balanced in nutrients. In the cohort not in HAART the mean BMI values showed an increases but not significant (initial value: 21.9 ± 2.9; final value: 22.5 ± 3.3 ) and the mean haemoglobin values (g/dl) showed a significant increases (initial value: 10.5+ 2.1; final value: 11.5 ± 1.7 p< 0.024) . In the cohort in HAART, both the mean of BMI value (initial value: 20.7 ± 3.9; final value: 21.9 ± 3.3 p< 0.001) and of haemoglobin (initial value: 9.9 ± 2.2; final value: 10.8 ± 1.7 p< 0.001) showed a higher significant increase. The increase in BMI was statistically associated with the DDS in HAART patients. In conclusion nutritional status improvement was observed in both cohorts. The improvement

  5. Morbidity and Mortality Patterns of Hospitalised Adult HIV/AIDS Patients in the Era of Highly Active Antiretroviral Therapy: A 4-year Retrospective Review from Zaria, Northern Nigeria

    PubMed Central

    Ogoina, Dimie; Obiako, Reginald O.; Muktar, Haruna M.; Adeiza, Mukhtar; Babadoko, Aliyu; Hassan, Abdulaziz; Bansi, Isa; Iheonye, Henry; Iyanda, Matthew; Tabi-Ajayi, Eric

    2012-01-01

    Background. This study, undertaken in major tertiary hospital in northern Nigeria, examined the morbidity and mortality patterns of hospitalised adult HIV/AIDS patients in the HAART era. Methods. Between January 2006 and December 2009, admission records and causes of deaths of hospitalised medical HIV-infected patients were retrieved and analysed according to antiretroviral (ART) status. Results. Of the 207 HIV/AIDS patients reviewed, majority were newly diagnosed (73.4%), and most were hospitalised and died from various AIDS-defining illnesses, mainly disseminated tuberculosis and sepsis. Immune-inflammatory-reconstitution-syndrome, ART-toxicity and ART-failure, contributed to morbidity and mortality in patients receiving ART. Sixty six (31.9%) patients died, with higher mortality in males and in those with lower CD4-cell count, lower PCV, and shorter hospital stay. However, hospital stay ≤3 days and severe anaemia (PCV < 24%) were independent predictors of mortality. Conclusion. In the current HAART era, late presentation and tuberculosis continue to fuel the HIV/AIDS pandemic in Africa, with emerging challenges due to ART-related complications. PMID:23019521

  6. Reduction of Maternal Mortality with Highly Active Antiretroviral Therapy in a Large Cohort of HIV-Infected Pregnant Women in Malawi and Mozambique

    PubMed Central

    Liotta, Giuseppe; Mancinelli, Sandro; Nielsen-Saines, Karin; Gennaro, E.; Scarcella, Paola; Magid, Nurja Abdul; Germano, Paola; Jere, Haswell; Guidotti, Gianni; Buonomo, Ersilia; Ciccacci, Fausto; Palombi, Leonardo; Marazzi, Maria Cristina

    2013-01-01

    Background HIV infection is a major contributor to maternal mortality in resource-limited settings. The Drug Resource Enhancement Against AIDS and Malnutrition Programme has been promoting HAART use during pregnancy and postpartum for Prevention-of-mother-to-child-HIV transmission (PMTCT) irrespective of maternal CD4 cell counts since 2002. Methods Records for all HIV+ pregnancies followed in Mozambique and Malawi from 6/2002 to 6/2010 were reviewed. The cohort was comprised by pregnancies where women were referred for PMTCT and started HAART during prenatal care (n = 8172, group 1) and pregnancies where women were referred on established HAART (n = 1978, group 2). Results 10,150 pregnancies were followed. Median (IQR) baseline values were age 26 years (IQR:23–30), CD4 count 392 cells/mm3 (IQR:258–563), Viral Load log10 3.9 (IQR:3.2–4.4), BMI 23.4 (IQR:21.5–25.7), Hemoglobin 10.0 (IQR: 9.0–11.0). 101 maternal deaths (0.99%) occurred during pregnancy to 6 weeks postpartum: 87 (1.1%) in group 1 and 14 (0.7%) in group 2. Mortality was 1.3% in women with Antiretrovirals for PMTCT purposes have significant impact on maternal mortality as do CD4 counts and nutritional status. In resource-limited settings, PMTCT programs should provide universal HAART to all HIV+ pregnant women given its impact in prevention of

  7. The long-term outcomes of antiretroviral treatment initiated with mono or dual nucleoside reverse transcriptase inhibitors in HIV-1-infected children: an Asian observational study

    PubMed Central

    Wittawatmongkol, Orasri; Mohamed, Thahira J; Le, Thoa PK; Ung, Vibol; Maleesatharn, Alan; Hansudewechakul, Rawiwan; Nguyen, Lam V; Kumarasamy, Nagalingeswaran; Lumbiganon, Pagakrong; Sudjaritruk, Tavitiya; Bunupuradah, Torsak; Yusoff, Nik KN; Kurniati, Nia; Fong, Moy S.; Nallusamy, Revathy; Kariminia, Azar; Sohn, Annette H.; Chokephaibulkit, Kulkanya

    2016-01-01

    After a median of 115.9 months of follow-up, 90% of 206 HIV-1-infected children in a cohort in Asia who initiated antiretroviral treatment (ART) with mono or dual nucleoside reverse transcriptase inhibitors were alive and had comparable immunological and virological outcomes as compared to the 1,915 children who had started with highly active antiretroviral regimens. However, these children had higher rates of treatment-related adverse events, opportunistic infections, and cumulative mortality, and were more likely to require protease inhibitor-containing regimens or other more novel ART-based regimens. PMID:27076917

  8. A Decade of Combination Antiretroviral Treatment in Asia: The TREAT Asia HIV Observational Database Cohort.

    PubMed

    2016-08-01

    Asian countries have seen the expansion of combination antiretroviral therapy (cART) over the past decade. The TREAT Asia HIV Observational Database (TAHOD) was established in 2003 comprising 23 urban referral sites in 13 countries across the region. We examined trends in treatment outcomes in patients who initiated cART between 2003 and 2013. Time of cART initiation was grouped into three periods: 2003-2005, 2006-2009, and 2010-2013. We analyzed trends in undetectable viral load (VL; defined as VL <400 copies/ml), CD4 changes from pre-cART levels, and overall survival. Of 6,521 patients included, the overall median CD4 count at cART initiation was 120 cells/μl (interquartile range: 38-218). Despite an increase over time, pre-cART CD4 counts remained <200 cells/μl. Adjusted analyses showed undetectable VL was more likely when starting cART in later years [2006-2009: odds ratio (OR) = 1.76, 95% confidence interval (CI) (1.45, 2.15); and 2010-2013: OR = 3.04, 95% CI (2.33, 3.97), all p < .001, compared to 2003-2005], and survival was improved [2006-2009: subdistribution hazard ratio (SHR) = 0.41, 95% CI (0.27, 0.61), 2010-2013: SHR = 0.29, 95% CI (0.17, 0.49), all p < .001, compared to 2003-2005]. No differences in CD4 response was observed over time. Age and CD4 levels prior to cART initiation were associated with all three treatment outcomes, with older age and higher CD4 counts being associated with undetectable VL. Survival and VL response on cART have improved over the past decade in TAHOD, although CD4 count at cART initiation remained low. Greater effort should be made to facilitate earlier HIV diagnosis and linkage to care and treatment, to achieve greater improvements in treatment outcomes. PMID:27030657

  9. Atypical manifestation of progressive outer retinal necrosis in AIDS patient with CD4+ T-cell counts more than 100 cells/microL on highly active antiretroviral therapy.

    PubMed

    Vichitvejpaisal, Pornpattana; Reeponmahar, Somporn; Tantisiriwat, Woraphot

    2009-06-01

    Typical progressive outer retinal necrosis (PORN) is an acute ocular infectious disease in acquired immunodeficiency syndrome (AIDS) patients with extremely low CD4+ T-cell counts. It is a form of the Varicella- zoster virus (VZV) infection. This destructive infection has an extremely rapid course that may lead to blindness in affected eyes within days or weeks. Attempts at its treatment have had limited success. We describe the case of a bilateral PORN in an AIDS patient with an initial CD4+ T-cell count >100 cells/microL that developed after initiation of highly active antiretroviral therapy (HAART). A 29-year-old Thai female initially diagnosed with human immunodeficiency virus (HIV) in 1998, presented with bilaterally decreased visual acuity after initiating HAART two months earlier. Multiple yellowish spots appeared in the deep retina without evidence of intraocular inflammation or retinal vasculitis. Her CD4+ T-cell count was 127 cells/microL. She was diagnosed as having PORN based on clinical features and positive VZV in the aqueous humor and vitreous by polymerase chain reaction (PCR). Despite combined treatment with intravenous acyclovir and intravitreous ganciclovir, the patient's visual acuity worsened with no light-perception in either eye. This case suggests that PORN should be included in the differential diagnosis of reduced visual acuity in AIDS patients initiating HAART with higher CD4+ T-cell counts. PORN may be a manifestation of the immune reconstitution syndrome. PMID:19702067

  10. Liver Enzymes Abnormalities among Highly Active Antiretroviral Therapy Experienced and HAART Naïve HIV-1 Infected Patients at Debre Tabor Hospital, North West Ethiopia: A Comparative Cross-Sectional Study

    PubMed Central

    Tulu, Ketema Tafess; Zegeye, Amtatachew Moges; Wubante, Amarech Asratie

    2016-01-01

    Liver disease has emerged as the most common non-AIDS-related cause of death in HIV patients. However, there is limited data regarding this condition including our setting in Ethiopia. Hence, liver enzyme abnormalities among highly active antiretroviral therapy (HAART) experienced and HAART naïve patients were assessed in this study. A total of 164 HAART experienced and 164 HAART naïve patients were studied. Blood specimen was collected to determine alanine aminotransferase (ALT) and aspartate aminotransferase (AST), CD4 count, and viral hepatitis. The prevalence of liver enzyme abnormality was 20.1% and 22.0% among HAART experienced and HAART naïve patients, respectively. The HAART experienced patients had higher mean ALT than HAART naïve patients (P = 0.002). Viral hepatitis (AOR = 6.02; 95% CI = 1.87–19.39), opportunistic infections (AOR = 2.91; 95% CI = 1.04–8.19), current CD4 count <200 cells/mm3 (AOR = 2.16; 95% CI = 1.06–4.39), and male sex (AOR = 1.83; 95% CI = 1.001–3.33) were associated with elevated ALT and/or AST. In conclusion, liver enzyme abnormalities were high in both HAART experienced and HAART naïve HIV-1 infected patients. Hence, monitoring and management of liver enzyme abnormalities in HIV-1 infected patients are important in our setting. PMID:27493798

  11. Total Lymphocyte Count and Haemoglobin Concentration Combined as a Surrogate Marker for Initiating Highly Active Antiretroviral Therapy in a Resource-limited Setting as against CD4 Cell Count

    PubMed Central

    Dhamangaonkar, AC; Mathew, A; Pazare, AR

    2014-01-01

    ABSTRACT Aim: To find a sensitive and low-cost surrogate marker for CD4 count for initiating highly active antiretroviral therapy (HAART) [CD4 < 200 /mm3], in the form of total lymphocyte count (TLC) < 1200 /mm3 combined with haemoglobin (Hb) with multiple Hb cut-offs. Method: Two hundred and three consecutive treatment-naïve adult HIV positive outpatients attending the virology clinic in World Health Organization (WHO) clinical stage 1, 2 or 3 were enrolled in the study. Their complete blood counts and CD4 counts were done. Descriptive statistics was done by two methods correlating TLC alone with CD4 and the other using combined marker of TLC and Hb with CD4 count. Result: Total lymphocyte count alone did not correlate well with CD4 counts (r = 0.13; p = 0.065). Sensitivity of TLC < 1200 /mm3 to predict CD4 < 200 /mm3 was low (23.27%) and the sensitivity of the combined marker (TLC + Hb) increased with higher Hb cut-offs. Conclusion: Adding Hb to TLC markedly improved the sensitivity of the marker to predict CD4 count < 200/mm3. We also recommend a trade-off Hb cut-off of 10.5 g/dL for optimum sensitivity and specificity in this population subset. PMID:25781283

  12. Assessment of adherence to highly active antiretroviral therapy and associated factors among people living with HIV at Debrebrihan Referral Hospital and Health Center, Northeast Ethiopia: a cross-sectional study

    PubMed Central

    Ketema, Abush Kebede; Shewangizaw Weret, Zewdu

    2015-01-01

    Patient adherence to antiretroviral combination therapy is a critical component to successful treatment outcome. Nonadherence to antiretroviral therapy (ART) is a major challenge to AIDS care, and the risks associated with it are extensive. The intention of this study was to determine prevalence and associated factors with adherence to highly active ART among people living with HIV/AIDS (PLWHA) at the Debrebrihan Referral Hospital and Health Center, Northeast Ethiopia. A cross-sectional study design with systematic random sampling conducted by the use of a structured, pretested self-rating adherence questionnaire was used to conduct the study among 422 respondents from the Debrebrihan Referral Hospital and Health Center. A single population proportion formula at 95% CI with 5% of marginal error at 50% of prevalence of occurrence was used to determine sample size. Adherence was defined as not missing a single ART dose during the 30-day period prior to filling out the self-report. Adherence was measured by self-reports by the patients. These results were then used in binary logistic regression analysis. Covariates were analyzed by bivariate and multivariate logistic regression with SPSS statistical software. The total number of respondents in this study was 422; their median age was 35 years. Among the participants, 95.5% were taking their medication without missing a dose. Factors such as having emotional or practical support positively encouraged ART adherence (adjusted odds ratio 0.16 [95% CI 0.05–0.49]). However, users of traditional, complementary, and alternative medicine (TCAM) (adjusted odds ratio 4.7 [95% CI 1.06–21.22]) had nearly a five times higher risk for ART nonadherence (P<0.05) than those not using TCAM. Adherence to ART among PLWA is imperative and standard. But, there is still a need to boost psychological support and practical support for the clients, and there is also a need to create a more integrative approach with TCAM in order to increase

  13. Effect of directly observed antiretroviral therapy compared to self-administered antiretroviral therapy on adherence and virological outcomes among HIV-infected prisoners: a randomized controlled pilot study.

    PubMed

    White, Becky L; Golin, Carol E; Grodensky, Catherine A; Kiziah, C Nichole; Richardson, Amy; Hudgens, Michael G; Wohl, David A; Kaplan, Andrew H

    2015-01-01

    The effect of directly observed therapy (DOT) versus self-administered therapy (SAT) on antiretroviral (ART) adherence and virological outcomes in prison has never been assessed in a randomized, controlled trial. Prisoners were randomized to receive ART by DOT or SAT. The primary outcome was medication adherence [percent of ART doses measured by the medication event monitoring system (MEMS) and pill counts] at the end of 24 weeks. The changes in the plasma viral loads from baseline and proportion of participants virological suppressed (<400 copies/mL) at the end of 24 weeks were assessed. Sixty-six percent (90/136) of eligible prisoners declined participation. Participants in the DOT arm (n = 20) had higher viral loads than participants in the SAT (n = 23) arm (p = 0.23). Participants, with complete data at 24 weeks, were analyzed as randomized. There were no significant differences in median ART adherence between the DOT (n = 16, 99% MEMS [IQR 93.9, 100], 97.1 % pill count [IQR 95.1, 99.3]) and SAT (n = 21, 98.3 % MEMS [IQR 96.0, 100], 98.5 % pill count [95.8, 100]) arms (p = 0.82 MEMS, p = 0.40 Pill Count) at 24 weeks. Participants in the DOT arm had a greater reduction in viral load of approximately -1 log 10 copies/mL [IQR -1.75, -0.05] compared to -0.05 [IQR -0.45, 0.51] in the SAT arm (p value = 0.02) at 24 weeks. The proportion of participants achieving virological suppression in the DOT vs SAT arms was not statistically different at 24 weeks (53 % vs 32 %, p = 0.21). These findings suggest that DOT ART programs in prison settings may not offer any additional benefit on adherence than SAT programs. PMID:25055766

  14. Determining factors of observance of antiretroviral treatments in Cameroon during the start-up period (2000-2002)

    PubMed Central

    Commeyras, Christophe; Rey, Jean Loup; Badre-Sentenac, Stéphanie; Essomba-Ntsama, Claudine

    Objective: highlight the socioeconomic and environmental determining factors of long-term observance to antiretroviral treatments in developing countries. Method: The regularity of antiretroviral prescriptions renewal at the central pharmacy of the Yaounde Central Hospital (Cameroon) was measured through analysing the medical and pharmaceutical files of 230 patients over the 21 month start-up period. 99 patients were also interviewed during the last six months. The determining factors were analysed according to various socio-economic criteria, linked with the longitudinal study of treatment observance. Results: The huge price decrease of HIV treatments during the start-up period was conducive to an increase in new treatments by a factor 5.76. In this context of an exploding demand, the paper shows that observance is firstly dependent on quality information about illness and treatment protocols, while longer term adherence is partly dependent on financial capability, and includes the strong influence of living conditions and behaviours. Conclusion: The paper recommends the introduction of free treatment as an objective in national sector policies and the organisation of a long term following-up of patients. In the African context of poverty and actual decentralisation of healthcare, the question of the availability of human resources is profoundly enhanced. PMID:25214897

  15. Molecular characteristics of diffuse large B-cell lymphoma in human immunodeficiency virus-infected and -uninfected patients in the pre-highly active antiretroviral therapy and pre-rituximab era.

    PubMed

    Morton, Lindsay M; Kim, Clara J; Weiss, Lawrence M; Bhatia, Kishor; Cockburn, Myles; Hawes, Debra; Wang, Sophia S; Chang, Cindy; Altekruse, Sean F; Engels, Eric A; Cozen, Wendy

    2014-03-01

    Human immunodeficiency virus (HIV) infection substantially elevates diffuse large B-cell lymphoma (DLBCL) risk, but its impact on the distinct DLBCL subtypes defined by cell of origin is unclear. We compared DLBCL molecular characteristics and prognosis in 51 HIV-infected and 116 HIV-uninfected cases diagnosed during 1977-2003. Using immunohistochemistry to classify cell of origin based on the Tally algorithm, activated B-cell (ABC)-DLBCL was substantially more common in HIV-infected (83%) than in HIV-uninfected (54%) cases (p < 0.001). Epstein-Barr virus (EBV) was detected in 63% of DLBCLs in HIV-infected cases, occurring almost exclusively in ABC-DLBCL (74% vs. 13% of germinal center B-cell [GCB]-DLBCL, p = 0.002), but was rarely detected in DLBCLs among HIV-uninfected cases (3%). Among HIV-uninfected cases, MYC/IgH [t(8;14)(q24;q32)] and IgH/BCL2 [t(14;18)(q32;q21)] translocations were significantly more common and BCL6/IgH [t(3;14)(q27;q32)] significantly less common in GCB-DLBCL than in ABC-DLBCL (p = 0.010, < 0.001 and = 0.039, respectively). Among HIV-infected cases, translocations other than MYC/IgH [t(8;14)(q24;q32)] (21%) were rare (≤ 6%) and unrelated to cell of origin. ABC-DLBCL was associated with adverse overall survival compared with GCB-DLBCL regardless of HIV status (pHIV-infected = 0.066; pHIV-uninfected = 0.038). Our data demonstrate key differences in the molecular characteristics, cell of origin and prognosis of DLBCL by HIV status in the pre-highly active antiretroviral therapy (HAART) and pre-rituximab era, supporting biologic differences in lymphomagenesis in the presence of HIV. PMID:23772639

  16. A Comparison of the Diabetes Risk Score in HIV/AIDS Patients on Highly Active Antiretroviral Therapy (HAART) and HAART-Naïve Patients at the Limbe Regional Hospital, Cameroon

    PubMed Central

    Dimala, Christian Akem; Atashili, Julius; Mbuagbaw, Josephine C.; Wilfred, Akam; Monekosso, Gottlieb L.

    2016-01-01

    Background Highly active antiretroviral therapy (HAART) has been associated with dysglycaemia. However, there is scarce data on the risk of developing diabetes mellitus (DM) in HIV/AIDS patients in Africa. Objectives Primarily to quantify and compare the risk of having diabetes mellitus in HIV/AIDS patients on HAART and HAART-naïve patients in Limbe, Cameroon; and secondarily to determine if there is an association between HAART and increased DM risk. Methods A cross-sectional study was conducted at the Limbe Regional Hospital HIV treatment center between April and June 2013, involving 200 HIV/AIDS patients (100 on first-line HAART regimens for at least 12 months matched by age and gender to 100 HAART-naïve patients). The Diabetes Risk Score (DRS) was calculated using a clinically validated model based on routinely recorded primary care parameters. A DRS ≥ 7% was considered as indicative of an increased risk of developing DM. Results The median DRS was significantly higher in patients on HAART (2.30%) than in HAART-naïve patients (1.62%), p = 0.002. The prevalence of the increased DM risk (DRS ≥ 7%) was significantly higher in patients on HAART, 31% (95% CI: 22.13–41.03) than in HAART-naïve patients, 17% (95% CI: 10.23–25.82), p = 0.020. HAART was significantly associated with an increased DM risk, the odds ratio of the HAART group compared to the HAART-naïve group was 2.19 (95% CI: 1.12–4.30, p = 0.020). However, no association was found after adjusting for BMI-defined overweight, hypertension, age, sex, family history of DM and smoking (Odds ratio = 1.22, 95% CI: 0.42–3.59, p = 0.708). Higher BMI and hypertension accounted for the increased risk of DM in patients on HAART. Also, more than 82% of the participants were receiving or had ever used Zidovudine based HAART regimens. Conclusion HIV/AIDS patients on HAART could be at a greater risk of having DM than HAART-naïve patients as a result of the effect of HAART on risk factors of DM such as BMI

  17. Association between Highly Active Antiretroviral Therapy and Type of Infectious Respiratory Disease and All-Cause In-Hospital Mortality in Patients with HIV/AIDS: A Case Series

    PubMed Central

    Báez-Saldaña, Renata; Villafuerte-García, Adriana; Cruz-Hervert, Pablo; Delgado-Sánchez, Guadalupe; Ferreyra-Reyes, Leticia; Ferreira-Guerrero, Elizabeth; Mongua-Rodríguez, Norma; Montero-Campos, Rogelio; Melchor-Romero, Ada; García-García, Lourdes

    2015-01-01

    Background Respiratory manifestations of HIV disease differ globally due to differences in current availability of effective highly active antiretroviral therapy (HAART) programs and epidemiology of infectious diseases. Objective To describe the association between HAART and discharge diagnosis and all-cause in-hospital mortality among hospitalized patients with infectious respiratory disease and HIV/AIDS. Material and Methods We retrospectively reviewed the records of patients hospitalized at a specialty hospital for respiratory diseases in Mexico City between January 1st, 2010 and December 31st, 2011. We included patients whose discharge diagnosis included HIV or AIDS and at least one infectious respiratory diagnosis. The information source was the clinical chart. We analyzed the association between HAART for 180 days or more and type of respiratory disease using polytomous logistic regression and all-cause hospital mortality by multiple logistic regressions. Results We studied 308 patients, of whom 206 (66.9%) had been diagnosed with HIV infection before admission to the hospital. The CD4+ lymphocyte median count was 68 cells/mm3 [interquartile range (IQR): 30–150]. Seventy-five (24.4%) cases had received HAART for more than 180 days. Pneumocystis jirovecii pneumonia (PJP) (n = 142), tuberculosis (n = 63), and bacterial community-acquired pneumonia (n = 60) were the most frequent discharge diagnoses. Receiving HAART for more than 180 days was associated with a lower probability of PJP [Adjusted odd ratio (aOR): 0.245, 95% Confidence Interval (CI): 0.08–0.8, p = 0.02], adjusted for sociodemographic and clinical covariates. HAART was independently associated with reduced odds (aOR 0.214, 95% CI 0.06–0.75) of all-cause in-hospital mortality, adjusting for HIV diagnosis previous to hospitalization, age, access to social security, low socioeconomic level, CD4 cell count, viral load, and discharge diagnoses. Conclusions HAART for 180 days or more was associated

  18. Trends in First-Line Antiretroviral Therapy in Asia: Results from the TREAT Asia HIV Observational Database

    PubMed Central

    Boettiger, David Charles; Kerr, Stephen; Ditangco, Rossana; Merati, Tuti Parwati; Pham, Thuy Thi Thanh; Chaiwarith, Romanee; Kiertiburanakul, Sasisopin; Li, Chung Ki Patrick; Kumarasamy, Nagalingeswaran; Vonthanak, Saphonn; Lee, Christopher; Van Kinh, Nguyen; Pujari, Sanjay; Wong, Wing Wai; Kamarulzaman, Adeeba; Zhang, Fujie; Yunihastuti, Evy; Choi, Jun Yong; Oka, Shinichi; Ng, Oon Tek; Kantipong, Pacharee; Mustafa, Mahiran; Ratanasuwan, Winai; Sohn, Annette; Law, Matthew

    2014-01-01

    Background Antiretroviral therapy (ART) has evolved rapidly since its beginnings. This analysis describes trends in first-line ART use in Asia and their impact on treatment outcomes. Methods Patients in the TREAT Asia HIV Observational Database receiving first-line ART for ≥6 months were included. Predictors of treatment failure and treatment modification were assessed. Results Data from 4662 eligible patients was analysed. Patients started ART in 2003–2006 (n = 1419), 2007–2010 (n = 2690) and 2011–2013 (n = 553). During the observation period, tenofovir, zidovudine and abacavir use largely replaced stavudine. Stavudine was prescribed to 5.8% of ART starters in 2012/13. Efavirenz use increased at the expense of nevirapine, although both continue to be used extensively (47.5% and 34.5% of patients in 2012/13, respectively). Protease inhibitor use dropped after 2004. The rate of treatment failure or modification declined over time (22.1 [95%CI 20.7–23.5] events per 100 patient/years in 2003–2006, 15.8 [14.9–16.8] in 2007–2010, and 11.6 [9.4–14.2] in 2011–2013). Adjustment for ART regimen had little impact on the temporal decline in treatment failure rates but substantially attenuated the temporal decline in rates of modification due to adverse event. In the final multivariate model, treatment modification due to adverse event was significantly predicted by earlier period of ART initiation (hazard ratio 0.52 [95%CI 0.33–0.81], p = 0.004 for 2011–2013 versus 2003–2006), older age (1.56 [1.19–2.04], p = 0.001 for ≥50 years versus <30years), female sex (1.29 [1.11–1.50], p = 0.001 versus male), positive hepatitis C status (1.33 [1.06–1.66], p = 0.013 versus negative), and ART regimen (11.36 [6.28–20.54], p<0.001 for stavudine-based regimens versus tenofovir-based). Conclusions The observed trends in first-line ART use in Asia reflect changes in drug availability, global treatment recommendations and

  19. Long-Term Effectiveness of Antiretroviral Therapy in China: An Observational Cohort Study from 2003-2014.

    PubMed

    Huang, Peng; Tan, Jingguang; Ma, Wenzhe; Zheng, Hui; Lu, Yan; Wang, Ning; Peng, Zhihang; Yu, Rongbin

    2015-08-01

    In order to assess the effectiveness of the Chinese government's expanded access program, a cohort study on all adult HIV patients in Shenzhen was conducted from December 2003 to February 2014 to estimate the effects of antiretroviral therapy (ART) on mortality, tuberculosis and CD4 cell counts. Marginal structural regression models adjusted for baseline and time-varying covariates. Of the 6897 patients enrolled and followed up for a maximum of 178 months, 44.92% received ART. Among patients who commenced receiving ART during the study, there were 98 deaths and 59 new tuberculosis diagnoses, while there were 410 deaths and 201 new tuberculosis diagnoses among those without ART. ART was associated with both lower mortality (hazard ratio [HR] = 0.18; 95% confidence interval [CI] = 0.11-0.27) and the presence of tuberculosis (HR = 0.27; 95% CI = 0.19-0.37). Each month of ART was associated with an average increase in CD4 cell count of 6.52 cells/µL (95% CI = 6.08-7.12 cells/µL). In conclusions, the effectiveness of ART provided by China government health services is the same as that in higher-income countries. Accounting to higher mortality rates from the delay of starting ART, faster expansion and timely imitation of ART are urgent. PMID:26213959

  20. Modified Directly Observed Antiretroviral Therapy Compared with Self-Administered Therapy in Treatment-Naïve HIV-1 Infected Patients: A Randomized Trial

    PubMed Central

    Gross, Robert; Tierney, Camlin; Andrade, Adriana; Lalama, Christina; Rosenkranz, Susan; Eshleman, Susan H.; Flanigan, Timothy; Santana, Jorge; Salomon, Nadim; Reisler, Ronald; Wiggins, Ilene; Hogg, Evelyn; Flexner, Charles; Mildvan, Donna

    2009-01-01

    Context Success of antiretroviral therapy depends on high rates of adherence, but few interventions are effective. Objective Determine if modified directly observed therapy (mDOT) improves initial antiretroviral success. Design Open-label randomized trial comparing mDOT and self-administered therapy with lopinavir/ritonavir soft gel capsules 800 mg/200 mg, emtricitabine 200 mg, and either extended release stavudine 100 mg or tenofovir 300 mg, all once daily. Setting 23 U.S. AIDS Clinical Trials Group (ACTG) sites and one in South Africa between October 2002 and January 2006. Participants Plasma HIV RNA ≥2000 copies/ml and antiretroviral-naïve. 82 participants received mDOT and 161 self-administration. Participants were predominantly male (79%), median age 38 years, with 84 Latinos (35%), 74 non-Latino blacks (30%), and 79 non-Latino whites (33%). Intervention mDOT Monday through Friday for 24 weeks. Main Outcome Measure(s) Primary outcome was week 24 virologic success and secondary outcomes were week 48 virologic success, clinical progression, and adherence. Results mDOT had greater virologic success over 24 weeks [0.91 (95% CI: 0.81, 0.95)] than self-administered therapy [0.84 (95% CI: 0.77, 0.89)], but the difference [0.07 (lower bound 95% CI: −0.01)] did not reach the pre-specified threshold of 0.075. Over 48 weeks, virologic success was not significantly different between mDOT [0.72 (95% CI: 0.61, 0.81)] and self-administered therapy [0.78 (95% CI: 0.70, 0.84)], [−0.06 (95% CI: −0.18, 0.07); p=0.19)]. Conclusions The potential benefit of mDOT was marginal and not sustained after mDOT was discontinued. mDOT should not be incorporated routinely for care of treatment naïve HIV-1 infected patients. PMID:19597072

  1. Antiretroviral drug resistance and routine therapy, Cameroon.

    PubMed

    Laurent, Christian; Kouanfack, Charles; Vergne, Laurence; Tardy, Michèle; Zekeng, Léopold; Noumsi, Nathalie; Butel, Christelle; Bourgeois, Anke; Mpoudi-Ngolé, Eitel; Koulla-Shiro, Sinata; Peeters, Martine; Delaporte, Eric

    2006-06-01

    Among 128 patients routinely receiving highly active antiretroviral therapy in an HIV/AIDS outpatient clinic in Cameroon, 16.4% had drug resistance after a median of 10 months. Of these, 12.5% had resistance to nucleoside reverse transcriptase inhibitors (NRTIs), 10.2% to non-NRTIs, and 2.3% to protease inhibitors. PMID:16707062

  2. Pharmacokinetics and pharmacodynamics of antiretrovirals in the central nervous system.

    PubMed

    Calcagno, Andrea; Di Perri, Giovanni; Bonora, Stefano

    2014-10-01

    HIV-positive patients may be effectively treated with highly active antiretroviral therapy and such a strategy is associated with striking immune recovery and viral load reduction to very low levels. Despite undeniable results, the central nervous system (CNS) is commonly affected during the course of HIV infection, with neurocognitive disorders being as prevalent as 20-50 % of treated subjects. This review discusses the pathophysiology of CNS infection by HIV and the barriers to efficacious control of such a mechanism, including the available data on compartmental drug penetration and on pharmacokinetic/pharmacodynamic relationships. In the reviewed articles, a high variability in drug transfer to the CNS is highlighted with several mechanisms as well as methodological issues potentially influencing the observed results. Nevirapine and zidovudine showed the highest cerebrospinal fluid (CSF) to plasma ratios, although target concentrations are currently unknown for the CNS. The use of the composite CSF concentration effectiveness score has been associated with better virological outcomes (lower HIV RNA) but has been inconsistently associated with neurocognitive outcomes. These findings support the CNS effectiveness of commonly used highly antiretroviral therapies. The use of antiretroviral drugs with increased CSF penetration and/or effectiveness in treating or preventing neurocognitive disorders however needs to be assessed in well-designed prospective studies. PMID:25200312

  3. Antiretroviral therapy: current drugs.

    PubMed

    Pau, Alice K; George, Jomy M

    2014-09-01

    The rapid advances in drug discovery and the development of antiretroviral therapy is unprecedented in the history of modern medicine. The administration of chronic combination antiretroviral therapy targeting different stages of the human immunodeficiency virus' replicative life cycle allows for durable and maximal suppression of plasma viremia. This suppression has resulted in dramatic improvement of patient survival. This article reviews the history of antiretroviral drug development and discusses the clinical pharmacology, efficacy, and toxicities of the antiretroviral agents most commonly used in clinical practice to date. PMID:25151562

  4. Efficacy of second-line antiretroviral therapy among people living with HIV/AIDS in Asia: Results from the TREAT Asia HIV Observational Database

    PubMed Central

    BOETTIGER, David C; NGUYEN, Van Kinh; DURIER, Nicolas; BUI, Huy Vu; SIM, Benedict Lim Heng; AZWA, Iskandar; LAW, Matthew; RUXRUNGTHAM, Kiat

    2014-01-01

    Background Roughly 4% of the 1.25 million patients on antiretroviral therapy (ART) in Asia are using second-line therapy. To maximize patient benefit and regional resources it is important to optimize the timing of second-line ART initiation and use the most effective compounds available. Methods HIV positive patients enrolled in the TREAT Asia HIV Observational Database who had used second-line ART for ≥6 months were included. ART use and rates and predictors of second-line treatment failure were evaluated. Results There were 302 eligible patients. Most were male (76.5%) and exposed to HIV via heterosexual contact (71.5%). Median age at second-line initiation was 39.2 years, median CD4 cell count was 146 cells/mm3, and median HIV viral load was 16,224 copies/mL. Patients started second-line ART before 2007 (n=105), 2007-2010 (n=147) and after 2010 (n=50). Ritonavir-boosted lopinavir and atazanavir accounted for the majority of protease inhibitor use after 2006. Median follow-up time on second-line was 2.3 years. The rates of treatment failure and mortality per 100 patient/years were 8.8 (95%CI 7.1 to 10.9) and 1.1 (95%CI 0.6 to 1.9), respectively. Older age, high baseline viral load and use of a protease inhibitor other than lopinavir or atazanavir were associated with a significantly shorter time to second-line failure. Conclusions Increased access to viral load monitoring to facilitate early detection of first-line ART failure and subsequent treatment switch is important for maximizing the durability of second-line therapy in Asia. Although second-line ART is highly effective in the region, the reported rate of failure emphasizes the need for third-line ART in a small portion of patients. PMID:25590271

  5. Daily co-trimoxazole prophylaxis in severely immunosuppressed HIV-infected adults in Africa started on combination antiretroviral therapy: an observational analysis of the DART cohort

    PubMed Central

    Walker, AS; Ford, D; Gilks, CF; Munderi, P; Ssali, F; Reid, A; Katabira, E; Grosskurth, H; Mugyenyi, P; Hakim, J; Darbyshire, JH; Gibb, DM; Babiker, AG

    2010-01-01

    Summary Background Co-trimoxazole prophylaxis can reduce mortality from untreated HIV infection in Africa; whether benefits occur alongside combination antiretroviral therapy (ART) is unclear. We estimated the effect of prophylaxis after ART initiation in adults. Methods Participants in our observational analysis were from the DART randomised trial of management strategies in HIV-infected, symptomatic, previously untreated African adults starting triple-drug ART with CD4 counts lower than 200 cells per μL. Co-trimoxazole prophylaxis was not routinely used or randomly allocated, but was variably prescribed by clinicians. We estimated effects on clinical outcomes, CD4 cell count, and body-mass index (BMI) using marginal structural models to adjust for time-dependent confounding by indication. DART was registered, number ISRCTN13968779. Findings 3179 participants contributed 14 214 years of follow-up (8128 [57%] person-years on co-trimoxazole). Time-dependent predictors of co-trimoxazole use were current CD4 cell count, haemoglobin concentration, BMI, and previous WHO stage 3 or 4 events on ART. Present prophylaxis significantly reduced mortality (odds ratio 0·65, 95% CI 0·50–0·85; p=0·001). Mortality risk reduction on ART was substantial to 12 weeks (0·41, 0·27–0·65), sustained from 12–72 weeks (0·56, 0·37–0·86), but not evident subsequently (0·96, 0·63–1·45; heterogeneity p=0·02). Variation in mortality reduction was not accounted for by time on co-trimoxazole or current CD4 cell count. Prophylaxis reduced frequency of malaria (0·74, 0·63–0·88; p=0·0005), an effect that was maintained with time, but we observed no effect on new WHO stage 4 events (0·86, 0·69–1·07; p=0·17), CD4 cell count (difference vs non-users, −3 cells per μL [−12 to 6]; p=0·50), or BMI (difference vs non-users, −0·04 kg/m2 [−0·20 to 0·13); p=0·68]. Interpretation Our results reinforce WHO guidelines and provide strong motivation for provision

  6. Outcomes after viral load rebound on first-line antiretroviral therapy in HIV-infected children in the UK/Ireland: an observational cohort study

    PubMed Central

    CHILDS, Tristan; SHINGADIA, Delane; GOODALL, Ruth; DOERHOLT, Katja; LYALL, Hermione; DUONG, Trinh; JUDD, Ali; GIBB, Di M; COLLINS, Intira Jeannie

    2015-01-01

    Background Approximately one-third of HIV-infected children experience virological failure within two years of initiating antiretroviral therapy (ART). We determined the probability of switch to second-line ART or viral load (VL) re-suppression without switch among children who experienced VL rebound on first-line ART in an observational cohort in the UK/Ireland. Methods Children with VL rebound (confirmed VL>400c/ml following suppression <400c/ml) on first-line ART were included. Competing risk analysis estimated the probability of: switch to second-line; confirmed re-suppression (two consecutive VL<400c/ml) without switch; and continued VL>400c/ml without switch. Predictors of time to switch were assessed. Findings Of 900 children starting first-line ART who had VL<400c/ml by one year, 170 (19%) experienced VL rebound by median [IQR] 20·6 months [9·7-40·5]. At rebound, median age was 10·6 years [5·6-13·4], VL 3·6 log10c/ml [3·1-4·2], and CD4% 24 [17-32]. Eighty-nine (52%) switched to second-line ART at median 4·9 months [1·7-13·4] after VL rebound, 53 (31%) re-suppressed without switch (61% of those on PI-based and 24% of those on NNRTI-based first-line regimens), while 28 (16%) neither re-suppressed nor switched. At 12 months after rebound, probabilities of switch or re-suppression without switch were 38% (95% CI 30-45) and 27% (95% CI 21-34), respectively. Faster time to switch was associated with higher VL (p<0·0001), later calendar year (p=0·02) at VL rebound, and NNRTI- or triple NRTI- versus PI-based first-line (p=0·001). Interpretation One-third of children with VL rebound re-suppressed without switch. The possibility of re-suppression with adherence support should be considered prior to switching. Funding NHS England PMID:26413561

  7. Individualization of antiretroviral therapy - Pharmacogenomic aspect

    PubMed Central

    Dalal, Bhavik; Shankarkumar, Aruna; Ghosh, K.

    2015-01-01

    Combination therapy with three drug regimens for human immunodeficiency virus (HIV) infection significantly suppresses the viral replication. However, this therapeutic impact is restricted by adverse drug events and response in terms of short and long term efficacy. There are multiple factors involved in different responses to antiretrovirals (ARVs) such as age, body weight, disease status, diet and heredity. Pharmacogenomics deals with individual genetic make-up and its role in drug efficacy and toxicity. In depth genetic research has provided evidence to predict the risk of developing certain toxicities for which personalized screening and surveillance protocols may be developed to prevent side effects. Here we describe the use of pharmacogenomics for optimal use of HAART (highly active antiretroviral therapy). PMID:26831415

  8. Acceptability and feasibility of mHealth and community-based directly observed antiretroviral therapy to prevent mother-to-child HIV transmission in South African pregnant women under Option B+: an exploratory study

    PubMed Central

    Nachega, Jean B; Skinner, Donald; Jennings, Larissa; Magidson, Jessica F; Altice, Frederick L; Burke, Jessica G; Lester, Richard T; Uthman, Olalekan A; Knowlton, Amy R; Cotton, Mark F; Anderson, Jean R; Theron, Gerhard B

    2016-01-01

    Objective To examine the acceptability and feasibility of mobile health (mHealth)/short message service (SMS) and community-based directly observed antiretroviral therapy (cDOT) as interventions to improve antiretroviral therapy (ART) adherence for preventing mother-to-child human immunodeficiency virus (HIV) transmission (PMTCT). Design and methods A mixed-method approach was used. Two qualitative focus group discussions with HIV-infected pregnant women (n=20) examined the acceptability and feasibility of two ART adherence interventions for PMTCT: 1) SMS text messaging and 2) patient-nominated cDOT supporters. Additionally, 109 HIV-infected, pregnant South African women (18–30 years old) receiving PMTCT services under single-tablet antiretroviral therapy regimen during pregnancy and breastfeeding and continuing for life (“Option B+”) were interviewed about mobile phone access, SMS use, and potential treatment supporters. Setting A community primary care clinic in Cape Town, South Africa. Participants HIV-infected pregnant women. Main outcomes Acceptability and feasibility of mHealth and cDOT interventions. Results Among the 109 women interviewed, individual mobile phone access and SMS use were high (>90%), and 88.1% of women were interested in receiving SMS ART adherence support messages such as reminders, motivation, and medication updates. Nearly all women (95%) identified at least one person close to them to whom they had disclosed their HIV status and would nominate as a cDOT supporter. Focus group discussions revealed that cDOT supporters and adherence text messages were valued, but some concerns regarding supporter time availability and risk of unintended HIV status disclosure were expressed. Conclusion mHealth and/or cDOT supporter as interventions to improve ART adherence are feasible in this setting. However, safe HIV status disclosure to treatment supporters and confidentiality of text messaging content about HIV and ART were deemed crucial. PMID

  9. Neuropathic and neurocongnitive complications of antiretroviral therapy among HIV-infected patients.

    PubMed

    Suvada, Jose

    2013-09-01

    The neurologic events related to antiretroviral therapy (ART) in HIV-infected ART-naive patients are relatively common. Side effects of ART and complications of HIV infection may overlap significantly. Establishing etiology of neurologic (neuropathy and neuropathic pain, changes in cognition, dementia, and myelopathy) and psychiatric (neurocognitive disorders, depression, anxiety, substance abuse and dependence, and others) complications can present a significant challenge. It has long been documented that neurologic and psychological side effects can occur with many of the agents used to treat HIV infection. Particularly, efavirenz from the non-nucleoside reverse transcriptase inhibitor (NNRTI) has been associated with neurologic and psychological complaints that may be difficult to differentiate from pre-existing mental illness, substance abuse, and HIV-related neuropsychiatric symptoms. Peripheral neuropathy (PN) of at least 6 different types is a well-known adverse effect of treatment with nucleoside reverse transcriptase inhibitors (NRTIs) in HIV-infected patients. Lack of dealing with early stages of neurologic and psychological side effects of HIV infection and Highly Active Anti-retroviral Therapy (HAART) are observed in daily practice. The purpose of this article is to identify the neurologic, neuropsychiatric and psychiatric complications related to HIV and anti-retroviral therapy, to discuss current knowledge about these disorders, and to suggest strategies for their diagnosis and management. PMID:24013599

  10. The (political) economics of antiretroviral treatment in developing countries.

    PubMed

    Nattrass, Nicoli J

    2008-12-01

    Despite unprecedented international mobilisation to support universal provision of highly active antiretroviral therapy (HAART), national governments continue to play the key role in determining access to treatment. Whereas some AIDS-affected countries have performed as well as or better than expected given their level of development, institutional characteristics and demographic challenges (e.g. Thailand and Brazil), others (notably South Africa) have not. This article argues that the 'economics' of antiretroviral drug delivery is at heart a political-economy of access to treatment. It depends on commitment on the part of national governments to negotiate with pharmaceutical companies over patented antiretroviral drug prices, on their policy towards compulsory licensing, and on the approach they adopt to delivering HAART. Civil society has an important role to play in encouraging governments to become, and remain, committed to taking action to ensure sustainable and widespread access to HAART. PMID:18964022

  11. Transplacental transfer of antiretroviral drugs and newborn birth weight in HIV-infected pregnant women.

    PubMed

    Ivanovic, Jelena; Nicastri, Emanuele; Anceschi, Maurizio M; Ascenzi, Paolo; Signore, Fabrizio; Pisani, Giuseppe; Vallone, Cristina; Mattia, Elisabetta; Notari, Stefania; Tempestilli, Massimo; Pucillo, Leopoldo P; Narciso, Pasquale

    2009-11-01

    Although it is well known that antiretroviral drugs (ARVs) across the placenta in different extents, few data are available concerning the impact of the transplacental passage of ARVs on newborn outcome. The aim of this study is to evaluate the transplacental diffusion of ARVs and the clinical assessment of the newborn. Mother and cord lopinavir, nelfinavir, atazanavir and nevirapine plasma levels were determined by high-performance liquid chromatography. Newborn gestational age, weight, and Apgar score were recorded. Cord-to-mother ratio (C:M) was calculated to estimate the placental passage of ARVs. Preterm birth was defined as delivery at <37 weeks of gestation and low birth weight was defined as a birth weight of <2500g. Twenty-six HIV-infected pregnant women were enrolled. Nevirapine presented the highest C:M ratio (0.60 +/- 0.19), the C:M ratio of nelfinavir and atazanavir was 0.37 +/- 0.38 and 0.20 +/- 0.14, respectively. The lopinavir level in the cord was undetectable. The observed prevalence rate of neonatal low birth weight and preterm delivery was 19,2% (n = 5) and 15.4% (n = 4), respectively. A significant linear regression analysis was reported between the C:M ratio and newborn birth weight (p = 0.01). Although the role of highly active antiretroviral therapy (HAART) in preventing mother-to-child transmission is indisputable, these data indicate a pharmacological rationale to the association between birth weight and highly active antiretroviral therapy during pregnancy. PMID:19929798

  12. Unintended Pregnancies Observed With Combined Use of the Levonorgestrel Contraceptive Implant and Efavirenz-based Antiretroviral Therapy: A Three-Arm Pharmacokinetic Evaluation Over 48 Weeks

    PubMed Central

    Scarsi, Kimberly K.; Darin, Kristin M.; Nakalema, Shadia; Back, David J.; Byakika-Kibwika, Pauline; Else, Laura J.; Dilly Penchala, Sujan; Buzibye, Allan; Cohn, Susan E.; Merry, Concepta; Lamorde, Mohammed

    2016-01-01

    Background. Levonorgestrel subdermal implants are preferred contraceptives with an expected failure rate of <1% over 5 years. We assessed the effect of efavirenz- or nevirapine-based antiretroviral therapy (ART) coadministration on levonorgestrel pharmacokinetics. Methods. This nonrandomized, parallel group, pharmacokinetic evaluation was conducted in three groups of human immunodeficiency virus–infected Ugandan women: ART-naive (n = 17), efavirenz-based ART (n = 20), and nevirapine-based ART (n = 20). Levonorgestrel implants were inserted at baseline in all women. Blood was collected at 1, 4, 12, 24, 36, and 48 weeks. The primary endpoint was week 24 levonorgestrel concentrations, compared between the ART-naive group and each ART group by geometric mean ratio (GMR) with 90% confidence interval (CI). Secondary endpoints included week 48 levonorgestrel concentrations and unintended pregnancies. Results. Week 24 geometric mean levonorgestrel concentrations were 528, 280, and 710 pg/mL in the ART-naive, efavirenz, and nevirapine groups, respectively (efavirenz: ART-naive GMR, 0.53; 90% CI, .50, .55 and nevirapine: ART-naive GMR, 1.35; 90% CI, 1.29, 1.43). Week 48 levonorgestrel concentrations were 580, 247, and 664 pg/mL in the ART-naive, efavirenz, and nevirapine groups, respectively (efavirenz: ART-naive GMR, 0.43; 90% CI, .42, .44 and nevirapine: ART-naive GMR, 1.14; 90% CI, 1.14, 1.16). Three pregnancies (3/20, 15%) occurred in the efavirenz group between weeks 36 and 48. No pregnancies occurred in the ART-naive or nevirapine groups. Conclusions. Within 1 year of combined use, levonorgestrel exposure was markedly reduced in participants who received efavirenz-based ART, accompanied by contraceptive failures. In contrast, nevirapine-based ART did not adversely affect levonorgestrel exposure or efficacy. Clinical Trials Registration. NCT01789879. PMID:26646680

  13. Estimation of Mortality among HIV-infected people on antiretroviral therapy treatment in east Africa: a sampling based approach in an observational, multisite, cohort study

    PubMed Central

    Geng, Elvin H.; Odeny, Thomas A.; Lyamuya, Rita E.; Nakiwogga-Muwanga, Alice; Diero, Lameck; Bwana, Mwebesa; Muyindike, Winnie; Braitstein, Paula; Somi, Geoffrey R.; Kambugu, Andrew; Bukusi, Elizabeth A.; Wenger, Megan; Wools-Kaloustian, Kara K.; Glidden, David V.; Yiannoutsos, Constantin T.; Martin, Jeffrey

    2015-01-01

    Background Mortality after initiation of antiretroviral treatment (ART) among HIV-infected patients in resource limited settings is a critical measure of the effectiveness and comparative effectiveness of the global public health response. Unknown outcomes due to high loss to follow-up (LTFU) preclude accurate accounting of deaths and limit our understanding of effectiveness. Methods We evaluated in HIV-infected adults on ART in 14 clinics in five settings in Kenya, Uganda and Tanzania using a sampling-based approach in which we intensively traced a random sample of lost patients (> 90 days late for last scheduled visit) and incorporated their vital status outcomes into analyses of the entire clinic population through probability-weighted survival analyses. Findings We followed 34,277 adults on ART from Mbarara and Kampala, Uganda; Eldoret and Kisumu, Kenya; and Morogoro, Tanzania. The median age was 35 years, 34% were men, and median pre-therapy CD4 count was 154 cells/μl. Overall 5,780 (17%) were LTFU, 991 (17%) were randomly selected for tracing and vital status was ascertained in 860 of 991 (87%). Incorporating outcomes among the lost increased estimated 3-year mortality from 3.9% (95% CI: 3.6%-4.2%) to 12.5% (95% CI: 11.8%-13.3%). The sample-corrected, unadjusted 3-year mortality across settings ranged from 7.2% in Mbarara to 23.6% in Morogoro. After adjustment for age, sex, pre-therapy CD4 value, and WHO stage, the sample-corrected hazard ratio comparing the setting with highest vs. lowest mortality was 2.2 (95% CI: 1.5-3.4) and the risk difference for death at 3 years was 11% (95% CI: 5.0%-17.7%). Interpretation A sampling based approach is widely feasible and important for understanding mortality after starting ART. After adjustment for measured biological drivers, mortality differs substantially across settings despite delivery of a similar clinical package of treatment. Implementation research to understand the systems, community, and patient behaviors

  14. Antiretroviral Genotypic Resistance Mutations in HIV-1 Infected Korean Patients with Virologic Failure

    PubMed Central

    Chin, Bum Sik; Choi, Ju-Yeon; Choi, Jin Young; Kim, Gab Jung; Kee, Mee-Kyung; Kim, June Myung

    2009-01-01

    Resistance assays are useful in guiding decisions for patients experiencing virologic failure (VF) during highly-active antiretroviral therapy (HAART). We investigated antiretroviral resistance mutations in 41 Korean human immunodeficiency virus type 1 (HIV-1) infected patients with VF and observed immunologic/virologic response 6 months after HAART regimen change. Mean HAART duration prior to resistance assay was 45.3±27.5 months and commonly prescribed HAART regimens were zidovudine/lamivudine/nelfinavir (22.0%) and zidovudine/lamivudine/efavirenz (19.5%). Forty patients (97.6%) revealed intermediate to high-level resistance to equal or more than 2 antiretroviral drugs among prescribed HAART regimen. M184V/I mutation was observed in 36 patients (87.7%) followed by T215Y/F (41.5%) and M46I/L (34%). Six months after resistance assay and HAART regimen change, median CD4+ T cell count increased from 168 cells/µL (interquartile range [IQR], 62-253) to 276 cells/µL (IQR, 153-381) and log viral load decreased from 4.65 copies/mL (IQR, 4.18-5.00) to 1.91 copies/mL (IQR, 1.10-3.60) (P<0.001 for both values). The number of patients who accomplished viral load <400 copies/mL was 26 (63.4%) at 6 months follow-up. In conclusion, many Korean HIV-1 infected patients with VF are harboring strains with multiple resistance mutations and immunologic/virologic parameters are improved significantly after genotypic resistance assay and HAART regimen change. PMID:19949656

  15. Dermatologic adverse effects of antiretroviral therapy: recognition and management.

    PubMed

    Luther, Jay; Glesby, Marshall J

    2007-01-01

    Despite the decrease in opportunistic infections associated with HIV in the highly active antiretroviral treatment (HAART) era, a significant number of patients still present with skin pathology, some of which can be attributed directly or indirectly to antiretroviral therapy. The non-nucleoside reverse transcriptase inhibitors exhibit a class effect with regard to skin adverse manifestations, and the spectrum of disease can vary from a mild morbilliform rash to Stevens-Johnson syndrome. Certain protease inhibitors are associated with rash, and indinavir causes retinoid-like manifestations such as paronychia, alopecia, ingrown toe-nails, and curling of straight hair. Abacavir, a nucleoside reverse transcriptase inhibitor, is notorious for causing a hypersensitivity reaction in select patients. The fusion inhibitor enfuvirtide causes injection-site reactions in the overwhelming majority of patients, although a new method of delivery has decreased the rate and severity of these reactions. A syndrome of lipoatrophy with or without lipohypertrophy, often termed lipodystrophy, has been described in patients receiving HAART. Potential management of lipoatrophy includes switching antiretrovirals and surgical treatment with facial fillers. Lastly, skin manifestations of the immune reconstitution inflammatory syndrome, including herpes zoster and warts, must be recognized and treated accordingly. In the evaluation of the individual HIV-infected patient receiving antiretroviral therapy who presents with a skin disorder, clinicians should consider the CD4 cell count as a marker of the degree of immunodeficiency, the specific antiretrovirals used, and the timing of the initiation of antiretroviral therapy in order to formulate a rational differential diagnosis. Management should be individualized based on the specific drug that is implicated and the severity of the reaction. PMID:17645377

  16. Adherence to HIV antiretrovirals among persons with serious mental illness.

    PubMed

    Wagner, Glenn J; Kanouse, David E; Koegel, Paul; Sullivan, Greer

    2003-04-01

    Despite the absence of empirical evidence, serious mental illness is assumed to be a high risk factor for nonadherence to HIV antiretroviral regimens. To assess antiretroviral adherence among persons with serious mental illness, we conducted a study in which adherence was observed over a 2-week period with electronic monitoring bottle caps and self-report. Forty-seven participants enrolled, with all but two (96%) completing the study. Psychiatric diagnoses included bipolar depression (n = 24), schizophrenia (n = 12), schizoaffective disorder (n = 5), and major depression with psychotic features (n = 6). Mean adherence (proportion of prescribed doses taken) was 66% (standard deviation [SD] = 34), as measured by electronic monitoring; 40% demonstrated at least 90% adherence, but 31% had less than 50% adherence. Self-reported adherence to psychotropics was moderately correlated with self-reported (r = 0.45, p < 0.05) and electronically monitored (r = 0.39, p < 0.05) antiretroviral adherence. Viral load (log(10)) was negatively correlated with electronically monitored (r = -0.28, p < 0.10) and self-reported (r = -0.39, p < 0.05) antiretroviral adherence, after controlling for the length of time on treatment. These findings suggest that many patients with serious mental illness are able to adhere very well to antiretroviral regimens, yet a substantial proportion of our sample displayed poor adherence, indicating the need for research to further assess the factors that influence adherence to antiretrovirals in this population. PMID:12737641

  17. Prognostic significance of the intervals between the initiation of antiretroviral therapy and anti-tuberculosis treatment in HIV-tuberculosis co-infected patients: Results from the TREAT Asia HIV Observational Database

    PubMed Central

    Han, Sang Hoon; Zhou, Jialun; Lee, Man Po; Zhao, Hongxin; Chen, Yi-Ming Arthur; Kumarasamy, Nagalingeswaran; Pujari, Sanjay; Lee, Christopher; Faridah Syed Omar, Sharifah; Ditangco, Rossana; Phanuphak, Nittaya; Kiertiburanakul, Sasisopin; Chaiwarith, Romanee; Merati, Tuti Parwati; Yunihastuti, Evy; Tanuma, Junko; Saphonn, Vonthanak; Sohn, Annette H.; Choi, Jun Yong

    2013-01-01

    Objectives We evaluated the effect of time intervals between the initiation of antiretroviral therapy (ART) and tuberculosis (TB) treatment on clinical outcomes in HIV-TB co-infected patients in an Asian regional cohort. Methods Adult HIV-TB co-infected patients in an observational HIV cohort database who had a known date of ART initiation and history of TB treatment were eligible for study inclusion. The time intervals between the initiation of ART and TB treatment were categorized as follows: TB diagnosed while on ART, early ART (<90 days after TB treatment), delayed ART (>90 days after TB treatment), and ART not started. Outcomes were assessed using survival analyses. Results A total of 768 HIV-TB co-infected patients were included in this study. Median CD4 T-cell count at TB diagnosis was 100 (IQR 40–208) cells/µL. The treatment outcomes between early ART and delayed ART initiation were not significantly different. Kaplan-Meier analysis indicated that mortality was highest for those diagnosed with TB while on ART (3.77 deaths per 100 person-years), and the prognoses of other groups were not different (in deaths per 100 person-years: 2.12 early ART, 1.46 delayed ART, and 2.94 ART not started). In a multivariate model, the interval between ART initiation and TB therapy did not significantly impact all-cause mortality. Conclusions The negative impact of delayed ART in patients co-infected with TB was not observed in this observational cohort of moderately to severely immunosuppressed patients. The broader impact of earlier ART in actual clinical practice should be monitored more closely. PMID:23980589

  18. Antiretroviral therapy and the kidney.

    PubMed

    Wyatt, Christina M

    2014-01-01

    Acute kidney injury (AKI) and chronic kidney disease (CKD) are more common in the HIV-infected population than in the general population. AKI is associated with an increased risk of heart failure, cardiovascular disease, end-stage renal disease (ESRD), and mortality. Tenofovir is associated with severe AKI in a small percentage of patients and with subclinical abnormalities in many more. HIV-associated nephropathy is now a relatively rare form of CKD, because of the widespread use of potent antiretroviral therapy. The CKD spectrum in HIV-infected patients has become more frequently characterized by comorbid CKD, with an increased frequency of CKD related to diabetes or hypertension being observed. Kidney transplantation is a therapeutic option for HIV-infected patients with ESRD if their HIV infection is controlled, although rates of acute graft rejection and drug-drug interactions are high. This article summarizes a presentation by Christina M. Wyatt, MD, at the IAS-USA continuing education program held in Washington, DC, in June 2013. PMID:25101531

  19. Continuous evidence of fast HIV disease progression related to class-wide resistance to antiretroviral drugs: a 6 year follow-up analysis of a large observational database.

    PubMed

    Mauro, Zaccarelli; Federica, Forbici; Patrizia, Lorenzini; Francesca, Ceccherini-Silberstein; Valerio, Tozzi; Paola, Trotta Maria; Patrizia, Marconi; Pasquale, Narciso; Federico, Perno Carlo; Andrea, Antinori

    2007-08-20

    Class-wide resistance (CWR) was increasingly associated with a higher risk of HIV progression after 72 months of follow-up among 1392 patients genotypic-tested after failure (AIDS risk 13% for no CWR to 34% for three CWR; AIDS/death risk 21-54%). At multivariate analysis, the detection of two and three CWR was significantly associated with a two and threefold increased risk, respectively, of death and AIDS/death, suggesting that extended resistance is a marker of disease progression in long-term observation. PMID:17690586

  20. Antiretroviral therapy: Shifting sands.

    PubMed

    Sashindran, V K; Chauhan, Rajeev

    2016-01-01

    HIV/AIDS has been an extremely difficult pandemic to control. However, with the advent of antiretroviral therapy (ART), HIV has now been transformed into a chronic illness in patients who have continued treatment access and excellent long-term adherence. Existing indications for ART initiation in asymptomatic patients were based on CD4 levels; however, recent evidence has broken the shackles of CD4 levels. Early initiation of ART in HIV patients irrespective of CD4 counts can have profound positive impact on morbidity and mortality. Early initiation of ART has been found not only beneficial for patients but also to community as it reduces the risk of transmission. There have been few financial concerns about providing ART to all HIV-positive people but various studies have proven that early initiation of ART not only proves to be cost-effective but also contributes to economic and social growth of community. A novel multidisciplinary approach with early initiation and availability of ART at its heart can turn the tide in our favor in future. Effective preexposure prophylaxis and postexposure prophylaxis can also lower transmission risk of HIV in community. New understanding of HIV pathogenesis is opening new vistas to cure and prevention. Various promising candidate vaccines and drugs are undergoing aggressive clinical trials, raising optimism for an ever-elusive cure for HIV. This review describes various facets of tectonic shift in management of HIV. PMID:26900224

  1. Long-term outcome of patients after a single interruption of antiretroviral therapy: a cohort study

    PubMed Central

    2012-01-01

    Background To describe the long term outcome of patients who interrupted highly active antiretroviral therapy (HAART) once, identify the variables associated with earlier need to re-start HAART, and the response when therapy was resumed. A retrospective observational cohort of 66 adult patients with HIV-1 infection who interrupted HAART with a CD4+cell count ≥350 cells/μL and undetectable viral load (VL) was performed. The pre-established CD4+ cell count for restarting therapy was 300cells/μL. Cox regression was used to analyse the variables associated with earlier HAART reinitiation. Results The median follow-up was 209 weeks (range, 64–395). Rates of HIV-related or possible HIV-related events were 0.37 (one case of acute retroviral syndrome) and 1.49 per 100 patient-years, respectively. Two patients died after re-starting therapy and having reached undetectable VL. Three patients suffered a sexually transmitted disease while off therapy. Fifty patients (76%) resumed therapy after a median of 97 weeks (range, 17–267). Age, a nadir of CD4+ <250 cells/μL, and a mean VL during interruption of >10,000 copies/ml were independent predictors for earlier re-start. The intention-to-treat success rate of the first HAART resumed regimen was 85.4%. There were no differences by regimen used, nor between regimens that were the same as or different from the one that had been interrupted. Conclusions Our data suggest highly active antiretroviral therapy may be interrupted in selected patients because in these patients, when the HAART is restarted, the viral and clinical response may be achieved. PMID:23095460

  2. Antiretroviral therapy with heart.

    PubMed

    Randell, Paul; Moyle, Graeme

    2009-01-01

    Antiretroviral therapy (ART) has resulted in a substantial improvement in the morbidity and mortality associated with human immunodeficiency virus (HIV) infection. As this population ages, cardiovascular disease is becoming an increasingly important health burden. It is clear that many factors are involved in the development of this problem, with traditional risk factors (smoking, dyslipidemia, diabetes, family history, hypertension) the main contributors. ART and HIV infection itself can modify the risk of cardiovascular disease. Not only does this increased risk seem to be mediated through effects on traditional cardiovascular risk factors, namely dyslipidemia and insulin resistance, but there is also some evidence that HIV and ART may be associated with accelerated atherosclerosis and endothelial dysfunction. Current data are conflicting and further investigation into this area is needed. Drugs from both nucleoside reverse transcriptase inhibitor and protease inhibitor classes have been demonstrated to increase cardiovascular risk; however these effects are variable not only between classes but also between drugs in the same class. As newer therapies become available (in existing and new drug classes), the cardiovascular impact of these will need careful evaluation. Currently published guidelines suggest regular monitoring of cardiovascular risks (both before and after commencing ART) and pre-emptive treatment. Existing risk assessment tools have not been fully validated in an HIV setting and need to be used with caution. Lifestyle modification, in the first instance, and pharmacological intervention to reduce traditional risk factors are important management strategies. Initiating, or switching to, ART with a lower potential for metabolic derangement should also be considered. PMID:19940610

  3. Helping the urban poor stay with antiretroviral HIV drug therapy.

    PubMed Central

    Bamberger, J D; Unick, J; Klein, P; Fraser, M; Chesney, M; Katz, M H

    2000-01-01

    Recent studies have documented dramatic decreases in opportunistic infections, hospitalizations, and mortality among HIV-infected persons, owing primarily to the advent of highly active antiretroviral medications. Unfortunately, not all segments of the population living with HIV benefit equally from treatment. In San Francisco, only about 30% of the HIV-infected urban poor take combination highly active antiretroviral medications, as compared with 88% of HIV-infected gay men. Practitioners who care for the urban poor are reluctant to prescribe these medications, fearing inadequate or inconsistent adherence to the complicated medical regimen. Persons typically must take 2 to 15 pills at a time, 2 to 3 times a day. Some of the medications require refrigeration, which may not be available to the homeless poor. Most homeless persons do not have food available to them on a consistent schedule. Therefore, they may have difficulty adhering to instructions to take medications only on an empty stomach or with food. Lack of a safe place to store medications may be an issue for some. In addition, many urban poor live with drug, alcohol, or mental health problems, which can interfere with taking medications as prescribed. Inconsistent adherence to medication regimens has serious consequences. Patients do not benefit fully from treatments, and they will become resistant to the medications in their regimen as well as to other medications in the same classes as those in their regimen. Development of resistance has implications for the broader public health, because inadvertent transmission of multidrug-resistant strains of HIV has been demonstrated. Concern that the urban poor will not adhere to highly active antiretroviral medication regimens has led to debate on the role of clinicians and public health officials in determining who can comply with these regimens. Rather than define the characteristics that would predict adherence to these regimens, the San Francisco Department

  4. Recommendations in pediatric antiretroviral therapy.

    PubMed

    Ikeda, Takehisa; Ch'ng, Tong Wei; Oleske, James M

    2007-02-01

    The pathogenesis of HIV infection and the general principles of therapy are the same for HIV-infected adults, adolescents, children and infants. However, antiretroviral treatment of HIV infection in pediatrics requires the consideration of a number of factors specific to its population, including differences in drug pharmacokinetics and the use of virologic and immunologic markers, as well as age-related adherence issues. This review summarizes the text of the Guidelines for the Use of Antiretroviral Agents in Pediatric HIV Infection, which was updated in October 2006. The guidelines are the work of the Working Group on Antiretroviral Therapy and Medical Management of HIV-Infected Children, a group of the Office of AIDS Research Advisory Council of the National Institutes of Health, which reviews new data on an ongoing basis and provides regular updates to the guidelines. As these guidelines were developed for the US, they may not be applicable in other countries. This summary does not attempt to place the Working Group guidelines in the context of international guidelines, nor does it attempt to detail the use of antiretroviral medication in the prevention of perinatal transmission of HIV, such as addressing the use of zidovudine versus single-dose nevirapine. PMID:17257086

  5. Dyslipidaemia associated with antiretroviral therapy in HIV-infected patients.

    PubMed

    Calza, Leonardo; Manfredi, Roberto; Chiodo, Francesco

    2004-01-01

    Highly active antiretroviral therapy (HAART) has had a significant impact on the natural history of human immunodeficiency virus (HIV) infection, leading to a remarkable decrease in its morbidity and mortality, but is frequently associated with clinical and metabolic complications. Fat redistribution or lipodystrophy, hypertriglyceridaemia, hypercholesterolaemia, insulin resistance and diabetes mellitus have been extensively reported in subjects treated with protease inhibitor (PI)-based antiretroviral regimens. In particular, dyslipidaemia occurs in up to 70-80% of HIV-infected individuals receiving HAART and can be associated with all the available PIs, although hypertriglyceridaemia appears to be more frequent in patients treated with ritonavir, ritonavir-saquinavir, or ritonavir-lopinavir. The potential long-term consequences of HAART-associated hyperlipidaemia are not completely understood, but an increased risk of premature coronary artery disease has been reported in young HIV-positive persons receiving PIs. Dietary changes, regular aerobic exercise and switching to a PI-sparing regimen may act favourably on dyslipidaemia. Lipid-lowering therapy is often required with statins or fibrates. The choice of hypolipidaemic drugs should take into account potential pharmacological interactions with antiretroviral agents. PMID:14645323

  6. HIV-1 Encephalopathy among Perinatally Infected Children: Neuropathogenesis and Response to Highly Active Antiretroviral Therapy

    ERIC Educational Resources Information Center

    Mitchell, Charles D.

    2006-01-01

    HIV-1 encephalopathy among perinatally infected children in the United States was initially defined by a classic triad of findings that included: (1) developmental delay, (2) secondary or acquired microcephaly, and (3) pyramidal tract neuromotor deficits. The most severe form of this disorder typically occurred among young children who developed…

  7. Oral Adherence Monitoring Using a Breath Test to Supplement Highly Active Antiretroviral Therapy

    PubMed Central

    Morey, Timothy E.; Booth, Matthew; Wasdo, Scott; Wishin, Judith; Quinn, Brian; Gonzalez, Daniel; Derendorf, Hartmut; McGorray, Susan P.; Simoni, Jane; Melker, Richard J.; Dennis, Donn M.

    2012-01-01

    A breath-based adherence system to document ingestion of oral medications (e.g., HAART) was investigated. Specifically, the food additive 2-butanol, which can be easily packaged with a drug, is converted via alcohol dehydrogenase to the volatile metabolite 2-butanone that rapidly appears in breath, indicating adherence. In healthy adults using a portable sensor and GC-MS, the following experiments were performed: yield of 2-butanone in breath following ingestion of 2-butanol, adherence system accuracy, and potential interference of the adherence system by food or misplacement of 2-butanol on the tongue. During feasibility testing, every subject exhaled 2-butanone with 6.6±1.5 min to peak concentrations of 548±235 ppb following ingestion of 2-butanol (40 mg). ROC areas at 5 and 10 min were 0.95 (0.86–1.00) and 3 1.00 (1.00–1.00). Food did not interfere. Tongue application resulted in large concentrations of 2-butanol, but not 2-butanone. A breath test to provide definitive evidence of oral medication adherence appears technically feasible. PMID:23001413

  8. New antiretrovirals and new combinations.

    PubMed

    Havlir, D V; Lange, J M

    1998-01-01

    The appearance in the clinic of two to three new antiretroviral agents yearly since 1995 has permitted unprecedented advances in HIV treatment. This remarkable pace of drug development is a testimony to an extraordinary international effort involving scientists, clinicians, governments, community activists and industry dedicated to the rapid and safe development of novel therapies. New drugs present the opportunity to improve HIV therapy. They also create an enormous challenge to the clinician, who must constantly assimilate data on new drugs and incorporate this information into practical management strategies. Combination therapy has proven the most effective approach to treat HIV disease. The profound and sustained viral suppression achievable with combinations such as indinavir (IDV), lamivudine (3TC) and zidovudine (ZDV) have resulted in a dramatic shift in HIV treatment paradigms over the last year. The full potential of combination therapy with available drugs has yet to be realized as only a limited number of the possible combinations incorporating new drugs have been fully tested. Even drugs available for many years may have untapped potential. Didanosine (ddI) and stavudine (d4T), once thought to be contraindicated in combination because of their overlapping peripheral neuropathy toxicity, have proven well tolerated and effective. Combination therapy can increase antiviral suppression, prevent drug resistance, optimize drug exposure and simplify dosing, but it can also result in pharmacologic antagonism, subtherapeutic drug concentrations and unexpected toxicities. Clinical studies have confirmed in vitro studies showing pharmacologic antagonism for the combination of ZDV and d4T. Combining protease inhibitors with each other or with non-nucleoside reverse transcriptase inhibitors is complicated by effects both classes of drugs have on drug metabolism and clearance. These observations underline the importance of carefully conducted clinical studies to

  9. Clinically relevant drug-drug interactions between antiretrovirals and antifungals

    PubMed Central

    Vadlapatla, Ramya Krishna; Patel, Mitesh; Paturi, Durga K; Pal, Dhananjay; Mitra, Ashim K

    2015-01-01

    Introduction Complete delineation of the HIV-1 life cycle has resulted in the development of several antiretroviral drugs. Twenty-five therapeutic agents belonging to five different classes are currently available for the treatment of HIV-1 infections. Advent of triple combination antiretroviral therapy has significantly lowered the mortality rate in HIV patients. However, fungal infections still represent major opportunistic diseases in immunocompromised patients worldwide. Areas covered Antiretroviral drugs that target enzymes and/or proteins indispensable for viral replication are discussed in this article. Fungal infections, causative organisms, epidemiology and preferred treatment modalities are also outlined. Finally, observed/predicted drug-drug interactions between antiretrovirals and antifungals are summarized along with clinical recommendations. Expert opinion Concomitant use of amphotericin B and tenofovir must be closely monitored for renal functioning. Due to relatively weak interactive potential with the CYP450 system, fluconazole is the preferred antifungal drug. High itraconazole doses (> 200 mg/day) are not advised in patients receiving booster protease inhibitor (PI) regimen. Posaconazole is contraindicated in combination with either efavirenz or fosamprenavir. Moreover, voriconazole is contraindicated with high-dose ritonavir-boosted PI. Echino-candins may aid in overcoming the limitations of existing antifungal therapy. An increasing number of documented or predicted drug-drug interactions and therapeutic drug monitoring may aid in the management of HIV-associated opportunistic fungal infections. PMID:24521092

  10. Antiretroviral therapy: 'the state of the art'.

    PubMed

    Montaner, J S; Montessori, V; Harrigan, R; O'Shaughnessy, M; Hogg, R

    1999-03-01

    The field of antiretroviral therapy is evolving at a very rapid pace. At this time, the initiation and optimization of antiretroviral therapy is based on serial plasma viral load determinations which aim to suppress viral replication to as low as possible for as long as possible, thus preventing disease progression. Currently available antiretrovirals require combination therapy with at least three agents to achieve this goal. Increasing availability of newer and more potent antiretroviral regimens will continue to enhance and simplify the number of therapeutic options available in the not too distant future. PMID:10337460

  11. Antiretroviral Regimens in Pregnancy and Breast-Feeding in Botswana

    PubMed Central

    Shapiro, R.L.; Hughes, M.D.; Ogwu, A.; Kitch, D.; Lockman, S.; Moffat, C.; Makhema, J.; Moyo, S.; Thior, I.; McIntosh, K.; van Widenfelt, E.; Leidner, J.; Powis, K.; Asmelash, A.; Tumbare, E.; Zwerski, S.; Sharma, U.; Handelsman, E.; Mburu, K.; Jayeoba, O.; Moko, E.; Souda, S.; Lubega, E.; Akhtar, M.; Wester, C.; Tuomola, R.; Snowden, W.; Martinez-Tristani, M.; Mazhani, L.; Essex, M.

    2010-01-01

    BACKGROUND The most effective highly active antiretroviral therapy (HAART) to prevent mother-to-child transmission of human immunodeficiency virus type 1 (HIV-1) in pregnancy and its efficacy during breast-feeding are unknown. METHODS We randomly assigned 560 HIV-1–infected pregnant women (CD4+ count, ≥200 cells per cubic millimeter) to receive coformulated abacavir, zidovudine, and lamivudine (the nucleoside reverse-transcriptase inhibitor [NRTI] group) or lopinavir–ritonavir plus zidovudine-lamivudine (the protease-inhibitor group) from 26 to 34 weeks’ gestation through planned weaning by 6 months post partum. A total of 170 women with CD4+ counts of less than 200 cells per cubic millimeter received nevirapine plus zidovudine–lamivudine (the observational group). Infants received single-dose nevirapine and 4 weeks of zidovudine. RESULTS The rate of virologic suppression to less than 400 copies per milliliter was high and did not differ significantly among the three groups at delivery (96% in the NRTI group, 93% in the protease-inhibitor group, and 94% in the observational group) or throughout the breast-feeding period (92% in the NRTI group, 93% in the protease-inhibitor group, and 95% in the observational group). By 6 months of age, 8 of 709 live-born infants (1.1%) were infected (95% confidence interval [CI], 0.5 to 2.2): 6 were infected in utero (4 in the NRTI group, 1 in the protease-inhibitor group, and 1 in the observational group), and 2 were infected during the breast-feeding period (in the NRTI group). Treatment-limiting adverse events occurred in 2% of women in the NRTI group, 2% of women in the protease-inhibitor group, and 11% of women in the observational group. CONCLUSIONS All regimens of HAART from pregnancy through 6 months post partum resulted in high rates of virologic suppression, with an overall rate of mother-to-child transmission of 1.1%. (ClinicalTrials.gov number, NCT00270296.) PMID:20554983

  12. Death rates in HIV-positive antiretroviral-naive patients with CD4 count greater than 350 cells per microL in Europe and North America: a pooled cohort observational study

    PubMed Central

    2011-01-01

    Background It is unclear whether antiretroviral (ART) naive HIV-positive individuals with high CD4 counts have a raised mortality risk compared with the general population, but this is relevant for considering earlier initiation of antiretroviral therapy. Methods Pooling data from 23 European and North American cohorts, we calculated country-, age-, sex-, and year-standardised mortality ratios (SMRs), stratifying by risk group. Included patients had at least one pre-ART CD4 count above 350 cells/mm3. The association between CD4 count and death rate was evaluated using Poisson regression methods. Findings Of 40,830 patients contributing 80,682 person-years of follow up with CD4 count above 350 cells/mm3, 419 (1.0%) died. The SMRs (95% confidence interval) were 1.30 (1.06-1.58) in homosexual men, and 2.94 (2.28-3.73) and 9.37 (8.13-10.75) in the heterosexual and IDU risk groups respectively. CD4 count above 500 cells/mm3 was associated with a lower death rate than 350-499 cells/mm3: adjusted rate ratios (95% confidence intervals) for 500-699 cells/mm3 and above 700 cells/mm3 were 0.77 (0.61-0.95) and 0.66 (0.52-0.85) respectively. Interpretation In HIV-infected ART-naive patients with high CD4 counts, death rates were raised compared with the general population. In homosexual men this was modest, suggesting that a proportion of the increased risk in other groups is due to confounding by other factors. Even in this high CD4 count range, lower CD4 count was associated with raised mortality. PMID:20638118

  13. Pharmacological interactions between rifampicin and antiretroviral drugs: challenges and research priorities for resource-limited settings.

    PubMed

    Semvua, Hadija H; Kibiki, Gibson S; Kisanga, Elton R; Boeree, Martin J; Burger, David M; Aarnoutse, Rob

    2015-02-01

    Coadministration of antituberculosis and antiretroviral therapy is often inevitable in high-burden countries where tuberculosis (TB) is the most common opportunistic infection associated with HIV/AIDS. Concurrent use of rifampicin and many antiretroviral drugs is complicated by pharmacokinetic drug-drug interactions. Rifampicin is a very potent enzyme inducer, which can result in subtherapeutic antiretroviral drug concentrations. In addition, TB drugs and antiretroviral drugs have additive (pharmacodynamic) interactions as reflected in overlapping adverse effect profiles. This review provides an overview of the pharmacological interactions between rifampicin-based TB treatment and antiretroviral drugs in adults living in resource-limited settings. Major progress has been made to evaluate the interactions between TB drugs and antiretroviral therapy; however, burning questions remain concerning nevirapine and efavirenz effectiveness during rifampicin-based TB treatment, treatment options for TB-HIV-coinfected patients with nonnucleoside reverse transcriptase inhibitor resistance or intolerance, and exact treatment or dosing schedules for vulnerable patients including children and pregnant women. The current research priorities can be addressed by maximizing the use of already existing data, creating new data by conducting clinical trials and prospective observational studies and to engage a lobby to make currently unavailable drugs available to those most in need. PMID:24943062

  14. When to Monitor CD4 Cell Count and HIV RNA to Reduce Mortality and AIDS-Defining Illness in Virologically Suppressed HIV-Positive Persons on Antiretroviral Therapy in High-Income Countries: A Prospective Observational Study

    PubMed Central

    Caniglia, Ellen C.; Sabin, Caroline; Robins, James M.; Logan, Roger; Cain, Lauren E.; Abgrall, Sophie; Mugavero, Michael J.; Hernandez-Diaz, Sonia; Meyer, Laurence; Seng, Remonie; Drozd, Daniel R.; Seage, George R.; Bonnet, Fabrice; Dabis, Francois; Moore, Richard R.; Reiss, Peter; van Sighem, Ard; Mathews, William C.; del Amo, Julia; Moreno, Santiago; Deeks, Steven G.; Muga, Roberto; Boswell, Stephen L.; Ferrer, Elena; Eron, Joseph J.; Napravnik, Sonia; Jose, Sophie; Phillips, Andrew; Olson, Ashley; Justice, Amy C.; Tate, Janet P.; Bucher, Heiner C.; Egger, Matthias; Touloumi, Giota; Sterne, Jonathan A.; Costagliola, Dominique; Saag, Michael; Hernán, Miguel A.

    2016-01-01

    Objective: To illustrate an approach to compare CD4 cell count and HIV-RNA monitoring strategies in HIV-positive individuals on antiretroviral therapy (ART). Design: Prospective studies of HIV-positive individuals in Europe and the USA in the HIV-CAUSAL Collaboration and The Center for AIDS Research Network of Integrated Clinical Systems. Methods: Antiretroviral-naive individuals who initiated ART and became virologically suppressed within 12 months were followed from the date of suppression. We compared 3 CD4 cell count and HIV-RNA monitoring strategies: once every (1) 3 ± 1 months, (2) 6 ± 1 months, and (3) 9–12 ± 1 months. We used inverse-probability weighted models to compare these strategies with respect to clinical, immunologic, and virologic outcomes. Results: In 39,029 eligible individuals, there were 265 deaths and 690 AIDS-defining illnesses or deaths. Compared with the 3-month strategy, the mortality hazard ratios (95% CIs) were 0.86 (0.42 to 1.78) for the 6 months and 0.82 (0.46 to 1.47) for the 9–12 month strategy. The respective 18-month risk ratios (95% CIs) of virologic failure (RNA >200) were 0.74 (0.46 to 1.19) and 2.35 (1.56 to 3.54) and 18-month mean CD4 differences (95% CIs) were −5.3 (−18.6 to 7.9) and −31.7 (−52.0 to −11.3). The estimates for the 2-year risk of AIDS-defining illness or death were similar across strategies. Conclusions: Our findings suggest that monitoring frequency of virologically suppressed individuals can be decreased from every 3 months to every 6, 9, or 12 months with respect to clinical outcomes. Because effects of different monitoring strategies could take years to materialize, longer follow-up is needed to fully evaluate this question. PMID:26895294

  15. Antiretroviral therapy-associated acute motor and sensory axonal neuropathy.

    PubMed

    Capers, Kimberly N; Turnacioglu, Sinan; Leshner, Robert T; Crawford, John R

    2011-01-01

    Guillain-Barré syndrome (GBS) has been reported in HIV-infected patients in association with the immune reconstitution syndrome whose symptoms can be mimicked by highly active antiretroviral therapy (HAART)-mediated mitochondrial toxicity. We report a case of a 17-year-old, HIV-infected patient on HAART with a normal CD4 count and undetectable viral load, presenting with acute lower extremity weakness associated with lactatemia. Electromyography/nerve conduction studies revealed absent sensory potentials and decreased compound muscle action potentials, consistent with a diagnosis of acute motor and sensory axonal neuropathy. Lactatemia resolved following cessation of HAART; however, neurological deficits minimally improved over several months in spite of immune modulatory therapy. This case highlights the potential association between HAART, mitochondrial toxicity and acute axonal neuropathies in HIV-infected patients, distinct from the immune reconstitution syndrome. PMID:21327178

  16. [Severe or life-threatening interactions between antiretrovirals and non-HIV drugs].

    PubMed

    Manzardo, Christian; Tuset, Montserrat; Miró, Jose M; Gatell, Jose M

    2015-01-01

    Highly active antiretroviral therapy has helped to improved control of the HIV infection, and has led to a progressively older population with the infection having a life expectancy quite similar to that of the general population. On the other hand, it is also known that HIV infection, even in patients with undetectable viral loads and good immunity, carries an increased cardiovascular risk, as well as an increased incidence of certain cancers. Therefore, the majority of HIV-infected patients receive several drugs (either prescribed by the physician or self-administered) combined with antiretrovirals. This article reviews the interactions between antiretrovirals and other drugs that can cause significant damage to patients, or even be life-threatening and of whom clinicians, especially those not directly treating HIV-infected patients, should be aware. A review is also presented on the implications of interactions between antiretrovirals and other drugs in special situations, such as the co-administration with cytostatics, immunesuppressants used in solid organ transplantation, or patients receiving new treatments for hepatitisC. Generally, combinations with two nucleos(t)ide reverse transcriptase inhibitors and raltegravir (or in the near future, dolutegravir) are those with less potential for clinically significant interactions. PMID:24913990

  17. The Roles of HIV-1 Proteins and Antiretroviral Drug Therapy in HIV-1-Associated Endothelial Dysfunction

    PubMed Central

    Kline, Erik R.; Sutliff, Roy L.

    2008-01-01

    Since the emergence of highly active antiretroviral therapy (HAART), human immunodeficiency virus-1 (HIV-1)-infected patients have demonstrated dramatic decreases in viral burden and opportunistic infections, and an overall increase in life expectancy. Despite these positive HAART-associated outcomes, it has become increasingly clear that HIV-1 patients have an enhanced risk of developing cardiovascular disease over time. Clinical studies are instrumental in our understanding of vascular dysfunction in the context of HIV-1 infection. However, most clinical studies often do not distinguish whether HIV-1 proteins, HAART, or a combination of these 2 factors cause cardiovascular complications. This review seeks to address the roles of both HIV-1 proteins and antiretroviral drugs in the development of endothelial dysfunction because endothelial dysfunction is the hallmark initial step of many cardiovascular diseases. We analyze recent in vitro and in vivo studies examining endothelial toxicity in response to HIV-1 proteins or in response to the various classes of antiretroviral drugs. Furthermore, we discuss the multiple mechanisms by which HIV-1 proteins and HAART injure the vascular endothelium in HIV-1 patients. By understanding the molecular mechanisms of HIV-1 protein- and antiretroviral-induced cardiovascular disease, we may ultimately improve the quality of life of HIV-1 patients through better drug design and the discovery of new pharmacological targets. PMID:18525451

  18. Cancellers - Exploring the Possibility of Receptor Decoy Traps As a Superior Anti-Retroviral Strategy.

    PubMed

    Jeremiah, Sundararaj Stanley; Ohba, Kenji; Yamamoto, Naoki

    2016-01-01

    The global Human Immunodeficiency Virus (HIV) pandemic is still spreading due to the lack of ideal anti-retroviral measures and their availability. Till date, all attempts to produce an efficient vaccine have ended with unsatisfactory results. The highly active anti-retroviral therapy (HAART) is the only effective weapon currently available and is widely being used for curtailing the HIV pandemic. However, the HAART is also expected to fail in the near future due to the emergence and dissemination of antiviral resistance. This review sheds light on the reasons for the failure of the conventional anti-viral measures against HIV and the novel anti-retroviral strategies currently being developed. The various principles to be considered for the success of a novel anti-retroviral strategy are elaborately emphasized and an innovative concept is proposed on these lines. The proposed concept intends to use receptor decoy traps (RDT) called cancellers which are erythrocytes expressing the HIV entry receptors on their surface. If successfully developed, the cancellers would be capable of active targeting of the free HIV particles leading to the trapping of the viruses within the canceller, resulting in the neutralization of infectivity of the trapped virus. The possible ways of translating this concept into reality and the probable hurdles that can be encountered in the process are subsequently discussed. Also, the scope of cancellers in therapeutic and/or preventive strategies against HIV infection is envisaged upon their successful development. PMID:25882216

  19. Pharmacogenetics of the metabolic disturbances and atherosclerosis associated with antiretroviral therapy in HIV-infected patients.

    PubMed

    Veloso, Sergi; Peraire, Joaquim; Viladés, Consuelo; López-Dupla, Miguel; Escoté, Xavier; Olona, Montserrat; Garcia-Pardo, Graciano; Gómez-Bertomeu, Frederic; Soriano, Antoni; Sirvent, Joan-Josep; Vidal, Francesc

    2010-10-01

    The availability of highly active antiretroviral therapy has markedly improved the survival rate and quality of life in patients infected with HIV. At present, however, there is still no cure for HIV and those undergoing treatment have to do so for life. The use of antiretroviral drugs has been associated with several toxicities that limit their success. Some acute and chronic toxicities associated with these drugs include hypersensitivity reactions, neurotoxicity, nephropathy, liver damage, the appearance of body fat redistribution syndrome and the different metabolic alterations that accompany it. Some of these toxicities are family- or even drug-specific. Since not all patients that take a particular antiretroviral medication develop the adverse effect that has been attributed to that drug, it has therefore been postulated that there must be a genetically-conditioned individual predisposition to developing the adverse effect. Pharmacogenetics is the science that studies interindividual variations in the response to and toxicity of drugs due to variations in the genetic composition of individuals. Sufficient advances have been made in this discipline to allow this fertile field of research to move out of the basic science laboratory and into clinical applications. The present article reviews the investigations that have been published regarding the association between the genetic determinants of persons infected with HIV and the metabolic toxicity and chronic vascular consequences resulting from antiretroviral drugs. The influence of host genetic variants on dyslipidemia, hyperglycemia and insulin resistance, lipodystrophy and atherosclerosis are presented and discussed. PMID:20687887

  20. Risk of premature atherosclerosis and ischemic heart disease associated with HIV infection and antiretroviral therapy.

    PubMed

    Calza, Leonardo; Manfredi, Roberto; Pocaterra, Daria; Chiodo, Francesco

    2008-07-01

    The use of new potent protease inhibitor-based antiretroviral therapies in patients with human immunodeficiency virus (HIV) infection has been increasingly associated with cardiovascular risk factors, including hyperlipidaemia, fat redistribution syndrome, insulin resistance, and diabetes mellitus. The introduction of highly active antiretroviral therapy (HAART) in clinical practice has remarkably changed the natural history of HIV disease, leading to a notable extension of life expectancy, and prolonged lipid and glucose metabolism abnormalities are expected to lead to significant effects on the long-term prognosis and outcome of HIV-infected patients. Prediction modeling, surrogate markers and hard cardiovascular endpoints suggest an increased incidence of cardiovascular diseases in HIV-infected subjects receiving HAART, even though the absolute risk of cardiovascular complications remains still low, and must be balanced against the evident virological, immunological, and clinical benefits descending from combination antiretroviral therapy. Nevertheless, the assessment of cardiovascular risk should be performed on regular basis in HIV-positive individuals, especially after initiation or change of antiretroviral treatment. Appropriate lifestyle measures (including smoking cessation, dietary changes, and aerobic physical activity) are critical points, and switching HAART may be considered, although maintaining viremic control should be the main goal of therapy. Pharmacological treatment of dyslipidaemia (usually with statins and fibrates), and hyperglycaemia (with insulin-sensitizing agents and thiazolidinediones), becomes suitable when lifestyle modifications and switching therapy are ineffective or not applicable. PMID:18358535

  1. Free HIV Antiretroviral Therapy Enhances Adherence among Individuals on Stable Treatment: Implications for Potential Shortfalls in Free Antiretroviral Therapy

    PubMed Central

    Byakika-Tusiime, Jayne; Polley, Eric C.; Oyugi, Jessica H.; Bangsberg, David R.

    2013-01-01

    Objective To estimate the population-level causal effect of source of payment for HIV medication on treatment adherence using Marginal Structural Models. Methods Data were obtained from an observational cohort of 76 HIV-infected individuals with at least 24 weeks of antiretroviral therapy treatment from 2002 to 2007 in Kampala, Uganda. Adherence was the primary outcome and it was measured using the 30-day visual analogue scale. Marginal structural models (MSM) were used to estimate the effect of source of payment for HIV medication on adherence, adjusting for confounding by income, duration on antiretroviral therapy (ART), timing of visit, prior adherence, prior CD4+ T cell count and prior plasma HIV RNA. Traditional association models were also examined and the results compared. Results Free HIV treatment was associated with a 3.8% improvement in adherence in the marginal structural model, while the traditional statistical models showed a 3.1–3.3% improvement in adherence associated with free HIV treatment. Conclusion Removing a financial barrier to treatment with ART by providing free HIV treatment appears to significantly improve adherence to antiretroviral therapy. With sufficient information on confounders, MSMs can be used to make robust inferences about causal effects in epidemiologic research. PMID:24039704

  2. [Adhesion to the antiretroviral treatment].

    PubMed

    Carballo, M

    2004-12-01

    The objective of the therapy antiretroviral is to improve the quality of life and the survival of the persons affected by the VIH through the suppression of the viral replication. Nevertheless one of the present problems is the resistant apparition of stumps to the new medicines caused by an incorrect management of the therapeutic plan; by an incorrect adhesion of the personal processing. Since the therapeutic success will depend, among others factors, and of important form of the degree of implication and commitment of the person affected, is a matter of identifying prematurely the possible situations concomitants (personal factors and of addiction, psycho-social, related to the processing and its possible secondary effects, associated factors to the own illness or even to the relation professional-patient) that can interfere in a correct adhesion. For it is necessary of the interaction multidisciplinary of the welfare team, and fundamental the work of nursing at the moment of to detect the possible determinant factors and the intervention definition of strategies arrived at by consensus with the own person, that they promote it or it improve. The quantification of the degree of adhesion (measure in %) values through various direct and indirect methods and should keep in mind in it takes of therapeutic decisions being able to come to be advised the suspension of the processing until obtaining to conscience to the person affected of the importance of a correct therapeutic compliance. PMID:15672996

  3. Effect of antiretroviral therapy in thromboregulation through the hydrolysis of adenine nucleotides in platelets of HIV patients.

    PubMed

    Rezer, João Felipe P; Souza, Viviane C G; Thorstenberg, Maria Luiza P; Ruchel, Jader B; Bertoldo, Tatiana M D; Zanini, Daniela; Silveira, Karine L; Leal, Claudio A M; Passos, Daniela F; Gonçalves, Jamile F; Abdalla, Fátima H; Schetinger, Maria Rosa C; Leal, Daniela B R

    2016-04-01

    The human immunodeficiency virus (HIV) infection results in biochemical and vascular dysfunctions. The highly active antiretroviral therapy (HAART) markedly reduces mortality and opportunistic diseases associated with acquired immunodeficiency syndrome (AIDS). This increased survival time predisposes the development of cardiovascular diseases. Platelets present purinergic system ectoenzymes such as E-NTPDase, E-5'-nucleotidase and E-ADA on its surface. In view of this, the aim of this study was to evaluate the activity of these ectoenzymes in platelets as well as the platelet aggregation and lipid profile of patients with HIV infection and also patients receiving HAART. The results showed an increase in the E-NTPDase activity for ATP hydrolysis in the HIV group compared with the control group and the HIV/HAART group. When assessing the activity E-NTPDase hydrolysis to ADP, the results revealed an increase in activity in the HIV group when compared to the control group, and a decrease in activity when in the HIV/HAART group when compared to the control and HIV groups. The activity of E-5'-nucleotidase revealed an increase in AMP hydrolysis in the HIV group, as the results from control and HIV/HAART groups showed no statistical difference. Regarding the E-ADA activity, the HIV and HIV/HAART groups revealed a decreased deamination of adenosine when compared with the control group. Furthermore, we observed an increased platelet aggregation of HIV/HAART group compared with the control group. Thus, our results suggest that antiretroviral treatment against HIV has a significant effect on the activity of purinergic system ectoenzymes demonstrating that thromboregulation is involved in the process. PMID:27044844

  4. Comparisons of anemia, thrombocytopenia, and neutropenia at initiation of HIV antiretroviral therapy in Africa, Asia, and the Americas

    PubMed Central

    Firnhaber, Cynthia; Smeaton, Laura; Saukila, Nasinuku; Flanigan, Timothy; Gangakhedkar, Raman; Kumwenda, Johnstone; La Rosa, Alberto; Kumarasamy, Nagalingeswaran; De Gruttola, Victor; Hakim, James Gita; Campbell, Thomas B.

    2010-01-01

    Summary Background Hematological abnormalities are common manifestations of advanced HIV-1 infection that could affect the outcomes of highly-active antiretroviral therapy (HAART). Although most HIV-1-infected individuals live in resource-constrained countries, there is little information about the frequency of hematological abnormalities such as anemia, neutropenia, and thrombocytopenia among individuals with advanced HIV-1 disease. Methods This study compared the prevalence of pre-antiretroviral therapy hematological abnormalities among 1571 participants in a randomized trial of antiretroviral efficacy in Africa, Asia, South America, the Caribbean, and the USA. Potential covariates for anemia, neutropenia, and thrombocytopenia were identified in univariate analyses and evaluated in separate multivariable models for each hematological condition. Results The frequencies of neutropenia (absolute neutrophil count ≤ 1.3 × 109/l), anemia (hemoglobin ≤ 10 g/dl), and thrombocytopenia (platelets ≤ 125 × 109/l) at initiation of antiretroviral therapy were 14%, 12%, and 7%, respectively, and varied by country (p < 0.0001 for each). In multivariable models, anemia was associated with gender, platelet count, and country; neutropenia was associated with CD4+ lymphocyte and platelet counts; and thrombocytopenia was associated with country, gender, and chronic hepatitis B infection. Conclusions Differences in the frequency of pretreatment hematological abnormalities could have important implications for the choice of antiretroviral regimen in resource-constrained settings. PMID:20961784

  5. Adherence to antiretrovirals in people coinfected with the human immunodeficiency virus and tuberculosis1

    PubMed Central

    Lemos, Larissa de Araújo; Fiuza, Maria Luciana Teles; Reis, Renata Karina; Ferrer, André Carvalho; Gir, Elucir; Galvão, Marli Teresinha Gimeniz

    2016-01-01

    Objective: assess the adherence levels to antiretroviral therapy in people coinfected with HIV/tuberculosis and correlate these levels with the sociodemographic and clinical variables of the study population. Method: cross-sectional study involving 74 male and female adults coinfected with HIV/tuberculosis. For the data collection, a sociodemographic and clinical assessment form and the Antiretroviral Treatment Adherence Assessment Questionnaire were used. For the data analysis, the software STATA version 11 was used, through descriptive statistics, Fisher's chi-square exact test and the probability test. Results: men were predominant (79.7%), between 30 and 39 years of age (35.1%), low income (75.7%) and pulmonary tuberculosis (71.6%). Adherence to antiretroviral therapy was inappropriate in 78.1% of the men; 61.0% of single people; 47.0% unemployed and 76.5% among people gaining less than one minimum wage. A significant difference was observed between compliance and length of use of antiretrovirals (p=0.018), sexual orientation (p=0.024) and number of children (p=0.029). Conclusion: the coinfected patients presented inappropriate adherence to the antiretrovirals, a fact that negatively affects the health conditions of the people living with HIV/tuberculosis coinfection. A statistically significant correlation was found between the levels of adherence and some sociodemographic and clinical characteristics. PMID:27192416

  6. Immunological profiling of tuberculosis-associated immune reconstitution inflammatory syndrome and non-immune reconstitution inflammatory syndrome death in HIV-infected adults with pulmonary tuberculosis starting antiretroviral therapy: a prospective observational cohort study

    PubMed Central

    Ravimohan, Shruthi; Tamuhla, Neo; Steenhoff, Andrew P.; Letlhogile, Rona; Nfanyana, Kebatshabile; Bellamy, Scarlett L.; MacGregor, Rob Roy; Gross, Robert; Weissman, Drew; Bisson, Gregory P.

    2015-01-01

    Summary Background Patients co-infected with advanced HIV and tuberculosis are at risk of tuberculosis-associated immune reconstitution inflammatory syndrome (IRIS) and death soon after initiation of antiretroviral therapy (ART). Tuberculosis-associated IRIS has been associated with quicker recovery of cellular immune responses after ART initiation and early mortality with slower recovery of these responses. We aimed to assess whether patients who have these outcomes have distinct immunological profiles before and after ART initiation. Methods We undertook this prospective cohort study at 22 public clinics and the main public hospital in Gaborone, Botswana, in ART-naive adults (aged ≥21 years) with advanced HIV (CD4 cell counts ≤125 cells per μL) and pulmonary tuberculosis. We obtained data for clinical variables and for levels of 29 plasma biomarkers, quantified by Luminex assay. We classified patients as having tuberculosis-associated IRIS, early mortality, or survival without a diagnosis of tuberculosis-associated IRIS (controls), on the basis of outcomes recorded in the 6 months after ART initiation. We used rank-sum or χ² tests, and logistic regression with odds ratios (OR) and 95% CIs, to assess the association between variables measured before and 4 weeks after ART initiation with death and tuberculosis-associated IRIS, compared with controls. Findings Between Nov 12, 2009, and July 3, 2013, we enrolled 201 participants. 31 (15%) patients left the study before ART initiation, leaving 170 (85%) patients for analysis. Patients with tuberculosis-associated IRIS had reduced pre-ART concentrations of several pro-inflammatory biomarkers, including interleukin (IL)-6 (adjusted OR per 1 log10 increase 0·40 [95% CI 0·18–0·89]). However, patients with early death had increased pre-ART concentrations of inflammatory biomarkers, including monocyte chemoattractant protein-1 (adjusted OR 9·0 [95% CI 1·0–80·0]) and tumour necrosis factor (TNF)-α (7·8 [1

  7. Use of Third Line Antiretroviral Therapy in Latin America

    PubMed Central

    Cesar, Carina; Shepherd, Bryan E.; Jenkins, Cathy A.; Ghidinelli, Massimo; Castro, Jose Luis; Veloso, Valdiléa Gonçalves; Cortes, Claudia P.; Padgett, Denis; Crabtree-Ramirez, Brenda; Gotuzzo, Eduardo; Fink, Valeria; Duran, Adriana; Sued, Omar; McGowan, Catherine C.; Cahn, Pedro

    2014-01-01

    Background Access to highly active antiretroviral therapy (HAART) is expanding in Latin America. Many patients require second and third line therapy due to toxicity, tolerability, failure, or a combination of factors. The need for third line HAART, essential for program planning, is not known. Methods Antiretroviral-naïve patients ≥18 years who started first HAART after January 1, 2000 in Caribbean, Central and South America Network (CCASAnet) sites in Argentina, Brazil, Honduras, Mexico, and Peru were included. Clinical trials participants were excluded. Third line HAART was defined as use of darunavir, tipranavir, etravirine, enfuvirtide, maraviroc or raltegravir. Need for third line HAART was defined as virologic failure while on second line HAART. Results Of 5853 HAART initiators followed for a median of 3.5 years, 310 (5.3%) failed a second line regimen and 44 (0.8%) received a third line regimen. Cumulative incidence of failing a 2nd or starting a 3rd line regimen was 2.7% and 6.0% three and five years after HAART initiation, respectively. Predictors at HAART initiation for failing a second or starting a third line included female sex (hazard ratio [HR] = 1.54, 95% confidence interval [CI] 1.18–2.00, p = 0.001), younger age (HR = 2.76 for 20 vs. 40 years, 95% CI 1.86–4.10, p<0.001), and prior AIDS (HR = 2.17, 95% CI 1.62–2.90, p<0.001). Conclusions Third line regimens may be needed for at least 6% of patients in Latin America within 5 years of starting HAART, a substantial proportion given the large numbers of patients on HAART in the region. Improved accessibility to third line regimens is warranted. PMID:25221931

  8. Antiretroviral Treatment Regimen Outcomes Among HIV-Infected Prisoners

    PubMed Central

    Springer, Sandra A.; Friedland, Gerald H.; Doros, Gheorghe; Pesanti, Edward; Altice, Frederick L.

    2008-01-01

    Background Despite the high prevalence of HIV in correctional settings, the duration of therapy and response to various highly active antiretroviral therapy (HAART) regimens in this setting is unknown. Method Using a retrospective cohort study (1997−2002) of HIV-infected prisoners in Connecticut that linked demographic, pharmacy, and laboratory data, we compared HIV-1 RNA (VL) and CD4 lymphocyte responses to four treatment strategies at baseline and at the end of incarceration. Results Using an analysis of 1,044 incarceration periods or 1,099 subjects for whom ≥6 months of continuous data were available, HAART regimens that included a triple NRTI, two NRTIs + either a PI or NNRTI, or a three-class (NRTI+NNRTI+PI) strategy demonstrated no difference in virological and immunological outcomes. The proportion of subjects who were initiated with NRTI, NNRTI, PI, or three-class regimens were 14%, 32%, 46%, and 8%, respectively. For all study groups, the mean change from baseline in CD4 and VL was +74 cells/μL and −0.93 log10 copies/mL (p < .0001), respectively. Overall, 59% of subjects had an HIV-1 RNA level below the level of detection (<400 copies/mL) by the end of their incarceration. Using Kaplan-Meier curves to examine the time to change in the initial HAART strategy over the incarceration period, the three-class strategy was significantly more likely to be changed earlier than all others (p < .05). Conclusion Although the three-class strategy was less durable, initiating HAART with any strategy resulted in similar and impressive virological and immunological outcomes by the end of incarceration, further supporting prison as an important site for the initiation and provision of effective antiretroviral therapy. PMID:17720660

  9. Adherence to Antiretroviral Therapy and Virologic Failure

    PubMed Central

    Bezabhe, Woldesellassie M.; Chalmers, Leanne; Bereznicki, Luke R.; Peterson, Gregory M.

    2016-01-01

    Abstract The often cited need to achieve ≥95% (nearly perfect) adherence to antiretroviral therapy (ART) for successful virologic outcomes in HIV may present a barrier to initiation of therapy in the early stages of HIV. This meta-analysis synthesized 43 studies (27,905 participants) performed across >26 countries, to determine the relationship between cut-off point for optimal adherence to ART and virologic outcomes. Meta-analysis was performed using a random-effect model to calculate pooled odds ratios with corresponding 95% confidence intervals. The mean rate of patients reporting optimal adherence was 63.4%. Compared with suboptimal adherence, optimal adherence was associated with a lower risk of virologic failure (0.34; 95% CI: 0.26–0.44). There were no significant differences in the pooled odds ratios among different optimal adherence thresholds (≥98–100%, ≥95%, ≥80–90%). Study design (randomized controlled trial vs observational study) (regression coefficient 0.74, 95% CI: 0.04–1.43, P < 0.05) and study region (developing vs developed countries; regression coefficient 0.56, 95% CI: 0.01–1.12, P < 0.05) remained as independent predictors of between-study heterogeneity, with more patients with optimal adherence from developing countries or randomized controlled trials experiencing virologic failure. The threshold for optimal adherence to achieve better virologic outcomes appears to be wider than the commonly used cut-off point (≥95% adherence). The cut-off point for optimal adherence could be redefined to a slightly lower level to encourage the prescribing ART at an early stage of HIV infection. PMID:27082595

  10. Progress in antiretroviral drug delivery using nanotechnology

    PubMed Central

    Mallipeddi, Rama; Rohan, Lisa Cencia

    2010-01-01

    There are currently a number of antiretroviral drugs that have been approved by the Food and Drug Administration for use in the treatment of human immunodeficiency virus (HIV). More recently, antiretrovirals are being evaluated in the clinic for prevention of HIV infection. Due to the challenging nature of treatment and prevention of this disease, the use of nanocarriers to achieve more efficient delivery of antiretroviral drugs has been studied. Various forms of nanocarriers, such as nanoparticles (polymeric, inorganic, and solid lipid), liposomes, polymeric micelles, dendrimers, cyclodextrins, and cell-based nanoformulations have been studied for delivery of drugs intended for HIV prevention or therapy. The aim of this review is to provide a summary of the application of nanocarrier systems to the delivery of anti-HIV drugs, specifically antiretrovirals. For anti-HIV drugs to be effective, adequate distribution to specific sites in the body must be achieved, and effective drug concentrations must be maintained at those sites for the required period of time. Nanocarriers provide a means to overcome cellular and anatomical barriers to drug delivery. Their application in the area of HIV prevention and therapy may lead to the development of more effective drug products for combating this pandemic disease. PMID:20957115

  11. CROI 2016: Advances in Antiretroviral Therapy.

    PubMed

    Taylor, Barbara S; Olender, Susan A; Tieu, Hong-Van; Wilkin, Timothy J

    2016-01-01

    The 2016 Conference on Retroviruses and Opportunistic Infections highlighted exciting advances in antiretroviral therapy, including important data on investigational antiretroviral drugs and clinical trials. Clinical trials demonstrated benefits from a long-acting injectable coformulation given as maintenance therapy, examined intravenous and subcutaneous administration of a monoclonal antibody directed at the CD4 binding site of HIV-1, and provided novel data on tenofovir alafenamide. Several studies focused on the role of HIV drug resistance, including the significance of minority variants, transmitted drug resistance, use of resistance testing, and drug class-related resistance. Novel data on the HIV care continuum in low- and middle-income settings concentrated on differentiated HIV care delivery models and outcomes. Data on progress toward reaching World Health Organization 90-90-90 targets as well as outcomes related to expedited initiation of HIV treatment and adherence strategies were presented. Results from a trial in Malawi showed reduced rates of mother-to-child transmission among HIV-infected women who initiated antiretroviral therapy prior to pregnancy, and several studies highlighted the effect of antiretroviral therapy in pediatric populations. A special session was dedicated to the findings of studies of Ebola virus disease and treatment during the outbreak in West Africa. PMID:27398863

  12. Pharmacokinetics of Antiretrovirals in Mucosal Tissue

    PubMed Central

    Cottrell, M.L.; Srinivas, N.; Kashuba, A.D.M.

    2015-01-01

    Introduction In the absence of an HIV vaccine or cure, antiretroviral (ARV) based prevention strategies are being investigated to reduce HIV incidence. These prevention strategies depend on achieving effective drug concentrations at the site HIV exposure which is most commonly the mucosal tissues of the lower gastrointestinal tract and the female genital tract. Areas covered This article collates all known data regarding drug exposure in these vulnerable mucosal tissues, and reviews important mechanisms of ARV drug distribution. Research papers and abstracts describing antiretroviral pharmacokinetics in the female genital tract and lower gastrointestinal mucosal tissues available in MEDLINE® or presented at scientific conferences prior to December 2014 are reviewed in detail. Important influences on ARV mucosal tissue distribution, including protein binding, active drug transport, and endogenous hormones, are also reviewed. Expert opinion ARVs exhibit highly variable pharmacokinetics in mucosal tissues. In general, antiretroviral exposure is higher in the lower gastrointestinal tract compared to the female genital tract, but concentrations required for protective efficacy are largely unknown. The expected site of HIV exposure represents an important consideration when designing and optimizing antiretroviral based prevention strategies. PMID:25797064

  13. Antiretroviral-Free HIV-1 Remission and Viral Rebound Following Allogeneic Stem Cell Transplantation: A Report of Two Cases

    PubMed Central

    Henrich, Timothy J.; Hanhauser, Emily; Marty, Francisco M.; Sirignano, Michael N.; Keating, Sheila; Lee, Tzong-Hae; Robles, Yvonne P.; Davis, Benjamin T.; Li, Jonathan Z.; Heisey, Andrea; Hill, Alison L.; Busch, Michael P.; Armand, Philippe; Soiffer, Robert J.; Altfeld, Marcus; Kuritzkes, Daniel R.

    2014-01-01

    Background It is unknown if the reduction in HIV-1 reservoirs observed following allogeneic hematopoietic stem cell transplantation (HSCT) with susceptible donor cells is sufficient to achieve sustained HIV-1 remission. Objective To characterize HIV-1 reservoirs in blood and tissues, and to perform analytical antiretroviral treatment interruptions to determine the potential for allogeneic HSCT to lead to sustained antiretroviral-free HIV-1 remission. Design Characterization of HIV-1 reservoirs and immunity before and after antiretroviral interruption. Setting Tertiary care center. Patients Two HIV-infected men with undetectable HIV-1 following allogeneic HSCT for hematologic malignancies. Measurements Quantification of HIV-1 in various tissues after HSCT and the duration of antiretroviral-free HIV-1 remission after treatment interruption. Results No HIV-1 was detected from peripheral blood or rectal mucosa prior to analytical treatment interruption. Plasma HIV-1 RNA and cell-associated HIV-1 DNA remained undetectable until 12 to 32 weeks after antiretroviral cessation. Both patients experienced rebound viremia with the development of acute retroviral syndrome within one to two weeks of the most recent negative viral load measurement. One patient developed new efavirenz resistance after re-initiation of antiretroviral therapy. Re-initiation of active therapy led to viral decay and resolution of symptoms in both patients. Limitations The study was limited to 2 patients. Conclusions Allogeneic HSCT may lead to loss of detectable HIV-1 from blood and gut tissue and variable periods of antiretroviral-free HIV-1 remission, but viral rebound can occur despite a minimum 3-log10 reduction in reservoir size. Long-lived tissue reservoirs may have contributed to viral persistence. Defining the nature and half-life of such reservoirs is essential in order to achieve durable antiretroviral-free HIV-1 remission. PMID:25047577

  14. HIV-1 Genital Shedding is Suppressed in the Setting of High Genital Antiretroviral Drug Concentrations Throughout the Menstrual Cycle

    PubMed Central

    Sheth, Anandi N.; Evans-Strickfaden, Tammy; Haaland, Richard; Martin, Amy; Gatcliffe, Chelsea; Adesoye, Adebola; Omondi, Michael W.; Lupo, L. Davis; Danavall, Damien; Easley, Kirk; Chen, Cheng-Yen; Pau, Chou-Pong; Hart, Clyde; Ofotokun, Igho

    2014-01-01

    Background. It is not known if fluctuations in genital tract antiretroviral drug concentrations correlate with genital virus shedding in human immunodeficiency virus (HIV)–infected women on antiretroviral therapy (ART). Methods. Among 20 HIV-infected women on ART (tenofovir [TFV], emtricitabine [FTC], and ritonavir-boosted atazanavir [ATV]) with suppressed plasma virus loads, blood and cervicovaginal samples collected twice weekly for 3 weeks were tested for antiretroviral concentrations, HIV-1 RNA, and proviral DNA. Results. Cervicovaginal:plasma antiretroviral concentration ratios were highest for FTC (11.9, 95% confidence interval [CI], 8.66–16.3), then TFV (3.52, 95% CI, 2.27–5.48), and ATV (2.39, 95% CI, 1.69–3.38). Within- and between-person variations in plasma and genital antiretroviral concentrations were observed. Low amounts of genital HIV-1 RNA (<50 copies/mL) were detected in 45% of women at 16% of visits. Genital HIV-1 DNA was detected in 70% of women at 35% of visits. Genital virus detection was associated with higher concentrations of mucosal leukocytes but not with genital antiretroviral concentrations, menstrual cycle phase, bacterial vaginosis, genital bleeding, or plasma virus detection. Conclusions. Standard doses of ART achieved higher genital than plasma concentrations across the menstrual cycle. Therapeutic ART suppresses genital virus shedding throughout the menstrual cycle, even in the presence of factors reported to increase virus shedding. PMID:24643223

  15. Adherence to HIV/AIDS antiretroviral therapy among drug users: A qualitative study in Iran

    PubMed Central

    Hosseini, Zahra; Eftkhar, Hasan; Nedjat, Saharnaz; Ebadi, Abbas; Abbasian, Ladan; Zamani, Fereshte; Aghamollaei, Teamur; Shojaeizade, Davood

    2016-01-01

    Background: The introduction of antiretroviral therapy has caused a remarkable decrease in the occurrence of diseases and mortality among HIV-positive patients, while this success has not been achieved among injection addicts due to a low adherence to antiretroviral medicine. This study aims at clarifying the important factors affecting adherence to treatment in addicts suffering from HIV. Materials and Methods: In this qualitative research, data were gathered through in-depth interviews and field notes, and were interpreted through content analysis in the form of constant comparison. The participants were 16 drug addicts living with HIV/AIDS. Most of them had records of imprisonment and were receiving Highly Active Antiretroviral Therapy (HAART) drug treatments in the AIDS center of Imam Khomeini Hospital complex, affiliated to Tehran University of Medical Sciences. Sampling was started in a purposive method and was continued until data were saturated. Results: Four main categories including psychological reactions, contradictory beliefs, perceived support, and individual and environmental barriers were extracted from the data, each having some sub-categories. Conclusions: The obtained results indicated that adherence to the treatment of HIV is not constant and mono-dimensional, but is a function of different factors. Hence, an individual having feeble adherence in a specific time and under specific circumstances may show desirable adherence under a different circumstance. Thus, treatment of addicts living with HIV/AIDS requires physical, psychological, and social attention along with drug treatments. PMID:26985220

  16. Evolution of hepatitis C virus in HIV coinfected patients under antiretroviral therapy.

    PubMed

    Sede, Mariano; Parra, Micaela; Manrique, Julieta M; Laufer, Natalia; Jones, Leandro R; Quarleri, Jorge

    2016-09-01

    Five patients (P) were followed-up for an average of 7.73years after highly active antiretroviral therapy (HAART) initiation. Patients' immune and virological status were determined by periodical CD4+T-cell counts and HIV and HCV viral load. HCV populations were studied using longitudinal high throughput sequence data obtained in parallel by virological and immunological parameters. Two patients (P7, P28) with sub-optimal responses to HAART presented HCV viral loads significantly higher than those recorded for two patients (P1, P18) that achieved good responses to HAART. Interestingly, HCV populations from P7 and P28 displayed a stable phylogenetic structure, whereas HCV populations from P1 and P18showeda significant increase in their phylogenetic structure, followed by a decrease after achieving acceptable CD4+T-cell counts (>500 cell/μl). The fifth patient (P25) presented high HCV viral loads, preserved CD4+T-cell counts from baseline and all along the follow-up, and displayed a constant viral phylogenetic structure. These results strongly suggest that HAART-induced immune recovery induces a decrease in HCV viral load and an increase in the HCV population phylogenetic structure likely reflecting the virus diversification in response to the afresh immune response. The relatively low HCV viral load observed in the HAART responder patients suggests that once HCV is adapted it reaches a maximum number of haplotypes higher than that achieved during the initial stages of the immune response as inferred from the two recovering patients. Future studies using larger number of patients are needed to corroborate these hypotheses. PMID:27234841

  17. Photosensitization is required for antiretroviral activity of hypericin

    NASA Astrophysics Data System (ADS)

    Carpenter, Susan; Tossberg, John; Kraus, George A.

    1991-06-01

    In a seminal series of papers, Meruelo and co-workers have described the potent antiretroviral effect of hypericin. Interestingly, hypericin was found to inhibit not only the production of infectious virus from chronically infected cells, but was also shown to directly inhibit reverse transcriptase activity of mature virions. The effect of hypericin on cells chronically infected with equine infectious anemia virus (EIAV), a retrovirus genetically related to HIV, is demonstrated. At concentrations of 10 (mu) g/ml, hypericin reduced production of infectious EIAV by 99.99 without causing obvious cytopathic effects. Interestingly, the results indicated that the antiretroviral activity of hypericin was wholly dependent on the presence of light. No decrease in viral infectivity was observed when hypericin and virus were incubated in the dark. Moreover, it appeared that light was an absolute requirement for the antiviral activity, as even high concentrations of hypericin (10 (mu) g/ml) were unable to reduce infectivity of as few as 100 infectious virions.

  18. Impact of therapeutic drug monitoring of antiretroviral drugs in routine clinical management of patients infected with human immunodeficiency virus and related health care costs: a real-life study in a large cohort of patients

    PubMed Central

    Perrone, Valentina; Cattaneo, Dario; Radice, Sonia; Sangiorgi, Diego; Federici, Augusto B; Gismondo, Maria Rita; Medaglia, Massimo; Micheli, Valeria; Vimercati, Stefania; Pallone, Enza; Esposti, Luca Degli; Clementi, Emilio

    2014-01-01

    Background Highly active antiretroviral therapy (HAART) has reduced morbidity and mortality in patients infected with human immunodeficiency virus (HIV). Studies have documented high interindividual variability in the pharmacokinetics of antiretroviral drugs, which may impair the success of HAART if not managed properly. Therapeutic drug monitoring (TDM) is a useful diagnostic tool that helps clinicians to optimize drug doses so that drug concentrations associated with the highest therapeutic efficacy are obtained with a reduced risk of concentration-dependent adverse effects. The aim of this study was to assess whether use of TDM improves clinical outcomes and cost of illness. Methods A retrospective cohort study was conducted at L Sacco University Hospital in Milan, Italy, in HIV-infected patients aged ≥18 years with at least one prescription of antiretroviral drugs for which TDM was applied. The inclusion period was from January 2010 to December 2011, with a follow-up period of up to 12 months. Laboratory and administrative databases were analyzed and matched with each other. Results The cohort consisted of 5,347 patients (3,861 males and 1,486 females) of mean age 43.9±12.5 years. We found that TDM had been used in 143 of these patients, among whom adherence with therapy was significantly higher than among those in whom TDM had not been used (94% versus 78%). In TDM-controlled patients, the mean length of HIV-related hospitalization stay and mean cost of hospitalization were significantly reduced with respect to those observed in the group in which TDM had not been used (7.21 days versus 29.47 days and €293 versus €688, respectively). Conclusion Inclusion of TDM as part of routine clinical optimization of drug dosing in HIV-infected patients is associated with higher adherence to therapy, reduced length of hospitalization stay, and reduced cost of illness. PMID:25053888

  19. A Reduction Grade of Lipodystrophy and Limited Side Effects after HAART Regimen with Raltegravir, Lamivudine, Darunavir and Ritonavir in an HIV-1 Infected Patient after Six Years of Antiretroviral Therapy

    PubMed Central

    Antoni, A Degli; Weimer, LE; Fragola, V; Giacometti, A; Sozio, F

    2015-01-01

    ABSTRACT HIV-associated lipodystrophy commonly presents with fat loss in the face, buttocks, arms and legs, hypocomplementaemia, glomerulonephritis and autoimmune disorders. The exact mechanism of HIV-associated lipodystrophy is not fully elucidated. There is evidence indicating that it can be caused by both antiretroviral medications and HIV infection in the absence of antiretroviral medication. Lipodystrophy seems to be mainly due to HIV-1 protease inhibitors. Interference with lipid metabolism is postulated as pathophysiology. Also, the development of lipodystrophy is associated with specific nucleoside reverse transcriptase inhibitors (NRTI). Mitochondrial toxicity is postulated to be involved in the pathogenesis associated with NRTI. Here, we analyse the side effects and examine the impact of the highly active antiretroviral therapy (HAART) regimen including raltegravir, lamivudine, darunavir and ritonavir in an HIV-1 infected patient with severe lipodystrophy after six years of antiretroviral therapy. PMID:26426188

  20. Antiretroviral Therapy and Central Nervous System HIV-1 Infection

    PubMed Central

    Price, Richard W.; Spudich, Serena

    2008-01-01

    Central nervous system (CNS) HIV-1 infection begins during primary viremia and continues throughout the course of untreated systemic infection. While frequently accompanied by local inflammatory reactions detectable in cerebrospinal fluid (CSF), CNS HIV-1 infection is not usually clinically apparent. In a minority of patients, CNS HIV-1 infection evolves late in the course of systemic infection into encephalitis, which compromises brain function and presents clinically as AIDS dementia complex (ADC). Combination highly active antiretroviral therapy (HAART) has had a major impact on all aspects of HIV-1 CNS infection and disease. In those with asymptomatic infection, HAART usually effectively suppresses CSF HIV-1 and markedly reduces the incidence of symptomatic ADC. In those presenting with ADC, HAART characteristically prevents neurological progression and leads to variable, and at times substantial, recovery. Treatment has similarly reduced CNS opportunistic infections. With better control of these severe disorders, attention has turned to the possible consequences of chronic silent infection, and the issue of whether indolent, low-grade brain injury might require earlier treatment intervention. PMID:18447615

  1. Drug Interactions with New and Investigational Antiretrovirals

    PubMed Central

    Brown, Kevin C.; Paul, Sunita; Kashuba, Angela D.M.

    2010-01-01

    More than 20 individual and fixed-dose combinations of antiretrovirals are approved for the treatment of human immunodeficiency virus (HIV) infection. However, owing to the ongoing limitations of drug resistance and adverse effects, new treatment options are still required. A number of promising new agents in existing or new drug classes are in development or have recently been approved by the US FDA. Since these agents will be used in combination with other new and existing antiretrovirals, understanding the potential for drug interactions between these compounds is critical to their appropriate use. This article summarizes the drug interaction potential of new and investigational protease inhibitors (darunavir), non-nucleoside reverse transcriptase inhibitors (etravirine and rilpivirine), chemokine receptor antagonists (maraviroc, vicriviroc and INCB 9471), integrase inhibitors (raltegravir and elvitegravir) and maturation inhibitors (bevirimat). PMID:19492868

  2. Factors related to lipodystrophy and metabolic alterations in patients with human immunodeficiency virus infection receiving highly active antiretroviral therapy.

    PubMed

    Savès, Marianne; Raffi, François; Capeau, Jacqueline; Rozenbaum, Willy; Ragnaud, Jean-Marie; Perronne, Christian; Basdevant, Arnaud; Leport, Catherine; Chêne, Geneviève

    2002-05-15

    Morphologic and metabolic changes associated with protease inhibitor (PI) therapy have been reported since the introduction of PIs for treatment of human immunodeficiency virus infection. These changes were measured 12-20 months after initiation of PI therapy in a cross-sectional study involving 614 patients from the Antiprotéases Cohorte (APROCO) Study (Agence Nationale de Recherches sur le Sida-EP11). The prevalence was 21% for isolated peripheral atrophy, 17% for isolated fat accumulation, 24% for mixed syndrome, 23% for glucose metabolism alterations, 28% for hypertriglyceridemia (triglyceride level, > or =2.2 mM), and 57% for hypercholesterolemia (cholesterol level, > or =5.5 mM). Age was significantly associated with different phenotypes of lipodystrophy and metabolic alterations, but body-mass index, CD4(+) cell count, and type of nucleoside reverse-transcriptase inhibitor or PI received were not constantly associated with these changes. Furthermore, in all models tested, exposure to stavudine was associated with lipoatrophy and exposure of ritonavir was associated with hypertriglyceridemia. Detection and management of these disorders should be implemented to prevent further complications. PMID:11981737

  3. High perceived social standing is associated with better health in HIV-infected Ugandan adults on highly active antiretroviral therapy.

    PubMed

    Ezeamama, A E; Guwatudde, D; Wang, M; Bagenda, D; Brown, K; Kyeyune, R; Smith, Emily; Wamani, H; Manabe, Y C; Fawzi, W W

    2016-06-01

    Perceived social standing (PSS) was evaluated as a determinant of differences in health outcomes among Ugandan HIV-infected adults from Kampala using cross-sectional study design. PSS was defined using the MacArthur scale of subjective social status translated and adapted for the study setting. Socio-demographic and psychosocial correlates of PSS ranking at enrollment were determined using linear regression models. High versus low PSS was defined based on the median PSS score and evaluated as a determinant of body mass index, hemoglobin, quality of life (QOL) and frailty-related phenotype via linear regression. A log-binomial regression model estimated the relative-risk of good, very good or excellent versus fair or poor self-rated health (SRH) in relation to PSS. Older age, increasing social support and material wealth were correlated with high PSS ranking, whereas female sex, experience of multiple stigmas and multiple depressive symptoms were correlated with low PSS ranking. High PSS participants were on average 1.1 kg/m(2) heavier, had 4.7 % lower frailty scores and 3.6 % higher QOL scores compared to low PSS patients (all p < 0.05); they were also more likely to self-classify as high SRH (RR 1.4, 95 % confidence interval 1.1, 1.7) but had comparable hemoglobin levels (p = 0.634). Low PSS correlated with poor physical and psychosocial wellbeing in HIV-positive Ugandan adults. The assessment of PSS as part of clinical management, combined with efforts to reduce stigma and improve social support, may identify and possibly reduce PSS-associated health inequality in Ugandan adults with HIV. PMID:26733010

  4. Review of screening guidelines for non-AIDS-defining malignancies: evolving issues in the era of highly active antiretroviral therapy.

    PubMed

    Tyerman, Zachary; Aboulafia, David M

    2012-01-01

    HIV-associated morbidity and mortality have declined dramatically in the era of HAART. Through direct and indirect benefits of HAART, people with HIV/AIDS are living longer, developing less AIDS-defining cancers and more cancers commonly seen in the seronegative population. Herein, we review cancer screening strategies for people living with HIV and compare and contrast them with those of the general population. The most noticeable differences occur in anal and cervical cancer screening. Although anal cancer is uncommon in the general population, it is more prevalent in men who have sex with men and people at high risk for human papillomavirus infection, especially those infected with HIV. To address this, we recommend that a digital rectal exam and a visual inspection be performed annually. In addition, an anal Pap test should be performed soon after the diagnosis of HIV infection, with follow-up testing every six months until two normal tests. Abnormal cytological results are then investigated with high-resolution anoscopy and biopsy of suspicious lesions. In screening for cervical cancer, a Pap test should be performed during the anogenital exam after initial HIV diagnosis, with a second Pap six months later, then annually if the results are normal. A colposcopy should follow an abnormal result. Human papillomavirus testing as a screening method for cervical cancer in women with HIV can also be efficacious. In lung cancer screening, preliminary data suggest that low-dose computerized tomography may play an important role, but further research is needed. Screening for breast and colon cancer should follow guidelines for the general population. Early screening for prostate cancer based on a diagnosis of HIV lacks clear benefit. PMID:22297500

  5. Global Challenges in the Development and Delivery of Paediatric Antiretrovirals

    PubMed Central

    Bowen, Asha; Palasanthiran, Pamela; Sohn, Annette H.

    2008-01-01

    By the end of 2006, compared with 28% coverage for adults, only 15% of children with HIV who needed antiretroviral treatment were receiving it. Major challenges in delivering treatment include the lack of paediatric antiretrovirals that can be dosed in small children and limited studies examining safety and efficacy for existing antiretroviral formulations. The high costs of treatment have been reduced through the use of generic, fixed-dose combination drugs. Evidence-based strategies for managing resistance and the scale-up of pharmacological trials for children in low- and middle-income countries are critical to the success and future development of paediatric antiretrovirals. PMID:18549980

  6. Dosing antiretroviral medication when crossing time zones: a review

    PubMed Central

    Lewis, Joseph M.; Volny-Anne, Alain; Waitt, Catriona; Boffito, Marta; Khoo, Saye

    2016-01-01

    International tourism continues to increase worldwide, and people living with HIV and their clinicians are increasingly confronted with the problem of how to dose antiretroviral therapy during transmeridian air travel across time zones. No guidance on this topic currently exists. This review is a response to requests from patient groups for clear, practical and evidence-based guidance for travelling on antiretroviral therapy; we present currently available data on the pharmacokinetic forgiveness and toxicity of various antiretroviral regimens, and synthesize this data to provide guidelines on how to safely dose antiretrovirals when travelling across time zones. PMID:26684823

  7. Dosing antiretroviral medication when crossing time zones: a review.

    PubMed

    Lewis, Joseph M; Volny-Anne, Alain; Waitt, Catriona; Boffito, Marta; Khoo, Saye

    2016-01-01

    International tourism continues to increase worldwide, and people living with HIV and their clinicians are increasingly confronted with the problem of how to dose antiretroviral therapy during transmeridian air travel across time zones. No guidance on this topic currently exists. This review is a response to requests from patient groups for clear, practical and evidence-based guidance for travelling on antiretroviral therapy; we present currently available data on the pharmacokinetic forgiveness and toxicity of various antiretroviral regimens, and synthesize this data to provide guidelines on how to safely dose antiretrovirals when travelling across time zones. PMID:26684823

  8. High-activity liquid packaging design criteria

    SciTech Connect

    Not Available

    1994-05-01

    In recent studies, it has been acknowledged that there is an emerging need for packaging to transport high-activity liquid off the Hanford Site to support characterization and process development activities of liquid waste stored in underground tanks. These studies have dealt with specimen testing needs primarily at the Hanford Site; however, similar needs appear to be developing at other US Department of Energy (DOE) sites. The need to ship single and multiple specimens to offsite laboratories is anticipated because it is predicted that onsite laboratories will be overwhelmed by an increasing number and size (volume) of samples. Potentially, the specimen size could range from 250 mL to greater than 50 L. Presently, no certified Type-B packagings are available for transport of high-activity liquid radioactive specimens in sizes to support Site missions.

  9. Genetic variation of the HIV-1 integrase region in newly diagnosed anti-retroviral drug-naïve patients with HIV/AIDS in Korea.

    PubMed

    Kim, J-Y; Kim, E-J; Choi, J-Y; Kwon, O-K; Kim, G J; Choi, S Y; Kim, S S

    2011-08-01

    The survival time of HIV/AIDS patients in Korea has increased since HAART (highly active anti-retroviral therapy) was introduced. However, the occurrence of drug-resistant strains requires new anti-retroviral drugs, one of which, an integrase inhibitor (INI), was approved by the US Food and Drug Administration (FDA) in 2007. INIs have been used for therapy in many countries and are about to be employed in Korea. Therefore, it is important to identify basic mutant variants prior to the introduction of INIs in order to estimate their efficacy. To monitor potential drug-resistant INI mutations in Korean HIV/AIDS patients, the polymorphism of the int gene was investigated together with the pol gene using a genotypic assay for 75 randomly selected Korean HIV-1 patients newly diagnosed in 2007. The drug-resistant mutation sequences were analysed using the Stanford HIV DB and the International AIDS Society resistance testing-USA panel (IAS-USA). Seventy strains of Korean subtype B were compared with foreign subtype-B strains, and there were no significantly different variants of the int gene region in the study population. Major mutation sites in the integrase (E92Q, F121Y, G140A/S, Y143C/R, Q148H/R/K and N155H) were not detected, and only a few minor mutation sites (L74M, V151I, E157Q, V165I, I203M, S230N and D232N) were identified in 21 strains (28%). Resistance due to mutations in the pol gene was observed in a single strain (1.3%) resistant to protease inhibitors (PIs) and in four strains (5.3%) resistant to reverse transcriptase inhibitors (RTIs). In summary, this demonstrates that INIs will be susceptible to drug naïve HIV/AIDS patients in Korea. PMID:20946407

  10. Dutrebis (lamivudine and raltegravir) for use in combination with other antiretroviral products for the treatment of HIV-1 infection.

    PubMed

    Casado, José Luis; Bañón, Sara

    2015-01-01

    Raltegravir and lamivudine have been part of highly active therapy regimens throughout the past years of antiretroviral therapy. A fixed-dose, single-tablet regimen comprising a non-poloxamer formulation of the integrase inhibitor raltegravir and the transcriptase inhibitor lamivudine (raltegravir/lamivudine; Dutrebis(®)) has been recently licensed for the treatment of HIV-1 infection. In several Phase I pharmacokinetic studies, one Dutrebis (150 mg lamivudine/300 mg raltegravir) fixed-dose combination tablet showed a higher bioavailability but comparable lamivudine and 400 mg raltegravir poloxamer exposures. Thus, the co-administration of raltegravir together with lamivudine created a potent, effective, well-tolerated antiretroviral combination, which could be more convenient for the patient. However, the disadvantage of twice a day administration, and the existence of other fixed-dose combinations limit its widespread clinical use. This article reviews pharmacokinetics data and appraises their potential use in current and future HIV therapy. PMID:26517111

  11. Spectrum of imaging appearances of intracranial cryptococcal infection in HIV/AIDS patients in the anti-retroviral therapy era.

    PubMed

    Offiah, Curtis E; Naseer, Aisha

    2016-01-01

    Cryptococcus neoformans infection is the most common fungal infection of the central nervous system (CNS) in advanced human immunodeficiency virus (HIV) and acquired immunodeficiency syndrome (AIDS) patients, but remains a relatively uncommon CNS infection in both the immunocompromised and immunocompetent patient population, rendering it a somewhat elusive and frequently overlooked diagnosis. The morbidity and mortality associated with CNS cryptococcal infection can be significantly reduced by early recognition of the imaging appearances by the radiologist in order to focus and expedite clinical management and treatment. The emergence and evolution of anti-retroviral therapy have also impacted significantly on the imaging appearances, morbidity, and mortality of this neuro-infection. The constellation of varied imaging appearances associated with cryptococcal CNS infection in the HIV and AIDS population in the era of highly active anti-retroviral therapy (HAART) will be presented in this review. PMID:26564776

  12. [Immunologic reconstruction after antiretroviral treatment].

    PubMed

    Tubiana, R; Carcelain, G; Mohand, H A; Li, T S; Renaud, M; Blanc, C; Calvez, V; Debré, P; Agut, H; Katlama, C; Autran, B; Bricaire, F

    1999-02-27

    DATA FAVORING IMMUNE RECONSTITUTION: Multiple drug therapies for HIV infection have enabled a major reduction in the viral load, higher CD4 counts, and a lower incidence of opportunistic infections and tumor formations, and subsequently lower hospitalization rates and mortality. TWO STAGES OF CD4 RECONSTITUTION: In HIV-positive patients with advanced stage disease treated with a protease inhibitor associated with 2 nucleoside analog reverse transcriptase inhibitors and followed prospectively, it has been observed that CD4 counts rise considerably, with a rapid increase during the first 2 months followed by a slower but still positive slope over a period of 18 months. Discordant results have however also been observed suggesting an ineffective anti-viral effect or a retarded immune reconstitution. SEVERAL MECHANISMS: The lymphocyte amplification observed during the early phase corresponds to re-circulation of CD4 and CD8 lymphocytes which had been sequestered in lymphoid organs; most of these CD4 lymphocytes are memory cells. A second phase corresponds to a more moderate and progressive rise in naive CD4 cells which originate from an unknown source. This biphasic reconstitution of CD4 lymphocytes is associated with a correction of the chronic lymphocyte overactivation. PARTIAL IMMUNE RECONSTITUTION: With treatment, the capacity to respond to known antigens reappears. This restored capacity is secondary to the amplification of CD4 memory cells and appears prior to the expansion phase of naive cells. The response remains moderate and is only observed against antigens from microorganisms highly prevalent during advanced stage infection. PMID:10093603

  13. Antiretroviral drugs and acute pancreatitis in HIV/AIDS patients: is there any association? A literature review.

    PubMed

    Oliveira, Natalia Mejias; Ferreira, Felipe Augusto Yamauti; Yonamine, Raquel Yumi; Chehter, Ethel Zimberg

    2014-01-01

    In HIV-seropositive individuals, the incidence of acute pancreatitis may achieve 40% per year, higher than the 2% found in the general population. Since 1996, when combined antiretroviral therapy, known as HAART (highly active antiretroviral therapy), was introduced, a broad spectrum of harmful factors to the pancreas, such as opportunistic infections and drugs used for chemoprophylaxis, dropped considerably. Nucleotide analogues and metabolic abnormalities, hepatic steatosis and lactic acidosis have emerged as new conditions that can affect the pancreas. To evaluate the role of antiretroviral drugs to treat HIV/AIDS in a scenario of high incidence of acute pancreatitis in this population, a systematic review was performed, including original articles, case reports and case series studies, whose targets were HIV-seropositive patients that developed acute pancreatitis after exposure to any antiretroviral drugs. This association was confirmed after exclusion of other possible etiologies and/or a recurrent episode of acute pancreatitis after re-exposure to the suspected drug. Zidovudine, efavirenz, and protease inhibitors are thought to lead to acute pancreatitis secondary to hyperlipidemia. Nucleotide reverse transcriptase inhibitors, despite being powerful inhibitors of viral replication, induce a wide spectrum of side effects, including myelotoxicity and acute pancreatitis. Didanosine, zalcitabine and stavudine have been reported as causes of acute and chronic pancreatitis. They pose a high risk with cumulative doses. Didanosine with hydroxyurea, alcohol or pentamidine are additional risk factors, leading to lethal pancreatitis, which is not a frequent event. In addition, other drugs used for prophylaxis of AIDS-related opportunistic diseases, such as sulfamethoxazole-trimethoprim and pentamidine, can produce necrotizing pancreatitis. Despite comorbidities that can lead to pancreatic involvement in the HIV/AIDS population, antiretroviral drug-induced pancreatitis

  14. Using Marginal Structural Measurement-Error Models to Estimate the Long-term Effect of Antiretroviral Therapy on Incident AIDS or Death

    PubMed Central

    Cole, Stephen R.; Jacobson, Lisa P.; Tien, Phyllis C.; Kingsley, Lawrence; Chmiel, Joan S.; Anastos, Kathryn

    2010-01-01

    To estimate the net effect of imperfectly measured highly active antiretroviral therapy on incident acquired immunodeficiency syndrome or death, the authors combined inverse probability-of-treatment-and-censoring weighted estimation of a marginal structural Cox model with regression-calibration methods. Between 1995 and 2007, 950 human immunodeficiency virus–positive men and women were followed in 2 US cohort studies. During 4,054 person-years, 374 initiated highly active antiretroviral therapy, 211 developed acquired immunodeficiency syndrome or died, and 173 dropped out. Accounting for measured confounders and determinants of dropout, the weighted hazard ratio for acquired immunodeficiency syndrome or death comparing use of highly active antiretroviral therapy in the prior 2 years with no therapy was 0.36 (95% confidence limits: 0.21, 0.61). This association was relatively constant over follow-up (P = 0.19) and stronger than crude or adjusted hazard ratios of 0.75 and 0.95, respectively. Accounting for measurement error in reported exposure using external validation data on 331 men and women provided a hazard ratio of 0.17, with bias shifted from the hazard ratio to the estimate of precision as seen by the 2.5-fold wider confidence limits (95% confidence limits: 0.06, 0.43). Marginal structural measurement-error models can simultaneously account for 3 major sources of bias in epidemiologic research: validated exposure measurement error, measured selection bias, and measured time-fixed and time-varying confounding. PMID:19934191

  15. Drug Interactions and Antiretroviral Drug Monitoring

    PubMed Central

    Foy, Matthew; Sperati, C. John; Lucas, Gregory M.

    2014-01-01

    Due to the improved longevity afforded by combination antiretroviral therapy (cART), HIV-infected individuals are developing several non-AIDS related comorbid conditions. Consequently, medical management of the HIV-infected population is increasingly complex, with a growing list of potential drug-drug interactions (DDIs). This article reviews some of the most relevant and emerging potential interactions between antiretroviral medications and other agents. The most common DDIs are those involving protease inhibitors or non-nucleoside reverse transcriptase inhibitors which alter the cytochrome P450 enzyme system and/or drug transporters such as p-glycoprotein. Of note are the new agents for the treatment of chronic hepatitis C virus infection. These new classes of drugs and others drugs which are increasingly used in this patient population represent a significant challenge with regard to achieving the goals of effective HIV suppression and minimization of drug-related toxicities. Awareness of DDIs and a multidisciplinary approach are imperative in reaching these goals. PMID:24950731

  16. Long-Term Effects of In Utero Antiretroviral Exposure: Systolic and Diastolic Function in HIV-Exposed Uninfected Youth.

    PubMed

    Guerra, Vitor; Leister, Erin C; Williams, Paige L; Starc, Thomas J; Lipshultz, Steven E; Wilkinson, James D; Van Dyke, Russell B; Hazra, Rohan; Colan, Steven D

    2016-07-01

    The aim of this study was to evaluate the association of in utero exposure to highly active antiretroviral therapy (HAART) with left ventricular (LV) function and structure in HIV-exposed uninfected (HEU) children. A prospective, multisite cohort study in HEU children was conducted by the Pediatric HIV/AIDS Cohort Study (PHACS). Echocardiographic measures of LV systolic and diastolic function and cardiac structure were obtained from HEU subjects aged ≥6 years enrolled in the PHACS Surveillance Monitoring of ART Toxicities study. Echocardiographic Z-scores were calculated using normative data from an established reference cohort. We used adjusted linear regression models to compare Z-scores for echocardiographic measures from HEU children exposed in utero to HAART with those exposed to non-HAART, adjusting for demographic and maternal health characteristics. One hundred seventy-four HEU subjects with echocardiograms and maternal ARV information were included (mean age 10.9 years; 48% male, 56% black non-Hispanic). Among 156 HEU youth with any ARV exposure, we observed no differences in Z-scores for LV systolic function measures between youth exposed in utero to HAART (39%) and HAART-unexposed youth in either unadjusted or adjusted models. In adjusted models, those exposed to HAART had significantly lower mitral late diastolic inflow velocities (adjusted mean Z-score = 0.00 vs. 0.52, p = .04) and significantly higher adjusted mean LV mass-to-volume ratio Z-scores (adjusted mean Z-score = 0.47 vs. 0.11, p = .03) than HAART-unexposed youth. Uninfected children with perinatal exposure to HAART had no difference in LV systolic function. However, small but significant differences in LV diastolic function and cardiac structure were observed, suggesting that continued monitoring for cardiac outcomes is warranted in this population. PMID:26794032

  17. Implementing a pharmacovigilance program to evaluate cutaneous adverse drug reactions in an antiretroviral access program

    PubMed Central

    Mudzviti, Tinashe; Sibanda, Marvelous; Gavi, Samuel; Maponga, Charles Chiedza; Morse, Gene D.

    2012-01-01

    Background Cutaneous adverse drug reactions (cADRs) can cause significant morbidity and distress in patients especially in the HIV infected population on antiretroviral therapy. Adverse Drug Reaction monitoring and ascertaining causality in resource limited settings still remains a challenge. This study was carried out to evaluate causality and measure incidence of cADRs in HIV infected patients on highly active antiretroviral therapy. The study was also designed to test a 3-step approach in the monitoring and evaluation of ADRs in resource limited settings. Methodology A retrospective patient medical records review was carried out at the Parirenyatwa Family Care Centre, (Harare, Zimbabwe). Cases of cADRs were reported to the Medicines Control Authority of Zimbabwe (Drug regulating body in Zimbabwe) for assessment and causality classification. Results Two hundred and twenty-one patient records were randomly selected and reviewed to determine if any diagnosis of cADRs was made by clinicians. Causality assessment revealed 13.1% of cADRs which were due to an offending agent in the antiretroviral therapy against an initial incidence of 17.6% which had been determined by the physicians. Conclusions cADRs had an incidence of 13.1% within the population under study due to non nucleoside reverse transcriptase inhibitors (NNRTIs). Most reactions were due to the NNRTIs which contributed 72.4 % of all cADRs. A panel of experts from the drug regulatory authority can be used as an implementation based mechanism in ascertaining causality objectively in settings where resources are constrained. PMID:23277506

  18. The Complexity of HIV Persistence and Pathogenesis in the Lung Under Antiretroviral Therapy: Challenges Beyond AIDS

    PubMed Central

    2014-01-01

    Abstract Antiretroviral therapy (ART) represents a significant milestone in the battle against AIDS. However, we continue learning about HIV and confronting challenges 30 years after its discovery. HIV has cleverly tricked both the host immune system and ART. First, the many HIV subtypes and recombinant forms have different susceptibilities to antiretroviral drugs, which may represent an issue in countries where ART is just being introduced. Second, even under the suppressive pressures of ART, HIV still increases inflammatory mediators, deregulates apoptosis and proliferation, and induces oxidative stress in the host. Third, the preference of HIV for CXCR4 as a co-receptor may also have noxious outcomes, including potential malignancies. Furthermore, HIV still replicates cryptically in anatomical reservoirs, including the lung. HIV impairs bronchoalveolar T-lymphocyte and macrophage immune responses, rendering the lung susceptible to comorbidities. In addition, HIV-infected individuals are significantly more susceptible to long-term HIV-associated complications. This review focuses on chronic obstructive pulmonary disease (COPD), pulmonary arterial hypertension, and lung cancer. Almost two decades after the advent of highly active ART, we now know that HIV-infected individuals on ART live as long as the uninfected population. Fortunately, its availability is rapidly increasing in low- and middle-income countries. Nevertheless, ART is not risk-free: the developed world is facing issues with antiretroviral drug toxicity, resistance, and drug–drug interactions, while developing countries are confronting issues with immune reconstitution inflammatory syndrome. Several aspects of the complexity of HIV persistence and challenges with ART are discussed, as well as suggestions for new avenues of research. PMID:24797368

  19. Unresolved antiretroviral treatment management issues in HIV-infected children.

    PubMed

    Heidari, Shirin; Mofenson, Lynne M; Hobbs, Charlotte V; Cotton, Mark F; Marlink, Richard; Katabira, Elly

    2012-02-01

    Antiretroviral therapy in children has expanded dramatically in low-income and middle-income countries. The World Health Organization revised its pediatric HIV guidelines to recommend initiation of antiretroviral therapy in all HIV-infected children younger than 2 years, regardless of CD4 count or clinical stage. The number of children starting life-long antiretroviral therapy should therefore expand dramatically over time. The early initiation of antiretroviral therapy has indisputable benefits for children, but there is a paucity of definitive information on the potential adverse effects. In this review, a comprehensive literature search was conducted to provide an overview of our knowledge about the complications of treating pediatric HIV. Antiretroviral therapy in children, as in adults, is associated with enhanced survival, reduction in opportunistic infections, improved growth and neurocognitive function, and better quality of life. Despite antiretroviral therapy, HIV-infected children may continue to lag behind their uninfected peers in growth and development. In addition, epidemic concurrent conditions, such as tuberculosis, malaria, and malnutrition, can combine with HIV to yield more rapid disease progression and poor treatment outcomes. Additional studies are required to evaluate the long-term effects of antiretroviral therapy in HIV-infected infants, children, and adolescents, particularly in resource-limited countries where concomitant infections and conditions may enhance the risk of adverse effects. There is an urgent need to evaluate drug-drug interactions in children to determine optimal treatment regimens for both HIV and coinfections. PMID:22138766

  20. HIV cell-to-cell transmission: effects on pathogenesis and antiretroviral therapy

    PubMed Central

    Agosto, Luis M.; Uchil, Pradeep D.; Mothes, Walther

    2015-01-01

    The human immunodeficiency virus (HIV) spreads more efficiently in vitro when infected cells directly contact uninfected cells to form virological synapses. A hallmark of virological synapses is that viruses can be transmitted at a higher multiplicity of infection (MOI) that, in vitro, results in a higher number of proviruses. Whether HIV also spreads by cell-cell contact in vivo is a matter of debate. Here we discuss recent data that suggest that contact-mediated transmission largely manifests itself in vivo as CD4+ T cell depletion. The assault of a cell by a large number of incoming particles is likely efficiently sensed by the innate cellular surveillance to trigger cell death. The large number of particles transferred across virological synapses has also been implicated in reduced efficacy of antiretroviral therapies. Thus, antiretroviral therapies must remain effective against the high MOI observed during cell-to-cell transmission to inhibit both viral replication and the pathogenesis associated with HIV infection. PMID:25766144

  1. Antiretroviral concentrations in small hair samples as a feasible marker of adherence in rural Kenya.

    PubMed

    Hickey, Matthew D; Salmen, Charles R; Tessler, Robert A; Omollo, Dan; Bacchetti, Peter; Magerenge, Richard; Mattah, Brian; Salmen, Marcus R; Zoughbie, Daniel; Fiorella, Kathryn J; Geng, Elvin; Njoroge, Betty; Jin, Chengshi; Huang, Yong; Bukusi, Elizabeth A; Cohen, Craig R; Gandhi, Monica

    2014-07-01

    Antiretroviral hair levels objectively quantify drug exposure over time and predict virologic responses. We assessed the acceptability and feasibility of collecting small hair samples in a rural Kenyan cohort. Ninety-five percentage of participants (354/373) donated hair. Although median self-reported adherence was 100% (interquartile range, 96%-100%), a wide range of hair concentrations likely indicates overestimation of self-reported adherence and the advantages of a pharmacologic adherence measure. Higher nevirapine hair concentrations observed in women and older adults require further study to unravel behavioral versus pharmacokinetic contributors. In resource-limited settings, hair antiretroviral levels may serve as a low-cost quantitative biomarker of adherence. PMID:24694932

  2. Antiretroviral treatment literacy among HIV voluntary counseling and testing clients in Moshi, Tanzania, 2003 to 2005.

    PubMed

    Landman, Keren Z; Thielman, Nathan M; Mgonja, Anna; Shao, Humphrey J; Itemba, Dafrosa K; Ndosi, Evelyn M; Tribble, Alison C; Shao, John F; Bartlett, John A; Crump, John A

    2007-03-01

    Antiretroviral treatment literacy leads to greater HIV testing and treatment and antiretroviral treatment adherence. Among northern Tanzanian subjects, antiretroviral treatment awareness was only 17%. Factors associated with low antiretroviral treatment literacy included having exchanged money or gifts for sex, living in rural areas, having more than 2 children, and having a primary education only. Previous HIV testing was protective against low antiretroviral treatment literacy. These results support refocusing HIV education efforts and increasing synergy between HIV prevention and treatment programs. PMID:17329501

  3. [Recommendations for initial antiretroviral treatment in HIV-infected children. Update 2003].

    PubMed

    2004-03-01

    Highly active antiretroviral therapy in HIV-infected children has been associated with a dramatic decrease in progression to AIDS and HIV-related deaths, and infected children currently have an excellent quality of life. Antiretroviral drugs cannot eradicate the virus, although they can achieve a situation of latent infection. However, chronic use of these drugs has multiple adverse effects, the most important of which are metabolic complications. The large number of drugs required and patient characteristics such as age, tolerance to drugs, adherence, and social problems make unifying the criteria for initial therapy in HIV-infected children difficult. A balance should be sought between not delaying the start of treatment, to avoid immunologic deterioration, and minimizing the long-term adverse effects of the therapy. The present treatment recommendations are adapted from international guidelines and are based on a literature review and on our own experience. Our group previously published recommendations on the treatment of HIV-infected children and the aim of the present article is to provide an update. PMID:14987518

  4. Current Perspectives on HIV-1 Antiretroviral Drug Resistance

    PubMed Central

    Iyidogan, Pinar; Anderson, Karen S.

    2014-01-01

    Current advancements in antiretroviral therapy (ART) have turned HIV-1 infection into a chronic and manageable disease. However, treatment is only effective until HIV-1 develops resistance against the administered drugs. The most recent antiretroviral drugs have become superior at delaying the evolution of acquired drug resistance. In this review, the viral fitness and its correlation to HIV-1 mutation rates and drug resistance are discussed while emphasizing the concept of lethal mutagenesis as an alternative therapy. The development of resistance to the different classes of approved drugs and the importance of monitoring antiretroviral drug resistance are also summarized briefly. PMID:25341668

  5. Stealth anti-CD4 conjugated immunoliposomes with dual antiretroviral drugs--modern Trojan horses to combat HIV.

    PubMed

    Ramana, Lakshmi Narashimhan; Sharma, Shilpee; Sethuraman, Swaminathan; Ranga, Udaykumar; Krishnan, Uma Maheswari

    2015-01-01

    Highly active antiretroviral therapy (HAART) is the currently employed therapeutic intervention against AIDS where a drug combination is used to reduce the viral load. The present work envisages the development of a stealth anti-CD4 conjugated immunoliposomes containing two anti-retroviral drugs (nevirapine and saquinavir) that can selectively home into HIV infected cells through the CD4 receptor. The nanocarrier was characterized using transmission electron microscopy, FTIR, differential scanning calorimetry, particle size and zeta potential. The cell uptake was also evaluated qualitatively using confocal microscopy and quantitatively by flow cytometry. The drug to lipid composition was optimized for maximum encapsulation of the two drugs. Both drugs were found to localize in different regions of the liposome. The release of the reverse transcriptase inhibitor was dominant during the early phases of the release while in the later phases, the protease inhibitor is the major constituent released. The drugs delivered via anti-CD4 conjugated immunoliposomes inhibited viral proliferation at a significantly lower concentration as compared to free drugs. In vitro studies of nevirapine to saquinavir combination at a ratio of 6.2:5 and a concentration as low as 5 ng/mL efficiently blocked viral proliferation suggesting that co-delivery of anti-retroviral drugs holds a greater promise for efficient management of HIV-1 infection. PMID:25500283

  6. Investigation of x ray variability in highly active cool stars

    NASA Technical Reports Server (NTRS)

    Stern, Robert A.

    1989-01-01

    Ginga x ray observations of highly active cool star coronae were obtained and analyzed in an effort to better understand the nature of their time variability. The possible types of variability studied included x ray occultations via eclipses in a binary system, rotational modulation of x ray emission, flares, and a search for microflaring. Observation of both sigma(sup 2) CrB and Algol were performed successfully by Ginga. The sigma(sup 2) CrB observations occurred on 27 to 30 June 1988, and the Algol observations on 12 to 14 January 1989. In the sigma(sup 2) CrB observation, simultaneous IUE and Very Large Array (VLA) observations were obtained during part of the Ginga observation. Flaring activity was detected on sigma(sup 2) CrB in the Ginga 1.7 to 11 KeV band and in the IUE microwave region. A large flare on Algol which lasted well over 12 hours was detected, began with a maximum temperature of 65 MK which gradually decayed to 36 MK, and evidence was shown of highly ionized Fe line emission.

  7. Life expectancy of individuals on combination antiretroviral therapy in high-income countries: a collaborative analysis of 14 cohort studies

    PubMed Central

    2011-01-01

    Summary Background Combination antiretroviral therapy has led to significant increases in survival and quality of life, but at a population-level the effect on life expectancy is not well understood. Our objective was to compare changes in mortality and life expectancy among HIV-positive individuals on combination antiretroviral therapy. Methods The Antiretroviral Therapy Cohort Collaboration is a multinational collaboration of HIV cohort studies in Europe and North America. Patients were included in this analysis if they were aged 16 years or over and antiretroviral-naive when initiating combination therapy. We constructed abridged life tables to estimate life expectancies for individuals on combination antiretroviral therapy in 1996–99, 2000–02, and 2003–05, stratified by sex, baseline CD4 cell count, and history of injecting drug use. The average number of years remaining to be lived by those treated with combination antiretroviral therapy at 20 and 35 years of age was estimated. Potential years of life lost from 20 to 64 years of age and crude death rates were also calculated. Findings 18 587, 13 914, and 10 854 eligible patients initiated combination antiretroviral therapy in 1996–99, 2000–02, and 2003–05, respectively. 2056 (4·7%) deaths were observed during the study period, with crude death rates decreasing from 16·3 deaths per 1000 person-years in 1996–99 to 10·0 deaths per 1000 person-years in 2003–05. Potential years of life lost per 1000 person-years also decreased over the same time, from 366 to 189 years. Life expectancy at age 20 years increased from 36·1 (SE 0·6) years to 49·4 (0·5) years. Women had higher life expectancies than men. Patients with presumed transmission via injecting drug use had lower life expectancies than those from other transmission groups (32·6 [1·1] years vs 44·7 [0·3] years in 2003–05). Life expectancy was lower in patients with lower baseline CD4 counts than in those with higher baseline counts

  8. Risk of Cardiovascular Events Among Patients Initiating Efavirenz-Containing Versus Efavirenz-Free Antiretroviral Regimens

    PubMed Central

    Rosenblatt, Lisa; Farr, Amanda M.; Johnston, Stephen S.; Nkhoma, Ella T.

    2016-01-01

    Background. Efavirenz (EFV), an antiretroviral medication used to treat human immunodeficiency virus (HIV) infection, can increase lipid levels. Because hyperlipidemia is associated with increased risk for cardiovascular (CV) events, this study compared the risk of CV events in patients initiating EFV-containing vs EFV-free antiretroviral regimens. Methods. Antiretroviral-naive HIV-positive (HIV+) patients ages 18–64 were selected from commercial and Medicaid insurance claims databases. Patients with ≥1 claim for antiretroviral medications between January 1, 2007 and December 31, 2013 were classified into 2 cohorts: EFV-containing or EFV-free regimens. Patients were required to have 6 months of continuous enrollment before initiation, with no evidence of a CV event during this time. Patients were observed from initiation until the occurrence of a CV event, disenrollment, or study end. Cardiovascular events were identified through diagnosis or procedure codes for myocardial infarction, stroke, percutaneous coronary intervention, or coronary artery bypass graft. We calculated unadjusted incidence rates (IRs) and fit propensity-score-weighted Cox proportional hazards models. Results. There were 22 212 patients (11 978 EFV-containing and 10 234 EFV-free) identified in the commercial database and 7400 patients identified (2943 EFV-containing and 4457 EFV-free) in the Medicaid database. Cardiovascular events were rare (commercial IR = 396 per 100 000 person-years; Medicaid IR = 973 per 100 000 person-years). In propensity-score-weighted models, hazards of CV events were significantly lower for EFV-containing regimens in the commercial database (hazard ratio [HR] = 0.68; 95% confidence interval [CI], .49–.93) No significant difference was found in the Medicaid database (HR = 0.83; 95% CI, .58–1.19). Conclusions. This analysis found no evidence of increased risk of CV events among HIV+ patients initiating EFV-containing regimens. PMID:27186585

  9. Risk of Cardiovascular Events Among Patients Initiating Efavirenz-Containing Versus Efavirenz-Free Antiretroviral Regimens.

    PubMed

    Rosenblatt, Lisa; Farr, Amanda M; Johnston, Stephen S; Nkhoma, Ella T

    2016-03-01

    Background.  Efavirenz (EFV), an antiretroviral medication used to treat human immunodeficiency virus (HIV) infection, can increase lipid levels. Because hyperlipidemia is associated with increased risk for cardiovascular (CV) events, this study compared the risk of CV events in patients initiating EFV-containing vs EFV-free antiretroviral regimens. Methods.  Antiretroviral-naive HIV-positive (HIV+) patients ages 18-64 were selected from commercial and Medicaid insurance claims databases. Patients with ≥1 claim for antiretroviral medications between January 1, 2007 and December 31, 2013 were classified into 2 cohorts: EFV-containing or EFV-free regimens. Patients were required to have 6 months of continuous enrollment before initiation, with no evidence of a CV event during this time. Patients were observed from initiation until the occurrence of a CV event, disenrollment, or study end. Cardiovascular events were identified through diagnosis or procedure codes for myocardial infarction, stroke, percutaneous coronary intervention, or coronary artery bypass graft. We calculated unadjusted incidence rates (IRs) and fit propensity-score-weighted Cox proportional hazards models. Results.  There were 22 212 patients (11 978 EFV-containing and 10 234 EFV-free) identified in the commercial database and 7400 patients identified (2943 EFV-containing and 4457 EFV-free) in the Medicaid database. Cardiovascular events were rare (commercial IR = 396 per 100 000 person-years; Medicaid IR = 973 per 100 000 person-years). In propensity-score-weighted models, hazards of CV events were significantly lower for EFV-containing regimens in the commercial database (hazard ratio [HR] = 0.68; 95% confidence interval [CI], .49-.93) No significant difference was found in the Medicaid database (HR = 0.83; 95% CI, .58-1.19). Conclusions.  This analysis found no evidence of increased risk of CV events among HIV+ patients initiating EFV-containing regimens. PMID:27186585

  10. “Risk factors associated with virologic failure in HIV-infected patients receiving antiretroviral therapy at a public hospital in Peru”

    PubMed Central

    Jorge, Alave R; Jorge, Paz B; Elsa, Gonzalez L; Miguel, Campos S; Rodriguez, Martin; Willig, James; Juan, Echevarría Z

    2013-01-01

    OBJECTIVE To describe clinical and biological characteristics of subjects with virologic failure who participated in the sexually transmitted diseases HIV/AIDS National Program from a Peruvian public hospital. MATERIALS AND METHODS An exploratory descriptive study was performed with data from subjects older than 18 who started high activity antiretroviral therapy (HAART) between May 2004 and December 2009 and who had a viral load control after 24 weeks of HAART. Virologic failure was defined as a viral load value above 1000 copies/mL on follow up after 24 weeks on HAART. RESULTS Of 1 478 records of patients on HAART analized, the median age was 35 years [IQR, 29-41] and 69.6% were male. Also, virologic failure occurred in 24% and 3.7% died. Of subjects with virologic failure, 9.5% died. On multivariate analysis, age, history of antiretroviral use before starting HAART, change of antiretroviral therapy due to toxicity, opportunistic infections during HAART, level of CD4 + lymphocytes below 100 cells/ml at start of HAART, adherence and clinical stage were independently associated with virologic failure. In the group of patient with no history of antiretroviral use before starting HAART, age, opportunistic infections during HAART were associated with virologic failure. CONCLUSION This study identified factors associated with virologic failure. Further studies are needed to evaluate whether the use of these factors can help to identify prospectively patients at high risk of failure, and to design interventions aimed to reduce this risk. PMID:23450408

  11. Activity Cycles in Stars with Highly Active Chromospheres

    NASA Astrophysics Data System (ADS)

    Guinan, Edward F.

    The extended lifetime of the IUE satellite has provided an unique and unanticipated opportunity to examine the long-term evolution of magnetic activity on active chromospheric stars. We propose to obtain further IUE observations of the highly active RS CVn stars V711 Tauri, lambda Andromedae, II Pegasi, and UX Arietis in conjunction with groundbased optical and radio observations, and possibly ROSAT X-ray observations. In addition we would continue IUE observations of the unusual rapidly rotating early G giant, FK Comae, which, although not in the RS CVn category, shares a similarly high level of magnetic activity. These five stars have the most extensive IUE archival coverage for stars of their type and have almost continuous ground-based photometric coverage from about 1975 onward. We aim to trace the long-term development of magnetic activity on these stars: a detailed study of the UV emission-like fluxes will enable us to follow the variations in chromospheric and transition-region activity over an interval of 12-16 years. Optical observations reveal variations in photospheric (starspot) activity: the starspot regions are large (up to 30% of the stellar surface) and vary significantly with time. The main aim of the proposed research is to examine the relationship between chromospheric, transition-region, and photospheric active regions. Elucidation of the role of white-light faculae vis-a-vis spots in effecting stellar irradiance changes is also desirable.

  12. Decreased human immunodeficiency virus type 1 plasma viremia during antiretroviral therapy reflects downregulation of viral replication in lymphoid tissue.

    PubMed Central

    Cohen, O J; Pantaleo, G; Holodniy, M; Schnittman, S; Niu, M; Graziosi, C; Pavlakis, G N; Lalezari, J; Bartlett, J A; Steigbigel, R T

    1995-01-01

    Although several immunologic and virologic markers measured in peripheral blood are useful for predicting accelerated progression of human immunodeficiency virus (HIV) disease, their validity for evaluating the response to antiretroviral therapy and their ability to accurately reflect changes in lymphoid organs remain unclear. In the present study, changes in certain virologic markers have been analyzed in peripheral blood and lymphoid tissue during antiretroviral therapy. Sixteen HIV-infected individuals who were receiving antiretroviral therapy with zidovudine for > or = 6 months were randomly assigned either to continue on zidovudine alone or to add didanosine for 8 weeks. Lymph node biopsies were performed at baseline and after 8 weeks. Viral burden (i.e., HIV DNA copies per 10(6) mononuclear cells) and virus replication in mononuclear cells isolated from peripheral blood and lymph node and plasma viremia were determined by semiquantitative polymerase chain reaction assays. Virologic and immunologic markers remained unchanged in peripheral blood and lymph node of patients who continued on zidovudine alone. In contrast, a decrease in virus replication in lymph nodes was observed in four of six patients who added didanosine to their regimen, and this was associated with a decrease in plasma viremia. These results indicate that decreases in plasma viremia detected during antiretroviral therapy reflect downregulation of virus replication in lymphoid tissue. Images Fig. 1 Fig. 2 Fig. 3 PMID:7597072

  13. Integration of Antiretroviral Therapy with Tuberculosis Treatment

    PubMed Central

    Abdool Karim, Salim S.; Naidoo, Kogieleum; Grobler, Anneke; Padayatchi, Nesri; Baxter, Cheryl; Gray, Andrew L.; Gengiah, Tanuja; Gengiah, Santhanalakshmi; Naidoo, Anushka; Jithoo, Niraksha; Nair, Gonasagrie; El-Sadr, Wafaa M.; Friedland, Gerald; Abdool Karim, Quarraisha

    2011-01-01

    Background We previously reported that integrating antiretroviral therapy (ART) with tuberculosis treatment reduces mortality. However, optimal time to initiate ART during tuberculosis treatment remains contentious. Methods To address this, we conducted a 3-arm, open-label randomized controlled trial in South Africa in acid-fast bacilli smear positive patients (n=642) with HIV and CD4+ counts <500 cells/mm3. Findings on the early therapy group (ART initiated within 4 weeks of tuberculosis treatment initiation, n=214) and late therapy group (ART initiated within the first 4 weeks of the continuation phase of tuberculosis treatment, n=215) are presented here. Results Median CD4+ count and viral load at baseline was 150 cells/mm3 and 161000 copies/ml, being similar in both groups. Incidence rate of AIDS or death was 6.9 (18/259.4) and 7.8 (19/244.2) per 100 person-years in the early and late therapy groups respectively (Incidence Rate Ratio (IRR)=0.89; 95%Confidence Interval (95%CI): 0.44,1.79; P=0.73). However, in patients with CD4+ counts <50 cells/mm3, the incidence rates of AIDS or death were 8.5 (early) and 26.3 (late) per 100 person-years (IRR=0.32; 95%CI: 0.07,1.13; P=0.06). Immune reconstitution inflammatory syndrome (IRIS) incidence rates were 20.2 (early) and 7.7 (late) per 100 person-years (IRR=2.62; 95%CI: 1.48,4.82; P<0.001). Adverse events requiring antiretroviral drug switches occurred in 10 (early) and 1 (late) patients (P=0.006). Conclusions The benefits of AIDS-free survival balanced against the risks of IRIS and ART-related adverse events, support early ART initiation in patients with CD4+ counts <50 cells/mm3 and deferred ART initiation to the continuation phase of tuberculosis treatment when CD4+ counts are higher. PMID:22010915

  14. Antiretroviral therapy management and rationalisation of available resources.

    PubMed

    Cirioni, Oscar; Castelletti, Sefora; Ucciferri, Claudio; Falasca, Katia; Orsetti, Elena; Mazzocato, Susanna; Valeriani, Chiara; Di Campli, Francesco Maria; Barchiesi, Francesco; Vecchiet, Jacopo; Giacometti, Andrea

    2015-12-01

    The treatment of HIV disease has led to a new division of management costs by shifting most of the necessary resources from inpatient treatment to outpatient management. Among the initiatives aimed at rationalising the resources available, we compared efficacy, tolerability and pharmacoeconomic impact of different regimes of antiretroviral therapy (ART). The survey covered the first 50 patients, clinically stable and with good viro-immunological response, who switched in June 2012 from an ART based on the triple combination of tenofovir (TDF), emtricitabine (FTC) and a protease inhibitor boosted with ritonavir (PI/r) or a non-nucleoside reverse transcriptase inhibitor (NNRTI), to a treatment based on abacavir (ABC), lamivudine (3TC) and a PI/r or NNRTI. Of the 50 patients who operated the switch, 39 replaced a PI with nevirapine (NVP), for which the largest group of patients was treated with ABC + 3TC + NVP. On 31 May 2015, all patients completed the observation period of 96 weeks, with a mean observation period of 132 weeks and clinical-laboratory checks every four months. Laboratory analysis revealed an optimal maintenance of viral suppression and absolute and relative number of CD4 + lymphocytes and improving trend of creatinine, proteinuria, serum phosphate and bone alkaline phosphatase. There was a variable effect on lipids, with a drop in triglycerides associated with a modest increase in total cholesterol. Much of the HIV-positive population reporting to our hospitals (>50%) comprises individuals who have for years been in stable viraemic suppression, making a satisfactory immune recovery while in good overall clinical condition. This type of patient was the target of the present survey. At the end of 96 weeks of observation the new regimes were well tolerated and did not lead to viro-immunological or clinical deterioration. Pharmacoeconomic analysis showed better containment of the overall costs. No patient needed to be hospitalised during the observation

  15. Sex Differences in Antiretroviral Therapy Initiation in Pediatric HIV Infection.

    PubMed

    Mori, Masahiko; Adland, Emily; Paioni, Paolo; Swordy, Alice; Mori, Luisa; Laker, Leana; Muenchhoff, Maximilian; Matthews, Philippa C; Tudor-Williams, Gareth; Lavandier, Nora; van Zyl, Anriette; Hurst, Jacob; Walker, Bruce D; Ndung'u, Thumbi; Prendergast, Andrew; Goulder, Philip; Jooste, Pieter

    2015-01-01

    The incidence and severity of infections in childhood is typically greater in males. The basis for these observed sex differences is not well understood, and potentially may facilitate novel approaches to reducing disease from a range of conditions. We here investigated sex differences in HIV-infected children in relation to antiretroviral therapy (ART) initiation and post-treatment outcome. In a South African cohort of 2,101 HIV-infected children, we observed that absolute CD4+ count and CD4% were significantly higher in ART-naïve female, compared to age-matched male, HIV-infected children. Absolute CD4 count and CD4% were also significantly higher in HIV-uninfected female versus male neonates. We next showed that significantly more male than female children were initiated on ART (47% female); and children not meeting criteria to start ART by >5 yrs were more frequently female (59%; p<0.001). Among ART-treated children, immune reconstitution of CD4 T-cells was more rapid and more complete in female children, even after adjustment for pre-ART absolute CD4 count or CD4% (p=0.011, p=0.030, respectively). However, while ART was initiated as a result of meeting CD4 criteria less often in females (45%), ART initiation as a result of clinical disease in children whose CD4 counts were above treatment thresholds occurred more often in females (57%, p<0.001). The main sex difference in morbidity observed in children initiating ART above CD4 thresholds, above that of TB disease, was as a result of wasting and stunting observed in females with above-threshold CD4 counts (p=0.002). These findings suggest the possibility that optimal treatment of HIV-infected children might incorporate differential CD4 treatment thresholds for ART initiation according to sex. PMID:26151555

  16. Antiretroviral procurement and supply chain management.

    PubMed

    Ripin, David J; Jamieson, David; Meyers, Amy; Warty, Umesh; Dain, Mary; Khamsi, Cyril

    2014-01-01

    Procurement, the country-level process of ordering antiretrovirals (ARVs), and supply chain management, the mechanism by which they are delivered to health-care facilities, are critical processes required to move ARVs from manufacturers to patients. To provide a glimpse into the ARV procurement and supply chain, the following pages provide an overview of the primary stakeholders, principal operating models, and policies and regulations involved in ARV procurement. Also presented are key challenges that need to be addressed to ensure that the supply chain is not a barrier to the goal of universal coverage. This article will cover the steps necessary to order and distribute ARVs, including different models of delivery, key stakeholders involved, strategic considerations that vary depending on context and policies affecting them. The single drug examples given illustrate the complications inherent in fragmented supply and demand-driven models of procurement and supply chain management, and suggest tools for navigating these hurdles that will ultimately result in more secure and reliable ARV provision. Understanding the dynamics of ARV supply chain is important for the global health community, both to ensure full and efficient treatment of persons living with HIV as well as to inform the supply chain decisions for other public health products. PMID:25310145

  17. Cerebrospinal Fluid HIV Escape from Antiretroviral Therapy.

    PubMed

    Ferretti, Francesca; Gisslen, Magnus; Cinque, Paola; Price, Richard W

    2015-06-01

    CNS infection is a nearly constant facet of systemic CNS infection and is generally well controlled by suppressive systemic antiretroviral therapy (ART). However, there are instances when HIV can be detected in the cerebrospinal fluid (CSF) despite suppression of plasma viruses below the clinical limits of measurement. We review three types of CSF viral escape: asymptomatic, neuro-symptomatic, and secondary. The first, asymptomatic CSF escape, is seemingly benign and characterized by lack of discernable neurological deterioration or subsequent CNS disease progression. Neuro-symptomatic CSF escape is an uncommon, but important, entity characterized by new or progressive CNS disease that is critical to recognize clinically because of its management implications. Finally, secondary CSF escape, which may be even more uncommon, is defined by an increase of CSF HIV replication in association with a concomitant non-HIV infection, as a consequence of the local inflammatory response. Understanding these CSF escape settings not only is important for clinical diagnosis and management but also may provide insight into the CNS HIV reservoir. PMID:25860317

  18. Interactions of antiretroviral drugs with the SLC22A1 (OCT1) drug transporter

    PubMed Central

    Moss, Darren M.; Liptrott, Neill J.; Siccardi, Marco; Owen, Andrew

    2015-01-01

    The SLC22A1 influx transporter is expressed on the basolateral membrane of hepatocytes and is involved in the excretion of numerous cations. Inhibition of SLC22A1 by several antiretrovirals, such as the protease inhibitor darunavir, has not previously been determined. In order to better understand and predict drug-SLC22A1 interactions, a range of antiretrovirals were screened for SLC22A1-associated inhibition and transport. Stable SLC22A1-expressing KCL22 cells were produced previously by nucleofection. Control KCL22 cells were transfected with the empty vector pcDNA3.1. Accumulation of tetraethylammonium (5.5 μM, 30 min) was determined in SLC22A1-expressing and mock-transfected cells with and without 50 μM of SLC22A1 inhibitor prazosin, or 50 μM of each antiretroviral drug. SLC22A1 IC50 values for efavirenz, darunavir, and prazosin were determined. Cellular accumulation of efavirenz and darunavir was also assessed in SLC22A1-expressing KCL22 cells and reversibility of this accumulation was assessed using prazosin. Tetraethylammonium accumulation was higher in SLC22A1-expressing cells compared to mock-transfected cells (10.6 ± 0.8 μM vs. 0.3 ± 0.004 μM, p = 0.009) and was significantly reduced in SLC22A1-expressing cells when co-incubated with all antiretrovirals tested except atazanavir, lamivudine, tenofovir, zidovudine, and raltegravir. Particularly noticeable was the predominance of SLC22A1 inhibitors in the protease inhibitor and non-nucleoside reverse transcriptase inhibitor classes. Absolute SLC22A1 IC50 values for efavirenz, darunavir, and prazosin were 21.8, 46.2, and 2.8 μM, respectively. Efavirenz accumulation was higher in SLC22A1-expressing cells compared to mock-transfected cells (17% higher, p = 0.009) which was reversed using prazosin, whereas no difference was observed for darunavir (p = 0.86). These data inform the mechanistic basis for disposition, drug-drug interactions and pharmacogenetic candidate gene selection for antiretroviral

  19. High Activity States of Blazars 1055+018 and 0954+658

    NASA Astrophysics Data System (ADS)

    Jorstad, Svetlana

    2015-02-01

    The BLLac object 1055+018 shows a high activity at optical wavelengths. Our observations at the Perkins telescope (Flagstaff, AZ) on February 17/18, 2015 show that the source is ~ 2mag (R~14.7) brighter and highly polarized (P~24%) than it was during our previous optical observations in 2014 June (R~17.0 and P~5%).

  20. Th1/17 Polarization of CD4 T Cells Supports HIV-1 Persistence during Antiretroviral Therapy

    PubMed Central

    Sun, Hong; Kim, Dhohyung; Li, Xiaodong; Kiselinova, Maja; Ouyang, Zhengyu; Vandekerckhove, Linos; Shang, Hong; Rosenberg, Eric S.; Yu, Xu G.

    2015-01-01

    ABSTRACT The ability to persist long term in latently infected CD4 T cells represents a characteristic feature of HIV-1 infection and the predominant barrier to efforts aiming at viral eradication and cure. Yet, increasing evidence suggests that only small subsets of CD4 T cells with specific developmental and maturational profiles are able to effectively support HIV-1 long-term persistence. Here, we analyzed how the functional polarization of CD4 T cells shapes and structures the reservoirs of HIV-1-infected cells. We found that CD4 T cells enriched for a Th1/17 polarization had elevated susceptibilities to HIV-1 infection in ex vivo assays, harbored high levels of HIV-1 DNA in persons treated with antiretroviral therapy, and made a disproportionately increased contribution to the viral reservoir relative to their contribution to the CD4 T memory cell pool. Moreover, HIV-1 DNA levels in Th1/17 cells remained stable over many years of antiretroviral therapy, resulting in a progressively increasing contribution of these cells to the viral reservoir, and phylogenetic studies suggested preferential long-term persistence of identical viral sequences during prolonged antiretroviral treatment in this cell compartment. Together, these data suggest that Th1/17 CD4 T cells represent a preferred site for HIV-1 DNA long-term persistence in patients receiving antiretroviral therapy. IMPORTANCE Current antiretroviral therapy is very effective in suppressing active HIV-1 replication but does not fully eliminate virally infected cells. The ability of HIV-1 to persist long term despite suppressive antiretroviral combination therapy represents a perplexing aspect of HIV-1 disease pathogenesis, since most HIV-1 target cells are activated, short-lived CD4 T cells. This study suggests that CD4 T helper cells with Th1/17 polarization have a preferential role as a long-term reservoir for HIV-1 infection during antiretroviral therapy, possibly because these cells may imitate some of the

  1. Complexities of Gut Microbiome Dysbiosis in the Context of HIV Infection and Antiretroviral Therapy.

    PubMed

    Li, S X; Armstrong, Ajs; Neff, C P; Shaffer, M; Lozupone, C A; Palmer, B E

    2016-06-01

    Human immunodeficiency virus (HIV) infection is associated with an altered gut microbiome that is not consistently restored with effective antiretroviral therapy (ART). Interpretation of the specific microbiome changes observed during HIV infection is complicated by factors like population, sample type, and ART-each of which may have dramatic effects on gut bacteria. Understanding how these factors shape the microbiome during HIV infection (which we refer to as the HIV-associated microbiome) is critical for defining its role in HIV disease, and for developing therapies that restore gut health during infection. PMID:26940481

  2. Factors influencing global antiretroviral procurement prices

    PubMed Central

    2009-01-01

    Background Antiretroviral medicines (ARVs) are one of the most costly parts of HIV/AIDS treatment. Many countries are struggling to provide universal access to ARVs for all people living with HIV and AIDS. Although substantial price reductions of ARVs have occurred, especially between 2002 and 2008, achieving sustainable access for the next several decades remains a major challenge for most low- and middle-income countries. The objectives of the present study were twofold: first, to analyze global ARV prices between 2005 and 2008 and associated factors, particularly procurement methods and key donor policies on ARV procurement efficiency; second, to discuss the options of procurement processes and policies that should be considered when implementing or reforming access to ARV programs. Methods An ARV-medicines price-analysis was carried out using the Global Price Reporting Mechanism from the World Health Organization. For a selection of 12 ARVs, global median prices and price variation were calculated. Linear regression models for each ARV were used to identify factors that were associated with lower procurement prices. Logistic regression models were used to identify the characteristics of those countries which procure below the highest and lowest direct manufactured costs. Results Three key factors appear to have an influence on a country's ARV prices: (a) whether the product is generic or not; (b) the socioeconomic status of the country; (c) whether the country is a member of the Clinton HIV/AIDS Initiative. Factors which did not influence procurement below the highest direct manufactured costs were HIV prevalence, procurement volume, whether the country belongs to the least developed countries or a focus country of the United States President's Emergency Plan For AIDS Relief. Conclusion One of the principal mechanisms that can help to lower prices for ARV over the next several decades is increasing procurement efficiency. Benchmarking prices could be one useful

  3. Persistent HIV-1 replication during antiretroviral therapy

    PubMed Central

    Martinez-Picado, Javier; Deeks, Steven G.

    2016-01-01

    Purpose of review The present review will highlight some of the recent findings regarding the capacity of HIV-1 to replicate during antiretroviral therapy (ART). Recent findings Although ART is highly effective at inhibiting HIV replication, it is not curative. Several mechanisms contribute to HIV persistence during ART, including HIV latency, immune dysfunction, and perhaps persistent low-level spread of the virus to uninfected cells (replication). The success in curing HIV will depend on efficiently targeting these three aspects. The degree to which HIV replicates during ART remains controversial. Most studies have failed to find any evidence of HIV evolution in blood, even with samples collected over many years, although a recent very intensive study of three individuals suggested that the virus population does shift, at least during the first few months of therapy. Stronger but still not definitive evidence for replication comes from a series of studies in which standard regimens were intensified with an integration inhibitor, resulting in changes in episomal DNA (blood) and cell-associated RNA (tissue). Limited drug penetration within tissues and the presence of immune sanctuaries have been argued as potential mechanisms allowing HIV to spread during ART. Mathematical models suggest that HIV replication and evolution is possible even without the selection of fully drug-resistant variants. As persistent HIV replication could have clinical consequences and might limit the efficacy of curative interventions, determining if HIV replicates during ART and why, should remain a key focus of the HIV research community. Summary Residual viral replication likely persists in lymphoid tissues, at least in a subset of individuals. Abnormal levels of immune activation might contribute to sustain virus replication. PMID:27078619

  4. Antiretroviral Drug Resistance Among Children and Youth in the United States With Perinatal HIV.

    PubMed

    Van Dyke, Russell B; Patel, Kunjal; Kagan, Ron M; Karalius, Brad; Traite, Shirley; Meyer, William A; Tassiopoulos, Katherine K; Seage, George R; Seybolt, Lorna M; Burchett, Sandra; Hazra, Rohan

    2016-07-01

    Among 234 US youths with perinatal human immunodeficiency virus, 75% had antiretroviral resistance, substantially higher than that of the reference laboratory overall (36%-44%). Resistance to newer antiretrovirals and to all antiretrovirals in a class was uncommon. The only factor independently associated with future resistance was a higher peak viral load. PMID:27056398

  5. Comparative efficacy versus effectiveness of initial antiretroviral therapy in clinical trials versus routine care

    PubMed Central

    Routman, Justin S.; Willig, James H.; Westfall, Andrew O.; Abroms, Sarah R.; Varshney, Mohit; Adusumilli, Sunil; Allison, Jeroan J.; Savage, Karen G.; Saag, Michael S.; Mugavero, Michael J.

    2009-01-01

    Summary The generalizability of clinical trial findings (efficacy) to routine care (effectiveness) may be limited. The present study found similar first year virologic and CD4 outcomes among antiretroviral-naïve patients treated through routine care vs. those participating in clinical trials. Background The generalizability of clinical trial findings (efficacy) to routine care (effectiveness) may be limited due to study eligibility criteria and volunteer bias. While well chronicled in many conditions, the efficacy vs. effectiveness of antiretroviral therapy (ART) remains understudied. Methods A retrospective study of the UAB 1917 Clinic Cohort evaluated naïve patients starting ART between 1/1/00–12/31/06. Patients received ART through clinical trials or routine care. Multivariable logistic and linear regression models were fit to evaluate factors associated with virologic failure (VF=VL>50 copies/mL) and change from baseline CD4 count 6 and 12 months after ART initiation. Sensitivity analyses evaluated the impact of missing data on outcomes. Results Among 570 patients starting ART during the study period, 121 (21%) enrolled in clinical trials vs. 449 (79%) receiving ART via routine care. ART receipt through routine care was not associated with VF at either 6 (OR=1.00;95%CI=0.54–1.86) or 12 (OR=1.56;95%CI=0.80–3.05) months in primary analyses. No significant differences in CD4 count responses at 6 and 12 months were observed. Conclusions Though marked differences in efficacy vs. effectiveness have been observed in the therapeutic outcomes of other conditions, our analyses found no evidence of such divergence among our patients initiating antiretroviral therapy for HIV. PMID:20067423

  6. Effects of combination antiretroviral therapies on the risk for myocardial infarction among HIV patients

    PubMed Central

    Brouwer, Emily S.; Napravnik, Sonia; Eron, Joseph J; Stalzer, Brant; Floris-Moore, Michelle; Simpson, Ross J; Stürmer, Til

    2014-01-01

    Background Cohort studies have demonstrated greater risk of myocardial infarction (MI) associated with specific antiretroviral use, while meta-analyses of randomized controlled trials have not. These differences may be due to inherent biases in the observational study design or to the limited duration of randomized trials. We conducted a new-user, active-comparator cohort study emulating a randomized controlled trial comparing initiation of several antiretrovirals as part of combination antiretroviral therapy (cART) and MI. Methods We included North Carolina (NC) Medicaid beneficiaries infected with HIV between 2002 and 2008 who were previously untreated with cART. We compared hazard ratios (HRs) and 95% confidence intervals (CIs) of MI between abacavir and tenofovir recipients, and lopinavir-ritonavir or atazanavir recipients and non-nucleoside-reverse-transcriptase-inhibitor (NNRTI) recipients. We adjusted for confounding through inverse-probability-weighting methods. Results There were 3,481 NC Medicaid new cART recipients who contributed 6,399 person-years and experienced 38 MI events. Receiving abacavir compared with tenofovir as part of cART was associated with an increased rate of MI unadjusted (HR= 2.70 [95% CI= 1.24 - 5.91]; HR= 2.05 [0.72 - 5.86]). Point estimates also suggest a relationship between receipt of atazanavir or lopinavir-ritonavir compared with an NNRTI and MI, although, estimates were imprecise. Conclusions We found an increased rate of MI among patients initiating abacavir compared with tenofovir although the association was decreased after confounding adjustment. Without a very large prospective comparative clinical trial, a much larger observational study of patients initiating cART would be needed to better define this apparent association. PMID:24713880

  7. Adherence to antiretroviral therapy: are we doing enough?

    PubMed

    Read, T; Mijch, A; Fairley, C K

    2003-01-01

    Adherence to antiretroviral therapy is a powerful predictor of response to therapy. For optimal antiretroviral therapy response, individuals need to take more than 95% of their prescribed medication. The most widely used method for measuring adherence is self-report of the number of missed doses and this should be done at every clinic visit. There are several well-recognized predictors of poor adherence, such as illicit drug use, depression, limited knowledge or ambivalence about starting treatment. Adherence can be improved by addressing these issues or through other means such as pill boxes or electronic reminders. PMID:12752896

  8. Antiretroviral Therapy as HIV Prevention: Status and Prospects

    PubMed Central

    Venkatesh, Kartik K.

    2010-01-01

    As antiretroviral treatment of HIV infection has become increasingly accessible, attention has focused on whether these drugs can used for prevention because of increased tolerability of newer medications, decreased cost, and the limitations of other approaches. We review the status of antiretroviral HIV prevention, including chemoprophylaxis, as well as the effects of treatment of infected individuals on prevention. It is possible that the life-saving agents that have transformed the natural history of AIDS can be a critical component of HIV prevention efforts, but their ultimate role in affecting HIV transmission dynamics remains to be defined. PMID:20724682

  9. Comparative manufacture and cell-based delivery of antiretroviral nanoformulations

    PubMed Central

    Balkundi, Shantanu; Nowacek, Ari S; Veerubhotla, Ram S; Chen, Han; Martinez-Skinner, Andrea; Roy, Upal; Mosley, R Lee; Kanmogne, Georgette; Liu, Xinming; Kabanov, Alexander V; Bronich, Tatiana; McMillan, JoEllyn; Gendelman, Howard E

    2011-01-01

    Nanoformulations of crystalline indinavir, ritonavir, atazanavir, and efavirenz were manufactured by wet milling, homogenization or sonication with a variety of excipients. The chemical, biological, immune, virological, and toxicological properties of these formulations were compared using an established monocyte-derived macrophage scoring indicator system. Measurements of drug uptake, retention, release, and antiretroviral activity demonstrated differences amongst preparation methods. Interestingly, for drug cell targeting and antiretroviral responses the most significant difference among the particles was the drug itself. We posit that the choice of drug and formulation composition may ultimately affect clinical utility. PMID:22267924

  10. Tuberculosis treatment and risk of stavudine substitution in first line antiretroviral therapy

    PubMed Central

    Westreich, Daniel J.; Sanne, Ian; Maskew, Mhairi; Malope-Kgokong, Babatyi; Conradie, Francesca; Majuba, Pappie; Funk, Michele Jonsson; Kaufman, Jay S.; Van Rie, Annelies; MacPhail, Patrick

    2009-01-01

    Background Treatment for tuberculosis (TB) is common among individuals receiving stavudine-containing highly active antiretroviral therapy (HAART), but the effect of TB treatment on stavudine toxicity has received little attention. We estimated the effect of TB treatment on risk of stavudine substitution among individuals receiving first-line HAART. Methods We evaluated a cohort of 7,066 patients who initiated HAART between April 2004 and March 2007 in Johannesburg, South Africa. Three exposure categories were considered: ongoing TB treatment at HAART initiation; concurrent initiation of TB treatment and HAART; incident TB treatment after HAART initiation. The outcome was single-drug stavudine substitution. Adjusted hazard ratios (aHRs) were estimated using marginal structural models to control for confounding, loss to follow-up, and competing risks. Results Individuals with ongoing and concurrent TB treatment were at increased risk of stavudine substitution, irrespective of stavudine dose. For ongoing TB treatment, aHR was 3.18 (95% confidence interval [CI] 1.82-5.56) in the first two months of HAART, 2.51 (95% CI 1.77-3.54) in months 3-6, and 1.19 (95% CI 0.94-1.52) thereafter. For concurrent TB treatment, aHR was 6.60 (95% CI 3.03-14.37) in the first two months,1.88 (95% CI 0.87-4.09) in months 3-6, and 1.07 (95% CI 0.65-1.76) thereafter. There was no effect of incident TB on stavudine substitution risk. Conclusions Risk of stavudine substitution was increased among patients receiving TB treatment, especially soon after HAART initiation. In settings where alternative antiretroviral drugs are available, initiation of stavudine in patients receiving TB treatment may need to be reconsidered. PMID:19385733

  11. Early antiretroviral therapy initiation in west Africa has no adverse social consequences: a 24-month prospective study.

    PubMed

    Jean, Kévin; Niangoran, Serge; Danel, Christine; Moh, Raoul; Kouamé, Gérard Menan; Badjé, Anani; Gabillard, Delphine; Eholié, Serge; Dray-Spira, Rosemary; Lert, France; Anglaret, Xavier; Desgrées-Du-LoÛ, Annabel

    2016-06-19

    Based on social indicators collected within the TEMPRANO-ANRS12136 trial, we assessed the social consequences of early antiretroviral therapy (ART) initiation in west Africa. We did not observe any significant differences in the levels or the time trends of various social indicators, including union status, HIV disclosure and HIV-related discrimination, between early and deferred ART initiation. Early ART does not carry detectable adverse social consequences that could impair its clinical and preventive benefits. PMID:27003034

  12. Enhanced Antiretroviral Therapy in Rhesus Macaques Improves RT-SHIV Viral Decay Kinetics

    PubMed Central

    North, Thomas W.; Villalobos, Andradi; Hurwitz, Selwyn J.; Deere, Jesse D.; Higgins, Joanne; Chatterjee, Payel; Tao, Sijia; Kauffman, Robert C.; Luciw, Paul A.; Kohler, James J.

    2014-01-01

    Using an established nonhuman primate model, rhesus macaques were infected intravenously with a chimeric simian immunodeficiency virus (SIV) consisting of SIVmac239 with the human immunodeficiency virus type 1 (HIV-1) reverse transcriptase from clone HXBc2 (RT-SHIV). The impacts of two enhanced (four- and five-drug) highly active antiretroviral therapies (HAART) on early viral decay and rebound were determined. The four-drug combination consisted of an integrase inhibitor, L-870-812 (L-812), together with a three-drug regimen comprising emtricitabine [(−)-FTC], tenofovir (TFV), and efavirenz (EFV). The five-drug combination consisted of one analog for each of the four DNA precursors {using TFV, (−)-FTC, (−)-β-d-(2R,4R)-1,3-dioxolane-2,6-diaminopurine (amdoxovir [DAPD]), and zidovudine (AZT)}, together with EFV. A cohort treated with a three-drug combination of (−)-FTC, TFV, and EFV served as treated controls. Daily administration of a three-, four-, or five-drug combination of antiretroviral agents was initiated at week 6 or 8 after inoculation and continued up to week 50, followed by a rebound period. Plasma samples were collected routinely, and drug levels were monitored using liquid chromatography-tandem mass spectrometry (LC–MS-MS). Viral loads were monitored with a standard TaqMan quantitative reverse transcriptase PCR (qRT-PCR) assay. Comprehensive analyses of replication dynamics were performed. RT-SHIV infection in rhesus macaques produced typical viral infection kinetics, with untreated controls establishing persistent viral loads of >104 copies of RNA/ml. RT-SHIV loads at the start of treatment (V0) were similar in all treated cohorts (P > 0.5). All antiretroviral drug levels were measureable in plasma. The four-drug and five-drug combination regimens (enhanced HAART) improved suppression of the viral load (within 1 week; P < 0.01) and had overall greater potency (P < 0.02) than the three-drug regimen (HAART). Moreover, rebound viremia occurred

  13. Successful antiretroviral therapy by using unusual antiretroviral combinations in heavily pre-treated patients: two case reports.

    PubMed

    Taramasso, Lucia; Dentone, Chiara; Alessandrini, Anna; Bruzzone, Bianca; Icardi, Giancarlo; Garraffo, Rodolphe; De Macina, Ilaria; Viscoli, Claudio; Di Biagio, Antonio

    2015-10-01

    In the context of HIV-infected patients with several past antiretroviral therapies and multiple failures, it is possible to be faced with viruses resistant to all drug classes. We report on two HIV-1 infected patients in which the historical genotype showed mutations against all the major drug classes and in which viral suppression has been obtained by non-conventional antiretroviral therapy regimens, including the combination of darunavir at high dosage (800 mg bid), dolutegravir (50 mg bid) and a third agent, i.e. enfuvirtide in the first case and etravirine in the second one. PMID:25332227

  14. Effect of antiretroviral therapy on mucocutaneous manifestations among Human Immunodeficiency Virus-infected patients in a tertiary care centre in South India

    PubMed Central

    Prabhakaran, Nagendran; Jaisankar, Telanseri J.; Hamide, Abdoul; Malathi, Munisamy; Kumari, Rashmi; Thappa, Devinder Mohan

    2015-01-01

    Background: Human Immunodeficiency Virus (HIV) infection produces a wide range of infectious and noninfectious dermatoses which correlate with the degree of immunodeficiency. Since the introduction of highly active antiretroviral therapy (HAART), there has been a dramatic decrease in the incidence of HIV-associated dermatoses. However, HAART itself causes various cutaneous adverse drug reactions. Aims: To assess the various mucocutaneous manifestations in HIV-infected individuals and its association with CD4 count and to assess the effect of HAART on mucocutaneous manifestations. Materials and Methods: Of the 170 patients recruited, 110 patients were previously diagnosed with HIV and were on follow-up. The rest 60 patients were newly diagnosed cases at recruitment, and these patients were followed up every month for mucocutaneous manifestations for a period of 6 months. Results: Of the 170 patients screened, 69.41% patients had at least one mucocutaneous lesion at presentation. Fungal, viral, and bacterial infections were observed present in 17.6%, 10.6%, and 9.4% patients, respectively. There was a significant difference in the occurrence of candidal infections in the HAART versus non-HAART group (P = 0.0002). Candidiasis (P ≤ 0.0001) and human papillomavirus infection (P = 0.0475) occurred more commonly with CD4 count <200 cells/mm 3 . Among the noninfectious dermatoses, inflammatory dermatoses (17.6%) were more commonly observed at recruitment followed by adverse cutaneous drug reactions (16.5%) and neoplasms (5.3%). Conclusion: HAART has significantly altered the patterns of mucocutaneous manifestations. The prevalence of both infectious and inflammatory dermatoses has come down. However, there is an increase in the incidence of adverse cutaneous drug reactions. PMID:26692610

  15. Antiretroviral adherence and treatment outcomes among adult Ethiopian patients.

    PubMed

    Bezabhe, Woldesellassie M; Chalmers, Leanne; Bereznicki, Luke R; Gee, Peter; Peterson, Gregory M

    2016-08-01

    Developing appropriate strategies to sustain optimal medication adherence among the increasing number of HIV-positive patients taking antiretroviral therapy (ART) in sub-Saharan Africa is a major challenge. The objective of this study was to determine patient, regimen, disease, patient-provider, and healthcare-related factors associated with adherence with ART over a one-year period, and assess the impact of adherence on treatment outcomes. We performed a prospective, observational study among 246 patients who were initiated on ART in Ethiopia. Of 172 who completed follow-up, 130 (75.6%) had ≥95% adherence. In the multivariate analyses, a higher baseline BMI (OR, 1.2; 95% CI 1.0, 1.4) and use of reminder devices (OR, 9.1; 95% CI 2.0, 41.6) remained positively associated with adherence, while a higher HIV symptom and adverse drug reaction distress score was an independent negative predictor of adherence (OR, 0.90; 95% CI 0.9, 1.0) CD4 count increase was significantly higher in the adherent patients compared to non-adherent patients at 12 months (159 cells/µL [interquartile range (IQR), 72-324 cells/µL] vs. 132 cells/µL [IQR, 43-190 cells/µL]; p = 0.026). Our findings indicate that interventions aimed at improving adherence and thereby treatment outcomes in patients initiated on ART should promote the use of reminder devices, and monitor HIV symptoms and adverse reaction distress and nutritional status. PMID:26829232

  16. HIV-1 Group O Genotypes and Phenotypes: Relationship to Fitness and Susceptibility to Antiretroviral Drugs.

    PubMed

    Tebit, Denis M; Patel, Hamish; Ratcliff, Annette; Alessandri, Elodie; Liu, Joseph; Carpenter, Crystal; Plantier, Jean-Christophe; Arts, Eric J

    2016-07-01

    Despite only 30,000 group O HIV-1 infections, a similar genetic diversity is observed among the O subgroups H (head) and T (tail) (previously described as subtypes A, B) as in the 9 group M subtypes (A-K). Group O isolates bearing a cysteine at reverse transcriptase (RT) position 181, predominantly the H strains are intrinsically resistant to non-nucleoside reverse transcriptase inhibitors (NNRTIs). However, their susceptibility to newer antiretroviral drugs such as etravirine, maraviroc, raltegravir (RAL), and elvitegravir (EVG) remains relatively unknown. We tested a large collection of HIV-1 group O strains for their susceptibility to four classes of antiretroviral drugs namely nucleoside RT, non-nucleoside RT, integrase, and entry inhibitors knowing in advance the intrinsic resistance to NNRTIs. Drug target regions were sequenced to determine various polymorphisms and were phylogenetically analyzed. Replication kinetics and fitness assays were performed in U87-CD4(+)CCR5 and CXCR4 cells and peripheral blood mononuclear cells. With all antiretroviral drugs, group O HIV-1 showed higher variability in IC50 values than group M HIV-1. The mean IC50 values for entry and nucleoside reverse transcriptase inhibitor (NRTI) were similar for group O and M HIV-1 isolates. Despite similar susceptibility to maraviroc, the various phenotypic algorithms failed to predict CXCR4 usage based on the V3 Env sequences of group O HIV-1 isolates. Decreased sensitivity of group O HIV-1 to integrase or NNRTIs had no relation to replicative fitness. Group O HIV-1 isolates were 10-fold less sensitive to EVG inhibition than group M HIV-1. These findings suggest that in regions where HIV-1 group O is endemic, first line treatment regimens combining two NRTIs with RAL may provide more sustained virologic responses than the standard regimens involving an NNRTI or protease inhibitors. PMID:26861573

  17. Social meanings of adherence to antiretroviral therapy in Cambodia.

    PubMed

    Elliott, Julian; Phlong, Pisith; Saphon, Vonthanak; Kaldor, John; Mean, Chhivun; Maher, Lisa

    2011-06-01

    Global expansion of antiretroviral therapy (ART) programmes for people living with HIV is the largest public health undertaking to date. Antiretroviral therapy adherence drives individual and programme outcomes, yet little is known regarding the determinants of these behaviours. We investigated beliefs and practices associated with ART use in Cambodia. In-depth interviews were conducted during 2005 with 27 people living with HIV who were recruited using a theoretical sampling strategy and analysed in Khmer and English using an inductive approach to code data and identify themes. Limited access to ART generated a sense of ART as rare and precious, with access granted by doctors once patients proved themselves dependable. The social construction of ART use was strict, precise and modern with ritualistic preparation and dosing procedures. Experiences of life-saving efficacy in self and others built a deep sense of trust. For many, ART was simply equated to life. Antiretroviral therapy dosing was prioritized and supported by an ever-present sense of remembering, reminder devices and social networks. Healthcare workers set norms and provided various forms of adherence support. Antiretroviral therapy use in Cambodia is shaped by the relationship between individuals and social and healthcare networks that set, encourage and enforce precise norms of ART use. PMID:21516534

  18. Clinical Pharmacokinetics of Antiretroviral Drugs in Older Persons

    PubMed Central

    Schoen, John C.; Erlandson, Kristine Mace

    2013-01-01

    Introduction Combination antiretroviral therapy has enabled HIV infected persons to reach older ages in high numbers. Hepatic and renal changes that normally occur with advancing age occur earlier and with higher incidence in HIV-infected individuals. A limited number of prospective controlled studies have demonstrated small reductions (17% to 41%) in lopinavir, atazanavir, and lamivudine clearance in older versus younger adults. A much larger number of retrospective studies in adults (age range ~20 to 60 years), including all antiretroviral drugs, have evaluated age as a covariate for pharmacokinetics. Most studies did not detect substantial associations between drug exposures and age. Areas Covered This review summarizes antiretroviral drug pharmacokinetics in older persons. The authors review articles from PubMed (search terms: elderly, antiretroviral, pharmacokinetics) in addition to the bibliographies of those selected. Expert Opinion The evidence to date does not support major pharmacokinetic changes in adults between ~20 and 60 years of age. However, additional prospective, well-controlled studies are needed in more persons > 60 years, including those with frailty and comorbidities, with assessment of unbound drug clearance, and incorporation of adherence, pharmacogenetics, and concomitant medications. Until then, guidelines for drug-drug interactions and dosing in renal and hepatic impairment should be followed in older HIV infected individuals. PMID:23514375

  19. Generic antiretroviral drugs and HIV care: An economic review.

    PubMed

    Yazdanpanah, Y; Schwarzinger, M

    2016-03-01

    The cost of HIV care in European countries is high. Direct medical costs, in France, have been estimated at 500,000 Euros per patient's lifetime (20,000 Euros/year/patient). Overall, 73% of these costs are related to antiretroviral treatments. In the current financial crisis context, some European countries are beginning to make economic decisions on the drugs to be used. These approaches are likely to become more frequent. It is obviously essential to prescribe the most effective, appropriate, best tolerated, and easy-to-use antiretroviral treatments to patients. However, while taking the above into consideration, and if various treatment options or combinations are available, cost should also be considered in the treatment choice. One may thus reflect on the use of generic antiretroviral agents as they have just been launched in France. We aimed to review the cost and cost-effectiveness of generic antiretroviral drugs and to review treatment strategies other than generic drugs that could help reduce HIV-related costs. HIV clinicians should consider treatment costs to avoid any future coercive measures. PMID:26905394

  20. Clinically Relevant Pharmacokinetic Herb-drug Interactions in Antiretroviral Therapy.

    PubMed

    Fasinu, Pius S; Gurley, Bill J; Walker, Larry A

    2015-01-01

    For healthcare professionals, the volume of literature available on herb-drug interactions often makes it difficult to separate experimental/potential interactions from those deemed clinically relevant. There is a need for concise and conclusive information to guide pharmacotherapy in HIV/AIDS. In this review, the bases for potential interaction of medicinal herbs with specific antiretroviral drugs are presented, and several botanicals are discussed for which clinically relevant interactions in humans are established. Such studies have provided, in most cases, sufficient ground to warrant the avoidance of concurrent administration of antiretroviral (ARVs) drugs with St John's wort (Hypericum perforatum), black pepper (Piper species) and grapefruit juice. Other botanicals that require caution in the use with antiretrovirals include African potato (Hypoxis hemerocallidea), ginkgo (Ginkgo biloba), ginseng (Panax species), garlic (Allium sativum), goldenseal (Hydrastis canadensis) and kava kava (Piper methysticum). The knowledge of clinically significant herb-drug interaction will be important in order to avoid herb-induced risk of sub-therapeutic exposure to ARVs (which can lead to viral resistance) or the precipitation of toxicity (which may lead to poor compliance and/or discontinuation of antiretroviral therapy). PMID:26526838

  1. Dynamics of the HIV infection under antiretroviral therapy: A cellular automata approach

    NASA Astrophysics Data System (ADS)

    González, Ramón E. R.; Coutinho, Sérgio; Zorzenon dos Santos, Rita Maria; de Figueirêdo, Pedro Hugo

    2013-10-01

    The dynamics of human immunodeficiency virus infection under antiretroviral therapy is investigated using a cellular automata model where the effectiveness of each drug is self-adjusted by the concentration of CD4+ T infected cells present at each time step. The effectiveness of the drugs and the infected cell concentration at the beginning of treatment are the control parameters of the cell population’s dynamics during therapy. The model allows describing processes of mono and combined therapies. The dynamics that emerges from this model when considering combined antiretroviral therapies reproduces with fair qualitative agreement the phases and different time scales of the process. As observed in clinical data, the results reproduce the significant decrease in the population of infected cells and a concomitant increase of the population of healthy cells in a short timescale (weeks) after the initiation of treatment. Over long time scales, early treatment with potent drugs may lead to undetectable levels of infection. For late treatment or treatments starting with a low density of CD4+ T healthy cells it was observed that the treatment may lead to a steady state in which the T cell counts are above the threshold associated with the onset of AIDS. The results obtained are validated through comparison to available clinical trial data.

  2. Cholelithiasis and Nephrolithiasis in HIV-Positive Patients in the Era of Combination Antiretroviral Therapy

    PubMed Central

    Lin, Kuan-Yin; Liao, Sih-Han; Liu, Wen-Chun; Cheng, Aristine; Lin, Shu-Wen; Chang, Sui-Yuan; Tsai, Mao-Song; Kuo, Ching-Hua; Wu, Mon-Ro; Wang, Hsiu-Po; Hung, Chien-Ching; Chang, Shan-Chwen

    2015-01-01

    -boosted atazanavir and incident cholelithiasis was also found (AOR, per 1-year exposure, 1.49; 95% CI, 1.05–2.10). The associated factors with incident nephrolithiasis were hyperlipidemia (AOR, 3.97; 95% CI, 1.32–11.93), hepatitis B or C coinfection (AOR, 3.41; 95% CI, 1.09–10.62), and exposure to abacavir (AOR, 12.01; 95% CI, 1.54–93.54). Of 180 patients who underwent therapeutic drug monitoring of plasma atazanavir concentrations and pharmacogenetic investigations, we found that the atazanavir concentrations and UGT 1A1*28 and MDR1 G2677T/A polymorphisms were not statistically significantly associated with incident cholelithiasis and nephrolithiasis. Conclusions In HIV-positive patients in the era of combination antiretroviral therapy, a high prevalence of cholelithiasis and nephrolithiasis was observed, and exposure to ritonavir-boosted atazanavir for >2 years was associated with incident cholelithiasis. PMID:26360703

  3. Socio-economic impact of antiretroviral treatment in HIV patients. An economic review of cost savings after introduction of HAART.

    PubMed

    Gonzalo, Teresa; García Goñi, Manuel; Muñoz-Fernández, María Angeles

    2009-01-01

    Star celebrities such as Rock Hudson, Freddie Mercury, Magic Johnson, and Isaac Asimov have unfortunately something in common: they were all victims of the HIV global pandemic. Since then HIV infection has become considered a pandemic disease, and it is regarded as a priority in healthcare worldwide. It is ranked as the first cause of death among young people in industrialized countries, and it is recognized as a public healthcare problem due to its human, social, mass media, and economic impact. Incorporation of new and highly active antiretroviral treatment, available since 1996 for HIV/AIDS treatment, has provoked a radical change in the disease pattern, as well as in the impact on patient survival and quality of life. The pharmaceutical industry's contribution, based on the research for more active new drugs, has been pivotal. Mortality rates have decreased significantly in 20 years by 50% and now AIDS is considered a chronic and controlled disease. In this review we have studied the impact of HAART treatment on infected patients, allowing them to maintain their status as active workers and the decreased absenteeism from work derived from this, contributing ultimately to overall social wealth and, thus, to economic growth. Furthermore, an analysis of the impact on healthcare costs, quality of life per year, life per year gained, cost economic savings and cost opportunity among other parameters has shown that society and governments are gaining major benefits from the inclusion of antiretroviral therapies in HIV/AIDS patients. PMID:19529748

  4. Pharmacokinetic and pharmacodynamic drug interactions between antiretrovirals and oral contraceptives.

    PubMed

    Tittle, Victoria; Bull, Lauren; Boffito, Marta; Nwokolo, Nneka

    2015-01-01

    More than 50 % of women living with HIV in low- and middle-income countries are of reproductive age, but there are limitations to the administration of oral contraception for HIV-infected women receiving antiretroviral therapy due to drug-drug interactions caused by metabolism via the cytochrome P450 isoenzymes and glucuronidation. However, with the development of newer antiretrovirals that use alternative metabolic pathways, options for contraception in HIV-positive women are increasing. This paper aims to review the literature on the pharmacokinetics and pharmacodynamics of oral hormonal contraceptives when given with antiretroviral agents, including those currently used in developed countries, older ones that might still be used in salvage regimens, or those used in resource-limited settings, as well as newer drugs. Nucleos(t)ide reverse transcriptase inhibitors (NRTIs), the usual backbone to most combined antiretroviral treatments (cARTs) are characterised by a low potential for drug-drug interactions with oral contraceptives. On the other hand non-NRTIs (NNRTIs) and protease inhibitors (PIs) may interact with oral contraceptives. Of the NNRTIs, efavirenz and nevirapine have been demonstrated to cause drug-drug interactions; however, etravirine and rilpivirine appear safe to use without dose adjustment. PIs boosted with ritonavir are not recommended to be used with oral contraceptives, with the exception of boosted atazanavir which should be used with doses of at least 35 µg of estrogen. Maraviroc, an entry inhibitor, is safe for co-administration with oral contraceptives, as are the integrase inhibitors (INIs) raltegravir and dolutegravir. However, the INI elvitegravir, which is given in combination with cobicistat, requires a dose of estrogen of at least 30 µg. Despite the growing evidence in this field, data are still lacking in terms of large cohort studies, randomised trials and correlations to real clinical outcomes, such as pregnancy rates, in women

  5. Low-Frequency Drug Resistance in HIV-Infected Ugandans on Antiretroviral Treatment Is Associated with Regimen Failure.

    PubMed

    Kyeyune, Fred; Gibson, Richard M; Nankya, Immaculate; Venner, Colin; Metha, Samar; Akao, Juliet; Ndashimye, Emmanuel; Kityo, Cissy M; Salata, Robert A; Mugyenyi, Peter; Arts, Eric J; Quiñones-Mateu, Miguel E

    2016-06-01

    Most patients failing antiretroviral treatment in Uganda continue to fail their treatment regimen even if a dominant drug-resistant HIV-1 genotype is not detected. In a recent retrospective study, we observed that approximately 30% of HIV-infected individuals in the Joint Clinical Research Centre (Kampala, Uganda) experienced virologic failure with a susceptible HIV-1 genotype based on standard Sanger sequencing. Selection of minority drug-resistant HIV-1 variants (not detectable by Sanger sequencing) under antiretroviral therapy pressure can lead to a shift in the viral quasispecies distribution, becoming dominant members of the virus population and eventually causing treatment failure. Here, we used a novel HIV-1 genotyping assay based on deep sequencing (DeepGen) to quantify low-level drug-resistant HIV-1 variants in 33 patients failing a first-line antiretroviral treatment regimen in the absence of drug-resistant mutations, as screened by standard population-based Sanger sequencing. Using this sensitive assay, we observed that 64% (21/33) of these individuals had low-frequency (or minority) drug-resistant variants in the intrapatient HIV-1 population, which correlated with treatment failure. Moreover, the presence of these minority HIV-1 variants was associated with higher intrapatient HIV-1 diversity, suggesting a dynamic selection or fading of drug-resistant HIV-1 variants from the viral quasispecies in the presence or absence of drug pressure, respectively. This study identified low-frequency HIV drug resistance mutations by deep sequencing in Ugandan patients failing antiretroviral treatment but lacking dominant drug resistance mutations as determined by Sanger sequencing methods. We showed that these low-abundance drug-resistant viruses could have significant consequences for clinical outcomes, especially if treatment is not modified based on a susceptible HIV-1 genotype by Sanger sequencing. Therefore, we propose to make clinical decisions using more

  6. Cliniconeuropathologic correlates of human immunodeficiency virus in the era of antiretroviral therapy.

    PubMed

    Everall, I; Vaida, F; Khanlou, N; Lazzaretto, D; Achim, C; Letendre, S; Moore, D; Ellis, R; Cherner, M; Gelman, B; Morgello, S; Singer, E; Grant, I; Masliah, E

    2009-09-01

    The objective of this study was to examine the spectrum of human immunodeficiency virus (HIV) brain pathology and its clinical correlates in the antiretroviral era. We carried out a cross-sectional survey, analyzing prospective clinical and neuropathological data collected by the National NeuroAIDS Tissue Consortium (NNTC), comprising 589 brain samples from individuals with advanced HIV disease collected from 1999 onwards. We assessed gender, ethnicity/race, mode of transmission, age, year of death, nadir CD4, plasma viral load, last antiretroviral regimen, presence of parenchymal HIV brain pathology, HIV-associated neurocognitive disorder, and major depressive disorder. We compared cohort demographic variables with Centers for Disease Control and Prevention US HIV/AIDS statistics and examined associations of parenchymal HIV brain pathology with demographic, clinical, and HIV disease factors. With regard to Centers for Disease Control and Prevention US data, the NNTC was similar in age distribution, but had fewer females and African Americans and more Hispanics and men who have sex with men. Only 22% of the brains examined were neuropathologically normal. Opportunistic infections occurred in 1% to 5% of the cohort. Parenchymal HIV brain pathology was observed in 17.5% of the cohort and was associated with nadir CD4 and plasma viral load. Brains without parenchymal HIV brain pathology often had other noninfectious findings or minimal nondiagnostic abnormalities that were associated with HIV-associated neurocognitive disorder. Clinically, 60% of the cohort reported a lifetime episode of major depressive disorder and 88% had a HIV-associated neurocognitive disorder. No pathological finding correlated with major depressive disorder. Both antiretroviral treatment regimen and elevated plasma HIV viral load were associated with presence of parenchymal HIV brain pathology; however, multivariate analyses suggest a stronger association with plasma viral load. The frequency

  7. Impact of antiretroviral therapy on lipid metabolism of human immunodeficiency virus-infected patients: Old and new drugs

    PubMed Central

    da Cunha, Joel; Maselli, Luciana Morganti Ferreira; Stern, Ana Carolina Bassi; Spada, Celso; Bydlowski, Sérgio Paulo

    2015-01-01

    For human immunodeficiency virus (HIV)-infected patients, the 1990s were marked by the introduction of highly active antiretroviral therapy (HAART) representing a new perspective of life for these patients. The use of HAART was shown to effectively suppress the replication of HIV-1 and dramatically reduce mortality and morbidity, which led to a better and longer quality of life for HIV-1-infected patients. Apart from the substantial benefits that result from the use of various HAART regimens, laboratory and clinical experience has shown that HAART can induce severe and considerable adverse effects related to metabolic complications of lipid metabolism, characterized by signs of lipodystrophy, insulin resistance, central adiposity, dyslipidemia, increased risk of cardiovascular disease and even an increased risk of atherosclerosis. New drugs are being studied, new therapeutic strategies are being implemented, and the use of statins, fibrates, and inhibitors of intestinal cholesterol absorption have been effective alternatives. Changes in diet and lifestyle have also shown satisfactory results. PMID:25964872

  8. Transcriptional Changes in CD8+ T Cells During Antiretroviral Therapy Intensified With Raltegravir

    PubMed Central

    Ouyang, Zhengyu; Buzon, Maria J.; Zheng, Lu; Sun, Hong; Yu, Xu G.; Bosch, Ronald J.; Mellors, John W.; Eron, Joseph J.; Gandhi, Rajesh T.; Lichterfeld, Mathias

    2015-01-01

    Background. Intensification of antiretroviral therapy with raltegravir does not affect levels of residual human immunodeficiency virus (HIV)-1 viremia, but it has led to increased levels of episomal HIV-1 DNA in some patients, suggesting antiviral activity against otherwise unresponsive components of the viral reservoir. Effects of raltegravir on host cells remain less well understood. Methods. We used comprehensive and unbiased microarray-based transcriptional profiling to analyze gene expression changes in CD8+ T cells from participants in a randomized clinical trial (AIDS Clinical Trials Group [ACTG] A5244) comparing raltegravir-intensified to nonintensified antiretroviral therapy. Results. Although raltegravir intensification failed to induce statistically significant changes in HIV-1 DNA or residual plasma viremia, we observed significant increases in the expression intensity of 121 host gene transcripts. In functional annotations of these transcripts, we found that they were mainly involved in glucose and carbohydrate metabolism, immune regulation, control of cell proliferation, and tumor suppression. Two of the raltegravir-responsive gene transcripts were statistically correlated with levels of residual HIV-1 RNA, but none of the remaining 119 transcripts were associated with immunologic or virologic characteristics of the study patients. Conclusions. Together, these findings demonstrate that raltegravir intensification can induce previously unrecognized, statistically significant gene expression changes in host CD8+ T lymphocytes. PMID:26380343

  9. Sequencing paediatric antiretroviral therapy in the context of a public health approach

    PubMed Central

    Boerma, Ragna S; Boender, T Sonia; van Hensbroek, Michael Boele; Rinke de Wit, Tobias F; Sigaloff, Kim CE

    2015-01-01

    Introduction As access to prevention of mother-to-child transmission (PMTCT) efforts has increased, the total number of children being born with HIV has significantly decreased. However, those children who do become infected after PMTCT failure are at particular risk of HIV drug resistance, selected by exposure to maternal or paediatric antiretroviral drugs used before, during or after birth. As a consequence, the response to antiretroviral therapy (ART) in these children may be compromised, particularly when non-nucleoside reverse transcriptase inhibitors (NNRTIs) are used as part of the first-line regimen. We review evidence guiding choices of first- and second-line ART. Discussion Children generally respond relatively well to ART. Clinical trials show the superiority of protease inhibitor (PI)- over NNRTI-based treatment in young children, but observational reports of NNRTI-containing regimens are usually favourable as well. This is reassuring as national guidelines often still recommend the use of NNRTI-based treatment for PMTCT-unexposed young children, due to the higher costs of PIs. After failure of NNRTI-based, first-line treatment, the rate of acquired drug resistance is high, but HIV may well be suppressed by PIs in second-line ART. By contrast, there are currently no adequate alternatives in resource-limited settings (RLS) for children failing either first- or second-line, PI-containing regimens. Conclusions Affordable salvage treatment options for children in RLS are urgently needed. PMID:26639116

  10. Antiretroviral agents used by HIV-uninfected persons for prevention: pre- and postexposure prophylaxis.

    PubMed

    Grant, Robert M

    2010-05-15

    Prophylactic use of antimicrobial agents and microbicides has been proven for many infections, including surgical, gastrointestinal, upper respiratory, and meningococcal infections. Antiretroviral therapy for pregnant women prevents mother-to-child transmission of human immunodeficiency virus (HIV), which has become rare in settings where access to therapy is widespread. Postexposure prophylaxis after needlestick injury or significant sexual exposure is recommended on the basis of animal studies and case-control observational studies, although use of these interventions is limited to those who recognize exposure, have access, and have the power to use the interventions. Clinical trials are evaluating whether regular or preexposure use of antiretroviral therapy provides additional protection for persons at high risk of infection who are also offered standard prevention care, including HIV testing, counseling, condoms, and management of sexually transmitted infections. Trials are evaluating topical or oral use. Concerns have arisen with regard to optimal dosing strategies, costs, access, drug resistance, risk behavior, and the role of communities. Future implementation, if warranted, will be guided by the results of clinical trials in progress and engagement of communities exposed to HIV. PMID:20397962

  11. Therapeutic Immunization In HIV Infected Ugandans Receiving Stable Antiretroviral Treatment: A Phase I Safety Study4

    PubMed Central

    Kityo, Cissy; Bousheri, Stephanie; Akao, Juliette; Ssali, Francis; Byaruhanga, Rose; Ssewanyana, Isaac; Muloma, Prossy; Myalo, Sula; Magala, Rose; Lu, Yichen; Mugyenyi, Peter; Cao, Huyen

    2011-01-01

    Therapeutic immunizations in HIV infection may boost immunity during antiretroviral treatment. We report on the first therapeutic vaccine trial in Uganda, Africa. This open label Phase I trial was designed to assess the safety, tolerability and immunogenicity of a therapeutic HIV-1 vaccine candidate. Thirty HIV positive volunteers receiving a stable regimen of antiretroviral therapy with CD4 counts > 400 were recruited for the safety evaluation of LFn-p24C, a detoxified anthrax-derived polypeptide fused to the subtype C HIV gag protein p24. The vaccine was well tolerated and HIV RNA levels remained undetectable following three immunizations. CD4 counts in vaccine recipients were significantly higher compared to the control individuals after 12 months. HIV-specific responses were associated with higher gain in CD4 counts following LFn-p24C immunizations. Volunteers were subsequently asked to undergo a 30-day period of observed treatment interruption. 8/24 (30%) individuals showed no evidence of viral rebound during treatment interruption. All demonstrated prompt suppression of viral load following resumption of ART. Our data demonstrates the safety of LFn-p24C and suggests that adjunct therapeutic immunization may benefit select individuals in further boosting an immune response. PMID:21211581

  12. Antiretroviral Therapy for the Prevention of HIV-1 Transmission.

    PubMed

    Cohen, Myron S; Chen, Ying Q; McCauley, Marybeth; Gamble, Theresa; Hosseinipour, Mina C; Kumarasamy, Nagalingeswaran; Hakim, James G; Kumwenda, Johnstone; Grinsztejn, Beatriz; Pilotto, Jose H S; Godbole, Sheela V; Chariyalertsak, Suwat; Santos, Breno R; Mayer, Kenneth H; Hoffman, Irving F; Eshleman, Susan H; Piwowar-Manning, Estelle; Cottle, Leslie; Zhang, Xinyi C; Makhema, Joseph; Mills, Lisa A; Panchia, Ravindre; Faesen, Sharlaa; Eron, Joseph; Gallant, Joel; Havlir, Diane; Swindells, Susan; Elharrar, Vanessa; Burns, David; Taha, Taha E; Nielsen-Saines, Karin; Celentano, David D; Essex, Max; Hudelson, Sarah E; Redd, Andrew D; Fleming, Thomas R

    2016-09-01

    Background An interim analysis of data from the HIV Prevention Trials Network (HPTN) 052 trial showed that antiretroviral therapy (ART) prevented more than 96% of genetically linked infections caused by human immunodeficiency virus type 1 (HIV-1) in serodiscordant couples. ART was then offered to all patients with HIV-1 infection (index participants). The study included more than 5 years of follow-up to assess the durability of such therapy for the prevention of HIV-1 transmission. Methods We randomly assigned 1763 index participants to receive either early or delayed ART. In the early-ART group, 886 participants started therapy at enrollment (CD4+ count, 350 to 550 cells per cubic millimeter). In the delayed-ART group, 877 participants started therapy after two consecutive CD4+ counts fell below 250 cells per cubic millimeter or if an illness indicative of the acquired immunodeficiency syndrome (i.e., an AIDS-defining illness) developed. The primary study end point was the diagnosis of genetically linked HIV-1 infection in the previously HIV-1-negative partner in an intention-to-treat analysis. Results Index participants were followed for 10,031 person-years; partners were followed for 8509 person-years. Among partners, 78 HIV-1 infections were observed during the trial (annual incidence, 0.9%; 95% confidence interval [CI], 0.7 to 1.1). Viral-linkage status was determined for 72 (92%) of the partner infections. Of these infections, 46 were linked (3 in the early-ART group and 43 in the delayed-ART group; incidence, 0.5%; 95% CI, 0.4 to 0.7) and 26 were unlinked (14 in the early-ART group and 12 in the delayed-ART group; incidence, 0.3%; 95% CI, 0.2 to 0.4). Early ART was associated with a 93% lower risk of linked partner infection than was delayed ART (hazard ratio, 0.07; 95% CI, 0.02 to 0.22). No linked infections were observed when HIV-1 infection was stably suppressed by ART in the index participant. Conclusions The early initiation of ART led to a sustained

  13. Nearly Full Employment Recovery Among South African HIV Patients On Antiretroviral Therapy: Evidence From A Large Population Cohort

    PubMed Central

    Bor, Jacob; Tanser, Frank; Newell, Marie-Louise; Bärnighausen, Till

    2013-01-01

    Antiretroviral therapy for HIV may have important economic benefits for patients and their households. We quantified the impact of HIV treatment on employment status among HIV patients in rural South Africa who were enrolled in a public-sector HIV treatment program supported by the U.S. President’s Emergency Plan for AIDS Relief. We linked clinical data from more than 2000 patients in the treatment program with ten years of longitudinal socioeconomic data from a complete community-based population cohort of over 30,000 adults residing in the clinical catchment area. We estimated the employment effects of HIV treatment in fixed effects regressions. Four years after the initiation of antiretroviral therapy, employment among HIV patients had recovered to about 90 percent of baseline rates observed in the same patients three to five years before they started treatment. Many patients initiated treatment early enough that they were able to avoid any loss of employment due to HIV. These results represent the first estimates of employment recovery among HIV patients in a general population, relative to the employment levels that these patients had prior to job-threatening illness and the decision to seek care. We find large economic benefits to HIV treatment. For some patients, further gains could be obtained from initiating antiretroviral therapy earlier, prior to HIV-related job loss. PMID:22778335

  14. Challenges and potential barriers to the uptake of antiretroviral-based prevention in Asia and the Pacific region.

    PubMed

    Lo, Ying-Ru; Kato, Masaya; Phanuphak, Nittaya; Fujita, Masami; Duc, Duong Bui; Sopheap, Seng; Pendse, Razia; Yu, Dongbao; Wu, Zunyou; Chariyalertsak, Suwat

    2014-07-01

    Evidence has emerged over the past few years on the effectiveness of antiretroviral-based prevention technologies to prevent (i) HIV transmission while decreasing morbidity and mortality in HIV-infected persons, and (ii) HIV acquisition in HIV-uninfected individuals through pre-exposure prophylaxis (PrEP). Only few of the planned studies on treatment as prevention (TasP) are conducted in Asia. TasP might be more feasible and effective in concentrated rather than in generalised epidemics, as resources for HIV testing and antiretroviral treatment could focus on confined and much smaller populations than in the generalised epidemics observed in sub-Saharan Africa. Several countries such as Cambodia, China, Thailand and Vietnam, are now paving the way to success. Similar challenges arise for both TasP and PrEP. However, the operational issues for PrEP are amplified by the need for frequent retesting and ensuring adherence. This paper describes challenges for the implementation of antiretroviral-based prevention and makes the case that TasP and PrEP implementation research in Asia is much needed to provide insights into the feasibility of these interventions in populations where firm evidence of 'real world' effectiveness is still lacking. PMID:25007911

  15. Predictors of new-onset distal neuropathic pain in HIV-infected individuals in the era of combination antiretroviral therapy.

    PubMed

    Malvar, Jemily; Vaida, Florin; Sanders, Chelsea Fitzsimons; Atkinson, J Hampton; Bohannon, William; Keltner, John; Robinson-Papp, Jessica; Simpson, David M; Marra, Christina M; Clifford, David B; Gelman, Benjamin; Fan, Juanjuan; Grant, Igor; Ellis, Ronald J

    2015-04-01

    Despite modern combination antiretroviral therapy, distal neuropathic pain (DNP) continues to affect many individuals with HIV infection. We evaluated risk factors for new-onset DNP in the CNS Antiretroviral Therapy Effects Research (CHARTER) study, an observational cohort. Standardized, semiannual clinical evaluations were administered at 6 US sites. Distal neuropathic pain was defined by using a clinician-administered instrument standardized across sites. All participants analyzed were free of DNP at study entry. New-onset DNP was recorded at the first follow-up visit at which it was reported. Mixed-effects logistic regression was used to evaluate potential predictors including HIV disease and treatment factors, demographics, medical comorbidities, and neuropsychiatric factors. Among 493 participants, 131 (27%) reported new DNP over 2306 visits during a median follow-up of 24 months (interquartile range 12-42). In multivariable regression, after adjusting for other covariates, significant entry predictors of new DNP were older age, female sex, current and past antiretroviral treatment, lack of virologic suppression, and lifetime history of opioid use disorder. During follow-up, more severe depression symptoms conferred a significantly elevated risk. The associations with opioid use disorders and depression reinforce the view that the clinical expression of neuropathic pain with peripheral nerve disease is strongly influenced by neuropsychiatric factors. Delineating such risk factors might help target emerging preventive strategies, for example, to individuals with a history of opioid use disorder, or might lead to new treatment approaches such as the use of tools to ameliorate depressed mood. PMID:25659067

  16. Gender and access to HIV testing and antiretroviral treatments in Thailand: why do women have more and earlier access?

    PubMed

    Le Coeur, Sophie; Collins, Intira J; Pannetier, Julie; Lelièvre, Eva

    2009-09-01

    In the recent scale-up of antiretroviral treatment, gender differences in access to treatment have been reported. In Thailand, as the HIV epidemic became more generalised, there has been a shift from men being disproportionately affected to increased vulnerability of women. In 2007, the Living with Antiretrovirals (LIWA-ANRS 12141) study investigated the gender distribution of all adult patients receiving antiretroviral therapy (N=513 patients) in four community hospitals in northern Thailand and factors influencing the disparities observed. From this retrospective life-event history survey, we found that proportionately more women (53%) were receiving antiretroviral therapy than men, an unexpected result for a country with a higher proportion of infections among men. They were more likely to initiate treatment within one year of diagnosis and were at a more advanced stage of the disease compared to women. This gender distribution is partly explained by the evolving dynamics of the HIV epidemic, initial prioritization of mothers for treatment and earlier access to HIV testing for women. These issues are also entangled with gender differences in the reasons and timing to HIV testing at the individual level. This study found that the majority of men underwent HIV testing for health reasons while the majority of women were tested following family events such as a spouse/child death or during pregnancy. Further qualitative research on gender specific barriers to HIV testing and care, such as perceived low risk of infection, poor access to medical care, lack of social support, actual or anticipated HIV/AIDS-related stigma would provide greater insight. In the meantime, urgent efforts are needed to increase access to voluntary counselling and testing inside and outside the family setting with targeted interventions for men. PMID:19573965

  17. Impact of HAART and CNS-penetrating antiretroviral regimens on HIV encephalopathy among perinatally infected children and adolescents

    PubMed Central

    Patel, Kunjal; Ming, Xue; Williams, Paige L.; Robertson, Kevin R.; Oleske, James M.; Seage, George R.

    2010-01-01

    Objectives Prior to antiretroviral treatment, HIV-infected children frequently developed encephalopathy, resulting in debilitating morbidity and mortality. This is the first large study to evaluate the impact of HAART and central nervous system (CNS)-penetrating antiretroviral regimens on the incidence of HIV encephalopathy and survival after diagnosis of HIV encephalopathy among perinatally infected children. Design A total of 2398 perinatally HIV-infected children with at least one neurological examination were followed in a US-based prospective cohort study conducted from 1993 to 2007. Methods Trends in incidence rates over calendar time were described and Cox regression models were used to estimate the effects of time-varying HAART and CNS-penetrating antiretroviral regimens on HIV encephalopathy and on survival after diagnosis of HIV encephalopathy. Results During a median of 6.4 years of follow-up, 77 incident cases of HIV encephalopathy occurred [incidence rate 5.1 cases per 1000 person-years, 95% confidence interval (CI) 4.0–6.3]. A 10-fold decline in incidence was observed beginning in 1996, followed by a stable incidence rate after 2002. HAART regimens were associated with a 50% decrease (95% CI 14–71%) in the incidence of HIV encephalopathy compared with non-HAART regimens. High CNS-penetrating regimens were associated with a substantial survival benefit (74% reduction in the risk of death, 95% CI 39–89%) after HIV encephalopathy diagnosis compared with low CNS-penetrating regimens. Conclusion A dramatic decrease in the incidence of HIV encephalopathy occurred after the introduction of HAART. The use of HAART was highly effective in reducing the incidence of HIV encephalopathy among perinatally infected children and adolescents. Effective CNS-penetrating antiretroviral regimens are important in affecting survival after diagnosis of HIV encephalopathy. PMID:19644348

  18. Natural pregnancies in HIV-serodiscordant couples receiving successful antiretroviral therapy.

    PubMed

    Barreiro, Pablo; del Romero, Jorge; Leal, Manuel; Hernando, Victoria; Asencio, Román; de Mendoza, Carmen; Labarga, Pablo; Núñez, Marina; Ramos, José Tomás; González-Lahoz, Juan; Soriano, Vincent

    2006-11-01

    Increasing numbers of HIV-serodiscordant heterosexual couples are concerned about the chances for pregnancy. We reviewed all natural pregnancies attained by HIV-serodiscordant couples seen in 3 clinics in Spain, in which the infected partner had undetectable plasma viremia while receiving highly active antiretroviral therapy (HAART). In the case of HIV-infected mothers, only those with undetectable viremia during pregnancy and at delivery were chosen. A total of 62 HIV-serodiscordant couples, 22 HIV-infected women (mean CD4 count of 522 cells/microL, 55% hepatitis C virus [HCV]-seropositive) and 40 HIV-infected men (mean CD4 count of 629 cells/microL, 75% HCV-seropositive), were recorded. Overall, 76 natural pregnancies occurred, and 68 children were born. There were 9 fetal deaths, 1 twin pregnancy, 6 couples with 2 consecutive babies, and 4 couples with 3 consecutive newborns. There were no cases of HIV seroconversion in uninfected sexual partners. One case of vertical HIV transmission occurred, however. Serodiscordant couples attaining natural pregnancy are exposed to a negligible risk of sexual transmission of HIV when the infected partner presents with complete suppression of plasma viremia while receiving HAART. PMID:17003695

  19. Antiretroviral Drugs-Loaded Nanoparticles Fabricated by Dispersion Polymerization with Potential for HIV/AIDS Treatment

    PubMed Central

    Ogunwuyi, Oluwaseun; Kumari, Namita; Smith, Kahli A.; Bolshakov, Oleg; Adesina, Simeon; Gugssa, Ayele; Anderson, Winston A.; Nekhai, Sergei; Akala, Emmanuel O.

    2016-01-01

    Highly active antiretroviral (ARV) therapy (HAART) for chronic suppression of HIV replication has revolutionized the treatment of HIV/AIDS. HAART is no panacea; treatments must be maintained for life. Although great progress has been made in ARV therapy, HIV continues to replicate in anatomical and intracellular sites where ARV drugs have restricted access. Nanotechnology has been considered a platform to circumvent some of the challenges in HIV/AIDS treatment. Dispersion polymerization was used to fabricate two types (PMM and ECA) of polymeric nanoparticles, and each was successfully loaded with four ARV drugs (zidovudine, lamivudine, nevirapine, and raltegravir), followed by physicochemical characterization: scanning electron microscope, particle size, zeta potential, drug loading, and in vitro availability. These nanoparticles efficiently inhibited HIV-1 infection in CEM T cells and peripheral blood mononuclear cells; they hold promise for the treatment of HIV/AIDS. The ARV-loaded nanoparticles with polyethylene glycol on the corona may facilitate tethering ligands for targeting specific receptors expressed on the cells of HIV reservoirs. PMID:27013886

  20. Antiretroviral Drugs-Loaded Nanoparticles Fabricated by Dispersion Polymerization with Potential for HIV/AIDS Treatment.

    PubMed

    Ogunwuyi, Oluwaseun; Kumari, Namita; Smith, Kahli A; Bolshakov, Oleg; Adesina, Simeon; Gugssa, Ayele; Anderson, Winston A; Nekhai, Sergei; Akala, Emmanuel O

    2016-01-01

    Highly active antiretroviral (ARV) therapy (HAART) for chronic suppression of HIV replication has revolutionized the treatment of HIV/AIDS. HAART is no panacea; treatments must be maintained for life. Although great progress has been made in ARV therapy, HIV continues to replicate in anatomical and intracellular sites where ARV drugs have restricted access. Nanotechnology has been considered a platform to circumvent some of the challenges in HIV/AIDS treatment. Dispersion polymerization was used to fabricate two types (PMM and ECA) of polymeric nanoparticles, and each was successfully loaded with four ARV drugs (zidovudine, lamivudine, nevirapine, and raltegravir), followed by physicochemical characterization: scanning electron microscope, particle size, zeta potential, drug loading, and in vitro availability. These nanoparticles efficiently inhibited HIV-1 infection in CEM T cells and peripheral blood mononuclear cells; they hold promise for the treatment of HIV/AIDS. The ARV-loaded nanoparticles with polyethylene glycol on the corona may facilitate tethering ligands for targeting specific receptors expressed on the cells of HIV reservoirs. PMID:27013886

  1. Mathematical Modeling of HIV Dynamics After Antiretroviral Therapy Initiation: A Review

    PubMed Central

    Moog, Claude H.; Stan, Guy-Bart; Brunet, Cecile; Raffi, François; Ferré, Virginie; Costanza, Vicente; Mhawej, Marie J.; Biafore, Federico; Ouattara, Djomangan A.; Ernst, Damien; Fonteneau, Raphael; Xia, Xiaohua

    2014-01-01

    Abstract This review shows the potential ground-breaking impact that mathematical tools may have in the analysis and the understanding of the HIV dynamics. In the first part, early diagnosis of immunological failure is inferred from the estimation of certain parameters of a mathematical model of the HIV infection dynamics. This method is supported by clinical research results from an original clinical trial: data just after 1 month following therapy initiation are used to carry out the model identification. The diagnosis is shown to be consistent with results from monitoring of the patients after 6 months. In the second part of this review, prospective research results are given for the design of individual anti-HIV treatments optimizing the recovery of the immune system and minimizing side effects. In this respect, two methods are discussed. The first one combines HIV population dynamics with pharmacokinetics and pharmacodynamics models to generate drug treatments using impulsive control systems. The second one is based on optimal control theory and uses a recently published differential equation to model the side effects produced by highly active antiretroviral therapy therapies. The main advantage of these revisited methods is that the drug treatment is computed directly in amounts of drugs, which is easier to interpret by physicians and patients. PMID:25371860

  2. Reasons for non-adherence to antiretroviral therapy: patients' perspectives provide evidence of multiple causes.

    PubMed

    Walsh, J C; Horne, R; Dalton, M; Burgess, A P; Gazzard, B G

    2001-12-01

    The objective of the study was to define common reasons for non-adherence (NA) to highly active antiretroviral therapy (HAART) and the number of reasons reported by non-adherent individuals. A confidential questionnaire was administered to HIV-seropositive patients taking proteinase inhibitor based HAART. Median self-reported adherence was 95% (n = 178, range = 60-100%). The most frequent reasons for at least 'sometimes' missing a dose were eating a meal at the wrong time (38.2%), oversleeping (36.3%), forgetting (35.0%) and being in a social situation (30.5%). The mean number of reasons occurring at least 'sometimes' was 3.2; 20% of patients gave six or more reasons; those reporting the lowest adherence reported a significantly greater numbers of reasons (rho = - 0.59; p < 0.001). Three factors were derived from the data by principal component analysis reflecting 'negative experiences of HAART', 'having a low priority for taking medication' and 'unintentionally missing doses', accounting for 53.8% of the variance. On multivariate analysis only the latter two factors were significantly related to NA (odds ratios 0.845 and 0.849, respectively). There was a wide spectrum of reasons for NA in our population. The number of reasons in an individual increased as adherence became less. A variety of modalities individualized for each patient are required to support patients with the lowest adherence. PMID:11720641

  3. Treatment adherence to an antiretroviral regime: the lived experience of Native Hawaiians and kokua.

    PubMed

    Ka'opua, L

    2001-09-01

    Treatment adherence to Highly Active Antiretroviral Therapy (HAART) is a critical issue in human immunodeficiency virus (HIV) care. HAART can extend the longevity of people living with HIV, but treatment efficacy relies on strict adherence that is difficult for many consumers to manage. Results presented in this article are based on semi-structured in-depth interviews with Native Hawaiian consumers (n = 6) who reported moderate to low levels of overall HAART adherence, and based on their kokua, or primary support. All interviews were recorded on audiotape, transcribed verbatim, and analyzed using Grounded Theory methods. Research questions that guided the inquiry, included: What are the challenges of Hawaiians who report moderate to low levels of HAART adherence? How does non-adherence occur? What is the role of the kokua (primary caregiver) and/or family members in treatment adherence? What types of support enhance adherence? The unpredictability of living with HIV was a major challenge to adherence. Symptom distress and active use of alcohol and other drugs interfered with the capacity to appropriately adhere. Two patterns of non-adherence were identified: interrupted regime and intermittent use. Tangible and emotional types of support, sometimes delivered in culture-specific ways, were viewed as helpful in maintaining compliance and in resuming the regime when difficulties arose. The findings complement extant research on HAART by providing an understanding of adherence as a lived experience among Native Hawaiians and their kokua. PMID:12180508

  4. Non-communicable diseases in antiretroviral therapy recipients in Kagera Tanzania: a cross-sectional study

    PubMed Central

    Magafu, Mgaywa Gilbert Mjungu Damas; Moji, Kazuhiko; Igumbor, Ehimario Uche; Magafu, Naoko Shimizu; Mwandri, Michael; Mwita, Julius Chacha; Habte, Dereje; Rwegerera, Godfrey Mutashambara; Hashizume, Masahiro

    2013-01-01

    Introduction The aim of this study was to describe the extent of self-reported non-communicable diseases (NCDs) among highly active antiretroviral therapy (HAART) recipients in Kagera region in Tanzania and their effect on health-related quality of life (HRQOL). This study was conducted 2 years after HAART administration was started in Kagera region. Methods The SF-36 questionnaire was used to collect the HRQOL data of 329 HAART recipients. Questions on the NCDs, socio-demographic characteristics and treatment information were validated and added to the SF-36. Bivariate analyses involving socio-demographic characteristics and SF-36 scores of the recipients were performed. Multiple logistic regression was employed to compute adjusted odds ratios for different explanatory variables on physical functioning and mental health scores. Results Respondents who reported having 1 or more NCDs were 57.8% of all the respondents. Arthritis was the commonest NCD (57.8%). Respondents with the NCDs were more likely to have HRQOL scores below the mean of the general Tanzanian population. The population attributable fraction (PAF) for the NCDs on physical functioning was 0.28 and on mental health was 0.22. Conclusion Self-reported NCDs were prevalent among the HAART recipients in Kagera region. They accounted for 28% of the physical functioning scores and 22% of the mental health scores that were below the mean of the general Tanzanian population. Therefore, the integration of NCD care is important in the management of HIV/AIDS. PMID:24711874

  5. Affective disorders in patients with HIV infection: impact of antiretroviral therapy.

    PubMed

    Arendt, Gabriele

    2006-01-01

    At the beginning of the AIDS pandemic, affective disorders (such as depressed mood) were seen in a considerable number of HIV-1-infected individuals. These disorders were a result of the poor physical condition of the patients, brain involvement by the virus (e.g. encephalopathy) or a reaction to disadvantageous living conditions (losing friends, jobs, etc.). In the era of highly active antiretroviral therapy (HAART), mental illness related to physical weakness is declining, as is the incidence of HIV-1-associated encephalopathy. However, depressed mood and fatigue caused by efavirenz (a standard component of HAART) is becoming increasingly important, particularly in individuals who are infected long-term with HIV-1. Whatever the cause of affective disorders, their presence has been shown to negatively influence adherence to HAART and HIV-1 disease progression. Specialist knowledge of HIV-1 infection, and HAART and its psychiatric complications (particularly in subgroups of patients such as drug abusers and older people), is needed to care adequately for patients. Furthermore, prospective studies are needed to more fully differentiate between the various aetiologies of affective disorders seen in individuals living with HIV/AIDS and to determine their incidence and prevalence. Such information is important to ensure that affective disorders are recognised and adequately treated, which will in turn improve the efficacy of HAART. PMID:16734500

  6. Pre-antiretroviral therapy serum selenium concentrations predict WHO stages 3, 4 or death but not virologic failure post-antiretroviral therapy.

    PubMed

    Shivakoti, Rupak; Gupte, Nikhil; Yang, Wei-Teng; Mwelase, Noluthando; Kanyama, Cecilia; Tang, Alice M; Pillay, Sandy; Samaneka, Wadzanai; Riviere, Cynthia; Berendes, Sima; Lama, Javier R; Cardoso, Sandra W; Sugandhavesa, Patcharaphan; Semba, Richard D; Christian, Parul; Campbell, Thomas B; Gupta, Amita

    2014-11-01

    A case-cohort study, within a multi-country trial of antiretroviral therapy (ART) efficacy (Prospective Evaluation of Antiretrovirals in Resource Limited Settings (PEARLS)), was conducted to determine if pre-ART serum selenium deficiency is independently associated with human immunodeficiency virus (HIV) disease progression after ART initiation. Cases were HIV-1 infected adults with either clinical failure (incident World Health Organization (WHO) stage 3, 4 or death by 96 weeks) or virologic failure by 24 months. Risk factors for serum selenium deficiency (<85 μg/L) pre-ART and its association with outcomes were examined. Median serum selenium concentration was 82.04 μg/L (Interquartile range (IQR): 57.28-99.89) and serum selenium deficiency was 53%, varying widely by country from 0% to 100%. In multivariable models, risk factors for serum selenium deficiency were country, previous tuberculosis, anemia, and elevated C-reactive protein. Serum selenium deficiency was not associated with either clinical failure or virologic failure in multivariable models. However, relative to people in the third quartile (74.86-95.10 μg/L) of serum selenium, we observed increased hazards (adjusted hazards ratio (HR): 3.50; 95% confidence intervals (CI): 1.30-9.42) of clinical failure but not virologic failure for people in the highest quartile. If future studies confirm this relationship of high serum selenium with increased clinical failure, a cautious approach to selenium supplementation might be needed, especially in HIV-infected populations with sufficient or unknown levels of selenium. PMID:25401501

  7. Dangerous medicines: Unproven AIDS cures and counterfeit antiretroviral drugs

    PubMed Central

    Amon, Joseph J

    2008-01-01

    Background Increasing access to antiretroviral therapy (ART) is a critical goal endorsed by the United Nations and all of its member states. At the same time, anecdotal accounts suggest that the promotion of unproven AIDS 'cures' and remedies are widespread, and in the case of The Gambia, Iran and South Africa, have been promoted by governments directly. Although a range of legislative and regulatory measures have been adopted by some governments, and technical assistance has been provided by international agencies to address counterfeit medicines generally, the threat of counterfeit antiretroviral drugs is not being addressed. Discussion Countries, charged with fulfilling the right to health and committed to expanding access to ART must explicitly recognize their obligation to combat unproven AIDS treatments and ensure the availability of a safe and efficacious drugs supply. International donors must help support and coordinate these efforts. PMID:18304316

  8. [SSRI AND BONE METABOLISM IN HIV + PATIENTS WITH ANTIRETROVIRAL THERAPY].

    PubMed

    Mazzoglio y Nabar, Martín J; Muñiz, Milagros María; Mejías Delamano, Alexis A; Muñoz, Santiago; Magrath Guimet, Nahuel

    2015-01-01

    We report a series of 9 male HIV + patients, average age of 41.2 years, viral load negative (<50 copies RNA/ml), treated with antiretroviral (nucleoside and non-nucleoside inhibitors of reverse transcriptase) without systemic infections, the CNS diseases or marker or corticoidoterapia in progress. Were evaluated and supported by their infectologists interconsultation during the period October 2008-October 2013 by depressive syndrome. Psychotherapeutic and psychiatric treatment was initiated with SSRIs and clonazepam; Neuroimaging control and biochemical laboratory studies at baseline and 2 months of treatment were conducted. In the course of psychopharmacological treatment not suffer fractures due to falls and alterations were detected in bone metabolism markers and images. He studied with endocrinology and interdisciplinary medical clinic, decided to withdraw the SSRIs with normalization of biochemical values and psychotherapeutic treatment was continued. We will raise the associations between the use of SSRIs, disturbances of bone metabolism with clinical correlation and possible drug interactions between antidepressants and antiretroviral. PMID:26650557

  9. Vibrational spectra and quantum mechanical calculations of antiretroviral drugs: Nevirapine

    NASA Astrophysics Data System (ADS)

    Ayala, A. P.; Siesler, H. W.; Wardell, S. M. S. V.; Boechat, N.; Dabbene, V.; Cuffini, S. L.

    2007-02-01

    Nevirapine (11-cyclopropyl-5,11-dihydro-4-methyl-6H-dipyrido[3,2-b:2',3'e][1,4]diazepin-6-one) is an antiretroviral drug belonging to the class of the non-nucleoside inhibitors of the HIV-1 virus reverse transcriptase. As most of this kind of antiretroviral drugs, nevirapine displays a butterfly-like conformation which is preserved in complexes with the HIV-1 reverse transcriptase. In this work, we present a detailed vibrational spectroscopy investigation of nevirapine by using mid-infrared, near-infrared, and Raman spectroscopies. These data are supported by quantum mechanical calculations, which allow us to characterize completely the vibrational spectra of this compound. Based on these results, we discuss the correlation between the vibrational modes and the crystalline structure of the most stable form of nevirapine.

  10. Governor signs bill seeking prompter access to antiretrovirals.

    PubMed

    1999-10-15

    California Governor Gray Davis signed legislation providing for more timely access to antiretroviral medications through the State's AIDS drug assistance program (ADAP). The bill requires that the State Department of Health Services make any HIV treatment antiretroviral drug approved for marketing by the Federal Food and Drug Administration (FDA) available within 30 days of the time the State Office of AIDS receives notice of FDA approval. The bill requires that the drug be validated for treatment by the State Office of AIDS and that enough money is budgeted by the agency to pay for the new medication. Consumer protection items are included, such as requiring prescriptions be filled within 24 hours of submission and providing information at appropriate literacy levels in English, Spanish, Mandarin/Cantonese, Tagalog and other languages. PMID:11367283

  11. Viral dynamics model with CTL immune response incorporating antiretroviral therapy.

    PubMed

    Wang, Yan; Zhou, Yicang; Brauer, Fred; Heffernan, Jane M

    2013-10-01

    We present two HIV models that include the CTL immune response, antiretroviral therapy and a full logistic growth term for uninfected CD4+ T-cells. The difference between the two models lies in the inclusion or omission of a loss term in the free virus equation. We obtain critical conditions for the existence of one, two or three steady states, and analyze the stability of these steady states. Through numerical simulation we find substantial differences in the reproduction numbers and the behaviour at the infected steady state between the two models, for certain parameter sets. We explore the effect of varying the combination drug efficacy on model behaviour, and the possibility of reconstituting the CTL immune response through antiretroviral therapy. Furthermore, we employ Latin hypercube sampling to investigate the existence of multiple infected equilibria. PMID:22930342

  12. The obligation to provide antiretroviral treatment in HIV prevention trials.

    PubMed

    Lo, Bernard; Padian, Nancy; Barnes, Mark

    2007-06-19

    Providing antiretroviral therapy (ART) to participants who seroconvert during HIV prevention trials in developing countries is an ethical expectation. Promising treatment to the few seroconverters widens disparities within a resource-poor country and would be unjust. Such an assurance should be done in a way that also improves access to ART for others in the country. US funds for ART in poor countries from the PEPFAR should be available to all countries that host HIV prevention and clinical trials. PMID:17545698

  13. Adverse effects of antiretroviral therapy for HIV infection.

    PubMed

    Montessori, Valentina; Press, Natasha; Harris, Marianne; Akagi, Linda; Montaner, Julio S G

    2004-01-20

    Long-term remission of HIV-1 disease can be readily achieved by combinations of antiretroviral agents. The suppression of plasma viral loads to less than the limit of quantification of the most sensitive commercially available assays (i.e., less than 50 copies/mL) and the coincident improvement in CD4 T cell counts is associated with resolution of established opportunistic infections and a decrease in the risk of new opportunistic infections. However, prolonged treatment with combination regimens can be difficult to sustain because of problems with adherence and toxic effects. All antiretroviral drugs can have both short-term and long-term adverse events. The risk of specific side effects varies from drug to drug, from drug class to drug class, and from patient to patient. A better understanding of the adverse effects of antiretroviral agents is of interest not only for HIV specialists as they try to optimize therapy, but also for other physicians who care for HIV-positive patients. PMID:14734438

  14. Care of Patients With HIV Infection: Antiretroviral Drug Regimens.

    PubMed

    Bolduc, Philip; Roder, Navid; Colgate, Emily; Cheeseman, Sarah H

    2016-04-01

    The advent of combination antiretroviral drug regimens has transformed HIV infection from a fatal illness into a manageable chronic condition. All patients with HIV infection should be considered for antiretroviral therapy, regardless of CD4 count or HIV viral load, for individual benefit and to prevent HIV transmission. Antiretroviral drugs affect HIV in several ways: entry inhibitors block HIV entry into CD4 T cells; nucleotide and nucleoside reverse transcriptase inhibitors prevent reverse transcription from RNA to DNA via chain-terminating proteins; nonnucleoside reverse transcriptase inhibitors prevent reverse transcription through enzymatic inhibition; integrase strand transfer inhibitors block integration of viral DNA into cellular DNA; protease inhibitors block maturation and production of the virus. Current guidelines recommend six combination regimens for initial therapy. Five are based on tenofovir and emtricitabine; the other uses abacavir and lamivudine. Five include integrase strand transfer inhibitors. HIV specialists should assist with treating patients with complicated HIV infection, including patients with treatment-resistant HIV infection, coinfection with hepatitis B or C virus, pregnancy, childhood infections, severe opportunistic infections, complex drug interactions, significant drug toxicity, or comorbidities. Family physicians can treat most patients with HIV infection effectively by choosing appropriate treatment regimens, monitoring patients closely, and retaining patients in care. PMID:27092564

  15. Antiretroviral drug development: the challenge of cost and access.

    PubMed

    Dunne, Michael

    2007-07-01

    The global threat of HIV infection requires sustainable solutions driven by investments from both the public and the private sector. The pharmaceutical industry has supported research and development of antiretroviral therapies that have prolonged the lives of individuals infected with HIV. The medical need for new antiretroviral agents remains great, however, a consequence of the progressive evolution of viral resistance. In order to meet this ongoing challenge, investment into research and development needs to continue. These investment decisions are made relative to other pressing healthcare concerns and are based on assessments of the likelihood of technical success, the ability to define the clinical value of any new medicine, the patient's perception of medical need, and the ability of society to support the patient's access to those medicines. Any new antiretroviral therapy must be anticipated not only to work against future resistant strains but to work well with other agents as part of combination therapies. Those challenges are coupled with the need for systems that optimize patients' access to treatment, including the global regulatory process, reliable and quality manufacturing and distribution systems, and basic healthcare delivery infrastructure. Synergies generated from the contributions to HIV care by both the public and private sector will, in the long and the short run, lead to improvements in the health and well-being of individuals living with HIV. PMID:17620756

  16. Differences in Salivary Flow Level, Xerostomia, and Flavor Alteration in Mexican HIV Patients Who Did or Did Not Receive Antiretroviral Therapy.

    PubMed

    López-Verdín, Sandra; Andrade-Villanueva, Jaime; Zamora-Perez, Ana Lourdes; Bologna-Molina, Ronell; Cervantes-Cabrera, José Justino; Molina-Frechero, Nelly

    2013-01-01

    Introduction. Objective and subjective alterations related to salivary flow have been reported in patients infected with human immunodeficiency virus (HIV), and these alterations are associated with the introduction of antiretroviral therapy. The aim of the current study was to discern whether these alterations are disease induced or secondary to drug therapy. Objective. The objective was to determine the relationships between low salivary flow, xerostomia, and flavor alterations in HIV patients who did or did not receive antiretroviral therapy. Materials and Methods. In this cross-sectional study, HIV patients were divided into two groups based on whether they had received antiretroviral therapy. Those patients with a previous diagnosis of any salivary gland disease were excluded. A survey was used to assess subjective variables, and colorimetry and salivary flow rates were measured using the Schirmer global test. Results. A total of 293 patients were included. The therapy group showed a significantly lower average salivary flow than did the group without therapy, and we observed that the flow rate tended to decrease after one year of therapy. The results were not conclusive, despite significant differences in xerostomia and flavor alteration between the groups. Conclusion. The study results suggest that antiretroviral therapy can cause cumulative damage that affects the amount of salivary flow. PMID:24455222

  17. Differences in Salivary Flow Level, Xerostomia, and Flavor Alteration in Mexican HIV Patients Who Did or Did Not Receive Antiretroviral Therapy

    PubMed Central

    López-Verdín, Sandra; Andrade-Villanueva, Jaime; Zamora-Perez, Ana Lourdes; Bologna-Molina, Ronell; Cervantes-Cabrera, José Justino

    2013-01-01

    Introduction. Objective and subjective alterations related to salivary flow have been reported in patients infected with human immunodeficiency virus (HIV), and these alterations are associated with the introduction of antiretroviral therapy. The aim of the current study was to discern whether these alterations are disease induced or secondary to drug therapy. Objective. The objective was to determine the relationships between low salivary flow, xerostomia, and flavor alterations in HIV patients who did or did not receive antiretroviral therapy. Materials and Methods. In this cross-sectional study, HIV patients were divided into two groups based on whether they had received antiretroviral therapy. Those patients with a previous diagnosis of any salivary gland disease were excluded. A survey was used to assess subjective variables, and colorimetry and salivary flow rates were measured using the Schirmer global test. Results. A total of 293 patients were included. The therapy group showed a significantly lower average salivary flow than did the group without therapy, and we observed that the flow rate tended to decrease after one year of therapy. The results were not conclusive, despite significant differences in xerostomia and flavor alteration between the groups. Conclusion. The study results suggest that antiretroviral therapy can cause cumulative damage that affects the amount of salivary flow. PMID:24455222

  18. Cationic zinc enolates as highly active catalysts for acrylate polymerization.

    PubMed

    Garner, Logan E; Zhu, Hongping; Hlavinka, Mark L; Hagadorn, John R; Chen, Eugene Y-X

    2006-11-22

    Unprecedented cationic zinc enolates have been generated by a novel activation route involving the amido to imino ligand transformation with B(C6F5)3, structurally characterized, and utilized as highly active catalysts for the production of high molecular weight polyacrylates at ambient temperature. PMID:17105289

  19. Issues and design concepts for high-activity liquid packaging

    SciTech Connect

    Meinert, N.M.; Riley, D.; Wells, A.H.

    1994-02-01

    The tank waste pretreatment process involves the separation of low-level and high-level constituents. The liquid high-level defense production waste will be vitrified into thousands of glass logs at the US DOE sites and then transported to a high-level repository for final disposal. Pretreatment and vitrification technology will need to be developed and tested to assess cost-effectiveness. The appropriate pretreatment strategy for complex high-activity liquid will depend on proving a competent process. As technology development matures, actual liquid will be substituted for simulants, and pilot scale plants will replace laboratory scale process demonstrations. Development of this strategy depends on tank waste sample analyses and a high-activity liquid supply for process testing. However, high-activity liquid transportation beyond DOE site boundaries is limited to Type B quantities in volumes less than 50 mL; no licensed packaging exists for greater than 50 mL quantities. The following paper summarizes the need for a high-activity liquid packaging, and identifies the agencies effecting packaging design and transportation. The high-activity liquid packaging concept retrofits licensed spent fuel casks by replacing the spent fuel basket with a sturdy containment vessel appropriate for the chemical nature of the liquid. A Nuclear Packaging (Pacific Nuclear`s NuPat{trademark} 125-B) spent fuel cask was hypothetically retrofitted with a containment vessel filled with liquid source term, the radionuclide inventory contained in the liquid. The structural, thermal, dose rate, and criticality consequences of retrofitting the cask body were evaluated based on data in the 125-B Cask Safety Analysis Report for Packaging. In addition, future packaging development work is discussed.

  20. Antibody Persistence and Immunologic Memory after Sequential Pneumococcal Conjugate and Polysaccharide Vaccination in HIV-Infected Children on Highly Active Antiretroviral Therapy

    PubMed Central

    Abzug, Mark J.; Song, Lin Ye; Levin, Myron J.; Nachman, Sharon A.; Borkowsky, William; Pelton, Stephen I.

    2013-01-01

    Background The capacity of pneumococcal vaccination to confer memory in HIV-infected children is critical for durable protection. Methods HIV-infected children 2–<19 years administered two doses of pneumococcal conjugate vaccine (PCV7) and one dose of polysaccharide vaccine (PPV) on HAART were randomized four-five years later to receive a PCV7 or PPV booster. Total and high avidity antibodies to serotypes 1 (PPV) and 6B and 14 (PCV7 and PPV) were determined by ELISA. Memory was defined as persistence of ≥0.5 mcg/mL of serotype-specific antibody on day 0 or change from <0.5 mcg/mL to ≥0.5 mcg/mL between day 0 and week 1, or, ≥4-fold antibody rise between day 0 and week 1. Results Prior to boosting, four to five years after the previous PCV7-PCV7-PPV series, geometric mean concentrations (GMCs) were 0.46 mcg/mL (serotype 1), 1.31 mcg/mL (serotype 6B), and 1.47 mcg/mL (serotype 14), with concentrations ≥0.5 mcg/mL in 41% (serotype 1) to 82% (serotypes 6B and 14). Memory based on antibody concentration ≥0.5 mcg/mL before or 1 week after boosting with PCV7 or PPV was demonstrated in 42–61% for serotype 1 and 87–94% for serotypes 6B and 14, with lower rates based on day 0 to week 1 ≥4-fold antibody rise (serotype 1, 3–13%; serotype 6B, 13–31%; serotype 14, 29–53%). Antibody concentrations post-boosting were greater following PCV7 than PPV for serotypes 6B and 14. Ratios of highly avid to total antibody pre- and post-boosting were 0.5–0.8. Predictors of memory included higher CD4% (nadir before HAART and at P1024 and P1061s entry), CD19% (at P1024 and P1061s entry), and antibody response after the PCV7-PCV7-PPV primary series and lower viral load (at P1024 and P1061s entry) and age. Conclusions Protective antibody concentrations, high avidity, and booster responses to PCV7 or PPV indicative of memory were present four-five years after PCV7-PCV7-PPV in HIV-infected children on HAART. PMID:23954381

  1. Efavirenz does not cause false-positive urine cannabis test in HIV-infected patients on Highly Active Anti-Retroviral Therapy.

    PubMed

    Koh, K C; Lee, W Y; Eh, Z W; Nor Julaika, I; Tee, P S; Azizon, O; Thilageswary, M

    2013-06-01

    Efavirenz is a non-nucleoside reverse transcriptase inhibitor used in combination with other drugs for the treatment of patients with HIV infection. Efavirenz has been reported to cause a positive urine cannabis test reaction which may create problems between HIV-infected patients on Efavirenz and law enforcement agencies. Doctors are at loss whether to issue documents certifying the potential false positive urine cannabis test with Efavirenz to patients. We investigated if the urine of HIV-infected patients on Efavirenz caused a positive urine cannabis test using the AxSYM Cannabinoids Assay®. Urine samples from 51 eligible patients on Efavirenz were tested for cannabis. All tested negative except for one who had used cannabis the day before. Efavirenz does not cause false positive urine cannabis test with the AxSYM Cannabinoids Assay®. Certification documents from doctors are therefore unnecessary. PMID:23749016

  2. Economic evaluation of initial antiretroviral therapy for HIV-infected patients: an update of Italian guidelines

    PubMed Central

    Colombo, Giorgio L; Di Matteo, Sergio; Antinori, Andrea; Medaglia, Massimo; Murachelli, Silvia; Rizzardini, Giuliano

    2013-01-01

    Introduction Highly active antiretroviral therapy (HAART) has allowed many HIV-infected patients to enjoy longer survival and a better quality of life. We performed an economic analysis to estimate the cost-effectiveness of HAART regimens in Italy for managing HIV-naïve infected patients with a viral load below 100,000 copies/mL. Patients and methods The population considered in the model consisted of adult subjects with an HIV viral load below 100,000 copies/mL who received antiretroviral HAART treatment for the first time, according to the Italian National Guidelines with recommendation grade A1. The incremental cost-effectiveness analysis of quality-adjusted life years (QALYs) was carried out by means of a Markov model. Both the outcomes (QALYs) and the costs were discounted by 3.5%. The time horizon adopted in the model was 10 years. The point of view of the analysis was that of the Italian national health service. Results The tenofovir (TDF)/emtricitabine (FTC)/rilpivirine (RPV) single-tablet regimen (STR) (€7,417.00) revealed the lowest mean treatment cost. TDF/FTC + raltegravir (RAL) showed a better quality of life (0.906 QALY/year), followed by TDF/FTC/RPV (STR; 0.900 QALY/year), TDF/FTC + RPV (multipill regimen) (0.889 QALY/year), and TDF/FTC + atazanavir (ATV/r) (0.886 QALY/year). TDF/FTC/RPV (STR) appeared to be the most cost-effective therapeutic choice (€13,655.00), followed by TDF/FTC + RPV (multipill regimen) (€15,803.00), and TDF/FTC + efavirenz (EFV) (€16,181.00). The sensitivity analysis on the main variables confirmed the validity of the base case scenario. Conclusion STR (TDF/FTC/RPV) is the most cost-effective treatment strategy compared with the other therapeutic regimens recommended by the Italian guidelines for the treatment of naïve patients with a viral load <100,000 copies/mL. The inclusion of adverse-event management of HIV-infected patients affects the cost-effectiveness ratio of all HAART regimens. PMID:24124383

  3. Cardiac Effects of Antiretroviral-Naïve versus Antiretroviral-Exposed HIV Infection in Children

    PubMed Central

    Grobbee, Diederick E.; Burgner, David; Kurniati, Nia

    2016-01-01

    Background Cardiac involvement in HIV infected children has been frequently reported, but whether this is due to HIV infection itself or to antiretroviral treatment (ART) is unknown. Methods This cross sectional study involved 114 vertically-acquired HIV-infected (56 ART-naive, 58 ART-exposed) and 51 healthy children in Jakarta, Indonesia. Echocardiography was performed to measure dimensions of the left ventricle (LV) and systolic functions. We applied general linear modeling to evaluate the associations between HIV infection/treatment status and cardiac parameters with further adjustment for potential confounders or explanatory variables. Findings are presented as (adjusted) mean differences between each of the two HIV groups and healthy children, with 95% confidence intervals and p values. Results Compared to healthy children, ART-naïve HIV-infected children did not show significant differences in age-and-height adjusted cardiac dimensions apart from larger LV internal diameter (difference 2.0 mm, 95%CI 0.2 to 3.7), whereas ART exposed HIV infection showed thicker LV posterior walls (difference = 1.1 mm, 95%CI 0.5 to 1.6), larger LV internal diameter (difference = 1.7 mm, 95%CI 0.2 to 3.2) and higher LV mass (difference = 14.0 g, 7.4 to 20.5). With respect to systolic function, reduced LV ejection fraction was seen in both ART-naïve HIV infected (adjusted difference = -6.7%, -11.4 to -2.0) and, to a lesser extent, in ART-exposed HIV infected children (difference = -4.5%, -8.5 to -0.4). Inflammation level seemed to be involved in most associations in ART-exposed HIV-infected, but few, if any, for decreased function in the ART-naive ones, whereas lower hemoglobin appeared to partially mediate chamber dilation in both groups and reduced function, mainly in ART-exposed children. Conclusions ART-naive HIV infected children have a substantial decrease in cardiac systolic function, whereas the ART-exposed have thicker ventricular walls with larger internal diameter

  4. Virological Response and Antiretroviral Drug Resistance Emerging during Antiretroviral Therapy at Three Treatment Centers in Uganda

    PubMed Central

    Kaleebu, Pontiano; Kirungi, Wilford; Watera, Christine; Asio, Juliet; Lyagoba, Fred; Lutalo, Tom; Kapaata, Anne A.; Nanyonga, Faith; Parry, Chris M.; Magambo, Brian; Nazziwa, Jamirah; Nannyonjo, Maria; Hughes, Peter; Hladik, Wolfgang; Ruberantwari, Anthony; Namuwenge, Norah; Musinguzi, Joshua; Downing, Robert; Katongole-Mbidde, Edward

    2015-01-01

    Background With the scale-up of antiretroviral therapy (ART), monitoring programme performance is needed to maximize ART efficacy and limit HIV drug resistance (HIVDR). Methods We implemented a WHO HIVDR prospective survey protocol at three treatment centers between 2012 and 2013. Data were abstracted from patient records at ART start (T1) and after 12 months (T2). Genotyping was performed in the HIV pol region at the two time points. Results Of the 425 patients enrolled, at T2, 20 (4.7%) had died, 66 (15.5%) were lost to follow-up, 313 (73.6%) were still on first-line, 8 (1.9%) had switched to second-line, 17 (4.0%) had transferred out and 1 (0.2%) had stopped treatment. At T2, 272 out of 321 on first and second line (84.7%) suppressed below 1000 copies/ml and the HIV DR prevention rate was 70.1%, just within the WHO threshold of ≥70%. The proportion of participants with potential HIVDR was 20.9%, which is higher than the 18.8% based on pooled analyses from African studies. Of the 35 patients with mutations at T2, 80% had M184V/I, 65.7% Y181C, and 48.6% (54.8% excluding those not on Tenofovir) had K65R mutations. 22.9% had Thymidine Analogue Mutations (TAMs). Factors significantly associated with HIVDR prevention at T2 were: baseline viral load (VL) <100,000 copies/ml [Adjusted odds ratio (AOR) 3.13, 95% confidence interval (CI): 1.36–7.19] and facility. Independent baseline predictors for HIVDR mutations at T2 were: CD4 count <250 cells/μl (AOR 2.80, 95% CI: 1.08–7.29) and viral load ≥100,000 copies/ml (AOR 2.48, 95% CI: 1.00–6.14). Conclusion Strengthening defaulter tracing, intensified follow-up for patients with low CD4 counts and/or high VL at ART initiation together with early treatment initiation above 250 CD4 cells/ul and adequate patient counselling would improve ART efficacy and HIVDR prevention. The high rate of K65R and TAMs could compromise second line regimens including NRTIs. PMID:26700639

  5. Transmitted drug resistance to rilpivirine in newly diagnosed antiretroviral naive adults.

    PubMed

    Alvarez, M; Monge, S; Chueca, N; Guillot, V; Viciana, P; Anta, L; Rodriguez, C; Gomez-Sirvent, J L; Navarro, G; de los Santos, I; Moreno, S; García, F

    2015-01-01

    We characterized transmitted drug resistance to rilpivirine and the predicted efficacy of first-line rilpivirine-containing regimens in antiretroviral-naive Spanish patients. International Antiviral Society-USA mutations were detected in 138 of 2781 patients (4.9%), E138A (3.4%) being the most prevalent. Using the Stanford Algorithm, 121 patients (4.4%) showed low-level or intermediate resistance. No differences in the predicted efficacy of first-line non-nucleoside reverse transcriptase inhibitor-based regimens were observed. As rilpivirine becomes more widely used in clinical practice, the evolution of its transmitted drug resistance will need to be monitored. In addition, the exact role of E138A singletons on rilpivirine activity as part of first-line regimens merits further evaluation. PMID:25636936

  6. Enhancing the benefits of antiretroviral therapy in Vietnam: towards ending AIDS.

    PubMed

    Kato, Masaya; Long, Nguyen Hoang; Duong, Bui Duc; Nhan, Do Thi; Nguyen, Thi Thuy Van; Hai, Nguyen Huu; Giang, Le Minh; Hoa, Do Mai; Van, Nguyen Thanh; Suthar, Amitabh B; Fontaine, Chris; Nadol, Patrick; Lo, Ying-Ru; McConnell, Michelle S

    2014-12-01

    Vietnam has a concentrated HIV epidemic, with the highest HIV prevalence being observed among people who inject drugs (PWID). Based on its experience scaling-up robust HIV interventions, Vietnam aims to further strengthen its response by harnessing the preventive benefits of antiretroviral therapy (ART). Mathematical modelling suggests that prioritizing key populations for earlier access to ART, combined with other prevention interventions, may have significant impact on the epidemic, cost-effectively reducing new HIV infections and deaths. Pilot studies are being conducted to assess feasibility and acceptability of expansion of HIV testing and counselling (HTC) and early ART among key populations and to demonstrate innovative service delivery models to address challenges in uptake of services across the care cascade. Earlier access of key populations to combination prevention interventions, combined with sustained political commitment and supportive environment for key populations, are essential for maximum impact of ART on the HIV epidemic in Vietnam. PMID:25472886

  7. A visual dosing aid for first-line pediatric antiretroviral treatment in resource-poor settings.

    PubMed

    Callens, Steven F J; Westreich, Daniel; Kitetele, Faustin; Lusiama, Jean; Shabani, Nicole; Belhorn, Tom; Colebunders, Robert; Behets, Frieda; Van Rie, Annelies

    2009-04-01

    The visual dosing aid (VDA) was developed to facilitate dosing calculations in response to children's; growth and weight during antiretroviral treatment. The theoretical accuracy of the VDA was assessed using anthropometric data from 55 children receiving care in the USA and 324 children in the Democratic Republic of the Congo. The VDA dose was similar to the WHO recommended dose. A potentially significant relative dosing difference of >or=20% occurred in <3% of children for NVP, AZT and d4T, but was observed in 20% for 3TC, overdosing being more frequent. The VDA compared well with generic pediatric fixed dose combination tablets. Results did not differ between sites. The VDA enables accurate dosing of pediatric ART in distinct populations and could facilitate roll-out of pediatric ART in resource-poor settings. PMID:19022850

  8. Antiretroviral therapy adherence: testing a social context model among Black men who use illicit drugs.

    PubMed

    Phillips, J Craig

    2011-01-01

    Individuals living with HIV who receive treatment and optimal care live longer and healthier lives. The purpose of this study was to develop a theoretical model to understand the effects of social context factors (individual, interpersonal, and social capital) that influence antiretroviral therapy (ART) adherence among a sample of HIV-infected Black men who use illicit drugs (N = 160). Ecosocial theory and social epidemiology provided the theoretical framework for this study. Multiple regression techniques and path analysis were used to test the model for these subjects. Homelessness among the subjects significantly affected adherence to ART. Tolerability of ART was observed to have a greater indirect effect on ART adherence than a direct effect. A positive state of mind and current illicit drug use indirectly affected ART adherence; however, significance was not achieved. Implications for the use of this theoretical model to guide research, clinical practice, and policy as part of a human rights approach to HIV disease is articulated. PMID:21123085

  9. Substance abuse, adherence with antiretroviral therapy, and clinical outcomes among HIV-infected individuals.

    PubMed

    Lucas, Gregory M

    2011-05-23

    Substance abuse and addiction are highly prevalent in HIV-infected individuals. Substance abuse is an important comorbidity that affects the delivery and outcomes of HIV medical management. In this paper I will review data examining the associations between substance abuse and HIV treatment and potential strategies to improve outcomes in this population that warrant further investigation. Current - but not past - substance abuse adversely affects engagement in care, acceptance of antiretroviral therapy, adherence with therapy, and long-term persistence in care. Substance abuse treatment appears to facilitate engagement in HIV care, and access to evidence-based treatment for substance abuse is central to addressing the HIV epidemic. Strategies that show promise for HIV-infected substance abusers include integrated treatment models, directly observed therapy, and incentive-based interventions. PMID:20888839

  10. Substance abuse, adherence with antiretroviral therapy, and clinical outcomes among HIV-infected individuals

    PubMed Central

    Lucas, Gregory M.

    2010-01-01

    Substance abuse and addiction are highly prevalent in HIV-infected individuals. Substance abuse is an important comorbidity that affects the delivery and outcomes of HIV medical management. In this paper I will review data examining the associations between substance abuse and HIV treatment and potential strategies to improve outcomes in this population that warrant further investigation. Current - but not past - substance abuse adversely affects engagement in care, acceptance of antiretroviral therapy, adherence with therapy, and long-term persistence in care. Substance abuse treatment appears to facilitate engagement in HIV care, and access to evidence-based treatment for substance abuse is central to addressing the HIV epidemic. Strategies that show promise for HIV-infected substance abusers include integrated treatment models, directly observed therapy, and incentive-based interventions. PMID:20888839

  11. HIV-1 drug resistance in recently HIV-infected pregnant mother’s naïve to antiretroviral therapy in Dodoma urban, Tanzania

    PubMed Central

    2013-01-01

    Background HIV resistance affects virological response to therapy and efficacy of prophylaxis in mother-to-child-transmission. The study aims to assess the prevalence of HIV primary resistance in pregnant women naïve to antiretrovirals. Methods Cross sectional baseline analysis of a cohort of HIV + pregnant women (HPW) enrolled in the study entitled Antiretroviral Management of Antenatal and Natal HIV Infection (AMANI, peace in Kiswahili language). The AMANI study began in May 2010 in Dodoma, Tanzania. In this observational cohort, antiretroviral treatment was provided to all women from the 28th week of gestation until the end of the breastfeeding period. Baseline CD4 cell count, viral load and HIV drug-resistance genotype were collected. Results Drug-resistance analysis was performed on 97 naïve infected-mothers. The prevalence of all primary drug resistance and primary non-nucleoside reverse-transcriptase inhibitors resistance was 11.9% and 7.5%, respectively. K103S was found in two women with no M184V detection. HIV-1 subtype A was the most commonly identified, with a high prevalence of subtype A1, followed by C, D, C/D recombinant, A/C recombinant and A/D recombinant. HIV drug- resistance mutations were detected in A1 and C subtypes. Conclusion Our study reports an 11.9% prevalence rate of primary drug resistance in naïve HIV-infected pregnant women from a remote area of Tanzania. Considering that the non-nucleoside reverse-transcriptase inhibitors are part of the first-line antiretroviral regimen in Tanzania and all of Africa, resistance surveys should be prioritized in settings where antiretroviral therapy programs are scaled up. PMID:24053581

  12. Measurement of actinides and strontium-90 in high activity waste

    SciTech Connect

    Maxwell, S.L. III; Nelson, M.R.

    1994-08-01

    The reliable measurement of trace radionuclides in high activity waste is important to support waste processing activities at SRS (F and H Area Waste Tanks, Extended Sludge Processing (ESP) and In-Tank precipitation (ITP) processing). Separation techniques are needed to remove high levels of gamma activity and alpha/beta interferences prior to analytical measurement. Using new extraction chromatographic resins from EiChrom Industries, Inc., the SRS Central Laboratory has developed new high speed separation methods that enable measurement of neptunium, thorium, uranium, plutonium, americium and strontium-90 in high activity waste solutions. Small particle size resin and applied vacuum are used to reduce analysis times and enhance column performance. Extraction chromatographic resins are easy to use and eliminate the generation of contaminated liquid organic waste.

  13. Strategies for Living with the Challenges of HIV and Antiretroviral Use in Zambia

    ERIC Educational Resources Information Center

    Jones, Deborah; Zulu, Isaac; Mumbi, Miriam; Chitalu, Ndashi; Vamos, Szonja; Gomez, Jacqueline; Weiss, Stephen M.

    2009-01-01

    This study sought to identify strategies for living with the challenges of HIV and antiretroviral (ARV) use among new medication users in urban Zambia. Participants (n = 160) were recruited from urban Lusaka, Zambia. Qualitative Data was drawn from monthly ARV treatment education intervention groups addressing HIV and antiretroviral use. Themes…

  14. Parenteral antiretroviral formulations are still urgently needed: a case report and commentary.

    PubMed

    Odongo, Fatuma Catherine Atieno

    2015-05-01

    This case report highlights a challenging clinical dilemma to administer antiretroviral therapy in a critically-ill human immunodeficiency virus-infected patient who presented with multiple opportunistic infections and a non-functional gastrointestinal tract. The need for parenteral antiretroviral drug options is discussed and investigational drugs are briefly reviewed. PMID:24890687

  15. Impact of a Rural Village Women (Asha) Intervention on Adherence to Antiretroviral Therapy in Southern India

    PubMed Central

    Nyamathi, Adeline; Hanson, Alecia Y.; Salem, Benissa E.; Sinha, Sanjeev; Ganguly, Kalyan K.; Leake, Barbara; Yadav, Kartik; Marfisee, Mary

    2012-01-01

    Background Despite the increased prevalence of HIV in the rural female population of India, adherence to antiretroviral therapy continues to be low due to several barriers which discourage rural women. Objectives To assess the effectiveness of an intervention (Asha-Life) delivered by Accredited Social Health Activists to improve antiretroviral therapy adherence of rural women living with AIDS in India compared to that of a usual care group. Method A total of 68 rural women living with AIDS, aged 18–45 years, participated in a prospective, randomized pilot clinical trial and were assessed for several factors affecting adherence, such as sociodemographic characteristics, health history, CD4 cell count, enacted stigma, depressive symptomology, help getting antiretroviral therapy, and perceived therapy benefits. Results Findings at 6 months revealed that, while both groups improved their adherence to antiretroviral therapy, there was greater improvement in the Asha-Life group (p < .001), who reported a greater reduction in barriers to antiretroviral therapy than those in the usual care group. Discussion Antiretroviral therapy adherence showed significant increase in the Asha-Life cohort, in which basic education on HIV/AIDS, counseling on antiretroviral therapy, financial assistance, and better nutrition was provided. The Asha-Life intervention may have great potential in improving antiretroviral therapy adherence and decreasing barriers among rural women living with AIDS in India. PMID:22872107

  16. Approaches to rationing antiretroviral treatment: ethical and equity implications.

    PubMed Central

    Bennett, Sara; Chanfreau, Catherine

    2005-01-01

    Despite a growing global commitment to the provision of antiretroviral therapy (ART), its availability is still likely to be less than the need. This imbalance raises ethical dilemmas about who should be granted access to publicly-subsidized ART programmes. This paper reviews the eligibility and targeting criteria used in four case-study countries at different points in the scale-up of ART, with the aim of drawing lessons regarding ethical approaches to rationing. Mexico, Senegal, Thailand and Uganda have each made an explicit policy commitment to provide antiretrovirals to all those in need, but are achieving this goal in steps--beginning with explicit rationing of access to care. Drawing upon the case-studies and experiences elsewhere, categories of explicit rationing criteria have been identified. These include biomedical factors, adherence to treatment, prevention-driven factors, social and economic benefits, financial factors and factors driven by ethical arguments. The initial criteria for determining eligibility are typically clinical criteria and assessment of adherence prospects, followed by a number of other factors. Rationing mechanisms reflect several underlying ethical theories and the ethical underpinnings of explicit rationing criteria should reflect societal values. In order to ensure this alignment, widespread consultation with a variety of stakeholders, and not only policy-makers or physicians, is critical. Without such explicit debate, more rationing will occur implicitly and this may be more inequitable. The effects of rationing mechanisms upon equity are critically dependent upon the implementation processes. As antiretroviral programmes are implemented it is crucial to monitor who gains access to these programmes. PMID:16175829

  17. Short course antiretroviral regimens to reduce maternal transmission of HIV.

    PubMed

    Wilkinson, D; Karim, S S; Coovadia, H M

    1999-02-20

    The ACTG076 trial showed that a complex and expensive antiretroviral regimen reduced mother-to-child HIV transmission by 67%. A more recent Bangkok perinatal HIV study found that oral zidovudine (AZT) given during late pregnancy and labor to non-breast-feeding women reduced the rate of vertical HIV transmission by 51%. These latter findings are particularly interesting to countries unable to afford the more expensive and complex 076 regimen. The reaction to the results of the Bangkok trial may, however, threaten the health of Africa's poorest women and children. Within days of the release of the Thai data, investigators studying other regimens closed recruitment to the placebo arms of their trials, and it has recently become clear that the National Institutes for Health will probably fund no more placebo-controlled trials of interventions designed to reduce maternal HIV transmission. The use of antiretroviral drugs in Africa is unlikely to ever significantly reduce maternal HIV transmission and the incidence of pediatric AIDS. While most of Africa's women have no option to breast-feed, breast-feeding is responsible for one-third of maternal HIV transmission cases. The results of the Thai trials only partially address the needs of African women, for the nutritional, immunological, and birth spacing benefits of breast-feeding should be retained if possible, and formula feeding may stigmatize HIV-infected mothers. The short-course regimen is still expensive to developing countries, and the implementation of a costly, vertical program may also draw financial and human resources from other programs. Placebo-controlled trials to develop simple, cheap, and effective potentially non-drug interventions against vertical HIV transmission should be encouraged in settings in which antiretroviral drugs and formula feeding cannot be safely delivered. PMID:10024252

  18. Medication Possession Ratio Predicts Antiretroviral Regimens Persistence in Peru

    PubMed Central

    Westfall, Andrew O.; Paz, Jorge; Moran, Fiorella; Carbajal-Gonzalez, Danny; Callacondo, David; Avalos, Odalie; Rodriguez, Martin; Gotuzzo, Eduardo; Echevarria, Juan; Willig, James H.

    2013-01-01

    Objectives In developing nations, the use of operational parameters (OPs) in the prediction of clinical care represents a missed opportunity to enhance the care process. We modeled the impact of multiple measurements of antiretroviral treatment (ART) adherence on antiretroviral treatment outcomes in Peru. Design And Methods Retrospective cohort study including ART naïve, non-pregnant, adults initiating therapy at Hospital Nacional Cayetano Heredia, Lima-Peru (2006-2010). Three OPs were defined: 1) Medication possession ratio (MPR): days with antiretrovirals dispensed/days on first-line therapy; 2) Laboratory monitory constancy (LMC): proportion of 6 months intervals with ≥1 viral load or CD4 reported; 3) Clinic visit constancy (CVC): proportion of 6 months intervals with ≥1 clinic visit. Three multi-variable Cox proportional hazard (PH) models (one per OP) were fit for (1) time of first-line ART persistence and (2) time to second-line virologic failure. All models were adjusted for socio-demographic, clinical and laboratory variables. Results 856 patients were included in first-line persistence analyses, median age was 35.6 years [29.4-42.9] and most were male (624; 73%). In multivariable PH models, MPR (per 10% increase HR=0.66; 95%CI=0.61-0.71) and LMC (per 10% increase 0.83; 0.71-0.96) were associated with prolonged time on first-line therapies. Among 79 individuals included in time to second-line virologic failure analyses, MPR was the only OP independently associated with prolonged time to second-line virologic failure (per 10% increase 0.88; 0.77-0.99). Conclusions The capture and utilization of program level parameters such as MPR can provide valuable insight into patient-level treatment outcomes. PMID:24098475

  19. Preventing antiretroviral anarchy in sub-Saharan Africa.

    PubMed

    Harries, A D; Nyangulu, D S; Hargreaves, N J; Kaluwa, O; Salaniponi, F M

    2001-08-01

    Combination antiretroviral therapy has dramatically improved the survival of patients living with HIV and AIDS in industrialised countries of the world. Despite this enormous benefit, there are some major problems and obstacles to be overcome.(1) Treatment of HIV-infection is likely to be lifelong.(2) Unfortunately, many HIV-infected individuals cannot tolerate the toxic effects of the drugs, or have difficulty complying with treatment which involves large numbers of pills and complicated dosing schedules. Poor adherence to treatment leads to the emergence of drug-resistant viral strains that need new combinations of drugs or new drugs altogether. PMID:11502341

  20. Combination antiretroviral studies for patients with primary biliary cirrhosis.

    PubMed

    Lytvyak, Ellina; Montano-Loza, Aldo J; Mason, Andrew L

    2016-01-01

    Following the characterization of a human betaretrovirus in patients with primary biliary cirrhosis (PBC), pilot studies using antiretroviral therapy have been conducted as proof of principal to establish a link of virus with disease and with the eventual aim to find better adjunct therapies for patients unresponsive to ursodeoxycholic acid. In the first open label pilot study, the reverse transcriptase inhibitor lamivudine had little demonstrable biochemical or histological effect after 1 year. Whereas, lamivudine in combination with zidovudine was associated with a significant reduction in alkaline phosphatase as well as improvement in necroinflammatory score, cholangitis and ductopenia over a 12 mo period. A double blind, multi-center randomized controlled trial using lamivudine with zidovudine for 6 mo confirmed a significant reduction in alkaline phosphatase, ALT and AST in patients on antiviral therapy. However, none of the patients achieved the stringent endpoint criteria for normalization of alkaline phosphatase. Furthermore, some patients developed biochemical rebound consistent with drug resistance. A major fault of these studies has been the inability to measure the viral load in peripheral blood and therefore, provide a direct correlation between improvement of hepatic biochemistry and reduction in viral load. Nevertheless, viral mutants to lamivudine with zidovudine were later characterized in the NOD.c3c4 mouse model of PBC that has been used to test other antiretroviral regimens to betaretrovirus. The combination of tenofovir and emtricitabine reverse transcriptase inhibitors and the HIV protease inhibitor, lopinavir were found to abrogate cholangitis in the NOD.c3c4 mouse model and the same regimen normalized the liver tests in a PBC patient with HIV and human betaretrovirus infection. This combination antiretroviral therapy has now been used in a double blind randomized controlled crossover study for patients with PBC followed by an open label

  1. Epidemiology and Management of Antiretroviral-Associated Cardiovascular Disease

    PubMed Central

    Chastain, Daniel B; Henderson, Harold; Stover, Kayla R

    2015-01-01

    Risk and manifestations of cardiovascular disease (CVD) in patients infected with human immunodeficiency virus (HIV) will continue to evolve as improved treatments and life expectancy of these patients increases. Although initiation of antiretroviral (ARV) therapy has been shown to reduce this risk, some ARV medications may induce metabolic abnormalities, further compounding the risk of CVD. In this patient population, both pharmacologic and nonpharmacologic strategies should be employed to treat and reduce further risk of CVD. This review summarizes epidemiology data of the risk factors and development of CVD in HIV and provides recommendations to manage CVD in HIV-infected patients. PMID:25866592

  2. Antiretroviral Therapy for Prevention of Human Immunodeficiency Virus Infection.

    PubMed

    Kalapila, Aley G; Marrazzo, Jeanne

    2016-07-01

    Human immunodeficiency virus (HIV) infection is considered a chronic medical condition. Several new drugs are available, including fixed-dose combination tablets, that have greatly simplified combination antiretroviral therapy (ART) regimens to treat HIV, while increasing the life-expectancy of infected individuals. In the last decade, multiple well-regarded studies have established the benefits of using ART in high-risk, HIV-negative persons to prevent HIV acquisition. The primary care provider must not only understand commonly encountered issues pertaining to ART, such as toxicities and drug interactions, but also needs to be aware of using ART for HIV prevention. PMID:27235622

  3. Combination antiretroviral studies for patients with primary biliary cirrhosis

    PubMed Central

    Lytvyak, Ellina; Montano-Loza, Aldo J; Mason, Andrew L

    2016-01-01

    Following the characterization of a human betaretrovirus in patients with primary biliary cirrhosis (PBC), pilot studies using antiretroviral therapy have been conducted as proof of principal to establish a link of virus with disease and with the eventual aim to find better adjunct therapies for patients unresponsive to ursodeoxycholic acid. In the first open label pilot study, the reverse transcriptase inhibitor lamivudine had little demonstrable biochemical or histological effect after 1 year. Whereas, lamivudine in combination with zidovudine was associated with a significant reduction in alkaline phosphatase as well as improvement in necroinflammatory score, cholangitis and ductopenia over a 12 mo period. A double blind, multi-center randomized controlled trial using lamivudine with zidovudine for 6 mo confirmed a significant reduction in alkaline phosphatase, ALT and AST in patients on antiviral therapy. However, none of the patients achieved the stringent endpoint criteria for normalization of alkaline phosphatase. Furthermore, some patients developed biochemical rebound consistent with drug resistance. A major fault of these studies has been the inability to measure the viral load in peripheral blood and therefore, provide a direct correlation between improvement of hepatic biochemistry and reduction in viral load. Nevertheless, viral mutants to lamivudine with zidovudine were later characterized in the NOD.c3c4 mouse model of PBC that has been used to test other antiretroviral regimens to betaretrovirus. The combination of tenofovir and emtricitabine reverse transcriptase inhibitors and the HIV protease inhibitor, lopinavir were found to abrogate cholangitis in the NOD.c3c4 mouse model and the same regimen normalized the liver tests in a PBC patient with HIV and human betaretrovirus infection. This combination antiretroviral therapy has now been used in a double blind randomized controlled crossover study for patients with PBC followed by an open label

  4. In utero and postnatal exposure to antiretrovirals among HIV-exposed but uninfected children in the United States.

    PubMed

    Griner, Raymond; Williams, Paige L; Read, Jennifer S; Seage, George R; Crain, Marilyn; Yogev, Ram; Hazra, Rohan; Rich, Kenneth

    2011-07-01

    An increasing number of antiretroviral agents (ARVs) are approved for use, but their use during pregnancy in the United States has not been completely described. We used data from the Pediatric HIV/AIDS Cohort Study (PHACS) Surveillance Monitoring for ART Toxicities (SMARTT) study, a United States-based prospective cohort study of HIV-exposed but uninfected children, to assess temporal trends and maternal characteristics associated with the use of ARVs during pregnancy. The proportion of children exposed in utero to ARVs was calculated over time. A multivariable logistic regression model was used to estimate associations of maternal characteristics with use of highly active antiretroviral therapy (HAART) during pregnancy. We studied 1768 HIV-exposed but uninfected children born between 1995 and 2009 and enrolled in SMARTT. Prenatal HAART exposure increased from 19% in 1997 to 88% in 2009. Of children born in 2009, 99% had prenatal exposure to NRTIs (including zidovudine, 73%; lamivudine, 72%; tenofovir, 39%; and emtricitabine, 37%). Exposure to protease inhibitors increased from 15% in 1997 to 86% in 2009, while exposure to non-nucleoside reverse transcriptase inhibitors (NNRTIs) declined from 33% in 2003 to 11% in 2009. Higher maternal HIV RNA viral load (VL) concentration, lower maternal CD4 count, and earlier timing of the first maternal CD4 or VL measurement during pregnancy were associated with increased odds of HAART exposure. Prenatal HAART exposure has increased but is not universal. As ARV use during pregnancy continues to evolve, follow-up of children is needed to assess long-term effects of ARV exposures. PMID:21992592

  5. Depressive and Anxiety Symptoms Predict Sustained Quality of Life Deficits in HIV-Positive Ugandan Adults Despite Antiretroviral Therapy

    PubMed Central

    Ezeamama, Amara E; Woolfork, Makhabele N; Guwatudde, David; Bagenda, Danstan; Manabe, Yukari C; Fawzi, Wafaie W; Smith Fawzi, Mary C

    2016-01-01

    Abstract The impact of psychosocial status at onset of antiretroviral therapy on changes in quality of life (QOL) and subjectively rated health (SRH) among adults on highly active antiretroviral therapy (HAART) in resource-limited settings is poorly understood. Therefore, we evaluate the association between stigma, anxiety, depression, and social support and change in QOL and SRH in HIV-infected Ugandan adults during an 18-month period. Psychosocial indicators were assessed at enrollment using structured questionnaires. QOL and SRH measures were assessed at months 0, 6, 12, and 18 using the Medical Outcomes Survey-HIV. Linear mixed models determined risk estimated differences in QOL and SRH in relation to quartiles of each psychosocial status indicator. Repeated measures generalized estimating equations modeling was implemented to assess differences in likelihood of improved versus nonimproved SRH during follow-up. QOL scores and SRH improved significantly for all participants over 18 months (P < 0.0001). The gain in QOL increased dose-dependently as baseline depressive symptoms (time∗depression P < 0.001) and anxiety levels (time∗anxiety P < 0.001) declined. Lower social support was associated with worse QOL at baseline (P = 0.0005) but QOL improvement during follow-up was not dependent on baseline level of social support (time∗social support P = 0.8943) or number of stigmatizing experiences (time∗stigma P = 0.8662). Psychosocial determinants did not predict changes in SRH in this study. High levels of depression and anxiety symptoms at HAART initiation predicts lower gains in QOL for HIV-positive patients for as long as 18 months. Long-term QOL improvements in HIV-infected adults may be enhanced by implementation of psychosocial interventions to reduce depression and anxiety in HIV-infected adults. PMID:26945347

  6. Formative evaluation of antiretroviral therapy scale-up efficiency in sub-Saharan Africa.

    PubMed

    Wagner, Glenn; Ryan, Gery; Taylor, Stephanie

    2007-11-01

    With millions in need of HIV antiretroviral therapy (ART) in the developing world, and scarce human and fiscal resources available, we conducted a formative evaluation of scale-up operations at clinics associated with AIDS Healthcare Foundation in Africa to identify lessons learned for improving scale-up efficiency. Site visits were made to six selected clinics in Uganda, Zambia, and South Africa, during which semistructured interviews with key stake-holders and observation of client flows and clinic operations were performed. This evaluation revealed the following lessons related to factors that are critical to efficient ART scale-up: (1) to ensure steady ART uptake, it is important to involve the community and community leaders in outreach, HIV education, and program decision-making; (2) minimizing bottlenecks to smooth patient flow requires efficient staff allocation to appropriate clinical duties, streamlined clinic visit schedule protocols, and tapping clients and the HIV community as a key source of labor; (3) to minimize clients dropping out of care, structures should be developed that enable clients to provide support and a "safety net" for helping each other remain in care; (4) computerized record management systems are essential for accurate antiretroviral inventory and dispensing records, quality assurance monitoring, and client enrollment records and visit scheduling; (5) effective organizational management and human resource policies are essential to maintain high job performance and satisfaction and limit burnout; (6) to maximize impact on social and economic health, it is important for ART programs to develop effective mechanisms for coordinating and referring clients to support service organizations. PMID:18240896

  7. Patterns of geographic mobility predict barriers to engagement in HIV care and antiretroviral treatment adherence.

    PubMed

    Taylor, Barbara S; Reyes, Emily; Levine, Elizabeth A; Khan, Shah Z; Garduño, L Sergio; Donastorg, Yeycy; Hammer, Scott M; Brudney, Karen; Hirsch, Jennifer S

    2014-06-01

    Migration and geographic mobility increase risk for HIV infection and may influence engagement in HIV care and adherence to antiretroviral therapy. Our goal is to use the migration-linked communities of Santo Domingo, Dominican Republic, and New York City, New York, to determine the impact of geographic mobility on HIV care engagement and adherence to treatment. In-depth interviews were conducted with HIV+Dominicans receiving antiretroviral therapy, reporting travel or migration in the past 6 months and key informants (n=45). Mobility maps, visual representations of individual migration histories, including lifetime residence(s) and all trips over the past 2 years, were generated for all HIV+ Dominicans. Data from interviews and field observation were iteratively reviewed for themes. Mobility mapping revealed five distinct mobility patterns: travel for care, work-related travel, transnational travel (nuclear family at both sites), frequent long-stay travel, and vacation. Mobility patterns, including distance, duration, and complexity, varied by motivation for travel. There were two dominant barriers to care. First, a fear of HIV-related stigma at the destination led to delays seeking care and poor adherence. Second, longer trips led to treatment interruptions due to limited medication supply (30-day maximum dictated by programs or insurers). There was a notable discordance between what patients and providers perceived as mobility-induced barriers to care and the most common barriers found in the analysis. Interventions to improve HIV care for mobile populations should consider motivation for travel and address structural barriers to engagement in care and adherence. PMID:24839872

  8. Patterns of Geographic Mobility Predict Barriers to Engagement in HIV Care and Antiretroviral Treatment Adherence

    PubMed Central

    Reyes, Emily; Levine, Elizabeth A.; Khan, Shah Z.; Garduño, L. Sergio; Donastorg, Yeycy; Hammer, Scott M.; Brudney, Karen; Hirsch, Jennifer S.

    2014-01-01

    Abstract Migration and geographic mobility increase risk for HIV infection and may influence engagement in HIV care and adherence to antiretroviral therapy. Our goal is to use the migration-linked communities of Santo Domingo, Dominican Republic, and New York City, New York, to determine the impact of geographic mobility on HIV care engagement and adherence to treatment. In-depth interviews were conducted with HIV+Dominicans receiving antiretroviral therapy, reporting travel or migration in the past 6 months and key informants (n=45). Mobility maps, visual representations of individual migration histories, including lifetime residence(s) and all trips over the past 2 years, were generated for all HIV+ Dominicans. Data from interviews and field observation were iteratively reviewed for themes. Mobility mapping revealed five distinct mobility patterns: travel for care, work-related travel, transnational travel (nuclear family at both sites), frequent long-stay travel, and vacation. Mobility patterns, including distance, duration, and complexity, varied by motivation for travel. There were two dominant barriers to care. First, a fear of HIV-related stigma at the destination led to delays seeking care and poor adherence. Second, longer trips led to treatment interruptions due to limited medication supply (30-day maximum dictated by programs or insurers). There was a notable discordance between what patients and providers perceived as mobility-induced barriers to care and the most common barriers found in the analysis. Interventions to improve HIV care for mobile populations should consider motivation for travel and address structural barriers to engagement in care and adherence. PMID:24839872

  9. Antiretroviral Therapy and Reproductive Life Projects: Mitigating the Stigma of AIDS in Nigeria

    PubMed Central

    Mbakwem, Benjamin C

    2010-01-01

    As millions of people infected with HIV in Africa are increasingly able to live longer and healthier lives because of access to antiretroviral therapy, concerns have emerged that people might eschew protective practices after their health improves. Extending beyond the notion of sexual “disinhibition,” researchers have begun to analyze the sexual behavior of people in treatment through the perspective of their marital and childbearing aspirations. This article explores the reproductive life projects of HIV-positive men and women in southeastern Nigeria, showing how actions that contradict medical advice are understandable in the context of patients’ socially normative desires for marriage and children. Based on in-depth interviews and observations (June–December 2004; June–July 2006; June–July 2007) of people enrolled in the region’s oldest treatment program, we argue that broadly held social expectations with regard to reproduction are experienced even more acutely by HIV-positive people. This is because in Nigeria the stigma associated with AIDS is closely tied to widespread perceptions of social and moral crisis, such that AIDS itself is seen as both a cause and a symptom of anxiety-producing forms of social change. Specifically, in an era of rapid societal transformation, Nigerians see sexual promiscuity and the alienation of young people from traditional obligations to kin and community as indicative of threatened social reproduction. For people who are HIV-positive, marrying and having children offer not only the opportunity to lead normal lives, but also a means to mitigate the stigma associated with the disease. Four ethnographic case studies are provided to exemplify how and why social and personal life projects can trump or complicate medical and public health priorities. These examples suggest that treatment programs must openly address and proactively support the life projects of people on antiretroviral therapy if the full benefits of

  10. [Factors associated to late clinical stage at the initiation of antiretroviral therapy].

    PubMed

    Warley, Eduardo; Fernández Galimberti, Guillermo; Vieni, María Inés; Tavella, Silvina; Salas, Mónica; Desse, Javier; D'Agostino, Graciela; Szyld, Edgardo

    2012-01-01

    In order to evaluate the frequency of a late clinical stage in HIV infected patients at onset of antiretroviral therapy (LART) and to identify possible associated factors, we performed a retrospective analysis of data reported in two prospective cohorts of HIV infected patients who started antiretroviral therapy for the first time between 2005 and 2009. Medical records of 265 patients -123 women (46.6%) and 141 men, median age 37.7 years old- were analyzed. LART was observed in 132 cases (50%), out of them 102 (77.2%) were associated to late diagnosis of HIV infection and 30 (22.8%) to patients that had not been retained in HIV care. The median of CD4 was 120 cells/ml and that of viral load 58 038 copies/ml. CD4 cells count was below 200 cells/ml in 174 patients (71.3%). There was a higher incidence of LART in men than in women (59.8% and 42.2% respectively). Diagnosis in women took place during pregnancy control in 25:2% of the cases. High alcohol consumption (p 0.006), single hood (p 0.04) and level of education lower than secondary (p 0.008) were associated to LART at bivariate analysis. Male sex (p 0.003) was the only associated factor both in bivariate and multivariate analysis. Our data reinforce the need of expanding HIV testing and should assist programs to define actions promoting early entry in HIV care. PMID:23089111

  11. Progressive cerebral injury in the setting of chronic HIV infection and antiretroviral therapy.

    PubMed

    Gongvatana, Assawin; Harezlak, Jaroslaw; Buchthal, Steven; Daar, Eric; Schifitto, Giovanni; Campbell, Thomas; Taylor, Michael; Singer, Elyse; Algers, Jeffrey; Zhong, Jianhui; Brown, Mark; McMahon, Deborah; So, Yuen T; Mi, Deming; Heaton, Robert; Robertson, Kevin; Yiannoutsos, Constantin; Cohen, Ronald A; Navia, Bradford

    2013-06-01

    Emerging evidence suggests that CNS injury and neurocognitive impairment persist in the setting of chronic HIV infection and combination antiretroviral therapy (CART). Yet, whether neurological injury can progress in this setting remains uncertain. Magnetic resonance spectroscopy and neurocognitive and clinical assessments were performed over 2 years in 226 HIV-infected individuals on stable CART, including 138 individuals who were neurocognitively asymptomatic (NA). Concentrations of N-acetylaspartate (NAA), creatine (Cr), choline (Cho), myoinositol, and glutamate/glutamine (Glx) were measured in the midfrontal cortex (MFC), frontal white matter (FWM), and basal ganglia (BG). Longitudinal changes in metabolite levels were determined using linear mixed effect models, as were metabolite changes in relation to global neurocognitive function. HIV-infected subjects showed significant annual decreases in brain metabolite levels in all regions examined, including NAA (2.95 %) and Cho (2.61 %) in the FWM; NAA (1.89 %), Cr (1.84 %), Cho (2.19 %), and Glx (6.05 %) in the MFC; and Glx (2.80 %) in the BG. Similar metabolite decreases were observed in the NA and subclinically impaired subgroups, including subjects with virologic suppression in plasma and CSF. Neurocognitive decline was associated with longitudinal decreases in Glx in the FWM and the BG, and in NAA in the BG. Widespread progressive changes in the brain, including neuronal injury, occur in chronically HIV-infected persons despite stable antiretroviral treatment and virologic suppression and can lead to neurocognitive declines. The basis for these findings is poorly understood and warrants further study. PMID:23613008

  12. Antiretroviral therapy, labor productivity, and gender: a longitudinal cohort study of tea pluckers in Kenya

    PubMed Central

    LARSON, Bruce. A.; FOX, Matthew P.; BII, Margaret; ROSEN, Sydney; ROHR, Julia; SHAFFER, Douglas; SAWE, Fredrick; WASUNNA, Monique; SIMON, Jonathon L.

    2014-01-01

    Objective To estimate the impact of antiretroviral therapy (ART) on labor productivity and income using detailed employment data from two large tea plantations in western Kenya for HIV-infected tea pluckers who initiated ART. Design Longitudinal study using primary data on key employment outcomes for a group of HIV-infected workers receiving anti-retroviral therapy (ART) and workers in the general workforce. Methods We used nearest-neighbor matching methods to estimate the impacts of HIV/AIDS and ART among 237 HIV-positive pluckers on ART (index group) over a four year period (2 years pre- and post-ART) on four monthly employment outcomes—days plucking tea, total kilograms harvested, total days working, and total labor income. Outcomes for the index group were compared to those for a matched reference group from the general workforce. Results We observed a rapid deterioration in all four outcomes for HIV-infected subjects in the period before ART initiation and then a rapid improvement after treatment initiation. By 18–24 months after treatment initiation, the index group harvested 8% (males) and 19% (females) less tea than reference subjects. The index group earned 6% (males) and 9% (females) less income from labor than reference subjects. Women’s income would have dropped further if they had not been able to offset their decline in tea plucking by spending more time on non-plucking assignments. Conclusions HIV-infected workers experienced long-term income reductions before and after initiating ART. The implications of such long-term impacts in low-income countries have not been adequately addressed. PMID:23014516

  13. Highly Active Multidentate Ligand-Based Alkyne Metathesis Catalysts.

    PubMed

    Du, Ya; Yang, Haishen; Zhu, Chengpu; Ortiz, Michael; Okochi, Kenji D; Shoemaker, Richard; Jin, Yinghua; Zhang, Wei

    2016-06-01

    Alkyne metathesis catalysts composed of molybdenum(VI) propylidyne and multidentate tris(2-hydroxylbenzyl)methane ligands have been developed, which exhibit excellent stability (remains active in solution for months at room temperature), high activity, and broad functional-group tolerance. The homodimerization and cyclooligomerization of monopropynyl or dipropynyl substrates, including challenging heterocycle substrates (e.g., pyridine), proceed efficiently at 40-55 °C in a closed system. The ligand structure and catalytic activity relationship has been investigated, which shows that the ortho groups of the multidentate phenol ligands are critical to the stability and activity of such a catalyst system. PMID:27113640

  14. Christian identity and men's attitudes to antiretroviral therapy in Zambia.

    PubMed

    Simpson, Anthony

    2010-12-01

    Increasing access to antiretroviral therapy (ART), especially in urban areas in Zambia, has transformed the landscape of the HIV epidemic to include hope. Drawing upon long-term ethnographic research, this article briefly describes the religious ideas of a cohort of former students of a Catholic mission boarding school for boys. The discussion outlines their understanding of masculinity and charts their responses, first to voluntary counselling and testing for HIV, and, more recently, to the 'miraculous' returns to health they have experienced or witnessed as a result of ART. The article examines the problems of self-disclosure among self-identified Catholics who are aware of their HIV-positive status and their reluctance to publically acknowledge that they are receiving ART. The research locates the source of this reluctance within existing associations of Christianity with 'civilisation' and 'respectability.' The article concludes that the Catholic Church in Zambia needs to do more to combat negative responses to people living with HIV, which cause both shame and loss of respect and militate against Zambians coming forward to access ART as well as against good antiretroviral adherence. One way in which this might be achieved is for the Catholic Church to be more open about priests and other members of the religious community who are receiving ART. PMID:25875888

  15. [Positioning of lopinavir/ritonavir in antiretroviral treatment schemes].

    PubMed

    Camacho, Ángela; Rivero, Antonio

    2014-11-01

    Lopinavir/ritonavir (LPV/r) was approved for use in the treatment of human immunodeficiency virus (HIV) infection in 2001 and is the protease inhibitor that has been most widely studied in clinical trials. Despite the time interval since its approval, all the evidence accumulated in the last 14 years indicates that LPV/r continues to occupy an important position among antiretroviral drugs. Firstly, LPV/r plus 2 nucleoside/nucleotide analogs is still considered a good option for initial antiretroviral therapy (ART). Secondly, numerous studies have evaluated the efficacy and safety of new initial ART strategies based on LPV/r in dual therapy. The results obtained suggest that LPV/r plus lamivudine (3TC) or raltegravir can be as effective in initial ART as standard triple therapy and justify their consideration as alternative regimens in this scenario. Thirdly, LPV/r is a pioneer drug, as well as being the agent with the largest amount of evidence from clinical trials on simplification to monotherapy (LPV/r) or dual therapy (LPV/r + 3TC). Lastly, LPV/r is highly useful is special situations. It has a low risk of liver toxicity in patients with chronic liver disease, its use is preferred in the treatment of patients with HIV-2, and it is safe and effective in preventing vertical HIV transmission. PMID:25542874

  16. Antiretroviral chemoprophylaxis: state of evidence and the research agenda.

    PubMed

    Mayer, Kenneth H

    2014-07-01

    Oral antiretroviral preexposure prophylaxis (PrEP) has been shown to decrease human immunodeficiency virus (HIV) incidence in studies of men who have sex with men, heterosexual men and women, and injecting drug users. One study of pericoital tenofovir gel demonstrated that it reduced HIV incidence in South African women. However, other studies of African women failed to demonstrate protection with either oral tenofovir or tenofovir-emtricitabine, or daily tenofovir gel. The magnitude of PrEP protection appears to be highly correlated with medication adherence. New studies are evaluating whether different antiretrovirals, including dapivirine, rilpivirine, maraviroc, and new integrase inhibitors. Different formulations are also being evaluated, including gels, films, vaginal rings, and injectable medication. Although PrEP efficacy has been demonstrated, and several normative bodies (eg, the US Food and Drug Administration) have approved PrEP for clinical use, uptake has been slow. Reasons may include lack of sufficient provider and consumer education, residual concerns about costs, potential long-term toxicities, and behavioral disinhibition. Additional work is under way to determine how to best educate consumers and providers about optimal adherence and to use PrEP in conjunction with risk mitigation. PMID:24926034

  17. Intellectual property rights, market competition and access to affordable antiretrovirals.

    PubMed

    Pascual, Fernando

    2014-01-01

    The number of patients receiving antiretroviral therapy (ART) has increased from around half a million in 2003 to almost 10 million in only 10 years, and will continue to increase in the coming years. Over 16 million more are eligible to start ART according to the last World Health Organization (WHO) guidelines. The demand is also switching from the less expensive antiretrovirals (ARVs) that allowed such scale-up to newer more expensive ones with fewer side effects or those that can be used by people who have developed resistance to first-line treatment. However, patents on these new drugs can delay robust generic competition and, consequently, price reduction made possible by economies of scale. Various ways to address this issue have been envisaged or implemented, including the use of the flexibilities available under the Agreement on Trade-Related Aspects of Intellectual Property Rights (TRIPS), systematic widespread voluntary licensing, of which the Medicines Patent Pool (MPP) is an example, and the application of different prices in different countries, called tiered pricing. This paper helps explain the impact of patents on market competition for ARVs and analyses various approaches available today to minimize this impact. PMID:25309984

  18. Antiretroviral Chemoprophylaxis: State of Evidence and the Research Agenda

    PubMed Central

    Mayer, Kenneth H.

    2014-01-01

    Oral antiretroviral preexposure prophylaxis (PrEP) has been shown to decrease human immunodeficiency virus (HIV) incidence in studies of men who have sex with men, heterosexual men and women, and injecting drug users. One study of pericoital tenofovir gel demonstrated that it reduced HIV incidence in South African women. However, other studies of African women failed to demonstrate protection with either oral tenofovir or tenofovir-emtricitabine, or daily tenofovir gel. The magnitude of PrEP protection appears to be highly correlated with medication adherence. New studies are evaluating whether different antiretrovirals, including dapivirine, rilpivirine, maraviroc, and new integrase inhibitors. Different formulations are also being evaluated, including gels, films, vaginal rings, and injectable medication. Although PrEP efficacy has been demonstrated, and several normative bodies (eg, the US Food and Drug Administration) have approved PrEP for clinical use, uptake has been slow. Reasons may include lack of sufficient provider and consumer education, residual concerns about costs, potential long-term toxicities, and behavioral disinhibition. Additional work is under way to determine how to best educate consumers and providers about optimal adherence and to use PrEP in conjunction with risk mitigation. PMID:24926034

  19. [Companion Diagnostics for Selecting Antiretroviral Drugs against HIV-1].

    PubMed

    Fukutake, Katsuyuki

    2015-11-01

    Currently, the treatment of human immunodeficiency virus involves combination therapy, as antiretroviral therapy(ART). The treatment has improved steadily since the advent of potent combination therapy in 1996. New drugs that offer new mechanisms of action, improvements in potency and activity even against multidrug-resistant viruses, dosing convenience, and tolerability have been approved. Among ART with useful drugs, there are two important examinations before starting the treatment using the two kinds of drug. CCR5 co-receptor antagonists, maraviroc, prevent HIV entry into target cells by binding to CCR5 receptors. Genotypic assays have been developed that can determine or predict the co-receptor tropism(i.e., CCR5, CXCR4, or both) of the patient's dominant virus population. The assay for HIV-1 co-receptor usage should be performed whenever the use of a CCR5 antagonist is being considered. One of the nucleoside/nucleotide reverse transcriptase inhibitors (NRTIs), abacavir, is an important agent to develop recommended regimens for antiretroviral therapy. Serious and sometimes fatal hypersensitivity reactions have been associated with abacavir-containing products, ZIAGEN, Epzicom, and Triumeq. Patients who carry the HLA-B*5701 allele are at high-risk of a hypersensitivity reaction to abacavir. Prior to initiating therapy with abacavir, performing a screening test for the HLA-B*5701 allele is recommended. [Review]. PMID:26995879

  20. Subclinical coronary atherosclerosis, HIV infection and antiretroviral therapy: Multicenter AIDS Cohort Study

    PubMed Central

    Kingsley, Lawrence A.; Cuervo-Rojas, Juliana; Muñoz, Alvaro; Palella, Frank J.; Post, Wendy; Witt, Mallory D.; Budoff, Matthew; Kuller, Lewis

    2010-01-01

    Objective To evaluate the association of HIV infection and cumulative exposure to highly active antiretroviral therapy (HAART) with the presence and extent of coronary artery calcification (CAC). Design A cross-sectional study of 947 male participants (332 HIV-seronegative, 84 HAART-naive and 531 HAART-experienced HIV-infected) from the Multicenter AIDS Cohort Study. Methods The main outcome was CAC score calculated as the geometric mean of the Agatston scores of two computed tomography replicates. Presence of CAC was defined as calcification score above 10, and extent of CAC by the score for those with CAC present. Multivariable regression was used to evaluate the association between HIV infection and HAART and presence and extent of calcification. Results Increasing age was most strongly associated with both prevalence and extent of CAC for all study groups. After adjustment for age, race, family history, smoking, high-density lipoprotein-C, low-density lipoprotein-C and hypertension, HIV infection (odds ratio, 1.35; 95% confidence interval, 0.70, 2.61) and long-term HAART use (odds ratio, 1.33; 95% confidence interval, 0.87, 2.05) increased the odds for presence of CAC. In contrast, after adjustment for these covariates, the extent of CAC was lower among HAART users. Among those not taking lipid-lowering therapy, HAART usage of at least 8 years was associated with significantly reduced CAC scores (relative CAC score, 0.43; 95% confidence interval, 0.24, 0.79). Conclusion HAART use may have different effects on the presence and extent of coronary calcification. Although prevalence of calcification was marginally increased among long-term HAART users, the extent of calcification was significantly reduced among HAART users compared with HIV-seronegative controls. PMID:18670218

  1. Self-reported adherence to antiretroviral therapy in HIV+ population from Bata, Equatorial Guinea.

    PubMed

    Salmanton-García, Jon; Herrador, Zaida; Ruiz-Seco, Pilar; Nzang-Esono, Jesús; Bendomo, Veronica; Bashmakovic, Emma; Nseng-Nchama, Gloria; Benito, Agustín; Aparicio, Pilar

    2016-05-01

    The human immunodeficiency virus (HIV) and the acquired immune deficiency syndrome (AIDS) represent a serious public health problem in Equatorial Guinea, with a prevalence of 6.2% among adults. the high-activity antiretroviral treatment (HAART) coverage data is 10 points below the overall estimate for Sub-Saharan Africa, and only 61% patients continue with HAART 12 months after it started. This study aims to assess HAART adherence and related factors in Litoral Province of Equatorial Guinea. In this cross-sectional study, socio-demographic and clinical data were collected at Regional Hospital of Bata, during June-July 2014. Adherence to treatment was assessed by using the Spanish version of CEAT-VIH. Bivariate and linear regression analyses were employed to assess HAART adherence-related factors. We interviewed 50 men (35.5%) and 91 women (64.5%), with a mean age of 47.7 ± 8.9 and 36.2 ± 11.2, respectively (p < .001). Overall, 55% patients had low or insufficient adherence. CEAT-VIH score varied by ethnic group (p = .005). There was a positive correlation between CEAT-VIH score and current CD4 T-cells count (p = .013). The Cronbach's α value was 0.52. To our knowledge, this is the first study to assess HAART adherence in Equatorial Guinea. Internal reliability for CEAT-VIH was low, nonetheless the positive correlation between the CEAT-VIH score and the immunological status of patients add value to our findings. Our results serve as baseline for future research and will also assist stakeholders in planning and undertaking contextual and evidence-based policy initiatives. PMID:26698540

  2. Using CD4 Percentage and Age to Optimize Pediatric Antiretroviral Therapy Initiation

    PubMed Central

    Warshaw, Meredith G.; Miller, William C.; Castro, Hannah; Fiscus, Susan A.; Harper, Lynda M.; Harrison, Linda J.; Klein, Nigel J.; Lewis, Joanna; Melvin, Ann J.; Tudor-Williams, Gareth; McKinney, Ross E.

    2014-01-01

    BACKGROUND: Quantifying pediatric immunologic recovery by highly active antiretroviral therapy (HAART) initiation at different CD4 percentage (CD4%) and age thresholds may inform decisions about timing of treatment initiation. METHODS: HIV-1-infected, HAART-naive children in Europe and the Americas were followed from 2002 through 2009 in PENPACT-1. Data from 162 vertically infected children, with at least World Health Organization “mild” immunosuppression and CD4% <10th percentile, were analyzed for improvement to a normal CD4% (≥10th percentile) within 4 years after HAART initiation. Data from 209 vertically infected children, regardless of immune status, were analyzed for CD4% outcomes at 4 years and viral failure within 4 years. RESULTS: Seventy-two percent of baseline immunosuppressed children recovered to normal within 4 years. Compared with “severe” immunosuppression, more children with “mild” immunosuppression (difference 36%, 95% confidence interval [CI]: 22% to 49%) or “advanced” immunosuppression (difference 20.8%, 95% CI: 5.8% to 35.9%) recovered a normal CD4%. For each 5-year increase in baseline age, the proportion of children achieving a normal CD4% declined by 19% (95% CI: 11% to 27%). Combining baseline CD4% and age effects resulted in >90% recovery when initiating HAART with “mild” immunosuppression at any age or “advanced” immunosuppression at age <3 years. Baseline CD4% effects became greater with increasing age (P = .02). At 4 years, most immunologic benefits were still significant but diminished. Viral failure was highest in infancy (56%) and adolescence (63%). CONCLUSIONS: Initiating HAART at higher CD4% and younger ages maximizes potential for immunologic recovery. Guidelines should weigh immunologic benefits against long-term risks. PMID:25266426

  3. Broadening the use of antiretroviral therapy: the case for feline leukemia virus

    PubMed Central

    Greggs, Willie M; Clouser, Christine L; Patterson, Steven E; Mansky, Louis M

    2011-01-01

    Antiretroviral drugs have saved and extended the lives of millions of individuals infected with HIV. The major classes of anti-HIV drugs include reverse transcriptase inhibitors, protease inhibitors, integrase inhibitors, and entry/fusion inhibitors. While antiretroviral drug regimens are not commonly used to treat other types of retroviral infections, there are instances where there is a perceived need for re-evaluation of the benefits of antiretroviral therapy. One case in point is that of feline leukemia virus (FeLV), an infection of companion felines. While vaccines exist to prevent FeLV infection and spread, they have not eliminated FeLV infection. For FeLV-infected felines and their human companions, antiretroviral therapy would be desirable and of practical importance if good options were available. Here, we discuss FeLV biology and current treatment options, and propose that there is a need for antiretroviral treatment options for FeLV infection. The comparative use and analysis of antiretroviral therapy can provide new insights into the mechanism of antiretroviral drug action. PMID:21479142

  4. Increasing use of 'party drugs' in people living with HIV on antiretrovirals: a concern for patient safety.

    PubMed

    Bracchi, Margherita; Stuart, David; Castles, Richard; Khoo, Saye; Back, David; Boffito, Marta

    2015-08-24

    Use of 'party drugs', a particular set of recreational drugs used in the context of 'ChemSex', is frequent among MSM living with HIV. A recently published observational study showed that more than half of HIV-infected MSM interviewed reported use of illicit substances in the previous 3 months, with frequent concomitant use of three or more drugs. These substances are a combination of 'club drugs' (methylenedioxymethamphetamine, gamma-hydroxybutyrate, ketamine, benzodiazepine) and drugs that are more specifically used in a sexualized context (methamphetamine, mephedrone, poppers and erectile dysfunction agents). Although formal data on pharmacokinetic or pharmacodynamic interactions between recreational drugs and antiretroviral agents are lacking, information regarding potentially toxic interactions can be theorized or sometimes conclusions may be drawn from case studies and cohort observational studies. However, the risk of coadministering party drugs and antiretrovirals should not be overestimated. The major risk for a drug-drug interaction is when using ritonavir-boosting or cobicistat-boosting agents, and maybe some nonnucleoside reverse transcriptase inhibitors. Knowledge of the metabolic pathways of 'party drugs' may help in advising patients on which illicit substances have a high potential for drug-drug interactions, as this is not the case for all. PMID:26372268

  5. Favorable therapeutic response with an antiretroviral salvage regimen in an HIV-1-positive subject infected with a CRF11-cpx virus.

    PubMed

    Tau, Pamela; Mancon, Alessandro; Mileto, Davide; Di Nardo Stuppino, Silvia; Bottani, Giulia; Gismondo, Maria Rita; Galli, Massimo; Micheli, Valeria; Rusconi, Stefano

    2014-05-01

    HIV drug resistance still represents a crucial problem in antiretroviral therapy. We report a case of a naive patient, harboring a CRF11-cpx virus, which showed drug resistance mutations in the reverse transcriptase. A drug resistance genotyping test was performed for the pol (protease, reverse transcriptase, and integrase) and V3 regions. The initial clinical parameter results showed a 4 log level of HIV-RNA (12,090 cp/ml) and a very low CD4(+) cell count (35 cells/μl). We designed an initial highly active antiretroviral therapy (HAART) regimen including lamivudine (3TC)+abacavir (ABC)+booster ritonavir (DRV/r). The virus was highly resistant to all nucleoside and nucleotide reverse transcriptase inhibitors (NRTIs) and nonnucleoside reverse transcriptase inhibitors (NNRTIs) except for ABC, tenofovir (TDF), and efavirenz (EFV) and was susceptible to all protease inhibitors (PIs) and integrase inhibitors (INIs). A salvage regimen including raltegravir (RAL)+DRV/r was started. Ten months later, the immunovirological status shows CD4(+) 142/μl and HIV-RNA <37 cp/ml. Our results demonstrate the effectiveness of a treatment combination that includes RAL+DRV/r in a patient infected with a complex X4-tropic CRF11-cpx virus. PMID:24279648

  6. Antiretroviral Therapies in Women after Single-Dose Nevirapine Exposure

    PubMed Central

    Lockman, S.; Hughes, M.D.; McIntyre, J.; Zheng, Y.; Chipato, T.; Conradie, F.; Sawe, F.; Asmelash, A.; Hosseinipour, M.C.; Mohapi, L.; Stringer, E.; Mngqibisa, R.; Siika, A.; Atwine, D.; Hakim, J.; Shaffer, D.; Kanyama, C.; Wools-Kaloustian, K.; Salata, R.A.; Hogg, E.; Alston-Smith, B.; Walawander, A.; Purcelle-Smith, E.; Eshleman, S.; Rooney, J.; Rahim, S.; Mellors, J.W.; Schooley, R.T.; Currier, J.S.

    2010-01-01

    BACKGROUND Peripartum administration of single-dose nevirapine reduces mother-to-child transmission of human immunodeficiency virus type 1 (HIV-1) but selects for nevirapine-resistant virus. METHODS In seven African countries, women infected with HIV-1 whose CD4+ T-cell counts were below 200 per cubic millimeter and who either had or had not taken single-dose nevirapine at least 6 months before enrollment were randomly assigned to receive antiretroviral therapy with tenofovir–emtricitabine plus nevirapine or tenofovir-emtricitabine plus lopinavir boosted by a low dose of ritonavir. The primary end point was the time to confirmed virologic failure or death. RESULTS A total of 241 women who had been exposed to single-dose nevirapine began the study treatments (121 received nevirapine and 120 received ritonavir-boosted lopinavir). Significantly more women in the nevirapine group reached the primary end point than in the ritonavir-boosted lopinavir group (26% vs. 8%) (adjusted P = 0.001). Virologic failure occurred in 37 (28 in the nevirapine group and 9 in the ritonavir-boosted lopinavir group), and 5 died without prior virologic failure (4 in the nevirapine group and 1 in the ritonavir-boosted lopinavir group). The group differences appeared to decrease as the interval between single-dose nevirapine exposure and the start of antiretroviral therapy increased. Retrospective bulk sequencing of baseline plasma samples showed nevirapine resistance in 33 of 239 women tested (14%). Among 500 women without prior exposure to single-dose nevirapine, 34 of 249 in the nevirapine group (14%) and 36 of 251 in the ritonavir-boosted lopinavir group (14%) had virologic failure or died. CONCLUSIONS In women with prior exposure to peripartum single-dose nevirapine (but not in those without prior exposure), ritonavir-boosted lopinavir plus tenofovir–emtricitabine was superior to nevirapine plus tenofovir–emtricitabine for initial antiretroviral therapy. (Funded by the National

  7. Direct-to-consumer advertisements for HIV antiretroviral medications: a progress report.

    PubMed

    Kallen, Alexander; Woloshin, Steven; Shu, Jennifer; Juhl, Ellen; Schwartz, Lisa

    2007-01-01

    Direct-to-consumer (DTC) prescription drug advertisements for HIV anti-retrovirals are controversial and have been criticized in the past for including deceptive images and underplaying HIV drug limitations. We sought to describe the state of recent DTC ads for HIV antiretrovirals in popular magazines by performing a content analysis of all complete DTC ads for antiretroviral medications appearing in eight national magazines during a one-year period. Current ads appear to have addressed previous concerns, but important problems still exist, such as failing to specify the medication's role in current treatment, to quantify drug efficacy, or to highlight life-threatening side effects. PMID:17848450

  8. Isotopic composition of high-activity particles released in the Chernobyl accident

    SciTech Connect

    Osuch, S.; Dabrowska, M.; Jaracz, P.; Kaczanowski, J.; Le Van Kho; Mirowski, S.; Piasecki, E.; Szeflinska, G.; Szeflinski, Z.; Tropilo, J.; )

    1989-11-01

    Gamma spectra were measured and activities of the detected isotopes were analyzed for 206 high-activity particles (hot particles, HPs) found in northeastern Poland after the Chernobyl accident. The isotopic composition of HPs observed in gamma-activity is compared with that of the general fallout and core inventory calculations. Particle formation and a process of depletion in Ru and Cs isotopes are discussed. On the basis of a search performed a year later, some comments on the behavior of HPs in the soil are made.

  9. Lipodystrophy among patients with HIV infection on antiretroviral therapy: a systematic review protocol

    PubMed Central

    Lana, Lorena Gomes Cunha; Junqueira, Daniela Rezende Garcia; Perini, Edson; Menezes de Pádua, Cristiane

    2014-01-01

    Introduction Lipodystrophy is a frequent and disfiguring adverse effect of antiretroviral therapy (ART) in patients with HIV. It affects the quality of life of the patient and adherence to treatment, and generates new needs for comprehensive healthcare services. The aim of this study will be to conduct a systematic review of the literature from observational studies and describe lipodystrophy among patients with HIV infection during current or previous use of ART. Methods and analysis A systematic review of observational studies published in MEDLINE, CINAHL, LILACS, EMBASE and International Pharmaceutical Abstracts will be carried out. Citations of included studies will be checked to identify additional studies not identified in the electronic searches. It will include any observational study that considered lipodystrophy as the primary or secondary outcome and that had enrolled adolescent and adult patients with HIV infection who were on current or previous ART for at least 6 months. Data extraction and analysis will be performed independently by two reviewers. The extracted data will be discussed, decisions documented and, where necessary, the authors of the studies will be contacted for clarification. Measures of frequency, prevalence and incidence of lipodystrophy will be stratified according to definition, method of diagnosis and risk factors of the outcome. Ethics and dissemination Ethics is not required given this is a protocol for a systematic review. The findings of this study will be widely disseminated through peer-reviewed publications and conference presentations. Updates of the review will be conducted to inform and guide healthcare practice. Protocol registration PROSPERO—42013005450. PMID:24625638

  10. Antiretroviral-based HIV prevention strategies for women

    PubMed Central

    Chirenje, Z Mike; Marrazzo, Jeanne; Parikh, Urvi M.

    2015-01-01

    Almost three decades have elapsed since researchers identified HIV as the cause of AIDS, with current estimates from UNAIDS that 33.4 million adults were living with HIV/AIDS in 2008. Two-thirds of this burden of disease is in Sub-Saharan Africa, and 60% of those infected are women. The disease still remains incurable and current prevention strategies including abstinence, male/female condom use and male circumcision are only partially effective. New strategies to curb the epidemic are urgently needed. Scientists are diligently exploring HIV prevention methods that are safe, effective and affordable. These new biological interventions include oral pre- exposure prophylaxis using oral antiretroviral (ARV) drugs, ARV treatment in HIV-infected persons to reduce transmission and topical ARV-based microbicide formulations. PMID:20954882

  11. Antiretroviral therapy and demand for HIV testing: Evidence from Zambia.

    PubMed

    Wilson, Nicholas

    2016-05-01

    This paper examines the effects of antiretroviral therapy (ART) on demand for HIV testing and of ART-induced testing on demand for risky sexual behavior. I provide a model of sexual behavior decision-making under uncertainty and estimate the structural parameters of the model using nationally representative survey data from Zambia on HIV testing decisions before and after the introduction of ART. The empirical results indicate that although the introduction of ART appears to have increased HIV testing rates by upwards of 50 percent, the ART allocation process may have limited the prevention benefit of ART-induced testing. Simulation results show that eliminating this prevention inefficiency while holding the supply of ART constant would increase the prevention impact of ART-induced testing more than four-fold. More generally, the analysis indicates that existing studies which examine "universal" testing or quasi-experimental testing programs understate the efficacy of standard voluntary counseling and testing programs. PMID:26970992

  12. Determinants of antiretroviral therapy coverage in Sub-Saharan Africa

    PubMed Central

    Hoque, Mohammad Zahirul

    2015-01-01

    Among 35 million people living with the human immunodeficiency virus (HIV) in 2013, only 37% had access to antiretroviral therapy (ART). Despite global concerted efforts to provide the universal access to the ART treatment, the ART coverage varies among countries and regions. At present, there is a lack of systematic empirical analyses on factors that determine the ART coverage. Therefore, the current study aimed to identify the determinants of the ART coverage in 41 countries in Sub-Saharan Africa. It employed statistical analyses for this purpose. Four elements, namely, the HIV prevalence, the level of national income, the level of medical expenditure and the number of nurses, were hypothesised to determine the ART coverage. The findings revealed that among the four proposed determinants only the HIV prevalence had a statistically significant impact on the ART coverage. In other words, the HIV prevalence was the sole determinant of the ART coverage in Sub-Saharan Africa. PMID:26664812

  13. Antiretroviral bioanalysis methods of tissues and body biofluids

    PubMed Central

    DiFrancesco, Robin; Maduke, Getrude; Patel, Rutva; Taylor, Charlene R; Morse, Gene D

    2013-01-01

    Research in the many areas of HIV treatment, eradication and prevention has necessitated measurement of antiretroviral (ARV) concentrations in nontraditional specimen types. To determine the knowledgebase of critical details for accurate bioanalysis, a review of the literature was performed and summarized. Bioanalytical assays for 31 ARVs, including metabolites, were identified in 205 publications measuring various tissues and biofluids. 18 and 30% of tissue or biofluid methods, respectively, analyzed more than one specimen type; 35–37% of the tissue or biofluid methods quantitated more than one ARV. 20 and 76% of tissue or biofluid methods, respectively, were used for the analysis of human specimens. HPLC methods with UV detection predominated, but chronologically MS detection began to surpass. 40% of the assays provided complete intra- and inter-assay validation data, but only 9% of publications provided any stability data with even less for the prevalent ARV in treatments. PMID:23394701

  14. [Lipodystrophy and metabolic disturbances as complications of antiretroviral therapy].

    PubMed

    Bociaga-Jasik, Monika; Kieć-Wilk, Beata; Kalinowska-Nowak, Anna; Mach, Tomasz; Garlicki, Aleksander

    2010-01-01

    Effective treatment of HIV infection with antiretroviral drugs significantly improve prognosis. Reduction of mortality and life prolongations in patients receiving such therapy have been also connected with the risk of side effects development. Among these complications metabolic disturbances such as lipodystrophy, dyslipidaemia, and insulin resistance which are present according some authors in up to 50% of patients receiving HAART play an important role. In spite of different investigations molecular basis of lipodystrophy development during HAART have not be fully understood, and the latest research revealed a lot of new aspects connected w adipocyte tissue pathophysiology, which were not taken up to know into consideration. In the presented publication the most important information about pathogenesis of lipodystrophy development in HIV infected patients treated with ARV drugs have been presented. PMID:21591364

  15. [Policy dilemmas in providing antiretroviral treatment in Brazil].

    PubMed

    do Lago, Regina Ferro; Costa, Nilson do Rosário

    2010-11-01

    This paper addresses institutional constraints that have affected Brazilian politics regarding provision of anti-retroviral treatment (ART) to HIV/Aids patients. We analyzed the normative conflict resulting from international agreements on intellectual property rights, especially patent protection, and the constitutional rights of Brazilian patients to universal and free access to ART. These constraints have not substantially changed the Brazilian public policy yet, but they may impact the future sustainability of this policy. As the main barrier to the production of patented drugs is not technological but institutional, Brazilian government faces a dilemma. It may either abide by existing monopolistic restrictions or it may incite competitiveness of domestic industries and developing countries in the pharmaceutical market. PMID:21120341

  16. Persistent apoptosis in HIV-1-infected individuals receiving potent antiretroviral therapy is associated with poor recovery of CD4 T lymphocytes.

    PubMed

    Hansjee, Natasha; Kaufmann, Gilbert R; Strub, Christoph; Weber, Rainer; Battegay, Manuel; Erb, Peter

    2004-06-01

    CD4 T-cell depletion in HIV-1 infection is partly the result of T-cell apoptosis. Spontaneous apoptosis (SA) and apoptosis markers Fas-associated death-domain-like IL-1 beta converting enzyme (FLICE)-like inhibitory protein (FLIP), Bcl-2, TRAIL (tumor necrosis factor-related apoptosis-inducing ligand), TRAIL receptor 1, and Fas were determined in 55 HIV-1 infected persons treated with highly active antiretroviral therapy (HAART) for 48 months. Despite suppressive HAART, SA remained elevated. Increased SA of peripheral blood mononuclear cells (PBMCs) and CD8 T lymphocytes and increased TRAIL receptor 1 expression strongly predicted a poorer recovery of CD4 T-cell count. HAART did not significantly alter anti-or proapoptotic markers in cultured PBMCs and T lymphocytes. The significant relationship between residual T-lymphocyte apoptosis and CD4 T-cell recovery suggests that persistent apoptosis may impede immune restoration. PMID:15167285

  17. Platelet count kinetics following interruption of antiretroviral treatment

    PubMed Central

    Zetterberg, Eva; Neuhaus, Jacqueline; Baker, Jason V.; Somboonwit, Charurut; Llibre, Josep M.; Palfreeman, Adrian; Chini, Maria; Lundgren, Jens D.

    2014-01-01

    Objectives To investigate the mechanisms of platelet kinetics in the Strategies for Management of Antiretroviral Therapy (SMART) study that demonstrated excess mortality with CD4 guided episodic antiretroviral therapy (ART) drug conservation compared with continuous treatment viral suppression. Follow-up analyses of stored plasma samples demonstrated increased activation of both inflammatory and coagulation pathways after stopping ART. Design SMART patients from sites that determined platelets routinely. Methods Platelet counts were retrospectively collected from 2206 patients from visits at study entry, and during follow-up. D-dimer levels were measured at study entry, month 1, and 2. Results Platelet levels decreased in the drug conservation group following randomization, but remained stable in the viral suppression group [median (IQR) decline from study entry to month 4: −24 000/µl (−54 000 to 4000) vs. 3000 (−22 000 to 24 000), respectively, P < 0.0001)] and the rate of developing thrombocytopenia (<100 000/µl) was significantly higher in the drug conservation vs. the viral suppression arm (unadjusted drug conservation/viral suppression [HR (95%CI) = 1.8 (1.2–2.7)]. The decline in platelet count among drug conservation participants on fully suppressive ART correlated with the rise in D-dimer from study entry to either month 1 or 2 (r = −0.41; P = 0.02). Among drug conservation participants who resumed ART 74% recovered to their study entry platelet levels. Conclusion Interrupting ART increases the risk of thrombocytopenia, but reinitiation of ART typically reverses it. Factors contributing to declines in platelets after interrupting ART may include activation of coagulation pathways or HIV-1 replication itself. The contribution of platelets in HIV-related procoagulant activity requires further study. PMID:23018440

  18. Cohort Profile: Antiretroviral Therapy Cohort Collaboration (ART-CC)

    PubMed Central

    May, Margaret T; Ingle, Suzanne M; Costagliola, Dominique; Justice, Amy C; de Wolf, Frank; Cavassini, Matthias; D’Arminio Monforte, Antonella; Casabona, Jordi; Hogg, Robert S; Mocroft, Amanda; Lampe, Fiona C; Dabis, François; Fätkenheuer, Gerd; Sterling, Timothy R; del Amo, Julia; Gill, M John; Crane, Heidi M; Saag, Michael S; Guest, Jodie; Brodt, Hans-Reinhard; Sterne, Jonathan AC

    2014-01-01

    The advent of effective combination antiretroviral therapy (ART) in 1996 resulted in fewer patients experiencing clinical events, so that some prognostic analyses of individual cohort studies of human immunodeficiency virus-infected individuals had low statistical power. Because of this, the Antiretroviral Therapy Cohort Collaboration (ART-CC) of HIV cohort studies in Europe and North America was established in 2000, with the aim of studying the prognosis for clinical events in acquired immune deficiency syndrome (AIDS) and the mortality of adult patients treated for HIV-1 infection. In 2002, the ART-CC collected data on more than 12,000 patients in 13 cohorts who had begun combination ART between 1995 and 2001. Subsequent updates took place in 2004, 2006, 2008, and 2010. The ART-CC data base now includes data on more than 70 000 patients participating in 19 cohorts who began treatment before the end of 2009. Data are collected on patient demographics (e.g. sex, age, assumed transmission group, race/ethnicity, geographical origin), HIV biomarkers (e.g. CD4 cell count, plasma viral load of HIV-1), ART regimen, dates and types of AIDS events, and dates and causes of death. In recent years, additional data on co-infections such as hepatitis C; risk factors such as smoking, alcohol and drug use; non-HIV biomarkers such as haemoglobin and liver enzymes; and adherence to ART have been collected whenever available. The data remain the property of the contributing cohorts, whose representatives manage the ART-CC via the steering committee of the Collaboration. External collaboration is welcomed. Details of contacts are given on the ART-CC website (www.art-cohort-collaboration.org). PMID:23599235

  19. Fanconi Syndrome and Antiretrovirals: It Is Never Too Late.

    PubMed

    Luni, Faraz Khan; Khan, Abdur Rahman; Prashar, Rohini; Vetteth, Sandeep; Duggan, Joan M

    2016-01-01

    Antiretroviral medications such as tenofovir have been associated with Fanconi syndrome (FS) usually identified within the first 1-29 months after exposure to the medication. We present a case of life-threatening FS which developed in a 37-year-old woman with HIV after 8 years of asymptomatic tenofovir use. The patient was diagnosed with HIV in 1996 at 20 years of age, hepatitis C 10 years later, and Staphylococcus aureus sepsis with secondary osteomyelitis of the spine 3 years before admission for FS. She developed nausea, vomiting, diarrhea, and generalized weakness over a 2-week time period and presented to the hospital. In the emergency department, her serum potassium was 1.5 mEq/L, bicarbonate was 12 mEq/L, chloride was 111 mEq/L, phosphorus was 1.8 mg/dL, and creatinine was 1.95 mg/dL (baseline, 1.4). Arterial blood gas revealed a non-anion gap (hyperchloremic) metabolic acidosis. Type 2 renal tubular acidosis induced by antiretroviral therapy (ART) was suspected and the ART was discontinued with resolution of the renal abnormalities within 7 days. A non-tenofovir-containing ART regimen consisting of lamivudine/abacavir and efavirenz was begun, and over the next 8 months, the patient was without recurrence of the FS. This case report demonstrates the acute development of FS after prolonged exposure to tenofovir without exposure to additional nephrotoxins such as nonsteroidal medications or aminoglycosides. Tenofovir can cause FS at any time and should be considered in any patient presenting with renal tubular acidosis type 2 while on tenofovir regardless of the duration of drug exposure. PMID:24914503

  20. What's new for antiretroviral treatment in women with HIV.

    PubMed

    Andany, Nisha; Walmsley, Sharon L

    2016-01-01

    Currently, women represent 52% of persons infected with HIV worldwide and 23% of those in the United States. Combination antiretroviral therapy (cART) has resulted in remarkable reductions in HIV-associated morbidity and mortality, and has dramatically improved life expectancy. Treatment guidelines do not differ for HIV-infected men and non-pregnant women. However, clinical trials of antiretroviral agents have limited female enrolment, and results from these predominantly male studies are extrapolated to the female population. Furthermore, many of these studies do not report gender subgroup analyses, and those that do are underpowered to detect differences between men and women, limiting the ability to assess if results are equally applicable to both sexes. Women may have differential responses to and adverse events from cART. A limited number of female-only clinical trials have demonstrated that female recruitment and retention in these studies is feasible. Therefore, urgent attention is required to improve the body of knowledge regarding clinical efficacy, safety and tolerability of cART in women. In particular, women living with HIV are faced with various sexual and reproductive health concerns that may influence choice of cART. These include potential interactions with hormonal contraception, safety in pregnancy, and the impact of the transition through menopause and development of age-related comorbidities. Finally, the ongoing advances in biomedical HIV prevention, particularly pre-exposure prophylaxis (PrEP), provide an enormous opportunity to enhance HIV prevention in high-risk women, in efforts to further reduce global burden of the pandemic. PMID:27482438

  1. Predicting virological decay in patients starting combination antiretroviral therapy

    PubMed Central

    2016-01-01

    Objective: Model trajectories of viral load measurements from time of starting combination antiretroviral therapy (cART), and use the model to predict whether patients will achieve suppressed viral load (≤200 copies/ml) within 6-months of starting cART. Design: Prospective cohort study including HIV-positive adults (UK Collaborative HIV Cohort Study). Methods: Eligible patients were antiretroviral naive and started cART after 1997. Random effects models were used to estimate viral load trends. Patients were randomly selected to form a validation dataset with those remaining used to fit the model. We evaluated predictions of suppression using indices of diagnostic test performance. Results: Of 9562 eligible patients 6435 were used to fit the model and 3127 for validation. Mean log10 viral load trajectories declined rapidly during the first 2 weeks post-cART, moderately between 2 weeks and 3 months, and more slowly thereafter. Higher pretreatment viral load predicted steeper declines, whereas older age, white ethnicity, and boosted protease inhibitor/non-nucleoside reverse transcriptase inhibitors based cART-regimen predicted a steeper decline from 3 months onwards. Specificity of predictions and the diagnostic odds ratio substantially improved when predictions were based on viral load measurements up to the 4-month visit compared with the 2 or 3-month visits. Diagnostic performance improved when suppression was defined by two consecutive suppressed viral loads compared with one. Conclusions: Viral load measurements can be used to predict if a patient will be suppressed by 6-month post-cART. Graphical presentations of this information could help clinicians decide the optimum time to switch treatment regimen during the first months of cART. PMID:27124894

  2. Mediators of antiretroviral adherence: a multisite international study.

    PubMed

    Corless, I B; Guarino, A J; Nicholas, P K; Tyer-Viola, L; Kirksey, K; Brion, J; Dawson Rose, C; Eller, L S; Rivero-Mendez, M; Kemppainen, J; Nokes, K; Sefcik, E; Voss, J; Wantland, D; Johnson, M O; Phillips, J C; Webel, A; Iipinge, S; Portillo, C; Chen, W-T; Maryland, M; Hamilton, M J; Reid, P; Hickey, D; Holzemer, W L; Sullivan, K M

    2013-01-01

    The purpose of this study was to investigate the effects of stressful life events (SLE) on medication adherence (3 days, 30 days) as mediated by sense of coherence (SOC), self-compassion (SCS), and engagement with the healthcare provider (eHCP) and whether this differed by international site. Data were obtained from a cross-sectional sample of 2082 HIV positive adults between September 2009 and January 2011 from sites in Canada, China, Namibia, Puerto Rico, Thailand, and US. Statistical tests to explore the effects of stressful life events on antiretroviral medication adherence included descriptive statistics, multivariate analysis of variance, analysis of variance with Bonferroni post-hoc analysis, and path analysis. An examination by international site of the relationships between SLE, SCS, SOC, and eHCP with adherence (3 days and 30 days) indicated these combined variables were related to adherence whether 3 days or 30 days to different degrees at the various sites. SLE, SCS, SOC, and eHCP were significant predictors of adherence past 3 days for the United States (p = < 0.001), Canada (p = 0.006), and Namibia (p = 0.019). The combined independent variables were significant predictors of adherence past 30 days only in the United States and Canada. Engagement with the provider was a significant correlate for antiretroviral adherence in most, but not all, of these countries. Thus, the importance of eHCP cannot be overstated. Nonetheless, our findings need to be accompanied by the caveat that research on variables of interest, while enriched by a sample obtained from international sites, may not have the same relationships in each country. PMID:22774796

  3. Integrating Cervical Cancer Screening with HIV Care in Cameroon: Comparative Risk Analysis of Cervical Disease in HIV-Infected Women Receiving Antiretroviral Therapy to Women in the General Population

    PubMed Central

    Bekolo, Cavin Epie; O’Bryan, Gillian; Tchago, François Edmond; Nangue, Charlette; Bekoule, Patrick Sylvestre; Kollo, Basile

    2016-01-01

    Background While the effect of highly active antiretroviral therapy (HAART) on natural history of cervical lesions remains controversial, resource limited countries need to understand the relevance of their own data to their settings. We compared the risk of cervical disease in HAART-experienced women with that in women in the general population of Cameroon. Methods A retrospective cross sectional survey of women aged 35 years and above, attending a voluntary screening campaign for cervical cancer at the Nkongsamba Regional Hospital in Cameroon between February and May 2014. Squamous intraepithelial lesions (SIL) were determined by Pap smear. Multiple logistic regression was used to compare the odds of SIL in women on HAART to women from the community with unknown HIV status. Results Included were 302 women of whom 131(43.4%) were HIV-infected and receiving HAART on the site while 171 (56.6%) were women from the community. Cervical disease was observed in 51(16.9%) persons of whom 15 (11.5%) cases in the HAART group and 36 (21.1%) cases in the general group (p = 0.027). After controlling for age and other covariates, women in the HAART group had a 67% reduction in the odds of cervical lesions compared with the community group [adjusted odd ratio (aOR) = 0.33, 95%CI: 0.15–0.73, p = 0.006). Conclusion HIV-infected women receiving HAART have a lower risk of cancer than women in the general population. This finding may not be attributed to HAART alone but to all the health benefits derived from receiving a comprehensive HIV care. PMID:26866371

  4. Antiretroviral therapy for HIV-infected people in Papua New Guinea: challenges and opportunities.

    PubMed

    McBride, W J; Bradford, D

    2004-01-01

    Antiretroviral treatment services for Papua New Guineans infected with HIV (human immunodeficiency virus) have been severely limited because of the expense and difficulty in gaining access to antiretroviral drugs and the tests that are required to monitor the response of patients to them. Because some Papua New Guineans are beginning to seek out these services in Australia, clinicians are being challenged to manage the condition properly across an international border. Several case histories presented here highlight such difficulties. Progress is being made to reduce drug prices and simplify tablet-taking regimens, which has made the use of antiretroviral therapy more feasible. We briefly discuss infrastructure requirements for the more widespread provision of antiretroviral treatment services within Papua New Guinea. PMID:16496512

  5. A Mathematical Model of Antiretroviral Therapy Evaluation for HIV Type 1

    NASA Astrophysics Data System (ADS)

    Raimundo, Silvia Martorano; Venturino, Ezio; Mo Yang, Hyun

    2009-09-01

    Treating HIV-infected patients with a combination of several antiretroviral drugs can lead to emergence of the drug-resistant strain. This work proposes a mathematical model to evaluate the emergence of HIV-1 drug resistant during antiretroviral therapy. The model assumes that all susceptible individuals who can be infected by the wildtype strain (sensible to the treatment) or by drug-resistant virus receive antiretroviral therapy. Patients on treatment regimen can evolve to a state of success or failure and for the individuals in therapeutic fail the therapeutic schema is changed. The analysis of system is performed. The existence and stability of the steady states are considered. We address an analytical expression for the reproductive number in a community where antiretroviral therapy are widely used to treat HIV and where both drug sensitive and drug resistant strains are co-circulating.

  6. Trends in Decline of Antiretroviral Resistance among ARV-Experienced Patients in the HIV Outpatient Study: 1999–2008

    PubMed Central

    Buchacz, Kate; Baker, Rose; Ward, Douglas J.; Palella, Frank J.; Chmiel, Joan S.; Young, Benjamin; Yangco, Bienvenido G.; Novak, Richard M.; Brooks, John T.

    2012-01-01

    Background. Little is known about temporal trends in frequencies of clinically relevant ARV resistance mutations in HIV strains from U.S. patients undergoing genotypic testing (GT) in routine HIV care. Methods. We analyzed cumulative frequency of HIV resistance among patients in the HIV Outpatient Study (HOPS) who, during 1999–2008 and while prescribed antiretrovirals, underwent GT with plasma HIV RNA >1,000 copies/mL. Exposure ≥4 months to each of three major antiretroviral classes (NRTI, NNRTI and PI) was defined as triple-class exposure (TCE). Results. 906 patients contributed 1,570 GT results. The annual frequency of any major resistance mutations decreased during 1999–2008 (88% to 79%, P = 0.05). Resistance to PIs decreased among PI-exposed patients (71% to 46%, P = 0.010) as exposure to ritonavir-boosted PIs increased (6% to 81%, P < 0.001). Non-significant declines were observed in resistance to NRTIs among NRTI-exposed (82% to 67%), and triple-class-resistance among TCE patients (66% to 41%), but not to NNRTIs among NNRTI-exposed. Conclusions. HIV resistance was common but declined in HIV isolates from subgroups of ARV-experienced HOPS patients during 1999–2008. Resistance to PIs among PI-exposed patients decreased, possibly due to increased representation of patients whose only PI exposures were to boosted PIs. PMID:22611484

  7. Impact of Extended Combination Antiretroviral Therapy on the Decline of HIV Prevalence in Pregnant Women in Malawi.

    PubMed

    Liotta, Giuseppe; Chimbwandira, Frank; Wouters, Kristien; Nielsen-Saines, Karin; Jere, Haswell; Mancinelli, Sandro; Ceffa, Susanna; Erba, Fulvio; Palombi, Leonardo; Marazzi, Maria Cristina

    2016-01-01

    Combination antiretroviral therapy has been shown to reduce HIV transmission and incident infections. In recent years, Malawi has significantly increased the number of individuals on combination antiretroviral drugs through more inclusive treatment policies. Using a retrospective observational cohort design, records with HIV test results were reviewed for pregnant women attending a referral hospital in Malawi over a 5-year period, with viral load measurements recorded. HIV prevalence over time was determined, and results correlated with population viral load. A total of 11 052 women were included in this analysis, with 440 (4.1%) HIV infections identified. HIV prevalence rates in pregnant women in Malawi halved from 6.4% to 3.0% over 5 years. Mean viral loads of adult patients decreased from 120 000 copies/mL to less than 20 000 copies/mL. Results suggest that community viral load has an effect on HIV incidence rates in the population, which in turn correlates with reduced HIV prevalence rates in pregnant women. PMID:26512040

  8. System-level factors as predictors of adherence to clinical appointment schedules in antiretroviral therapy in Cambodia.

    PubMed

    Daigle, Gary T; Jolly, Pauline E; Chamot, Eric A M; Ehiri, John; Zhang, Kui; Khan, Edward; Sou, Sanith

    2015-01-01

    Adherence to clinical appointment schedules by patients on antiretroviral therapy (ART) is necessary for the prevention of medication interruptions, viral rebound, and the development of drug resistance. An observational study conducted in 2010, Enablers and Adherence to Antiretroviral Therapy in Cambodia, sought to identify factors that predict on-time clinical appointment attendance by patients on ART. Clinical data, including appointment attendance across five consecutive visits, were collected from hospital records on a random sample of ART patients at government referral hospitals (RHs) in Battambang Province, Cambodia. Interviews were conducted to obtain quantitative information from patients on their experiences of support services provided by local NGOs and RHs. This information was used to identify ART patient care and support system factors that could potentially enable patients to adhere to clinical appointment schedules. These factors included adherence counseling, support groups, home-based care (HBC) services, and support provided for transportation to ART appointments. Bivariate and multivariable logistic regression analysis was done to assess relationships between system variables and the ART appointment adherence outcome. Of the 289 study participants, 20.4% had missed at least one of the five appointments in the study period. The hospital source of ART services, participation in a hospital-based support group, receiving a loan from a microfinance institution, and the frequency of adherence counseling were found to be associated with ART appointment adherence. No significant associations were found between other support system factors such as HBC, transportation support, food/monetary support, and appointment adherence. PMID:25803006

  9. Characteristics and genotype profiles of antiretroviral-naïve patients entering a Southern US HIV outpatient clinic 2009-2012.

    PubMed

    Seal, Paula S; Frontini, Maria; Jhita, Preya K; Deichmann, Paige C; Clark, Rebecca A

    2016-06-01

    The US city of New Orleans was ranked second in the nation for estimated HIV case rates in 2011. Opt-out testing was established at the Interim Louisiana Hospital in New Orleans in 2013. The majority of new diagnoses were referred to the HIV outpatient program. We conducted a retrospective chart review of newly referred antiretroviral-naïve patients establishing HIV care between January 2009 and June 2013 to characterise demographic and genotype profiles to assist in clinical management and needed services. Of the eligible 226 patients, 68% were men, and 88% were African American. Nearly half of the study patients were younger than 35 years of age. Forty-six percent had an initial CD4 count <200 cells/mm(3), and 39% had a HIV viral load >100,000 copies/mL. The antiretroviral class with the most common major mutation was the non-nucleoside reverse transcriptase inhibitors (NNRTIs) where K103N was the most common major NNRTI mutation at presentation. We observed that male patients showed more advanced disease with later presentation to care, confirming the need for earlier HIV diagnosis. When considering initial antiretroviral therapy, baseline genotype information is encouraged, particularly if considering a NNRTI-based regimen. PMID:26016726

  10. A trigger-based design for evaluating the safety of in utero antiretroviral exposure in uninfected children of human immunodeficiency virus-infected mothers.

    PubMed

    Williams, Paige L; Seage, George R; Van Dyke, Russell B; Siberry, George K; Griner, Raymond; Tassiopoulos, Katherine; Yildirim, Cenk; Read, Jennifer S; Huo, Yanling; Hazra, Rohan; Jacobson, Denise L; Mofenson, Lynne M; Rich, Kenneth

    2012-05-01

    The Pediatric HIV/AIDS Cohort Study's Surveillance Monitoring of ART Toxicities Study is a prospective cohort study conducted at 22 US sites between 2007 and 2011 that was designed to evaluate the safety of in utero antiretroviral drug exposure in children not infected with human immunodeficiency virus who were born to mothers who were infected. This ongoing study uses a "trigger-based" design; that is, initial assessments are conducted on all children, and only those meeting certain thresholds or "triggers" undergo more intensive evaluations to determine whether they have had an adverse event (AE). The authors present the estimated rates of AEs for each domain of interest in the Surveillance Monitoring of ART Toxicities Study. They also evaluated the efficiency of this trigger-based design for estimating AE rates and for testing associations between in utero exposures to antiretroviral drugs and AEs. The authors demonstrate that estimated AE rates from the trigger-based design are unbiased after correction for the sensitivity of the trigger for identifying AEs. Even without correcting for bias based on trigger sensitivity, the trigger approach is generally more efficient for estimating AE rates than is evaluating a random sample of the same size. Minor losses in efficiency when comparing AE rates between persons exposed and unexposed in utero to particular antiretroviral drugs or drug classes were observed under most scenarios. PMID:22491086

  11. The Pratt Pouch Provides a Three-Fold Access Increase to Antiretroviral Medication for Births outside Health Facilities in Southern Zambia

    PubMed Central

    Dahinten, Alexander P.; Malkin, Robert A.

    2016-01-01

    Introduction: Modern day antiretroviral therapy allows HIV+ pregnant women to lower the likelihood of viral transmission to their infants before, during, and after birth from 20-45% to less than 5%. In developing countries, where non-facility births may outnumber facility births, infant access to safe antiretroviral medication during the critical first three days after birth is often limited. A single-dose, polyethylene pouch (“Pratt Pouch”) addresses this challenge by allowing the medication to be distributed to mothers during antenatal care. Methods: The Pratt Pouch was introduced as part of a one year clinical feasibility study in two districts in Southern Province, Zambia. Participating nurses, community health workers, and pharmacists were trained before implementation. Success in achieving improved antiretroviral medication access was assessed via pre intervention and post intervention survey responses by HIV+ mothers. Results: Access to medication for HIV-exposed infants born outside of a health facility increased from 35% (17/51) before the introduction of the pouch to 94% (15/16) after (p<0.05). A non-significant increase in homebirth rates from 33% (pre intervention cohort) to 50% (post intervention cohort) was observed (p>0.05). Results remained below the national average homebirth rate of 52%. Users reported minimal spillage and a high level of satisfaction with the Pratt Pouch. Conclusion: The Pratt Pouch enhances access to infant antiretroviral medication in a rural, non-facility birth setting. Wide scale implementation could have a substantial global impact on HIV transmission rates from mother to child. PMID:27073584

  12. Supervision, monitoring and evaluation of nationwide scale-up of antiretroviral therapy in Malawi.

    PubMed Central

    Libamba, Edwin; Makombe, Simon; Mhango, Eustice; de Ascurra Teck, Olga; Limbambala, Eddie; Schouten, Erik J.; Harries, Anthony D.

    2006-01-01

    OBJECTIVE: To describe the supervision, monitoring and evaluation strategies used to assess the delivery of antiretroviral therapy during nationwide scale-up of treatment in Malawi. METHODS: In the first quarter of 2005, the HIV Unit of the Ministry of Health and its partners (the Lighthouse Clinic; Médecins Sans Frontières-Belgium, Thyolo district; and WHO's Country Office) undertook structured supervision and monitoring of all public sector health facilities in Malawi delivering antiretroviral therapy. FINDINGS: Data monitoring showed that by the end of 2004, there were 13,183 patients (5274 (40%) male, 12 527 (95%) adults) who had ever started antiretroviral therapy. Of patients who had ever started, 82% (10 761/13,183) were alive and taking antiretrovirals; 8% (1026/13,183) were dead; 8% (1039/13,183) had been lost to follow up; <1% (106/13,183) had stopped treatment; and 2% (251/13,183) had transferred to another facility. Of those alive and on antiretrovirals, 98% (7098/7258) were ambulatory; 85% (6174/7258) were fit to work; 10% (456/4687) had significant side effects; and, based on pill counts, 96% (6824/7114) had taken their treatment correctly. Mistakes in the registration and monitoring of patients were identified and corrected. Drug stocks were checked, and one potential drug stock-out was averted. As a result of the supervisory visits, by the end of March 2005 recruitment of patients to facilities scheduled to start delivering antiretroviral therapy had increased. CONCLUSION: This report demonstrates the importance of early supervision for sites that are starting to deliver antiretroviral therapy, and it shows the value of combining data collection with supervision. Making regular supervisory and monitoring visits to delivery sites are essential for tracking the national scale-up of delivery of antiretrovirals. PMID:16628306

  13. Correlates of antiretroviral and antidepressant adherence among depressed HIV-infected patients.

    PubMed

    Bottonari, Kathryn A; Tripathi, Shanti P; Fortney, John C; Curran, Geoff; Rimland, David; Rodriguez-Barradas, Maria; Gifford, Allen L; Pyne, Jeffrey M

    2012-05-01

    Although crucial for efficacy of pharmacotherapy, adherence to prescribed medication regimens for both antiretrovirals and antidepressants is often suboptimal. As many depressed HIV-infected individuals are prescribed both antiretrovirals and antidepressants, it is important to know whether correlates of nonadherence are similar or different across type of regimen. The HIV Translating Initiatives for Depression into Effective Solutions (HI-TIDES) study was a single-blinded, longitudinal, randomized controlled effectiveness trial comparing collaborative care to usual depression care at three Veterans Affairs HIV clinics. The current investigation utilized self-report baseline interview and chart-abstracted data. Participants were 225 depressed HIV-infected patients who were prescribed an antidepressant (n=146), an antiretroviral (n=192), or both (n=113). Treatment adherence over the last 4 days was dichotomized as "less than 90% adherence" or "90% or greater adherence." After identifying potential correlates of nonadherence, we used a seemingly unrelated regression (SUR) bivariate probit model, in which the probability of adherence to HIV medications and the probability of adherence to antidepressant medications are modeled jointly. Results indicated that 75.5% (n=146) of those prescribed antiretrovirals reported 90%-plus adherence to their antiretroviral prescription and 76.7% (n=112) of those prescribed antidepressants reported 90%-plus adherence to their antidepressant prescription, while 67% of those prescribed both (n=113) reported more than 90% adherence to both regimens. SUR results indicated that education, age, and HIV symptom severity were significant correlates of antiretroviral medication adherence while gender and generalized anxiety disorder diagnosis were significant correlates of adherence to antidepressant medications. In addition, antiretroviral adherence did not predict antidepressant adherence (β=1.62, p=0.17), however, antidepressant adherence

  14. The Impact of Non-Antiretroviral Polypharmacy on the Continuity of Antiretroviral Therapy (ART) Among HIV Patients.

    PubMed

    Krentz, Hartmut B; Gill, M John

    2016-01-01

    Improved survival achieved by many patients with HIV/AIDS has complicated their medical care as increasing numbers of co-morbidities leads to polypharmacy, increased pill burdens, and greater risks of drug-drug interactions potentially compromising antiretroviral treatment (ART). We examined the impact of non-antiretroviral polypharmacy on ART for all adults followed at the Southern Alberta Clinic, Calgary, Canada. Polypharmacy was defined as ≥5 daily medications. We compared the impact of polypharmacy on continuous (i.e., remaining on same ART for ≥6 months) vs. non-continuous (i.e., discontinuing or switching ART) ART dosing frequency, number of ART pills, number of non-ART medications, and age. Of 1190 (89.5%) patients on ART, 95% were on three-drug regimens, 63.9% on QD ART, and 62% ≥3 ART pills daily; 32.2% were experiencing polypharmacy. Polypharmacy was associated with lower CD4, AIDS, >180 months living with HIV, higher numbers of ART pills, and older age (all p < 0.01); 32.1% stopped or switched ART. Polypharmacy increased the risk for non-continuous ART (36.8% vs. 30.0%; p < 0.01). Non-continuous ART increased with daily ART pill count but not increased age. Non-adherence and adverse effects accounted for the majority of non-continuous ART. We found a strong association between polypharmacy and non-continuous ART, potentially leading to effective ART being compromised. Collaborative approaches are needed to anticipate the negative impacts of polypharmacy. PMID:26544766

  15. Highly active composite catalysts for reforming of methane into syngas

    SciTech Connect

    Inui, T.; Saigo, K.; Ichino, K.

    1997-12-31

    Development in highly active catalysts for the reforming of methane with H{sub 2}O, CO{sub 2}, H{sub 2}O + CO{sub 2}, and partial oxidation of methane was conducted to produce hydrogen with high reaction rates. A Ni-based four component catalyst, Ni-Ce{sub 2}O{sub 3}-Pt-Rh supported on an alumina wash-coated ceramic fiber in a plate shape was suitable for the objective reaction. By combining the catalytic combustion reaction, methane conversion was markedly enhanced. Furthermore, by combining the combustion of ethane or ethylene, significantly high space-time yields of hydrogen such as 6,731 mol/1-h or 6,907 mol/l{center_dot}h, respectively at 700{degrees}C. In a reaction of CH{sub 4}-CO{sub 2}-H{sub 2}O-O{sub 2} on the four component catalyst, an extraordinary high space-time yield of hydrogen, 12,190 mol/l{center_dot}h was realized even under the very rapid operation conditions as 3 m-sec short contact time.

  16. Microbial fuel cells with highly active aerobic biocathodes

    NASA Astrophysics Data System (ADS)

    Milner, Edward M.; Popescu, Dorin; Curtis, Tom; Head, Ian M.; Scott, Keith; Yu, Eileen H.

    2016-08-01

    Microbial fuel cells (MFCs), which convert organic waste to electricity, could be used to make the wastewater infrastructure more energy efficient and sustainable. However, platinum and other non-platinum chemical catalysts used for the oxygen reduction reaction (ORR) at the cathode of MFCs are unsustainable due to their high cost and long-term degradation. Aerobic biocathodes, which use microorganisms as the biocatalysts for cathode ORR, are a good alternative to chemical catalysts. In the current work, high-performing aerobic biocathodes with an onset potential for the ORR of +0.4 V vs. Ag/AgCl were enriched from activated sludge in electrochemical half-cells poised at -0.1 and + 0.2 V vs. Ag/AgCl. Gammaproteobacteria, distantly related to any known cultivated gammaproteobacterial lineage, were identified as dominant in these working electrode biofilms (23.3-44.3% of reads in 16S rRNA gene Ion Torrent libraries), and were in very low abundance in non-polarised control working electrode biofilms (0.5-0.7%). These Gammaproteobacteria were therefore most likely responsible for the high activity of biologically catalysed ORR. In MFC tests, a high-performing aerobic biocathode increased peak power 9-fold from 7 to 62 μW cm-2 in comparison to an unmodified carbon cathode, which was similar to peak power with a platinum-doped cathode at 70 μW cm-2.

  17. Centrosomal amplification and aneuploidy induced by the antiretroviral drug AZT in hamster and human cells

    PubMed Central

    Borojerdi, Jennifer P.; Ming, Jessica; Cooch, Catherine; Ward, Yvona; Semino-Mora, Cristina; Yu, Mia; Braun, Hannan M.; Taylor, Barbara J.; Poirier, Miriam C.; Olivero, Ofelia A.

    2009-01-01

    The centrosome directs chromosomal migration by a complex process of tubulin-chromatin binding. In this contribution centrosomal abnormalities, including centrosomal amplification, were explored in Chinese Hamster Ovary (CHO) and Normal Human Mammary Epithelial (NHMEC) cells exposed to the antiretroviral drug zidovudine (3’-azido-3’-deoxythymidine, AZT). Centrosomal amplification/fragmentation was observed in both cell types and kinetochore positive micronuclei were found in AZT-exposed CHO cells in correlation with dose. Normal human mammary epithelial cell (NMHEC), strain M99005, previously identified as a strain that incorporates high levels of AZT into DNA (High incorporator, HI), showed greater centrosomal amplification when compared with a second strain, NHMEC M98040, which did not incorporate AZT into DNA (Low incorporator, LI). Additionally, an abnormal tubulin distribution was observed in AZT-exposed HI cells bearing multiple centrosomes. Immunofluorescent staining of human cells with Aurora A, a kinase involved in the maturation of the centrosome, confirmed the induction of centrosomal amplification and revealed multipolar mitotic figures. Flow cytometric studies revealed that cells bearing abnormal numbers of centrosomes and abnormal tubulin distribution had similar S-phase percentages suggesting that cells bearing unbalanced chromosomal segregation could divide. Therefore, AZT induces genomic instability and clastogenicity as well as alterations in proteins involved in centrosomal activation, all of which may contribute to the carcinogenic properties of this compound. PMID:19427513

  18. Shortcomings of adherence counselling provided to caregivers of children receiving antiretroviral therapy in rural South Africa.

    PubMed

    Coetzee, Bronwyne; Kagee, Ashraf; Bland, Ruth

    2016-03-01

    In order to achieve optimal benefits of antiretroviral therapy (ART), caregivers of children receiving ART are required to attend routine clinic visits monthly and administer medication to the child as prescribed. Yet, the level of adherence to these behaviours varies considerably in many settings. As a way to achieve optimal adherence in rural KwaZulu-Natal, caregivers are required to attend routine counselling sessions at HIV treatment clinics that are centred on imparting information, motivation, and behavioural skills related to medication administration. According to the information-motivation-behavioural skills model, information related to adherence, motivation, and behavioural skills are necessary and fundamental determinants of adherence to ART. The purpose of the study was to observe and document the content of adherence counselling sessions that caregivers attending rural clinics in KwaZulu Natal receive. We observed 25 adherence counselling sessions, which lasted on average 8.1 minutes. Counselling typically consisted of counsellors recording patient attendance, reporting CD4 count and viral load results to caregivers, emphasising dose times, and asking caregivers to name their medications and dosage amounts. Patients were seldom asked to demonstrate how they measure the medication. They were also not probed for problems regarding treatment, even when an unsuppressed VL was reported to a caregiver. This paper calls attention to the sub-optimal level of counselling provided to patients on ART and the urgent need to standardise and improve the training, support, and debriefing provided to counsellors. PMID:27392000

  19. Shortcomings of adherence counselling provided to caregivers of children receiving antiretroviral therapy in rural South Africa

    PubMed Central

    Coetzee, Bronwyne; Kagee, Ashraf; Bland, Ruth

    2016-01-01

    ABSTRACT In order to achieve optimal benefits of antiretroviral therapy (ART), caregivers of children receiving ART are required to attend routine clinic visits monthly and administer medication to the child as prescribed. Yet, the level of adherence to these behaviours varies considerably in many settings. As a way to achieve optimal adherence in rural KwaZulu-Natal, caregivers are required to attend routine counselling sessions at HIV treatment clinics that are centred on imparting information, motivation, and behavioural skills related to medication administration. According to the information-motivation-behavioural skills model, information related to adherence, motivation, and behavioural skills are necessary and fundamental determinants of adherence to ART. The purpose of the study was to observe and document the content of adherence counselling sessions that caregivers attending rural clinics in KwaZulu Natal receive. We observed 25 adherence counselling sessions, which lasted on average 8.1 minutes. Counselling typically consisted of counsellors recording patient attendance, reporting CD4 count and viral load results to caregivers, emphasising dose times, and asking caregivers to name their medications and dosage amounts. Patients were seldom asked to demonstrate how they measure the medication. They were also not probed for problems regarding treatment, even when an unsuppressed VL was reported to a caregiver. This paper calls attention to the sub-optimal level of counselling provided to patients on ART and the urgent need to standardise and improve the training, support, and debriefing provided to counsellors. PMID:27392000

  20. Nutritional status changes in HIV-infected children receiving combined antiretroviral therapy including protease inhibitors.

    PubMed

    Fiore, P; Donelli, E; Boni, S; Pontali, E; Tramalloni, R; Bassetti, D

    2000-11-01

    Maintaining linear growth and weight gain in HIV-infected children is often difficult. Nutritional evaluation and support are recognised as important factors to improve their quality of life. Combination antiretroviral therapy including protease inhibitors (HAART) reduces HIV-viral load and improves survival, quality of life and nutritional status. Our study aimed to determine changes in nutrional status based on body weight, height and nutritional habits, of HIV-infected children receiving HAART. Possible side effects of lipid metabolism were also studied. Twenty five children, 13 treated with HAART (group B) were followed up for 12 months. We did not observe statistically significant differences in nutritional status over that time or between groups A and B. Inadequate energy intake was more common in patients with advanced HIV-disease. Hyperlipidemia was found in 70% of children receiving ritonavir and in approximately 50% of children receiving nelfinavir. We observed an important although not statistically significative modification in the height of those in group B. PMID:11091066

  1. Clinical management of dyslipidaemia associated with combination antiretroviral therapy in HIV-infected patients.

    PubMed

    Calza, Leonardo; Colangeli, Vincenzo; Manfredi, Roberto; Bon, Isabella; Re, Maria Carla; Viale, Pierluigi

    2016-06-01

    The introduction of potent combination antiretroviral therapy (cART) has had a remarkable impact on the natural history of HIV infection, leading to a dramatic decline in the mortality rate and a considerable increase in the life expectancy of HIV-positive people. However, cART use is frequently associated with several metabolic complications, mostly represented by lipid metabolism alterations, which are reported very frequently among persons treated with antiretroviral agents. In particular, hyperlipidaemia occurs in up to 70%-80% of HIV-positive subjects receiving cART and is mainly associated with specific antiretroviral drugs belonging to three classes of antiretroviral agents: NRTIs, NNRTIs and PIs. The potential long-term consequences of cART-associated dyslipidaemia are not completely understood, but an increased risk of premature coronary heart disease has been reported in HIV-infected patients on cART, so prompt correction of lipid metabolism abnormalities is mandatory in this population. Dietary changes, regular aerobic exercise and switching to a different antiretroviral regimen associated with a more favourable metabolic profile are the first steps in clinical management, but lipid-lowering therapy with fibrates or statins is often required. In this case, the choice of hypolipidaemic drugs should take into account the potential pharmacokinetic interactions with many antiretroviral agents. PMID:26846208

  2. Genotypic Variability of HIV-1 Reverse Transcriptase Gene from Long-Term Antiretroviral-Experienced Patients in Kenya

    PubMed Central

    Nzomo, Timothy J.; Kitawi, Rose C.; Mwatelah, Ruth S.; Aman, Rashid; Kimulwo, Maureen J.; Masankwa, Geoffrey; Okendo, Javan; Lwembe, Raphael M.; Ogutu, Bernhards; Muigai, Anne

    2015-01-01

    Abstract There is continuous need to track genetic profiles of HIV strains circulating in different geographic settings to hasten vaccine discovery and inform public health and intervention policies. We partially sequenced the reverse transcriptase region of the HIV-1 pol gene from a total of 54 Kenyan patients aged 18–56 years who continued highly active antiretroviral treatment (HAART) for between 8 and 102 months. Subtyping was done using both the JPHMM tool and phylogenetic method. HIV-1 subtype A1 was the predominant strain in circulation, representing 57.4% and 70.4% of all isolates as determined by JPHMM and phylogenetic methods, respectively. Subtypes D (14.8%, 7.4%), C (5.6%, 9.3%), and A2 (0%, 5.6%) were determined at respective prevalence by both methods. JPHMM identified 22.2% of the isolates as recombinants. This surveillance focused on the RT gene and reaffirms the predominance of subtype A and an increasing proportion of recombinant strains in the Kenyan epidemic. PMID:25748548

  3. Alcohol Consumption, Progression of Disease and Other Comorbidities, and Responses to Antiretroviral Medication in People Living with HIV

    PubMed Central

    Neuman, Manuela G.; Schneider, Michelle; Nanau, Radu M.; Parry, Charles

    2012-01-01

    The present paper describes the possible connection between alcohol consumption and adherence to medicine used to treat human deficiency viral (HIV) infection. Highly active antiretroviral therapy (HAART) has a positive influence on longevity in patients with HIV, substantially reducing morbidity and mortality, including resource-poor settings such as South Africa. However, in a systematic comparison of HAART outcomes between low-income and high-income countries in the treatment of HIV-patients, mortality was higher in resource-poor settings. Specifically, in South Africa, patients often suffer from concomitant tuberculosis and other infections that may contribute to these results. Alcohol influences the use of medicine for opportunistic infections (e.g., pneumonia, tuberculosis), or coinfections HIV-hepatitis viruses-B (HBV) and C (HCV), cytomegalovirus, or herpes simplex virus. Furthermore, alcohol use may negatively impact on medication adherence contributing to HIV progression. The materials used provide a data-supported approach. They are based on analysis of published (2006–2011) world literature and the experience of the authors in the specified topic. Intended for use by health care professionals, these recommendations suggest approaches to the therapeutic and preventive aspects of care. Our intention was to fully characterize the quality of evidence supporting recommendations, which are reflecting benefit versus risk, and assessing strength or certainty. PMID:22496971

  4. Genotypic Variability of HIV-1 Reverse Transcriptase Gene from Long-Term Antiretroviral-Experienced Patients in Kenya.

    PubMed

    Nzomo, Timothy J; Kitawi, Rose C; Mwatelah, Ruth S; Aman, Rashid; Kimulwo, Maureen J; Masankwa, Geoffrey; Okendo, Javan; Lwembe, Raphael M; Ogutu, Bernhards; Muigai, Anne; Ochieng, Washingtone

    2015-05-01

    There is continuous need to track genetic profiles of HIV strains circulating in different geographic settings to hasten vaccine discovery and inform public health and intervention policies. We partially sequenced the reverse transcriptase region of the HIV-1 pol gene from a total of 54 Kenyan patients aged 18-56 years who continued highly active antiretroviral treatment (HAART) for between 8 and 102 months. Subtyping was done using both the JPHMM tool and phylogenetic method. HIV-1 subtype A1 was the predominant strain in circulation, representing 57.4% and 70.4% of all isolates as determined by JPHMM and phylogenetic methods, respectively. Subtypes D (14.8%, 7.4%), C (5.6%, 9.3%), and A2 (0%, 5.6%) were determined at respective prevalence by both methods. JPHMM identified 22.2% of the isolates as recombinants. This surveillance focused on the RT gene and reaffirms the predominance of subtype A and an increasing proportion of recombinant strains in the Kenyan epidemic. PMID:25748548

  5. Antiretroviral Drug Interactions: Overview of Interactions Involving New and Investigational Agents and the Role of Therapeutic Drug Monitoring for Management

    PubMed Central

    Rathbun, R. Chris; Liedtke, Michelle D.

    2011-01-01

    Antiretrovirals are prone to drug-drug and drug-food interactions that can result in subtherapeutic or supratherapeutic concentrations. Interactions between antiretrovirals and medications for other diseases are common due to shared metabolism through cytochrome P450 (CYP450) and uridine diphosphate glucuronosyltransferase (UGT) enzymes and transport by membrane proteins (e.g., p-glycoprotein, organic anion-transporting polypeptide). The clinical significance of antiretroviral drug interactions is reviewed, with a focus on new and investigational agents. An overview of the mechanistic basis for drug interactions and the effect of individual antiretrovirals on CYP450 and UGT isoforms are provided. Interactions between antiretrovirals and medications for other co-morbidities are summarized. The role of therapeutic drug monitoring in the detection and management of antiretroviral drug interactions is also briefly discussed. PMID:24309307

  6. Antiretroviral Therapy for HIV Infection: When to Initiate Therapy, Which Regimen to Use, and How to Monitor Patients on Therapy.

    PubMed

    Johnson, Steven C

    Antiretroviral therapy is recommended for all patients with HIV infection. The benefit of immediate antiretroviral therapy was confirmed by results from the START (Strategic Timing of Antiretroviral Treatment) trial, which showed a 57% reduction in risk for the composite end point of AIDS-related events, serious non-AIDS-related events, or death from any cause with immediate treatment in antiretroviral therapy-naive participants with CD4+ cell counts above 500/µL. Other changes in HIV care include the widespread adoption of integrase strand transfer inhibitor-based regimens. Considerations regarding when to initiate antiretroviral therapy, which initial regimens to use, and appropriate monitoring of individuals taking antiretroviral therapy are discussed. This article summarizes an IAS-USA continuing education webinar presented by Steven C. Johnson, MD, in July 2015. PMID:27398769

  7. Expansion of highly activated invariant natural killer T cells with altered phenotype in acute dengue infection.

    PubMed

    Kamaladasa, A; Wickramasinghe, N; Adikari, T N; Gomes, L; Shyamali, N L A; Salio, M; Cerundolo, V; Ogg, G S; Malavige, G Neelika

    2016-08-01

    Invariant natural killer T (iNKT) cells are capable of rapid activation and production of cytokines upon recognition of antigenic lipids presented by CD1d molecules. They have been shown to play a significant role in many viral infections and were observed to be highly activated in patients with acute dengue infection. In order to characterize further their role in dengue infection, we investigated the proportion of iNKT cells and their phenotype in adult patients with acute dengue infection. The functionality of iNKT cells in patients was investigated by both interferon (IFN)-γ and interleukin (IL)-4 ex-vivo enzyme-linked immunospot (ELISPOT) assays following stimulation with alpha-galactosyl-ceramide (αGalCer). We found that circulating iNKT cell proportions were significantly higher (P = 0·03) in patients with acute dengue when compared to healthy individuals and were predominantly of the CD4(+) subset. iNKT cells of patients with acute dengue had reduced proportions expressing CD8α and CD161 when compared to healthy individuals. The iNKT cells of patients were highly activated and iNKT activation correlated significantly with dengue virus-specific immunoglobulin (Ig)G antibody levels. iNKT cells expressing Bcl-6 (P = 0·0003) and both Bcl-6 and inducible T cell co-stimulator (ICOS) (P = 0·006) were increased significantly in patients when compared to healthy individuals. Therefore, our data suggest that in acute dengue infection there is an expansion of highly activated CD4(+) iNKT cells, with reduced expression of CD161 markers. PMID:26874822

  8. Does Once-Daily Raltegravir Have Any Role in the Antiretroviral Treatment?

    PubMed Central

    Gutierrez-Valencia, Alicia; Chacón-Mora, Natalia; Ruiz-Valderas, Rosa; Ben-Marzouk-Hidalgo, Omar J.; Torres-Cornejo, Almudena; Viciana, Pompeyo; Lopez-Cortes, Luis F.

    2015-01-01

    Abstract Administering raltegravir once daily would make adherence to antiretroviral treatment easier, especially if the concomitant drugs are also administered once daily. We report our experience on the use of raltegravir, both once- and twice-daily. Retrospective review of HIV-infected patients on treatment with raltegravir 800 mg once or 400 mg twice a day plus 2 analogs. Patients were classified as group A (subjects switched to raltegravir due to adverse events on a previous regimen or drug–drug interactions) and group B (subjects who restarted antiretroviral treatment after a previous drop-out). The primary clinical endpoint was the percentage of subjects with virological suppression after 96 weeks. Treatment's effectiveness (noncomplete/missing equals failure) was also evaluated. Pharmacokinetic study was performed in unselected patients. Plasma raltegravir concentrations were determined by high-performance liquid chromatography coupled with mass spectrometry. A total of 133 patients were included in the study (74 and 59 on raltegravir once- and twice-daily). There were only 4 virological failures in the entire cohort during the follow-up. Thus, the Kaplan–Meier estimation of efficacy by on-treatment analysis was 96.3% (CI95, 92.8–99.8) at week 96, independently of the dosing regimen and of the raltegravir concentrations. Similar exposures to raltegravir based on AUC0–τ, but higher Cmax and significantly lower Ctrough were observed when raltegravir was given once daily compared with 400 mg twice daily. In fact, 14 out of 56 Ctrough concentrations (25%) from patients taking raltegravir once daily were below the IC95 of wild-type HIV-1 clinical isolates while only 2 samples from patients receiving 400 mg twice a day were below this value, although no relationship between Ctrough and efficacy was found. The main limitations of the study are that the raltegravir dosing regimen was not randomized and more than 50% of the patients were

  9. Antiretroviral Treatment and Sexual Risk Behavior in South Africa.

    PubMed

    Risher, Kathryn; Rehle, Thomas; Simbayi, Leickness; Shisana, Olive; Celentano, David D

    2016-04-01

    The sexual behavior of individuals living with HIV determines the onward transmission of HIV. With the understanding that antiretroviral therapy (ART) prevents transmission of HIV, the sexual behaviors of the individuals not on ART with unsuppressed viral loads becomes of the greatest importance in elucidating transmission. We assessed the association between being on ART and sexual risk behavior among those living with HIV in a nationally representative population-based cross-sectional survey of households in South Africa that was conducted in 2012. Of 2237 adults (aged 15-49) who tested HIV-seropositive, 667 (29.8 %) had detectable antiretroviral drugs in their blood specimens. Among males, 77.7 % of those on ART reported having had sex in the past year contrasted with 88.4 % of those not on ART (p = 0.001); among females, 72.2 % of those on ART reported having had sex in the past year while 80.3 % of those not on ART did (p < 0.001). For males and females, the odds of reporting consistent condom use and condom use at last sex were statistically significantly higher for individuals on ART compared to those not on ART (males: consistent condom use aOR 2.8, 95 % CI 1.6-4.9, condom use at last sex aOR 2.6, 95 % CI 1.5-4.6; females: consistent condom use aOR 2.3, 95 % CI 1.7-3.1, condom use at last sex aOR 2.3, 95 % CI 1.7-3.1), while there were no statistically significant differences in odds of reporting multiple sexual partners in the past year. In this nationally representative population-based survey of South African adults, we found evidence of less risky sexual risk behavior among people living with HIV on ART compared to those not on ART. PMID:26194426

  10. In vitro-in vivo Pharmacokinetic correlation model for quality assurance of antiretroviral drugs

    PubMed Central

    Restrepo Valencia, Piedad

    2015-01-01

    Introduction: The in vitro-in vivo pharmacokinetic correlation models (IVIVC) are a fundamental part of the drug discovery and development process. The ability to accurately predict the in vivo pharmacokinetic profile of a drug based on in vitro observations can have several applications during a successful development process. Objective: To develop a comprehensive model to predict the in vivo absorption of antiretroviral drugs based on permeability studies, in vitro and in vivo solubility and demonstrate its correlation with the pharmacokinetic profile in humans. Methods: Analytical tools to test the biopharmaceutical properties of stavudine, lamivudine y zidovudine were developed. The kinetics of dissolution, permeability in caco-2 cells and pharmacokinetics of absorption in rabbits and healthy volunteers were evaluated. Results: The cumulative areas under the curve (AUC) obtained in the permeability study with Caco-2 cells, the dissolution study and the pharmacokinetics in rabbits correlated with the cumulative AUC values in humans. These results demonstrated a direct relation between in vitro data and absorption, both in humans and in the in vivo model. Conclusions: The analytical methods and procedures applied to the development of an IVIVC model showed a strong correlation among themselves. These IVIVC models are proposed as alternative and cost/effective methods to evaluate the biopharmaceutical properties that determine the bioavailability of a drug and their application includes the development process, quality assurance, bioequivalence studies and pharmacosurveillance. PMID:26600625

  11. Interventions to increase antiretroviral adherence in sub-Saharan Africa: a systematic review of evaluation studies

    PubMed Central

    Bärnighausen, Till; Chaiyachati, Krisda; Chimbindi, Natsayi; Peoples, Ashleigh; Haberer, Jessica; Newell, Marie-Louise

    2014-01-01

    The success of potent antiretroviral treatment (ART) for HIV infection is primarily determined by the level of medication adherence. We systematically review the evidence on effectiveness of interventions to enhance ART adherence in sub-Saharan Africa (SSA), where four fifths of the more than five million people receiving ART live. We identified 26 relevant publications reporting on 25 studies, conducted between 2003 and 2010, of behavioural, cognitive, biological, structural, and combination interventions. The majority (16) of the studies took place in hospital outpatient facilities in urban settings. Studies differed widely in design, sample size, length of follow-up, and outcome measurement. Despite study diversity and limitations, the evidence to date suggest that treatment supporters, directly observed therapy, cell phone short message services, diary cards and food rations and can be effective in increasing adherence in some settings in SSA. However, our synthesis of studies also shows that some interventions are unlikely to produce large or lasting effects, while other interventions are effective in some but not in other settings, emphasizing the need for more research, in particular, RCTs, to allow examination of the influence of context and particular features of intervention content on effectiveness. Important avenues for future work include intervention targeting and selection of interventions based on behavioural theories relevant to SSA. PMID:22030332

  12. Antiretroviral Therapy-Induced Mitochondrial Toxicity: Potential Mechanisms Beyond Polymerase-γ Inhibition

    PubMed Central

    Selvaraj, Shanmugapriya; Ghebremichael, Musie; Li, Min; Foli, Yram; Langs-Barlow, Allison; Ogbuagu, Arit; Barakat, Lydia; Tubridy, Elizabeth; Edifor, Regina; Lam, Wing; Cheng, Yung-Chi; Paintsil, Elijah

    2014-01-01

    We hypothesized that competition between NRTI-triphosphate and endogenous deoxyribonucleoside triphosphate (dNTP) may lead to depletion of dNTP pools and mitochondrial dysfunction independent of Pol-γ inhibition. We collected peripheral blood mononuclear cells from 75 adults (25 cases: HIV-infected with mitochondrial toxicity, 25 HIV-infected positive controls, and 25 HIV-negative controls). We observed statistically significant individual and group differences in ribonucleotide (RN) and deoxyribonucleotide (dRN) pools. The median RN pool was 10062 (IQR, 7090 – 12590), 4360 (IQR, 3058 –6838), and 2968 (IQR, 2538 – 4436) pmol/106 cells for negative controls, positive controls, and cases, respectively. Cases had significantly higher absolute mtDNA copy number compared to negative controls (p<0.05). Cases had significantly higher expression of Pol-γ, nucleoside transporters, cellular kinases, and ABC compared to controls. Antiretroviral therapy perturbs ribonucleotide and deoxyribonucleotide pools. Depletion of RN and dRN pools may be associated with ART-induced mitochondrial toxicity independent of Pol-γ inhibition. PMID:24637942

  13. Poly(lactic-co-glycolic) Acid-Chitosan Dual Loaded Nanoparticles for Antiretroviral Nanoformulations.

    PubMed

    Makita-Chingombe, Faithful; Kutscher, Hilliard L; DiTursi, Sara L; Morse, Gene D; Maponga, Charles C

    2016-01-01

    Poly(lactic-co-glycolic acid) (PLGA) chitosan (CS) coated nanoparticles (NPs) were loaded with two antiretrovirals (ARVs) either lamivudine (LMV) which is hydrophilic or nevirapine (NVP) which is hydrophobic or both LMV and NVP. These ARVs are of importance in resource-limited settings, where they are commonly used in human immunodeficiency virus (HIV-1) treatment due to affordability and accessibility. NPs prepared by a water-oil-water emulsion and reduced pressure solvent evaporation technique were determined to have a positive zeta potential, a capsule-like morphology, and an average hydrodynamic diameter of 240 nm. Entrapment of NVP as a single ARV had a notable increase in NP size compared to LMV alone or in combination with LMV. NPs stored at room temperature in distilled water maintained size, polydispersity (PDI), and zeta potential for one year. No changes in size, PDI, and zeta potential were observed for NPs in 10% sucrose in lyophilized or nonlyophilized states stored at 4°C and -20°C, respectively. Freezing NPs in the absence of sucrose increased NP size. Drug loading, encapsulation efficiency, and kinetic release profiles were quantified by high performance liquid chromatography (HPLC). Our novel nanoformulations have the potential to improve patient outcomes and expand drug access in resource-limited countries for the treatment of HIV-1. PMID:27190651

  14. Antiretroviral Therapy Use, Medication Adherence, and Viral Suppression Among PLWHA with Panic Symptoms.

    PubMed

    Sam, Tanyka Suzanne; Hutton, Heidi E; Lau, Bryan; McCaul, Mary E; Keruly, Jeanne; Moore, Richard; Chander, Geetanjali

    2015-11-01

    Panic symptoms are prevalent among PLWHAs, yet few studies have examined their relationship with HIV outcomes. Using data from an observational cohort study in Baltimore, MD, we examined the association between panic symptoms and antiretroviral therapy (ART) use, medication adherence, and viral suppression. Data were analyzed using generalized estimating equations and adjusted for age, sex, race/ethnicity, cocaine and/or heroin use, clinic enrollment time, alcohol use, and depressive symptoms. Between June 2010 and September 2012, 1195 individuals participated in 2080 audio computer assisted interviews; 9.9 % (n = 118) of individuals endorsed current panic symptoms. In multivariate analysis, panic symptoms were associated with decreased ART use (IRR 0.94; p = 0.05). Panic symptoms were neither associated with medication adherence nor viral suppression. These findings were independent of depressive symptoms and substance use. Panic symptoms are under-recognized in primary care settings and present an important barrier to ART use. Further studies investigating the reasons for this association are needed. PMID:25903506

  15. Service delivery interventions to improve adolescents' linkage, retention and adherence to antiretroviral therapy and HIV care*

    PubMed Central

    MacPherson, Peter; Munthali, Chigomezgo; Ferguson, Jane; Armstrong, Alice; Kranzer, Katharina; Ferrand, Rashida A; Ross, David A

    2015-01-01

    Objectives Adolescents living with HIV face substantial difficulties in accessing HIV care services and have worse treatment outcomes than other age groups. The objective of this review was to evaluate the effectiveness of service delivery interventions to improve adolescents' linkage from HIV diagnosis to antiretroviral therapy (ART) initiation, retention in HIV care and adherence to ART. Methods We systematically searched the Medline, SCOPUS and Web of Sciences databases and conference abstracts from the International AIDS Conference and International Conference on AIDS and STIs in Africa (ICASA). Studies published in English between 1st January 2001 and 9th June 2014 were included. Two authors independently evaluated reports for eligibility, extracted data and assessed methodological quality using the Cochrane risk of bias tool and Newcastle–Ottawa Scale. Results Eleven studies from nine countries were eligible for review. Three studies were randomised controlled trials. Interventions assessed included individual and group counselling and education; peer support; directly observed therapy; financial incentives; and interventions to improve the adolescent-friendliness of clinics. Most studies were of low to moderate methodological quality. Conclusions This review identified limited evidence on the effectiveness of service delivery interventions to support adolescents' linkage from HIV diagnosis to ART initiation, retention on ART and adherence to ART. Although recommendations are qualified because of the small numbers of studies and limited methodological quality, offering individual and group education and counselling, financial incentives, increasing clinic accessibility and provision of specific adolescent-tailored services appear promising interventions and warrant further investigation. PMID:25877007

  16. Viraemia and HIV-1 drug resistance mutations among patients receiving antiretroviral treatment in Mozambique.

    PubMed

    Maldonado, F; Biot, M; Roman, F; Masquelier, C; Anapenge, M; Bastos, R; Chuquela, H C; Arendt, V; Schmit, J C; Zachariah, R

    2009-06-01

    This study was conducted among individuals taking first-line antiretroviral treatment (ART) for at least 12 months under programme conditions in Maputo, Mozambique in order to report on the level of detectable viraemia and the proportion and types of drug resistance mutations among those with detectable viral loads. HIV-1 RNA viral load levels (lower detection limit <50 copies/ml) were measured, and resistance mutations were sequenced. One hundred and forty-nine consecutive patients (69% females, median age 36 years) were included after a mean follow-up time of 23 months. One hundred and seven (72%; 95% CI 64-79) had undetectable viral load, while in 42 (28%, 95% CI 21-36) viral load was detectable (range 50-58884 copies/ml). From 15 patients with viral load >1000 copies/ml, 12 viruses were sequenced: eight were C subtypes and four were circulating recombinant forms (CRF08). Eight (5%; 95% CI 2-9) patients with detectable viral load had one or more major resistance mutations. Nucleoside reverse transcriptase inhibitor (NRTI) and non-NRTI mutations were observed. There were no major mutations for resistance to protease inhibitors. In Maputo, the level of detectable viraemia is reassuringly low. While embarking on ART scale-up, wider surveillance is warranted to monitor programme quality and limit the development of drug resistance, which remains a major potential challenge for the future of ART in Africa. PMID:18804251

  17. Interventions for Enhancing Adherence to Antiretroviral Therapy (ART): A Systematic Review of High Quality Studies

    PubMed Central

    Sivaramalingam, Bhairavi; Navarro, Tamara; Hobson, Nicholas; Keepanasseril, Arun; Wilczynski, Nancy J.; Haynes, R. Brian

    2015-01-01

    Abstract We sought to review the effectiveness of interventions designed to improve adherence to antiretroviral therapy (ART) from studies included in a recent Cochrane review that reported a clinical and an adherence outcome, with at least 80% follow-up for 6 months or more. Data were extracted independently and in duplicate, with an adjudicator for disagreements. Risk of bias was assessed using the Cochrane Risk of Bias tool. Of 182 relevant studies in the Cochrane review, 49 were related to ART. Statistical pooling was not warranted due to heterogeneity in interventions, participants, treatments, adherence measures and outcomes. Many studies had high risk of bias in elements of design and outcome ascertainment. Only 10 studies improved both adherence and clinical outcomes. These used the following interventions: adherence counselling (two studies); a once-daily regimen (compared to twice daily); text messaging; web-based cognitive behavioral intervention; face-to-face multi-session intensive behavioral interventions (two studies); contingency management; modified directly observed therapy; and nurse-delivered home visits combined with telephone calls. Patient-related adherence interventions were the most frequently tested. Uniform adherence measures and higher quality studies of younger populations are encouraged. PMID:25825938

  18. Drug–drug interactions between anti-retroviral therapies and drugs of abuse in HIV systems

    PubMed Central

    Rao, PSS; Earla, Ravindra; Kumar, Anil

    2015-01-01

    Introduction Substance abuse is a common problem among HIV-infected individuals. Importantly, addictions as well as moderate use of alcohol, smoking, or other illicit drugs have been identified as major reasons for non-adherence to antiretroviral therapy (ART) among HIV patients. The literature also suggests a decrease in the response to ART among HIV patients who use these substances, leading to failure to achieve optimal virological response and increased disease progression. Areas covered This review discusses the challenges with adherence to ART as well as observed drug interactions and known toxicities with major drugs of abuse, such as alcohol, smoking, methamphetamine, cocaine, marijuana, and opioids. The lack of adherence and drug interactions potentially lead to decreased efficacy of ART drugs and increased ART, and drugs of abuse-mediated toxicity. As CYP is the common pathway in metabolizing both ART and drugs of abuse, we discuss the possible involvement of CYP pathways in such drug interactions. Expert opinion We acknowledge that further studies focusing on common metabolic pathways involving CYP and advance research in this area would help to potentially develop novel/alternate interventions and drug dose/regimen adjustments to improve medication outcomes in HIV patients who consume drugs of abuse. PMID:25539046

  19. Rapid HIV Viral Load Suppression in those Initiating Antiretroviral Therapy at First Visit after HIV Diagnosis.

    PubMed

    Hoenigl, Martin; Chaillon, Antoine; Moore, David J; Morris, Sheldon R; Mehta, Sanjay R; Gianella, Sara; Amico, K Rivet; Little, Susan J

    2016-01-01

    Expert guidelines for antiretroviral therapy (ART) now recommend ART as soon as possible in all HIV infected persons to reduce the risk of disease progression and prevent transmission. The goal of this observational study was to evaluate the impact of very early ART initiation and regimen type on time to viral suppression. We evaluated time to viral suppression among 86 persons with newly-diagnosed HIV infection who initiated ART within 30 days of diagnosis. A total of 36 (42%) had acute, 27 (31%) early, and 23 (27%) had established HIV infection. The median time from an offer of immediate ART to starting ART was 8 days. A total of 56/86 (65%) initiated an integrase inhibitor-based regimen and 30/86 (35%) a protease inhibitor-based regimen. The time to viral suppression was significantly shorter in those receiving an integrase inhibitor- versus a protease inhibitor-based regimen (p = 0.022). Twenty-two (26%) initiated ART at their HIV care intake visit and 79% of these participants achieved viral suppression at week 12, 82% at week 24 and 88% at week 48. ART initiated at the intake visit led to rapid and reliable viral suppression in acute, early and chronic HIV infection, in particular when integrase inhibitor-based regimens were used. PMID:27597312

  20. Poly(lactic-co-glycolic) Acid-Chitosan Dual Loaded Nanoparticles for Antiretroviral Nanoformulations

    PubMed Central

    Makita-Chingombe, Faithful; Kutscher, Hilliard L.; DiTursi, Sara L.; Morse, Gene D.; Maponga, Charles C.

    2016-01-01

    Poly(lactic-co-glycolic acid) (PLGA) chitosan (CS) coated nanoparticles (NPs) were loaded with two antiretrovirals (ARVs) either lamivudine (LMV) which is hydrophilic or nevirapine (NVP) which is hydrophobic or both LMV and NVP. These ARVs are of importance in resource-limited settings, where they are commonly used in human immunodeficiency virus (HIV-1) treatment due to affordability and accessibility. NPs prepared by a water-oil-water emulsion and reduced pressure solvent evaporation technique were determined to have a positive zeta potential, a capsule-like morphology, and an average hydrodynamic diameter of 240 nm. Entrapment of NVP as a single ARV had a notable increase in NP size compared to LMV alone or in combination with LMV. NPs stored at room temperature in distilled water maintained size, polydispersity (PDI), and zeta potential for one year. No changes in size, PDI, and zeta potential were observed for NPs in 10% sucrose in lyophilized or nonlyophilized states stored at 4°C and −20°C, respectively. Freezing NPs in the absence of sucrose increased NP size. Drug loading, encapsulation efficiency, and kinetic release profiles were quantified by high performance liquid chromatography (HPLC). Our novel nanoformulations have the potential to improve patient outcomes and expand drug access in resource-limited countries for the treatment of HIV-1. PMID:27190651

  1. In what ways do communities support optimal antiretroviral treatment in Zimbabwe?

    PubMed Central

    Scott, K.; Campbell, C.; Madanhire, C.; Skovdal, M.; Nyamukapa, C.; Gregson, S.

    2014-01-01

    Little research has been conducted on how pre-existing indigenous community resources, especially social networks, affect the success of externally imposed HIV interventions. Antiretroviral treatment (ART), an externally initiated biomedical intervention, is being rolled out across sub-Saharan Africa. Understanding the ways in which community networks are working to facilitate optimal ART access and adherence will enable policymakers to better engage with and bolster these pre-existing resources. We conducted 67 interviews and eight focus group discussions with 127 people from three key population groups in Manicaland, eastern Zimbabwe: healthcare workers, adults on ART and carers of children on ART. We also observed over 100 h of HIV treatment sites at local clinics and hospitals. Our research sought to determine how indigenous resources were enabling people to achieve optimal ART access and adherence. We analysed data transcripts using thematic network technique, coding references to supportive community networks that enable local people to achieve ART access and adherence. People on ART or carers of children on ART in Zimbabwe report drawing support from a variety of social networks that enable them to overcome many obstacles to adherence. Key support networks include: HIV groups; food and income support networks; home-based care, church and women's groups; family networks; and relationships with healthcare providers. More attention to the community context in which HIV initiatives occur will help ensure that interventions work with and benefit from pre-existing social capital. PMID:23503291

  2. Rapid HIV Viral Load Suppression in those Initiating Antiretroviral Therapy at First Visit after HIV Diagnosis

    PubMed Central

    Hoenigl, Martin; Chaillon, Antoine; Moore, David J.; Morris, Sheldon R.; Mehta, Sanjay R.; Gianella, Sara; Amico, K. Rivet; Little, Susan J.

    2016-01-01

    Expert guidelines for antiretroviral therapy (ART) now recommend ART as soon as possible in all HIV infected persons to reduce the risk of disease progression and prevent transmission. The goal of this observational study was to evaluate the impact of very early ART initiation and regimen type on time to viral suppression. We evaluated time to viral suppression among 86 persons with newly-diagnosed HIV infection who initiated ART within 30 days of diagnosis. A total of 36 (42%) had acute, 27 (31%) early, and 23 (27%) had established HIV infection. The median time from an offer of immediate ART to starting ART was 8 days. A total of 56/86 (65%) initiated an integrase inhibitor-based regimen and 30/86 (35%) a protease inhibitor-based regimen. The time to viral suppression was significantly shorter in those receiving an integrase inhibitor- versus a protease inhibitor-based regimen (p = 0.022). Twenty-two (26%) initiated ART at their HIV care intake visit and 79% of these participants achieved viral suppression at week 12, 82% at week 24 and 88% at week 48. ART initiated at the intake visit led to rapid and reliable viral suppression in acute, early and chronic HIV infection, in particular when integrase inhibitor-based regimens were used. PMID:27597312

  3. In what ways do communities support optimal antiretroviral treatment in Zimbabwe?

    PubMed

    Scott, K; Campbell, C; Madanhire, C; Skovdal, M; Nyamukapa, C; Gregson, S

    2014-12-01

    Little research has been conducted on how pre-existing indigenous community resources, especially social networks, affect the success of externally imposed HIV interventions. Antiretroviral treatment (ART), an externally initiated biomedical intervention, is being rolled out across sub-Saharan Africa. Understanding the ways in which community networks are working to facilitate optimal ART access and adherence will enable policymakers to better engage with and bolster these pre-existing resources. We conducted 67 interviews and eight focus group discussions with 127 people from three key population groups in Manicaland, eastern Zimbabwe: healthcare workers, adults on ART and carers of children on ART. We also observed over 100 h of HIV treatment sites at local clinics and hospitals. Our research sought to determine how indigenous resources were enabling people to achieve optimal ART access and adherence. We analysed data transcripts using thematic network technique, coding references to supportive community networks that enable local people to achieve ART access and adherence. People on ART or carers of children on ART in Zimbabwe report drawing support from a variety of social networks that enable them to overcome many obstacles to adherence. Key support networks include: HIV groups; food and income support networks; home-based care, church and women's groups; family networks; and relationships with healthcare providers. More attention to the community context in which HIV initiatives occur will help ensure that interventions work with and benefit from pre-existing social capital. PMID:23503291

  4. METHADONE MAINTENANCE THERAPY PROMOTES INITIATION OF ANTIRETROVIRAL THERAPY AMONG INJECTION DRUG USERS

    PubMed Central

    Uhlmann, Sasha; Milloy, M-J; Kerr, Thomas; Zhang, Ruth; Guillemi, Silvia; Marsh, David; Hogg, Robert S.; Montaner, Julio S. G.; Wood, Evan

    2010-01-01

    Aims Despite proven benefits of antiretroviral therapy (ART), many HIV-infected injection drug users (IDU) do not access treatment even in settings with free health care. We examined whether methadone maintenance therapy (MMT) increased initiation and adherence to ART among an IDU population with free health care. Design We prospectively examined a cohort of opioid-using antiretroviral-naïve HIV-infected IDU and investigated factors associated with initiation of antiretroviral therapy as well as subsequent adherence. Factors independently associated with time to first initiation of antiretroviral therapy were modelled using Cox proportional hazards regression. Findings Between May 1996 and April 2008, 231 antiretroviral-naïve HIV-infected opioid using IDU were enrolled, among whom 152 (65.8%) initiated ART, for an incidence density of 30.5 (95% confidence interval [CI]: 25.9–35.6) per 100 person-years. After adjustment for time-updated clinical characteristics and other potential confounders, use of MMT was independently associated with more rapid uptake of antiretroviral therapy (relative hazard = 1.62 [95% CI: 1.15–2.28]; p = 0.006). Those prescribed methadone also had higher rates of ART adherence after first antiretroviral initiation (odds ratio = 1.49 [95% CI: 1.07–2.08]; p = 0.019). Conclusion These results demonstrate that MMT contributes to more rapid initiation and subsequent adherence to ART among opioid-using HIV-infected IDU. Addressing international barriers to the use and availability of methadone may dramatically increase uptake of HIV treatment among this population. PMID:20331553

  5. Antiretroviral treatment of HIV infection: Swedish recommendations 2007.

    PubMed

    Josephson, Filip; Albert, Jan; Flamholc, Leo; Gisslén, Magnus; Karlström, Olof; Lindgren, Susanne-Rosa; Navér, Lars; Sandström, Eric; Svedhem-Johansson, Veronica; Svennerholm, Bo; Sönnerborg, Anders

    2007-01-01

    On 3 previous occasions, in 2002, 2003 and 2005, the Swedish Medical Products Agency (Läkemedelsverket) and the Swedish Reference Group for Antiviral Therapy (RAV) have jointly published recommendations for the treatment of HIV infection. An expert group, under the guidance of RAV, has now revised the text again. Since the publication of the previous treatment recommendations, 1 new drug for the treatment of HIV has been approved - the protease inhibitor (PI) darunavir (Prezista). Furthermore, 3 new drugs have become available: the integrase inhibitor raltegravir (MK-0518), the CCR5-inhibitor maraviroc (Celsentri), both of which have novel mechanisms of action, and the non-nucleoside reverse transcriptase inhibitor (NNRTI) etravirine (TMC-125). The new guidelines differ from the previous ones in several respects. The most important of these are that abacavir is now preferred to tenofovir and zidovudine, as a first line drug in treatment-naïve patients, and that initiation of antiretroviral treatment is now recommended before the CD4 cell count falls below 250/microl, rather than 200/microl. Furthermore, recommendations on the treatment of HIV infection in children have been added to the document. As in the case of the previous publication, recommendations are evidence-graded in accordance with the Oxford Centre for Evidence Based Medicine, 2001 (see http://www.cebm.net/levels_of_evidence.asp#levels). PMID:17577810

  6. Experiences of participating in an antiretroviral treatment adherence club

    PubMed Central

    Dudhia, Raashika; Kagee, Ashraf

    2015-01-01

    In an effort to streamline the management of large numbers of patients receiving antiretroviral therapy (ART) in South Africa, adherence clubs were introduced in some districts in the Western Cape since 2008. Adherence clubs are group clinic visits of approximately thirty ART users who receive group adherence counselling and obtain a supply of medication. We sought to document the experiences of patients attending adherence clubs and health care workers at clinics where clubs were operating. Participants were six ART adherence club members and seven health care workers, which included HIV nurses, medical doctors, pharmacists and counsellors. Data in the form of one-on-one interviews were collected at the Infectious Diseases Clinic of a large district hospital in a peri-urban area in the Western Cape region of South Africa. The interviews covered ART users’ experiences of the clubs, advantages and challenges that arose in the context of the club-based method of providing treatment, and the concerns facing ART users and health care workers (HCW’s) with regard to the clubs. The data were analysed using thematic analysis. There were clear benefits to the introduction of adherence clubs, most importantly the reduced amount of time ART users needed to spend at the clinic. Yet, various problems also emerged, the most important one being the logistical problems associated with the timely and correct delivery of drugs. These benefits and disadvantages are discussed in the context of providing ART services to large numbers of patients in post-apartheid South Africa. PMID:25168720

  7. Antiretroviral treatment induced catatonia in 16-year-old boy.

    PubMed

    Lingeswaran, Anand

    2014-01-01

    We present a 16-year-old boy, who had presented to us with catatonic features of mutism, withdrawal, passive negativism, grimacing, gesturing, echopraxia, and excitement of 5 days duration while taking antiretroviral therapy (ART) for a period of 2 years. He had history of birth asphyxia and acquired HIV infection from his father when the same syringe and needle was used on both of them in a medical setting where the father and son had consulted for treatment of pyrexia of unknown origin. He was the eldest of a three children family in which the biologic father had acquired HIV through extramarital sexual contact with HIV-infected sex workers but was unaware of his HIV positive status till our patient, the 16-year-old was admitted and treated for pulmonary tuberculosis at 14 years of age. The boy's mother had only acquired HIV after having three children with the HIV-positive husband, thus leaving the other two children HIV negative. The catatonia completely resolved within 2 days after the ART was withheld, and risperidone 1 mg twice a day was prescribed. This case highlights the risks of ART and breach of universal precautions. PMID:25624940

  8. The first decade of antiretroviral therapy in Africa

    PubMed Central

    2011-01-01

    The past decade has seen remarkable progress in increasing access to antiretroviral therapy in resource-limited settings. Early concerns about the cost and complexity of treatment were overcome thanks to the efforts of a global coalition of health providers, activists, academics, and people living with HIV/AIDS, who argued that every effort must be made to ensure access to essential care when millions of lives depended on it. The high cost of treatment was reduced through advocacy to promote access to generic drugs; care provision was simplified through a public health approach to treatment provision; the lack of human resources was overcome through task-shifting to support the provision of care by non-physicians; and access was expanded through the development of models of care that could work at the primary care level. The challenge for the next decade is to further increase access to treatment and support sustained care for those on treatment, while at the same time ensuring that the package of care is continuously improved such that all patients can benefit from the latest improvements in drug development, clinical science, and public health. PMID:21958478

  9. The first decade of antiretroviral therapy in Africa.

    PubMed

    Ford, Nathan; Calmy, Alexandra; Mills, Edward J

    2011-01-01

    The past decade has seen remarkable progress in increasing access to antiretroviral therapy in resource-limited settings. Early concerns about the cost and complexity of treatment were overcome thanks to the efforts of a global coalition of health providers, activists, academics, and people living with HIV/AIDS, who argued that every effort must be made to ensure access to essential care when millions of lives depended on it. The high cost of treatment was reduced through advocacy to promote access to generic drugs; care provision was simplified through a public health approach to treatment provision; the lack of human resources was overcome through task-shifting to support the provision of care by non-physicians; and access was expanded through the development of models of care that could work at the primary care level. The challenge for the next decade is to further increase access to treatment and support sustained care for those on treatment, while at the same time ensuring that the package of care is continuously improved such that all patients can benefit from the latest improvements in drug development, clinical science, and public health. PMID:21958478

  10. Cost-Effectiveness of Antiretroviral Therapy for Prevention

    PubMed Central

    Kahn, James G; Marseille, Elliot A; Bennett, Rod; Williams, Brian G; Granich, Reuben

    2011-01-01

    Recent empirical studies and analyses have heightened interest in the use of expanded antiretroviral therapy (ART) for prevention of HIV transmission. However, ART is expensive, approximately $600 per person per year, raising issues of the cost and cost-effectiveness of ambitious ART expansion. The goal of this review is to equip the reader with the conceptual tools and substantive background needed to understand and evaluate the policy and programmatic implications of cost-effectiveness assessments of ART for prevention. We provide this review in six sections. We start by introducing and explaining basic concepts of health economics as they relate to this issue, including resources, costs, health metrics (such as Disability-Adjusted Life Years), and different types of economic analysis. We then review research on the cost and cost-effectiveness of ART as treatment, and on the cost-effectiveness of traditional HIV prevention. We describe critical issues in the epidemic impact of ART, such as suppression of transmission and the role of the acute phase of infection. We then present a conceptual model for conducting and interpreting cost-effectiveness analyses of ART as prevention, and review the existing preliminary estimates in this area. We end with a discussion of future directions for programmatic demonstrations and evaluation. PMID:21999776

  11. Namibian prisoners describe barriers to HIV antiretroviral therapy adherence.

    PubMed

    Shalihu, Nauyele; Pretorius, Louise; van Dyk, Agnes; Vander Stoep, Ann; Hagopian, Amy

    2014-01-01

    Little is available in scholarly literature about how HIV-positive prisoners, especially in low-income countries, access antiretroviral therapy (ART) medication. We interviewed 18 prisoners at a large prison in Namibia to identify barriers to medication adherence. The lead nurse researcher was a long-standing clinic employee at the prison, which afforded her access to the population. We identified six significant barriers to adherence, including (1) the desire for privacy and anonymity in a setting where HIV is strongly stigmatized; (2) the lack of simple supports for adherence, such as availability of clocks; (3) insufficient access to food to support the toll on the body of ingesting taxing ART medications; (4) commodification of ART medication; (5) the brutality and despair in the prison setting, generally leading to discouragement and a lack of motivation to strive for optimum health; and (6) the lack of understanding about HIV, how it is transmitted, and how it is best managed. Because most prisoners eventually transition back to communitysettings when their sentences are served, investments in prison health represent important investments in public health. PMID:24499371

  12. Novel drug delivery approaches on antiviral and antiretroviral agents

    PubMed Central

    Sharma, Pooja; Chawla, Anuj; Arora, Sandeep; Pawar, Pravin

    2012-01-01

    Viruses have the property to replicate very fast in host cell. It can attack any part of host cell. Therefore, the clinical efficacy of antiviral drugs and its bioavailability is more important concern taken into account to treat viral infections. The oral and parenteral routes of drug administration have several shortcomings, however, which could lead to the search for formulating better delivery systems. Now, a day's novel drug delivery systems (NDDS) proved to be a better approach to enhance the effectiveness of the antivirals and improve the patient compliance and decrease the adverse effect. The NDDS have reduced the dosing frequency and shorten the duration of treatment, thus, which could lead the treatment more cost-effective. The development of NDDS for antiviral and antiretroviral therapy aims to deliver the drug devoid of toxicity, with high compatibility and biodegradability, targeting the drug to specific sites for viral infection and in some instances it also avoid the first pass metabolism effect. This article aims to discuss the usefulness of novel delivery approaches of antiviral agents such as niosomes, microspheres, microemulsions, nanoparticles that are used in the treatment of various Herpes viruses and in human immunodeficiency virus (HIV) infections. PMID:23057001

  13. Evolving Human Rights and the Science of Antiretroviral Medicine.

    PubMed

    Kavanagh, Matthew; Cohn, Jennifer; Mabote, Lynette; Meier, Benjamin Mason; Williams, Brian; Russell, Asia; Sikwese, Kenly; Baker, Brook

    2015-01-01

    Recent years have seen significant advances in the science of using antiretroviral medicines (ARVs) to fight HIV. Where not long ago ARVs were used late in disease to prevent sick people from dying, today people living with HIV can use ARVs to achieve viral suppression early in the course of disease. This article reviews the mounting new scientific evidence of major clinical and prevention ARV benefits. This has changed the logic of the AIDS response, eliminating competition between "treatment" and "prevention" and encouraging early initiation of treatment for individual and public health benefit. These breakthroughs have implications for the health-related human rights duties of States. With medical advance, the "highest attainable standard" of health has taken a leap, and with it the rights obligations of States. We argue that access to early treatment for all is now a core State obligation and restricting access to, or failing to provide accurate information about, it violates both individual and collective rights. In a context of real political and technical challenges, however, in this article we review the policy implications of evolving human rights obligations given the new science. National and international legal standards require action on budget, health and intellectual property policy, which we outline. PMID:26204587

  14. Public health implications of antiretroviral therapy and HIV drug resistance.

    PubMed

    Wainberg, M A; Friedland, G

    1998-06-24

    Widespread use of antiretroviral agents and increasing occurrence of human immunodeficiency virus (HIV) strains resistant to these drugs have given rise to a number of important issues. Some of these concerns are distinct from the obvious question of the relationship between drug resistance and treatment failure and have potentially widespread public health implications. The relevant issues include but are not limited to the following: (1) frequency with which drug-resistant virus may be transmitted via sexual, intravenous, or mother-to-child routes; (2) ability of drug-resistant variants to be transmitted, a question that relates, in part, to the relative fitness of such strains; (3) effectiveness of antiviral therapy in diminishing viral burden in both blood and genital secretions, and whether this may be compromised in persons harboring resistant virus; and (4) importance of patient adherence to antiviral therapy and its relationship to sustained reduction in viral load to minimize the appearance in and transmission of drug-resistant virus from both blood and genital secretions. Thus, prevention of both development of HIV drug resistance as well as transmission of drug-resistant variants is a central issue of public health importance. Unless this topic is appropriately addressed, the likelihood is that drug-resistant variants of HIV, if able to successfully replicate, will sustain the epidemic and limit the effectiveness of antiviral therapy. PMID:9643862

  15. The Impact of Antiretroviral Therapy on Lung Immunology.

    PubMed

    Cribbs, Sushma K; Fontenot, Andrew P

    2016-04-01

    Despite the introduction of antiretroviral therapy (ART), human immunodeficiency virus-1 (HIV) continues to cause a major impact worldwide. HIV-induced lung disease continues to represent a significant source of morbidity and mortality, although the spectrum of pulmonary diseases has changed. HIV significantly affects the lung, causing acute and chronic cellular changes in the alveolar space. The impact of ART on lung immunology still needs to be fully elucidated. Similar to the periphery, ART affects HIV viral load and reconstitutes CD4(+) T cells in the lung. ART has been associated with significant decreases in bronchoalveolar lavage lymphocytes and increases in B-cell numbers and functionality, resulting in improved immune responses to vaccinations. There are substantial clinical implications of these ART-induced alterations, including the emergence of immune reconstitution inflammatory syndrome and the increased incidences of noninfectious lung diseases, such as lung cancer and chronic obstructive lung disease. There continues to be many unanswered questions regarding the effects of ART on lung health and, in particular, the immune system. Growing knowledge in this area will hopefully diminish the incidence of these noninfectious lung diseases and further improve the health of individuals living with HIV. PMID:26974295

  16. Expenditures for the care of HIV-infected patients in rural areas in China's antiretroviral therapy programs

    PubMed Central

    2011-01-01

    Background The Chinese government has provided health services to those infected by the human immunodeficiency virus (HIV) under the acquired immunodeficiency syndrome (AIDS) care policy since 2003. Detailed research on the actual expenditures and costs for providing care to patients with AIDS is needed for future financial planning of AIDS health care services and possible reform of HIV/AIDS-related policy. The purpose of the current study was to determine the actual expenditures and factors influencing costs for untreated AIDS patients in a rural area of China after initiating highly active antiretroviral therapy (HAART) under the national Free Care Program (China CARES). Methods A retrospective cohort study was conducted in Yunnan and Shanxi Provinces, where HAART and all medical care are provided free to HIV-positive patients. Health expenditures and costs in the first treatment year were collected from medical records and prescriptions at local hospitals between January and June 2007. Multivariate linear regression was used to determine the factors associated with the actual expenditures in the first antiretroviral (ARV) treatment year. Results Five ARV regimens are commonly used in China CARES: zidovudine (AZT) + lamivudine (3TC) + nevirapine (NVP), stavudine (D4T) + 3TC + efavirenz (EFV), D4T + 3TC + NVP, didanosine (DDI) + 3TC + NVP and combivir + EFV. The mean annual expenditure per person for ARV medications was US$2,242 (US$1 = 7 Chinese Yuan (CNY)) among 276 participants. The total costs for treating all adverse drug events (ADEs) and opportunistic infections (OIs) were US$29,703 and US$23,031, respectively. The expenses for treatment of peripheral neuritis and cytomegalovirus (CMV) infections were the highest among those patients with ADEs and OIs, respectively. On the basis of multivariate linear regression, CD4 cell counts (100-199 cells/μL versus <100 cells/μL, P = 0.02; and ≥200 cells/μL versus <100 cells/μL, P < 0.004), residence in Mangshi

  17. Antiretroviral Drug Use in a Cohort of HIV-Uninfected Women in the United States: HIV Prevention Trials Network 064.

    PubMed

    Chen, Iris; Clarke, William; Ou, San-San; Marzinke, Mark A; Breaud, Autumn; Emel, Lynda M; Wang, Jing; Hughes, James P; Richardson, Paul; Haley, Danielle F; Lucas, Jonathan; Rompalo, Anne; Justman, Jessica E; Hodder, Sally L; Eshleman, Susan H

    2015-01-01

    Antiretroviral (ARV) drug use was analyzed in HIV-uninfected women in an observational cohort study conducted in 10 urban and periurban communities in the United States with high rates of poverty and HIV infection. Plasma samples collected in 2009-2010 were tested for the presence of 16 ARV drugs. ARV drugs were detected in samples from 39 (2%) of 1,806 participants: 27/181 (15%) in Baltimore, MD and 12/179 (7%) in Bronx, NY. The ARV drugs detected included different combinations of non-nucleoside reverse transcriptase inhibitors and protease inhibitors (1-4 drugs/sample). These data were analyzed in the context of self-reported data on ARV drug use. None of the 39 women who had ARV drugs detected reported ARV drug use at any study visit. Further research is needed to evaluate ARV drug use by HIV-uninfected individuals. PMID:26445283

  18. Antiretroviral Drug Use in a Cohort of HIV-Uninfected Women in the United States: HIV Prevention Trials Network 064

    PubMed Central

    Chen, Iris; Clarke, William; Ou, San-San; Marzinke, Mark A.; Breaud, Autumn; Emel, Lynda M.; Wang, Jing; Hughes, James P.; Richardson, Paul; Haley, Danielle F.; Lucas, Jonathan; Rompalo, Anne; Justman, Jessica E.; Hodder, Sally L.; Eshleman, Susan H.

    2015-01-01

    Antiretroviral (ARV) drug use was analyzed in HIV-uninfected women in an observational cohort study conducted in 10 urban and periurban communities in the United States with high rates of poverty and HIV infection. Plasma samples collected in 2009–2010 were tested for the presence of 16 ARV drugs. ARV drugs were detected in samples from 39 (2%) of 1,806 participants: 27/181 (15%) in Baltimore, MD and 12/179 (7%) in Bronx, NY. The ARV drugs detected included different combinations of non-nucleoside reverse transcriptase inhibitors and protease inhibitors (1–4 drugs/sample). These data were analyzed in the context of self-reported data on ARV drug use. None of the 39 women who had ARV drugs detected reported ARV drug use at any study visit. Further research is needed to evaluate ARV drug use by HIV-uninfected individuals. PMID:26445283

  19. Adherence to Antiretroviral Medications among Persons who Inject Drugs in Transitional, Low and Middle Income Countries: An International Systematic Review

    PubMed Central

    Feelemyer, Jonathan; Jarlais, Don Des; Arasteh, Kamyar; Uuskula, Anneli

    2014-01-01

    Adherence to antiretroviral (ART) medication is vital to reducing morbidity and mortality among HIV positive persons. People who inject drugs (PWID) are at high risk for HIV infection in transitional/low/middle income countries (TLMIC). We conducted a systematic review of studies reporting adherence to ARTs among persons with active injection drug use and/or histories of injection drug use in TLMIC. Meta-regression was performed to examine relationships between location, adherence measurements, and follow-up period. Fifteen studies were included from seven countries. Adherence levels ranged from 33% to 97%; mean weighted adherence was 72%. ART adherence was associated with different methods of measuring adherence and studies conducted in Eastern Europe and East Asia. The great heterogeneity observed precludes generalization to TLMIC as a whole. Given the critical importance of ART adherence more research is needed on ART adherence among PWID in TLMIC, including the use of standardized methods for reporting adherence to ARTs. PMID:25331268

  20. Antiretroviral Therapy Fails to Restore Levels of HIV-1 Restriction miRNAs in PBMCs of HIV-1-infected MSM

    PubMed Central

    Liu, Man-Qing; Zhao, Min; Kong, Wen-Hua; Peng, Jin-Song; Wang, Fang; Qiu, Hong-Yan; Zhu, Ze-Rong; Tang, Li; Sang, Ming; Wu, Jian-Guo; Ho, Wen-Zhe; Zhou, Wang

    2015-01-01

    Abstract A number of cellular microRNAs (miRNAs) have been identified to have the ability to inhibit HIV-1 replication. In this study, we examined the impact of combination antiretroviral therapy (cART) on the expression of HIV-1 restriction miRNAs in peripheral blood mononuclear cells of HIV-1–infected men who have sex with men (MSM). Compared with male healthy donors, HIV-infected MSM had significantly lower levels of 9 HIV-1 restriction miRNAs. The treatment of HIV-1–infected MSM with cART, however, failed to restore the levels of these miRNAs in peripheral blood mononuclear cells. These observations suggest that the suppression of the cellular restriction miRNAs by HIV-1 may attribute to the virus latency during cART. PMID:26579828

  1. Antiretroviral Therapy Fails to Restore Levels of HIV-1 Restriction miRNAs in PBMCs of HIV-1-infected MSM.

    PubMed

    Liu, Man-Qing; Zhao, Min; Kong, Wen-Hua; Peng, Jin-Song; Wang, Fang; Qiu, Hong-Yan; Zhu, Ze-Rong; Tang, Li; Sang, Ming; Wu, Jian-Guo; Ho, Wen-Zhe; Zhou, Wang

    2015-11-01

    A number of cellular microRNAs (miRNAs) have been identified to have the ability to inhibit HIV-1 replication. In this study, we examined the impact of combination antiretroviral therapy (cART) on the expression of HIV-1 restriction miRNAs in peripheral blood mononuclear cells of HIV-1-infected men who have sex with men (MSM). Compared with male healthy donors, HIV-infected MSM had significantly lower levels of 9 HIV-1 restriction miRNAs. The treatment of HIV-1-infected MSM with cART, however, failed to restore the levels of these miRNAs in peripheral blood mononuclear cells. These observations suggest that the suppression of the cellular restriction miRNAs by HIV-1 may attribute to the virus latency during cART. PMID:26579828

  2. Brief Report: HIV Drug Resistance in Adults Failing Early Antiretroviral Treatment: Results From the HIV Prevention Trials Network 052 Trial.

    PubMed

    Fogel, Jessica M; Hudelson, Sarah E; Ou, San-San; Hart, Stephen; Wallis, Carole; Morgado, Mariza G; Saravanan, Shanmugam; Tripathy, Srikanth; Hovind, Laura; Piwowar-Manning, Estelle; Sabin, Devin; McCauley, Marybeth; Gamble, Theresa; Zhang, Xinyi C; Eron, Joseph J; Gallant, Joel E; Kumwenda, Johnstone; Makhema, Joseph; Kumarasamy, Nagalingeswaran; Chariyalertsak, Suwat; Hakim, James; Badal-Faesen, Sharlaa; Akelo, Victor; Hosseinipour, Mina C; Santos, Breno R; Godbole, Sheela V; Pilotto, Jose H; Grinsztejn, Beatriz; Panchia, Ravindre; Mayer, Kenneth H; Chen, Ying Q; Cohen, Myron S; Eshleman, Susan H

    2016-07-01

    Early initiation of antiretroviral treatment (ART) reduces HIV transmission and has health benefits. HIV drug resistance can limit treatment options and compromise use of ART for HIV prevention. We evaluated drug resistance in 85 participants in the HIV Prevention Trials Network 052 trial who started ART at CD4 counts of 350-550 cells per cubic millimeter and failed ART by May 2011; 8.2% had baseline resistance and 35.3% had resistance at ART failure. High baseline viral load and less education were associated with emergence of resistance at ART failure. Resistance at ART failure was observed in 7 of 8 (87.5%) participants who started ART at lower CD4 cell counts. PMID:26859828

  3. A ‘good hospital’: Nurse and patient perceptions of good clinical care for HIV-positive people on antiretroviral treatment in rural Zimbabwe—A mixed-methods qualitative study

    PubMed Central

    Campbell, Catherine; Scott, Kerry; Madanhire, Claudius; Nyamukapa, Constance; Gregson, Simon

    2011-01-01

    Background Antiretroviral treatment for HIV is gradually being made available across sub-Saharan Africa. With antiretroviral treatment, HIV can be approached as a chronic, manageable condition rather than a shorter-term issue of palliative care. This treatment involves repeated interaction between health staff and patients for ongoing check-ups and prescription refills. Objective This study aimed to understand patient and healthcare staff perceptions of good clinical antiretroviral treatment care. Design Over 100 h of ethnographic observation at healthcare sites; interviews and focus groups with 25 healthcentre workers (mostly nurses), 53 HIV-positive adults taking ARVs and 40 carers of children on ART. The data were analyzed using thematic content analysis. Setting Three healthcare sites providing free antiretroviral drugs in rural Zimbabwe, where the adult HIV infection rate is approximately 20%. Results Contrary to reports of poor antiretroviral treatment adherence and task-oriented rather than patient-oriented nursing, our study found great patient commitment to adherence, outstanding nurse dedication and a pervasive sense of hope about coping with HIV. Within this context however there were some situations where patients and nurses had different expectations of the medical encounter, leading to stress and dissatisfaction. Patients and staff both emphasized the importance of nurse kindness, understanding, confidentiality and acceptance (i.e. treating HIV patients ‘like normal’) and patient adherence to medical directions. However, nurses at times overlooked the negative effects of long wait times and frequent hospital visits. Further, nurses sometimes conflated medical adherence with general patient obedience in all aspects of the nurse–patient relationships. Patients and staff were frustrated by the ambiguity and unpredictability surrounding key elements of hospital visits such as how much patients had to pay for service, how long it would take to be

  4. A Randomized Trial of Time-Limited Antiretroviral Therapy in Acute/Early HIV Infection

    PubMed Central

    Margolick, Joseph B.; Apuzzo, Linda; Singer, Joel; Wong, Hubert; Lee, Terry; Gallant, Joel E.; El-Helou, Phillippe; Loutfy, Mona R.; Rachlis, Anita; Fraser, Christopher; Kasper, Kenneth; Tremblay, Cécile; Tossonian, Harout; Conway, Brian

    2015-01-01

    Background It has been proposed that initiation of antiretroviral treatment (ART) very soon after establishment of HIV infection may be beneficial by improving host control of HIV replication and delaying disease progression. Methods People with documented HIV infection of less than 12 months’ duration in Baltimore MD and seven Canadian sites were randomized to either a) observation and deferred ART, or b) immediate treatment with ART for 12 months. All subjects not receiving ART were followed quarterly and permanent ART was initiated according to contemporaneous treatment guidelines. The endpoint of the trial was total ART-free time from study entry until initiation of permanent ART. Results One hundred thirteen people were randomized, 56 to the observation arm and 57 to the immediate treatment arm. Twenty-three had acute (<2 months) infection and 90 early (2–12 months) infection. Of those randomized to the immediate treatment arm, 37 completed 12 months of ART according to protocol, 9 declined to stop ART after 12 months, and 11 were nonadherent to the protocol or lost to follow-up. Comparing those in the observation arm to either those who completed 12 months of ART or all 56 who were randomized to immediate ART, there was no significant difference between the arms in treatment-free interval after study entry, which was about 18 months in both arms. Conclusions This study did not find a benefit from administration of a brief, time-limited (12-month) course of ART in acute or early HIV infection. Trial Registration ClinicalTrials.gov NCT00106171 PMID:26600459

  5. Self-reported adverse reactions among patients initiating antiretroviral therapy in Brazil.

    PubMed

    Pádua, Cristiane A Menezes de; César, Cibele C; Bonolo, Palmira F; Acurcio, Francisco A; Guimarães, Mark Drew C

    2007-02-01

    A cross-sectional analysis was carried out to describe adverse reactions to antiretroviral therapy (ART) reported by HIV-infected patients initiating treatment at two public health AIDS referral centers in Belo Horizonte, Brazil, 2001-2003 and to verify their association with selected variables. Adverse reactions were obtained through interview at the first follow-up visit (first month) after the antiretroviral prescription. Socio-demographic and behavioral variables related to ART were obtained from baseline and follow-up interviews and clinical variables from medical charts. Patients with four or more reactions were compared to those with less than four. Odds ratio with 95% confidence interval were estimated using logistic regression model for both univariate and multivariate analyses. At least one adverse reaction was reported by 92.2% of the participants while 56.2% reported four or more different reactions. Antiretroviral regimens including indinavir/ritonavir, irregular use of antiretrovirals and switch in regimens were independently associated with four or more adverse reactions (OR=7.92, 5.73 and 2.03, respectively). The initial period of ARV treatment is crucial and patients' perception of adverse reactions should be carefully taken into account. Strategies for monitoring and management of adverse reactions including the choice of regimens and the prevention of irregular ART should be developed in AIDS/HIV referral centers in Brazil to promote better adherence to antiretroviral therapy. PMID:17625721

  6. Challenges of malnutrition care among HIV-infected children on antiretroviral treatment in Africa.

    PubMed

    Jesson, J; Leroy, V

    2015-05-01

    More than 90% of the estimated 3.2 million children with HIV worldwide, at the end of 2013, were living in sub-Saharan Africa. The management of these children was still difficult in 2014 despite the progress in access to antiretroviral drugs. A great number of HIV-infected children are not diagnosed at 6 weeks and start antiretroviral treatment late, at an advanced stage of HIV disease complicated by other comorbidities such as malnutrition. Malnutrition is a major problem in the sub-Saharan Africa global population; it is an additional burden for HIV-infected children because they do not respond as well as non-infected children to the usual nutritional care. HIV infection and malnutrition interact, creating a vicious circle. It is important to understand the relationship between these 2 conditions and the effect of antiretroviral treatment on this circle to taking them into account for an optimal management of pediatric HIV. An improved monitoring of growth during follow-up and the introduction of a nutritional support among HIV-infected children, especially at antiretroviral treatment initiation, are important factors that could improve response to antiretroviral treatment and optimize the management of pediatric HIV in resource-limited countries. PMID:25861689

  7. Alcohol-antiretroviral therapy interactive toxicity beliefs and daily medication adherence and alcohol use among people living with HIV.

    PubMed

    Pellowski, Jennifer A; Kalichman, Seth C; Kalichman, Moira O; Cherry, Chauncey

    2016-08-01

    Alcohol-antiretroviral therapy (ART) interactive toxicity beliefs reflect perceived adverse outcomes of mixing alcohol and ART. Previous research has shown a significant relationship between alcohol-ART interactive toxicity beliefs and ART non-adherence, over and above other correlates of non-adherence such as human immunodeficiency virus (HIV)symptoms and frequency of alcohol use. Most past studies have collected data over extended periods and have not determined if alcohol use and missed medications occur at the day-level among people holding interactive toxicity beliefs. Previous daily analyses, however, have been limited by self-reported adherence and relatively short periods of observation. To address these gaps in the literature, men and women living with HIV in Atlanta, GA, were enrolled in a 45-day observational cohort study. Daily alcohol use was collected using two-way interactive text message surveys and daily adherence was collected via the Wisepill device. Fifty-seven participants completed a measure of alcohol-ART interactive toxicity beliefs and contributed 2565 days of daily data. Participants who endorsed high levels of interactive toxicity beliefs had significantly more days when they missed doses of medication. Alcohol-antiretroviral toxicity beliefs predicted missing doses of medication on days when participants were drinking and on days when they were not drinking. Multilevel multivariate regressions showed that these toxicity beliefs predicted daily missed doses of medication over and above quantity of alcohol consumed, depression and general medication concerns. This study replicates and extends previous literature and indicates the necessity of addressing alcohol-ART toxicity beliefs within adherence interventions. PMID:26964014

  8. Long-Term Antiretroviral Treatment Initiated at Primary HIV-1 Infection Affects the Size, Composition, and Decay Kinetics of the Reservoir of HIV-1-Infected CD4 T Cells

    PubMed Central

    Buzon, Maria J.; Martin-Gayo, Enrique; Pereyra, Florencia; Ouyang, Zhengyu; Sun, Hong; Li, Jonathan Z.; Piovoso, Michael; Shaw, Amy; Dalmau, Judith; Zangger, Nadine; Martinez-Picado, Javier; Zurakowski, Ryan; Yu, Xu G.; Telenti, Amalio; Walker, Bruce D.; Rosenberg, Eric S.

    2014-01-01

    ABSTRACT Initiation of antiretroviral therapy during the earliest stages of HIV-1 infection may limit the seeding of a long-lasting viral reservoir, but long-term effects of early antiretroviral treatment initiation remain unknown. Here, we analyzed immunological and virological characteristics of nine patients who started antiretroviral therapy at primary HIV-1 infection and remained on suppressive treatment for >10 years; patients with similar treatment duration but initiation of suppressive therapy during chronic HIV-1 infection served as controls. We observed that independently of the timing of treatment initiation, HIV-1 DNA in CD4 T cells decayed primarily during the initial 3 to 4 years of treatment. However, in patients who started antiretroviral therapy in early infection, this decay occurred faster and was more pronounced, leading to substantially lower levels of cell-associated HIV-1 DNA after long-term treatment. Despite this smaller size, the viral CD4 T cell reservoir in persons with early treatment initiation consisted more dominantly of the long-lasting central-memory and T memory stem cells. HIV-1-specific T cell responses remained continuously detectable during antiretroviral therapy, independently of the timing of treatment initiation. Together, these data suggest that early HIV-1 treatment initiation, even when continued for >10 years, is unlikely to lead to viral eradication, but the presence of low viral reservoirs and durable HIV-1 T cell responses may make such patients good candidates for future interventional studies aiming at HIV-1 eradication and cure. IMPORTANCE Antiretroviral therapy can effectively suppress HIV-1 replication to undetectable levels; however, HIV-1 can persist despite treatment, and viral replication rapidly rebounds when treatment is discontinued. This is mainly due to the presence of latently infected CD4 T cells, which are not susceptible to antiretroviral drugs. Starting treatment in the earliest stages of HIV-1

  9. HBV influence on Response to Antiretroviral Therapy in Horizontally HIV-HBV Coinfected Patient during Early Childhood

    PubMed Central

    Niculescu, Irina; Cupşa, A.M.; Stoian, Andreea Cristina; Dumitrescu, FLorentina; Giubelan, L.I.; Alexandru, D.O.

    2013-01-01

    Background: There are few studies on pediatric HIV-HBV coinfection, so evidences about relationships between the two viruses are scarce. Objectives: influence of HBV infection on virological and immunological response to antiretroviral therapy (ART) in antiretroviral-naïve horizontally HIV-HBV coinfected subjects during early childhood. Material and methods: observational study on 826 HIV+ subjects in evidence of Craiova Regional Centre (CRC); we analyzed the immunological and virological response at 6-12 months after starting first antiretroviral regimens compared in 2 groups: horizontally HIV-HBV coinfected subjects during early childhood (CoS) versus horizontally HIV infected subjects during early childhood without HBV infection (non-CoS). Results: Number of subjects: CoS-66 subjects, non-CoS-132 subjects. Demographic data: CoS-gender ratio F:M=0.886, the majority lived in rural area (57.58%), mean age on diagnosis-9.288±4.607 years, non-CoS-gender ratio F:M=0.859, the majority lived in urban area (53.79%), mean age on diagnosis-10.742±5.107 years. At baseline, HIV category was: CoS-A-1.52%, B-80.30%, C-18.18%, non-CoS-A-2.27%, B-70.45%, C-27.27% (p Chi2=0.332), the mean CD4+ cell count was: CoS-148.33±148.10 cells/ml, non-CoS-163.17±155.39 cells/ml (p Student=0.521) and the mean HIV viral load (HIV VL) was: CoS-5.06±0.80 lgcopies/ml (for 29 subjects), non-CoS-5.04±0.84 lgcopies/ml (for 61 subjects) (p Student=0.978). At the end of the studied period, the mean increase in CD4+ cell count was: CoS-177.068±141.676 cells/ml, non-CoS-176.015±191.751 cells/ml (p Student=0.969) and the mean decrease in HIV VL was: CoS-5.04±0.79 lgcopies/ml, non-COS-4.69±2.04 lgcopies/ml (p Student=0.911). Conclusions: The presence of HBV coinfection does not influence immunological or virological response to ART. PMID:24778861

  10. Cellular Responses and Tissue Depots for Nanoformulated Antiretroviral Therapy

    PubMed Central

    Martinez-Skinner, Andrea L.; Araínga, Mariluz A.; Puligujja, Pavan; Palandri, Diana L.; Baldridge, Hannah M.; Edagwa, Benson J.; McMillan, JoEllyn M.; Mosley, R. Lee; Gendelman, Howard E.

    2015-01-01

    Long-acting nanoformulated antiretroviral therapy (nanoART) induces a range of innate immune migratory, phagocytic and secretory cell functions that perpetuate drug depots. While recycling endosomes serve as the macrophage subcellular depots, little is known of the dynamics of nanoART-cell interactions. To this end, we assessed temporal leukocyte responses, drug uptake and distribution following both intraperitoneal and intramuscular injection of nanoformulated atazanavir (nanoATV). Local inflammatory responses heralded drug distribution to peritoneal cell populations, regional lymph nodes, spleen and liver. This proceeded for three days in male Balb/c mice. NanoATV-induced changes in myeloid populations were assessed by fluorescence-activated cell sorting (FACS) with CD45, CD3, CD11b, F4/80, and GR-1 antibodies. The localization of nanoATV within leukocyte cell subsets was determined by confocal microscopy. Combined FACS and ultra-performance liquid chromatography tandem mass-spectrometry assays determined nanoATV carriages by cell-based vehicles. A robust granulocyte, but not peritoneal macrophage nanoATV response paralleled zymosan A treatment. ATV levels were highest at sites of injection in peritoneal or muscle macrophages, dependent on the injection site. The spleen and liver served as nanoATV tissue depots while drug levels in lymph nodes were higher than those recorded in plasma. Dual polymer and cell labeling demonstrated a nearly exclusive drug reservoir in macrophages within the liver and spleen. Overall, nanoART induces innate immune responses coincident with rapid tissue macrophage distribution. Taken together, these works provide avenues for therapeutic development designed towards chemical eradication of human immunodeficiency viral infection. PMID:26716700

  11. Alcohol use disorders and antiretroviral therapy among prisoners in Argentina

    PubMed Central

    Alpert, Michael; Wickersham, Jeffrey A.; Vázquez, Mariana; Altice, Frederick L.

    2013-01-01

    Purpose While Argentina has significantly improved access to HIV care and antiretroviral therapy (ART) for both the general population and prisoners, the prevalence of alcohol use disorders (AUDs) among HIV-infected prisoners and their relationship to accessing ART in Argentina is currently unknown. This study aims to characterize the substance abuse patterns of HIV-infected prisoners in Argentina and to assess the independent correlates of receipt of pre-incarceration ART. Design/methodology/approach An anonymous, cross-sectional survey of 100 HIV-infected federal prisoners was conducted in the Buenos Aires municipality from July–December 2010. AUDs were assessed using the AUDIT scale. Findings A majority (63 per cent) of participants met criteria for AUDs, 45 per cent of subjects were diagnosed with HIV in prison and one-quarter had initiated ART during the current incarceration. In addition, over one-third (35 per cent) of participants did not receive ART during the pre-incarceration period despite receiving it upon incarceration. This correlated significantly with the presence of having an AUD (AOR 0.20, 95 per cent CI 0.06–0.74, p = 0.016). Practical implications AUDs are prevalent among HIV-infected prisoners in Argentina and are significantly related to negative secondary HIV prevention and treatment outcomes. While Argentina has provided an exemplary model of HIV-related health care reform within its prisons, future efforts to provide screening and treatment for AUDs are needed to improve the health of the nation’s incarcerated population. Originality/value This paper is the first to describe pre-incarceration drug and alcohol use disorders and issues related to access to ART among prisoners in Argentina. PMID:24772187

  12. Contagiousness under antiretroviral therapy and stigmatization toward people with HIV.

    PubMed

    Drewes, Jochen; Kleiber, Dieter

    2014-01-01

    Perceived contagiousness is a major dimension underlying HIV-related stigmatization. Antiretroviral therapy (ART) can diminish contagiousness by reducing viral load levels in HIV-infected individuals. To test the assumption that reductions in contagiousness can lead to a decrease in stigmatizing reactions, we conducted an experimental online study. A sample of 752 participants (50.9% female) read a short vignette depicting an HIV-positive individual with either a high or a low viral load and were either given or not given information about the association between viral load and contagiousness. Subsequently, participants were asked to rate their willingness to stigmatize this individual by responding to two measures of social and physical distance. Differences between the low and the high viral load information groups and the combined no-information groups (forming a quasi-control group) were analyzed using analysis of covariance (ANCOVA), controlling for gender and baseline perceptions of contagiousness. The covariates, perceived contagiousness at baseline and gender, were associated with social and physical distancing, but the viral load/information factor was only significant in physical distancing. Planned contrast analyses confirmed that physical distancing in the informed group was lower in the low viral load condition compared to the high viral load condition and to the control group. We thus found evidence for the significant role of perceived contagiousness in the HIV-related stigma and were able to experimentally demonstrate the potential of ART to reduce HIV-related stigmatization by lowering viral load and contagiousness, when these changes are accompanied by a decreased perception of contagiousness. PMID:24779483

  13. Reforming antiretroviral price negotiations and public procurement: the Mexican experience.

    PubMed

    Adesina, Adebiyi; Wirtz, Veronika J; Dratler, Sandra

    2013-01-01

    Since antiretroviral (ARV) medicines represent one of the most costly components of therapy for HIV in middle-income countries, ensuring their efficient procurement is highly relevant. In 2008, Mexico created a national commission for the negotiation of ARV prices to achieve price reductions for their public HIV treatment programmes. The objective of this study is to assess the immediate impact of the creation of the Mexican Commission for Price Negotiation on ARV prices and expenditures. A longitudinal retrospective analysis of procurement prices, volumes and type of the most commonly prescribed ARVs procured by the two largest providers of HIV/AIDS care in Mexico between 2004 and 2009 was carried out. These analyses were combined with 26 semi-structured key informant interviews to identify changes in the procurement process. Prices for ARVs dropped by an average of 38% after the first round of negotiations, indicating that the Commission was successful in price negotiations. However, when compared with other upper-middle-income countries, Mexico continues to pay an average of six times more for ARVs. The Commission's negotiations were successful in achieving lower ARV prices. However, price reduction in upper-middle-income countries suggests that the price decrease in Mexico cannot be entirely attributed to the Commission's first round of negotiations. In addition, key informants identified inefficiencies in the forecasting and procurement processes possibly affecting the efficiency of the negotiation process. A comprehensive approach to improving efficiency in the purchasing and delivery of ARVs is necessary, including a better clarification in the roles and responsibilities of the Commission, improving supply data collection and integration in forecasting and procurement, and the creation of a support system to monitor and provide feedback on patient ARV use. PMID:22375026

  14. The HIV antiretroviral drug efavirenz has LSD-like properties.

    PubMed

    Gatch, Michael B; Kozlenkov, Alexey; Huang, Ren-Qi; Yang, Wenjuan; Nguyen, Jacques D; González-Maeso, Javier; Rice, Kenner C; France, Charles P; Dillon, Glenn H; Forster, Michael J; Schetz, John A

    2013-11-01

    Anecdotal reports have surfaced concerning misuse of the HIV antiretroviral medication efavirenz ((4S)-6-chloro-4-(2-cyclopropylethynyl)-4-(trifluoromethyl)-2,4-dihydro-1H-3,1-benzoxazin-2-one) by HIV patients and non-infected teens who crush the pills and smoke the powder for its psychoactive effects. Molecular profiling of the receptor pharmacology of efavirenz pinpointed interactions with multiple established sites of action for other known drugs of abuse including catecholamine and indolamine transporters, and GABAA and 5-HT(2A) receptors. In rodents, interaction with the 5-HT(2A) receptor, a primary site of action of lysergic acid diethylamine (LSD), appears to dominate efavirenz's behavioral profile. Both LSD and efavirenz reduce ambulation in a novel open-field environment. Efavirenz occasions drug-lever responding in rats discriminating LSD from saline, and this effect is abolished by selective blockade of the 5-HT(2A) receptor. Similar to LSD, efavirenz induces head-twitch responses in wild-type, but not in 5-HT(2A)-knockout, mice. Despite having GABAA-potentiating effects (like benzodiazepines and barbiturates), and interactions with dopamine transporter, serotonin transporter, and vesicular monoamine transporter 2 (like cocaine and methamphetamine), efavirenz fails to maintain responding in rats that self-administer cocaine, and it fails to produce a conditioned place preference. Although its molecular pharmacology is multifarious, efavirenz's prevailing behavioral effect in rodents is consistent with LSD-like activity mediated via the 5-HT(2A) receptor. This finding correlates, in part, with the subjective experiences in humans who abuse efavirenz and with specific dose-dependent adverse neuropsychiatric events, such as hallucinations and night terrors, reported by HIV patients taking it as a medication. PMID:23702798

  15. HIV, antiretroviral treatment, hypertension, and stroke in Malawian adults

    PubMed Central

    Corbett, Elizabeth L.; Connor, Myles D.; Mzinganjira, Henry; Kampondeni, Sam; Choko, Augustine; Hopkins, Mark; Emsley, Hedley C.A.; Bryer, Alan; Faragher, Brian; Heyderman, Robert S.; Allain, Theresa J.; Solomon, Tom

    2016-01-01

    Objective: To investigate HIV, its treatment, and hypertension as stroke risk factors in Malawian adults. Methods: We performed a case-control study of 222 adults with acute stroke, confirmed by MRI in 86%, and 503 population controls, frequency-matched for age, sex, and place of residence, using Global Positioning System for random selection. Multivariate logistic regression models were used for case-control comparisons. Results: HIV infection (population attributable fraction [PAF] 15%) and hypertension (PAF 46%) were strongly linked to stroke. HIV was the predominant risk factor for young stroke (≤45 years), with a prevalence of 67% and an adjusted odds ratio (aOR) (95% confidence interval) of 5.57 (2.43–12.8) (PAF 42%). There was an increased risk of a stroke in patients with untreated HIV infection (aOR 4.48 [2.44–8.24], p < 0.001), but the highest risk was in the first 6 months after starting antiretroviral therapy (ART) (aOR 15.6 [4.21–46.6], p < 0.001); this group had a lower median CD4+ T-lymphocyte count (92 vs 375 cells/mm3, p = 0.004). In older participants (HIV prevalence 17%), HIV was associated with stroke, but with a lower PAF than hypertension (5% vs 68%). There was no interaction between HIV and hypertension on stroke risk. Conclusions: In a population with high HIV prevalence, where stroke incidence is increasing, we have shown that HIV is an important risk factor. Early ART use in immunosuppressed patients poses an additional and potentially treatable stroke risk. Immune reconstitution inflammatory syndrome may be contributing to the disease mechanisms. PMID:26683649

  16. The Survival Benefits of Antiretroviral Therapy in South Africa

    PubMed Central

    April, Michael D.; Wood, Robin; Berkowitz, Bethany K.; Paltiel, A. David; Anglaret, Xavier; Losina, Elena; Freedberg, Kenneth A.; Walensky, Rochelle P.

    2014-01-01

    Background. We sought to quantify the survival benefits attributable to antiretroviral therapy (ART) in South Africa since 2004. Methods. We used the Cost-Effectiveness of Preventing AIDS Complications–International model (CEPAC) to simulate 8 cohorts of human immunodeficiency virus (HIV)–infected patients initiating ART each year during 2004–2011. Model inputs included cohort-specific mean CD4+ T-cell count at ART initiation (112–178 cells/µL), 24-week ART suppressive efficacy (78%), second-line ART availability (2.4% of ART recipients), and cohort-specific 36-month retention rate (55%–71%). CEPAC simulated survival twice for each cohort, once with and once without ART. The sum of the products of per capita survival differences and the total numbers of persons initiating ART for each cohort yielded the total survival benefits. Results. Lifetime per capita survival benefits ranged from 9.3 to 10.2 life-years across the 8 cohorts. Total estimated population lifetime survival benefit for all persons starting ART during 2004–2011 was 21.7 million life-years, of which 2.8 million life-years (12.7%) had been realized by December 2012. By 2030, benefits reached 17.9 million life-years under current policies, 21.7 million life-years with universal second-line ART, 23.3 million life-years with increased linkage to care of eligible untreated patients, and 28.0 million life-years with both linkage to care and universal second-line ART. Conclusions. We found dramatic past and potential future survival benefits attributable to ART, justifying international support of ART rollout in South Africa. PMID:24307741

  17. Antiretroviral therapy for prevention of HIV transmission in HIV-discordant couples

    PubMed Central

    Anglemyer, Andrew; Rutherford, George W; Horvath, Tara; Baggaley, Rachel C; Egger, Matthias; Siegfried, Nandi

    2014-01-01

    Background Antiretroviral drugs have been shown to reduce risk of mother-to-child transmission of human immunodeficiency virus (HIV) and are also widely used for post-exposure prophylaxis for parenteral and sexual exposures. Sexual transmission may be lower in couples in which one partner is infected with HIV and the other is not and the infected partner is on antiretroviral therapy (ART). Objectives To determine if ART use in an HIV-infected member of an HIV-discordant couple is associated with lower risk of HIV transmission to the uninfected partner compared to untreated discordant couples. Search methods We used standard Cochrane methods to search electronic databases and conference proceedings with relevant search terms without limits to language. Selection criteria Randomised controlled trials (RCT), cohort studies and case-control studies of HIV-discordant couples in which the HIV-infected member of the couple was being treated or not treated with ART Data collection and analysis Abstracts of all trials identified by electronic or bibliographic scanning were examined independently by two authors. We initially identified 3,833 references and examined 87 in detail for study eligibility. Data were abstracted independently using a standardised abstraction form. Main results One RCT and nine observational studies were included in the review. These ten studies identified 2,112 episodes of HIV transmission, 1,016 among treated couples and 1,096 among untreated couples. The rate ratio for the single randomised controlled trial was 0.04 [95% CI 0.00, 0.27]. All index partners in this study had CD4 cell counts at baseline of 350–550 cells/µL. Similarly, the summary rate ratio for the nine observational studies was 0.58 [95% CI 0.35, 0.96], with substantial heterogeneity (I2=64%). After excluding two studies with inadequate person-time data, we estimated a summary rate ratio of 0.36 [95%CI 0.17, 0.75] with substantial heterogeneity (I2=62%). We also performed

  18. Relatively High Prevalence of Drug Resistance Among Antiretroviral-Naive Patients from Henan, Central China

    PubMed Central

    Li, Lingnuo; Sun, Binlian; Zeng, Haiyan; Sun, Zhiwu; Sun, Guoqing

    2014-01-01

    Abstract To elucidate the prevalence of HIV-1 subtypes and transmitted drug resistance in Henan, central China, HIV-1-positive blood samples from 187 antiretroviral-naive patients were collected in our study from August 2009 to November 2010. Subtype B′ (92.0%, 172 of 187) remains the predominant HIV-1 subtype in Henan province and was prevalent in all risk populations and geographic regions. Of 98 pol sequences 67 (68.4%) harbored drug resistance mutations, and only 14 (14.3%, 14 of 98) sequences have mutations associated with significantly reduced phenotypic susceptibility to antiretroviral drugs. The unexpectedly high percentage of drug resistance in Henan province is mainly due to the prevalence of minor mutations in the protease and integrase regions, especially A71T/V and L68V/I/IM/LV. In all, we detected a relatively high prevalence of drug resistance with unique mutation distributions among antiretroviral-naive patients from Henan province. PMID:23800338

  19. Current strategies for improving access and adherence to antiretroviral therapies in resource-limited settings

    PubMed Central

    Scanlon, Michael L; Vreeman, Rachel C

    2013-01-01

    The rollout of antiretroviral therapy (ART) significantly reduced human immunodeficiency virus (HIV)-related morbidity and mortality, but good clinical outcomes depend on access and adherence to treatment. In resource-limited settings, where over 90% of the world’s HIV-infected population resides, data on barriers to treatment are emerging that contribute to low rates of uptake in HIV testing, linkage to and retention in HIV care systems, and suboptimal adherence rates to therapy. A review of the literature reveals limited evidence to inform strategies to improve access and adherence with the majority of studies from sub-Saharan Africa. Data from observational studies and randomized controlled trials support home-based, mobile and antenatal care HIV testing, task-shifting from doctor-based to nurse-based and lower level provider care, and adherence support through education, counseling and mobile phone messaging services. Strategies with more limited evidence include targeted HIV testing for couples and family members of ART patients, decentralization of HIV care, including through home- and community-based ART programs, and adherence promotion through peer health workers, treatment supporters, and directly observed therapy. There is little evidence for improving access and adherence among vulnerable groups such as women, children and adolescents, and other high-risk populations and for addressing major barriers. Overall, studies are few in number and suffer from methodological issues. Recommendations for further research include health information technology, social-level factors like HIV stigma, and new research directions in cost-effectiveness, operations, and implementation. Findings from this review make a compelling case for more data to guide strategies to improve access and adherence to treatment in resource-limited settings. PMID:23326204

  20. Outcomes of antiretroviral therapy among younger versus older adolescents and adults in an urban clinic, Zimbabwe

    PubMed Central

    Takarinda, K. C.; Owiti, P.; Mutasa-Apollo, T.; Mugurungi, O.; Buruwe, L.; Reid, A. J.

    2016-01-01

    Setting: A non-governmental organisation-supported clinic offering health services including antiretroviral therapy (ART). Objective: To compare ART retention between younger (age 10–14 years) vs. older (age 15–19 years) adolescents and younger (age 20–29 years) vs. older (age ⩾30 years) adults and determine adolescent- and adult-specific attrition-associated factors among those initiated on ART between 2010 and 2011. Design: Retrospective cohort study. Results: Of 110 (7%) adolescents and 1484 (93%) adults included in the study, no differences in retention were observed between younger vs. older adolescents at 6, 12 and 24 months. More younger adolescents were initiated with body mass index <16 kg/m2 compared with older adolescents (64% vs. 47%; P = 0.04). There were more females (74% vs. 52%, P < 0.001) and fewer patients initiating ART with CD4 count ⩽350 cells/mm3 (77% vs. 81%, P = 0.007) among younger vs. older adults. Younger adults demonstrated more attrition than older adults at all time-points. No attrition risk factors were observed among adolescents. Attrition-associated factors among adults included being younger, having a lower CD4 count and advanced human immunodeficiency virus disease at initiation, and initiation on a stavudine-based regimen. Conclusion: Younger adults demonstrated greater attrition and may require more attention. We were unable to demonstrate differences in attrition among younger vs. older adolescents. Loss to follow-up was the main reason for attrition across all age groups. Overall, earlier presentation for ART care appears important for improved ART retention among adults. PMID:27358802

  1. Public sector antiretroviral treatment programme in South Africa: health care workers' attention to mental health problems.

    PubMed

    Pappin, Michele; Wouters, Edwin; Booysen, Frederik L R; Lund, Crick

    2015-01-01

    Although there is a high prevalence of anxiety and depression amongst people receiving antiretroviral treatment (ART), many patients are not screened, diagnosed or referred for mental health problems. This study aims to determine whether public sector health care workers in South Africa observe, screen, diagnose and refer ART patients that show symptoms of common mental disorders. It also aims to ascertain the extent of mental health training received by public sector health care workers working in ART. The study was cross-sectional in design. Self-administered questionnaires were completed by 40 nurses and structured interviews were conducted with 23 lay workers across the five districts in the Free State between July 2009 and October 2009. STATA version 12 was used to perform statistical data analysis. The health care workers reported observing a high frequency of symptoms of common mental disorders among public sector ART patients. While 70% of nurses screened and diagnosed, only 40% of lay workers screened and diagnosed patients on ART for a mental disorder. Health care workers who had received training in mental health were more likely to screen or diagnose a mental disorder, but only 14% of the workers had received such training. We recommend that health care workers should receive task-specific training to screen and/or diagnose patients on ART for common mental disorders using the guidelines of the South African HIV Clinicians Society. A positive diagnosis should be referred to a health care practitioner for appropriate evidence-based treatment in the form of medication or psychotherapy. PMID:25317991

  2. Self-Efficacy and Depression as Mediators of the Relationship between Pain and Antiretroviral Adherence

    PubMed Central

    Berg, Karina M.; Cooperman, Nina A.; Newville, Howard; Arnsten, Julia H.

    2009-01-01

    The goals of this study were to examine the association between pain and antiretroviral adherence, and to estimate the mediating effect of adherence self-efficacy and depression symptom severity. Surveys using audio computer-assisted self-interview were conducted among 70 HIV-infected current and former drug users enrolled in a methadone program. We assessed antiretroviral adherence and adherence self-efficacy using questions from the Adult Clinical Trials Group survey. We considered participants adherent if they reported taking at least 95% of prescribed antiretrovirals over the past seven days. We assessed depression symptom severity using the depression subscale of the Brief Symptom Inventory. Participants reported pain of any duration in response to a question from the Brief Pain Inventory. Participants reporting pain were 87% less likely to be classified as adherent compared to those without pain [ORunadj = 0.13 (95%CI 0.03–0.52)]. When we examined adherence self-efficacy as a mediator of the relationship between pain and adherence, criteria for partial mediation were met. Adjusting for self-efficacy, the beta coefficient for pain decreased by 23% but the independent relationship between pain and antiretroviral adherence was maintained. Mediation criteria were not met when we examined the mediating effect of depression symptom severity on the relationship between pain and adherence. Adjusting for depression symptom severity, the beta coefficient for pain decreased by 9% and the relationship between pain and antiretroviral adherence remained significant. Our results indicate that neither adherence self-efficacy nor depression symptom severity fully mediated the relationship between pain and adherence. HIV providers should recognize the potential impact of pain on antiretroviral adherence among current and former drug users. PMID:19229695

  3. Antiretroviral adherence and use of alternative therapies among older HIV-infected adults.

    PubMed Central

    Wutoh, A. K.; Brown, C. M.; Kumoji, E. K.; Daftary, M. S.; Jones, T.; Barnes, N. A.; Powell, N. J.

    2001-01-01

    OBJECTIVE: To investigate adherence to antiretroviral therapy and use of alternative therapies among older human immunodeficiency virus (HIV)-infected adults, and to assess relationships between antiretroviral adherence and clinical outcomes. METHODS: One hundred older HIV-infected patients, aged 50 and over, treated at two large HIV clinics in Washington, DC, were enrolled. A cross-sectional methodology used structured interviews to investigate antiretroviral regimens, use of alternative therapies, and demographics. Medical records provided viral load and CD4 count within 3 months of interview. RESULTS: The mean self-reported adherence was 94%, and 55 patients reported 100% adherence to antiretroviral therapy. Correlation analysis showed a significant negative correlation between adherence and viral load (r = -312, p = 0.005). There was no significant difference in adherence based on race, gender, mode of transmission, or education. Twenty-one patients (21%) reported the use of an alternative therapy, with several patients using multiple alternative therapies. There was no significant difference in adherence score (p = 0.514) or viral load (p = 0.860) based upon use of alternative therapies. CONCLUSIONS: Older HIV-infected study patients reported high levels of adherence to antiretroviral regimens, and adherence was highly correlated with HIV viral load. Use of alternative therapies did not significantly impact adherence to antiretroviral agents or viral load. High adherence among this older population may be related to older patients' familiarity with medication usage, their increasing awareness of HIV as a disease that requires optimal adherence, and educational efforts promoted by the two clinics in which they are clients. PMID:11491273

  4. NR Peg: A new highly active semi-detached binary

    NASA Astrophysics Data System (ADS)

    Erdem, A.; Sürgit, D.; Kurpińska-Winiarska, M.; Oblak, E.

    2014-11-01

    This paper presents the first analysis of spectroscopic and photometric observations of the eclipsing binary star NR Peg. ELODIE Hα observations indicate that the secondary component is a chromospherically active star; however, the spectral line profiles (especially of neutral metals) of NR Peg are very wide and have a complex structure with asymmetric bubbles on its branches, which could be interpreted as traces of stellar magnetic activity in both components. The 2007 and 2008 BVR light curves are generally those of β Lyrae-type eclipsing binaries, however, there are large asymmetries between maxima. We explained these peculiar asymmetries in terms of large dark spots on the primary component. ELODIE spectroscopic data and 2008 BVR light curves were solved simultaneously using Wilson-Devinney code. The results describe NR Peg as a RS CVn type binary star with a semi-detached configuration. The masses of the components were found to be 1.60 ± 0.03 M⊙ and 0.57 ± 0.02 M⊙ and the radii to be 3.35 ± 0.07 R⊙ and 3.55 ± 0.08 R⊙ for the primary and secondary components, respectively. Both components of NR Peg appear to have evolved behind the terminal age main sequence. However, the less-massive secondary component is significantly oversized and overluminous compared to theoretical evolution models. The distance of NR Peg was calculated as 138 ± 12 pc, taking into account interstellar extinction, in agreement with the HIPPARCOS value.

  5. Development of highly active and stable hybrid cathode catalyst for PEMFCs

    NASA Astrophysics Data System (ADS)

    Jung, Won Suk

    Polymer electrolyte membrane fuel cells (PEMFCs) are attractive power sources of the future for a variety of applications including portable electronics, stationary power, and automobile application. However, sluggish cathode kinetics, high Pt cost, and durability issues inhibit the commercialization of PEMFCs. To overcome these drawbacks, research has been focused on alloying Pt with transition metals since alloy catalysts show significantly improved catalytic properties like high activity, selectivity, and durability. However, Pt-alloy catalysts synthesized using the conventional impregnation method exhibit uneven particle size and poor particle distribution resulting in poor performance and/or durability in PEMFCs. In this dissertation, a novel catalyst synthesis methodology is developed and compared with catalysts prepared using impregnation method and commercial catalysts. Two approaches are investigated for the catalyst development. The catalyst durability was studied under U. S. DRIVE Fuel Cell Tech Team suggested protocols. In the first approach, the carbon composite catalyst (CCC) having active sites for oxygen reduction reaction (ORR) is employed as a support for the synthesis of Pt/CCC catalyst. The structural and electrochemical properties of Pt/CCC catalyst are investigated using high-resolution transmission electron microscopy, X-ray diffraction, and X-ray photoelectron spectroscopy, while RDE and fuel cell testing are carried out to study the electrochemical properties. The synergistic effect of CCC and Pt is confirmed by the observed high activity towards ORR for the Pt/CCC catalyst. The second approach is the synthesis of Co-doped hybrid cathode catalysts (Co-doped Pt/CCC) by diffusing the Co metal present within the CCC support into the Pt nanoparticles during heat-treatment. The optimized Co-doped Pt/CCC catalyst performed better than the commercial catalysts and the catalyst prepared using the impregnation method in PEMFCs and showed high

  6. Atomically monodisperse nickel nanoclusters as highly active electrocatalysts for water oxidation

    NASA Astrophysics Data System (ADS)

    Joya, Khurram S.; Sinatra, Lutfan; Abdulhalim, Lina G.; Joshi, Chakra P.; Hedhili, M. N.; Bakr, Osman M.; Hussain, Irshad

    2016-05-01

    Achieving water splitting at low overpotential with high oxygen evolution efficiency and stability is important for realizing solar to chemical energy conversion devices. Herein we report the synthesis, characterization and electrochemical evaluation of highly active nickel nanoclusters (Ni NCs) for water oxidation at low overpotential. These atomically precise and monodisperse Ni NCs are characterized by using UV-visible absorption spectroscopy, single crystal X-ray diffraction and mass spectrometry. The molecular formulae of these Ni NCs are found to be Ni4(PET)8 and Ni6(PET)12 and are highly active electrocatalysts for oxygen evolution without any pre-conditioning. Ni4(PET)8 are slightly better catalysts than Ni6(PET)12 which initiate oxygen evolution at an amazingly low overpotential of ~1.51 V (vs. RHE; η ~ 280 mV). The peak oxygen evolution current density (J) of ~150 mA cm-2 at 2.0 V (vs. RHE) with a Tafel slope of 38 mV dec-1 is observed using Ni4(PET)8. These results are comparable to the state-of-the-art RuO2 electrocatalyst, which is highly expensive and rare compared to Ni-based materials. Sustained oxygen generation for several hours with an applied current density of 20 mA cm-2 demonstrates the long-term stability and activity of these Ni NCs towards electrocatalytic water oxidation. This unique approach provides a facile method to prepare cost-effective, nanoscale and highly efficient electrocatalysts for water oxidation.Achieving water splitting at low overpotential with high oxygen evolution efficiency and stability is important for realizing solar to chemical energy conversion devices. Herein we report the synthesis, characterization and electrochemical evaluation of highly active nickel nanoclusters (Ni NCs) for water oxidation at low overpotential. These atomically precise and monodisperse Ni NCs are characterized by using UV-visible absorption spectroscopy, single crystal X-ray diffraction and mass spectrometry. The molecular formulae of these

  7. Response to antiretroviral therapy in occult hepatitis B and HIV co-infection in West Africa.

    PubMed

    Chadwick, David; Stanley, Alastair; Sarfo, Stephen; Appiah, Lambert; Ankcorn, Michael; Foster, Geraldine; Schwab, Uli; Phillips, Richard; Geretti, Anna M

    2013-01-01

    This study evaluated the outcome of first-line antiretroviral therapy among 35 Ghanaians with occult HBV/HIV co-infection, comparing them over 2 years to 120 patients with HBsAg+ HBV/HIV co-infection and 230 patients without HBV co-infection. Increases in CD4 cell count and BMI were similar, whereas elevations of hepatic transaminases were more frequent in both the occult HBV and HBsAg+ patients. Occult HBV/HIV co-infection appears not to impact adversely on response to antiretroviral therapy in Ghana. PMID:22874516

  8. Central Nervous System Strongyloidiasis and Cryptococcosis in an HIV-Infected Patient Starting Antiretroviral Therapy

    PubMed Central

    Rodríguez, Mónica; Flores, Paúl; Ahumada, Víctor; Vázquez-Vázquez, Lorena; Alvarado-de la Barrera, Claudia; Reyes-Terán, Gustavo

    2012-01-01

    We report a case of Strongyloides stercoralis hyperinfection syndrome with central nervous system involvement, in a patient with late human immunodeficiency virus (HIV) infection starting antiretroviral therapy, in whom Strongyloides stercoralis larvae and Cryptococcus neoformans were isolated antemortem from cerebrospinal fluid. Our patient was not from an endemic region for the parasite, so strongyloidiasis was not originally suspected. For this reason, we conclude that Strongyloides stercoralis infection should be suspected in HIV-infected patients starting antiretroviral therapy in order to avoid potential fatal outcomes. PMID:22924046

  9. Delayed onset renal failure in a patient on tenofovir based antiretroviral regimen.

    PubMed

    Krishna, M Murali; Subbalaxmi, M V S; Uppin, Megha; Radhika, S

    2014-01-01

    Tenofovir is recommended as one of the first line agents in combination with other antiretroviral drugs for management of human immunodeficiency virus (HIV). It is known to cause renal failure after exposure for a median duration of 5 months. We report tenofovir induced adverse drug reaction in a 56-year-old female patient who was diagnosed to have HIV 1 infection since 10 years. The combination antiretroviral treatment included tenofovir, emtricitabine and ritonavir/lopinavir regimen since the last 6 years. She presented with recent onset renal failure and renal biopsy showed interstitial nephritis which could probably attributable to tenofovir. PMID:24741201

  10. Prevention of mother-to-child HIV-1 transmission in Burkina Faso: evaluation of vertical transmission by PCR, molecular characterization of subtypes and determination of antiretroviral drugs resistance

    PubMed Central

    Sagna, Tani; Bisseye, Cyrille; Compaore, Tegewende R.; Kagone, Therese S.; Djigma, Florencia W.; Ouermi, Djeneba; Pirkle, Catherine M.; Zeba, Moctar T. A.; Bazie, Valerie J. T.; Douamba, Zoenabo; Moret, Remy; Pietra, Virginio; Koama, Adjirita; Gnoula, Charlemagne; Sia, Joseph D.; Nikiema, Jean-Baptiste; Simpore, Jacques

    2015-01-01

    Background Vertical human immunodeficiency virus (HIV) transmission is a public health problem in Burkina Faso. The main objective of this study on the prevention of mother-to-child HIV-1 transmission was to determine the residual risk of HIV transmission in infants born to mothers receiving highly active antiretroviral therapy (HAART). Moreover, we detect HIV antiretroviral (ARV) drug resistance among mother–infant pairs and identify subtypes and circulating recombinant forms (CRF) in Burkina Faso. Design In this study, 3,215 samples of pregnant women were analyzed for HIV using rapid tests. Vertical transmission was estimated by polymerase chain reaction in 6-month-old infants born to women who tested HIV positive. HIV-1 resistance to ARV, subtypes, and CRFs was determined through ViroSeq kit using the ABI PRISM 3,130 sequencer. Results In this study, 12.26% (394/3,215) of the pregnant women were diagnosed HIV positive. There was 0.52% (2/388) overall vertical transmission of HIV, with rates of 1.75% (2/114) among mothers under prophylaxis and 0.00% (0/274) for those under HAART. Genetic mutations were also isolated that induce resistance to ARV such as M184V, Y115F, K103N, Y181C, V179E, and G190A. There were subtypes and CRF of HIV-1 present, the most common being: CRF06_CPX (58.8%), CRF02_AG (35.3%), and subtype G (5.9%). Conclusions ARV drugs reduce the residual rate of HIV vertical transmission. However, the virus has developed resistance to ARV, which could limit future therapeutic options when treatment is needed. Resistance to ARV therefore requires a permanent interaction between researchers, physicians, and pharmacists, to strengthen the network of monitoring and surveillance of drug resistance in Burkina Faso. PMID:25630709

  11. Reasons for and correlates of antiretroviral treatment interruptions in a cohort of patients from public and private clinics in southern India

    PubMed Central

    Vallabhaneni, Snigdha; Chandy, Sara; Heylen, Elsa; Ekstrand, Maria

    2012-01-01

    Understanding the prevalence and correlates of treatment interruptions (TIs) in resource-limited settings is important for improving adherence. HIV-infected adults on highly active antiretroviral therapy (HAART) in Bangalore, India, were enrolled into a prospective cohort study assessing HAART adherence. Participants underwent a structured interview assessing adherence, including occurrence of TI > 48 hours since HAART initiation, length of TI, and self-reported reasons for TI. Serum HIV viral load (VL) and CD4 was measured at 6-month intervals. Baseline data are presented in this article. For the 552 participants mean age was 37.8, 32% were female, 70% were married, 45% earned < $2/day. Eighty-four percent were on nevirapine-based antiretroviral therapy; median duration on HAART was 18 months (range: 1–175) and median CD4 count was 318 cells/µl (IQR: 195–460) at time of study enrollment. Twenty percent (n = 110) reported at least one TI; of these, 33% (n = 36) reported more than one TI. Median length of most recent TI was 10 days (range: 2–1095). TI was associated with a higher probability of having VL > 400 copies/ml (43% versus 12%; p < 0.001). After controlling for time on HAART, TI was more likely among those who were unmarried (OR: 1.9; CI: 1.2–3.1), those treated in a private clinic setting (OR: 2.7; CI: 1.6–4.6 compared with public, and OR: 4.1; CI: 1.9–9.0 compared with public–private setting), and those on efavirenz-based therapy (OR: 2.0; CI: 1.1–3.6). The most common self-reported reason for TI was “side effects” (n = 28; 25%), followed by cost of therapy (n = 24; 22%). We discuss implications for both individual and structural level interventions to reduce TIs. PMID:22107044

  12. Design of a high activity and selectivity alcohol catalyst

    SciTech Connect

    Foley, H.C.; Mills, G.A.

    1992-02-07

    Results of the pyridine adsorption, studies on native and K-doped alumina provide fundamental grounding for the observed methanol dehydration activity of these samples. Both the reactor studies and the pyridine adsorption studies support the conclusion that the K-doped sample had reduced Lewis acidity. Moreover, we were able to measurably alter the acidity of the support surface by our ion exchange treatment. More significantly, when reactor results for transition-metal loaded samples are reconsidered in combination with their surface characteristics suggested by our pyridine adsorption studies, our hypothesis that Rh and Mo have ultimately titrated the support surface seems all the more convincing. Hence, in light of the pyridine adsorption results, the attenuation of a transition-metal based decomposition pathway for methanol on the metal-loaded samples-as seen in the reactor testing-is all the more reasonable.

  13. Perception of Antiretroviral Generic Medicines: One-Day Survey of HIV-Infected Patients and Their Physicians in France

    PubMed Central

    Jacomet, Christine; Allavena, Clotilde; Peyrol, Fleur; Pereira, Bruno; Joubert, Laurence Morand; Bagheri, Haleh; Cotte, Laurent; Garaffo, Rodolphe; Gerbaud, Laurent; Dellamonica, Pierre

    2015-01-01

    Background In the interest of cost effectiveness, switching antiretroviral brand name medications to generics is recommended in France since 2013. The study objective was to evaluate the perception of generics per se and antiretroviral generics in HIV-infected patients and their hospital physicians Methods and Findings 556 out of 703 (79%) adult HIV+ outpatients and 116 physicians in 33 clinics were included in a multicentric cross-sectional survey performed in September 2013. Patients completed a self-questionnaire on their perception and acceptability of generics. Physicians completed a questionnaire on their acceptability of switching antiretroviral to generic. Socio-demographic data, medical history and HIV history were collected. Among the 556 patients with a median HIV duration of 13 years, 77% were France native, 59% in active employment, 100% covered by social insurance, 95% on antiretroviral therapy. Seventy-six percent of the patients accepted generics and 55% trusted them overall. Antiretroviral generics were accepted by 44% of them but only by 17% if the pill burden was going to increase. The factor significantly associated with acceptability of antiretroviral generics was acceptance of generics per se (p<0.001). Among the 116 physicians following a median of 100 HIV-patients/year, 75% would prescribe generics, dropping to 26% if the combo had to be broken. Factors significantly associated with willingness to prescribe antiretroviral generics were the absence of concern regarding the chemical entity (OR = 0.33), being aware that the patient would accept generics for other pathologies (OR = 2.04) and would accept antiretroviral generics (OR = 1.94). No factor related to sociodemographic conditions, HIV status or comorbidities was associated with the acceptability of antiretroviral generics. Conclusions Acceptability of antiretroviral generics in this French population was mostly dictated by the patient’s and physician’s knowledge and use of generics

  14. Atomically monodisperse nickel nanoclusters as highly active electrocatalysts for water oxidation.

    PubMed

    Joya, Khurram S; Sinatra, Lutfan; AbdulHalim, Lina G; Joshi, Chakra P; Hedhili, M N; Bakr, Osman M; Hussain, Irshad

    2016-05-14

    Achieving water splitting at low overpotential with high oxygen evolution efficiency and stability is important for realizing solar to chemical energy conversion devices. Herein we report the synthesis, characterization and electrochemical evaluation of highly active nickel nanoclusters (Ni NCs) for water oxidation at low overpotential. These atomically precise and monodisperse Ni NCs are characterized by using UV-visible absorption spectroscopy, single crystal X-ray diffraction and mass spectrometry. The molecular formulae of these Ni NCs are found to be Ni4(PET)8 and Ni6(PET)12 and are highly active electrocatalysts for oxygen evolution without any pre-conditioning. Ni4(PET)8 are slightly better catalysts than Ni6(PET)12 which initiate oxygen evolution at an amazingly low overpotential of ∼1.51 V (vs. RHE; η≈ 280 mV). The peak oxygen evolution current density (J) of ∼150 mA cm(-2) at 2.0 V (vs. RHE) with a Tafel slope of 38 mV dec(-1) is observed using Ni4(PET)8. These results are comparable to the state-of-the-art RuO2 electrocatalyst, which is highly expensive and rare compared to Ni-based materials. Sustained oxygen generation for several hours with an applied current density of 20 mA cm(-2) demonstrates the long-term stability and activity of these Ni NCs towards electrocatalytic water oxidation. This unique approach provides a facile method to prepare cost-effective, nanoscale and highly efficient electrocatalysts for water oxidation. PMID:27109550

  15. Plasma Micronutrient Concentrations Are Altered by Antiretroviral Therapy and Lipid-Based Nutrient Supplements in Lactating HIV-Infected Malawian Women123

    PubMed Central

    Flax, Valerie L; Adair, Linda S; Allen, Lindsay H; Shahab-Ferdows, Setarah; Hampel, Daniela; Chasela, Charles S; Tegha, Gerald; Daza, Eric J; Corbett, Amanda; Davis, Nicole L; Kamwendo, Deborah; Kourtis, Athena P; van der Horst, Charles M; Jamieson, Denise J; Bentley, Margaret E

    2015-01-01

    Background: Little is known about the influence of antiretroviral therapy with or without micronutrient supplementation on the micronutrient concentrations of HIV-infected lactating women in resource-constrained settings. Objective: We examined associations of highly active antiretroviral therapy (HAART) and lipid-based nutrient supplements (LNS) with concentrations of selected micronutrients in HIV-infected Malawian women at 24 wk postpartum. Methods: Plasma micronutrient concentrations were measured in a subsample (n = 690) of Breastfeeding, Antiretrovirals, and Nutrition (BAN) study participants who were randomly assigned at delivery to receive HAART, LNS, HAART+LNS, or no HAART/no LNS (control). HAART consisted of protease inhibitor–based triple therapy. LNS (140 g/d) met energy and micronutrient requirements of lactation. Multivariable linear regression tested the association of HAART and LNS, plus their interaction, with micronutrient concentrations, controlling for season, baseline viral load, and baseline CD4 count. Results: We found significant HAART by LNS interactions for folate (P = 0.051), vitamin B-12 (P < 0.001), and transferrin receptors (TfRs) (P = 0.085). HAART was associated with lower folate (with LNS: −27%, P < 0.001; without LNS: −12%, P = 0.040) and higher TfR concentrations (with LNS: +14%, P = 0.004; without LNS: +28%, P < 0.001), indicating iron deficiency. LNS increased folate (with HAART: +17%, P = 0.037; without HAART: +39%, P < 0.001) and decreased TfR concentrations (with HAART only: −12%, P = 0.023). HAART was associated with lower vitamin B-12 concentrations only when LNS was present (−18%, P = 0.001), whereas LNS increased vitamin B-12 only when no HAART was present (+27%, P < 0.001). HAART, but not LNS, was associated with higher retinol-binding protein (RBP; +10%, P = 0.007). We detected no association of HAART or LNS with selenium, ferritin, or hemoglobin. Conclusion: The association of HAART with lower folate, iron

  16. Adherence to Concurrent Tuberculosis Treatment and Antiretroviral Treatment among Co-Infected Persons in South Africa, 2008–2010

    PubMed Central

    Webb Mazinyo, Ernesha; Kim, Lindsay; Masuku, Sikhethiwe; Lancaster, Joey L.; Odendaal, Ronel; Uys, Margot; Podewils, Laura Jean; Van der Walt, Martie L.

    2016-01-01

    Background Adherence to tuberculosis (TB) treatment and antiretroviral therapy (ART) reduces morbidity and mortality among persons co-infected with TB/HIV. We measured adherence and determined factors associated with non-adherence to concurrent TB treatment and ART among co-infected persons in two provinces in South Africa. Methods A convenience sample of 35 clinics providing integrated TB/HIV care was included due to financial and logistic considerations. Retrospective chart reviews were conducted among persons who received concurrent TB treatment and ART and who had a TB treatment outcome recorded during 1 January 2008–31 December 2010. Adherence to concurrent TB and HIV treatment was defined as: (1) taking ≥80% of TB prescribed doses by directly observed therapy (DOT) as noted in the patient card; and (2) taking >90% ART doses as documented in the ART medical record during the concurrent treatment period (period of time when the patient was prescribed both TB treatment and ART). Risk ratios (RRs) and 95% confidence intervals (CIs) were used to identify factors associated with non-adherence. Results Of the 1,252 persons receiving concurrent treatment, 138 (11.0%) were not adherent. Non-adherent persons were more likely to have extrapulmonary TB (RR: 1.71, 95% CI: 1.12 to 2.60) and had not disclosed their HIV status (RR: 1.96, 95% CI: 1.96 to 3.76). Conclusions The majority of persons with TB/HIV were adherent to concurrent treatment. Close monitoring and support of persons with extrapulmonary TB and for persons who have not disclosed their HIV status may further improve adherence to concurrent TB and antiretroviral treatment. PMID:27442440

  17. CD4+ and viral load outcomes of antiretroviral therapy switch strategies after virologic failure of combination antiretroviral therapy in perinatally HIV-infected youth in the United States

    PubMed Central

    Fairlie, Lee; Karalius, Brad; Patel, Kunjal; van Dyke, Russell B.; Hazra, Rohan; Hernán, Miguel A.; Siberry, George K.; Seage, George R.; Agwu, Allison; Wiznia, Andrew

    2015-01-01

    Objective: This study compared 12-month CD4+ and viral load outcomes in HIV-infected children and adolescents with virological failure, managed with four treatment switch strategies. Design: This observational study included perinatally HIV-infected (PHIV) children in the Pediatric HIV/AIDS Cohort Study (PHACS) and Pediatric AIDS Clinical Trials (PACTG) Protocol 219C. Methods: Treatment strategies among children with virologic failure were compared: continue failing combination antiretroviral therapy (cART); switch to new cART; switch to drug-sparing regimen; and discontinue all ART. Mean changes in CD4+% and viral load from baseline (time of virologic failure) to 12 months follow-up in each group were evaluated using weighted linear regression models. Results: Virologic failure occurred in 939 out of 2373 (40%) children. At 12 months, children switching to new cART (16%) had a nonsignificant increase in CD4+% from baseline, 0.59 percentage points [95% confidence interval (95% CI) −1.01 to 2.19], not different than those who continued failing cART (71%) (−0.64 percentage points, P = 0.15) or switched to a drug-sparing regimen (5%) (1.40 percentage points, P = 0.64). Children discontinuing all ART (7%) experienced significant CD4+% decline −3.18 percentage points (95% CI −5.25 to −1.11) compared with those initiating new cART (P = 0.04). All treatment strategies except discontinuing ART yielded significant mean decreases in log10VL by 12 months, the new cART group having the largest drop (−1.15 log10VL). Conclusion: In PHIV children with virologic failure, switching to new cART was associated with the best virological response, while stopping all ART resulted in the worst immunologic and virologic outcomes and should be avoided. Drug-sparing regimens and continuing failing regimens may be considered with careful monitoring. PMID:26182197

  18. Glucose Metabolism Disorders, HIV and Antiretroviral Therapy among Tanzanian Adults

    PubMed Central

    Maganga, Emmanuel; Smart, Luke R.; Kalluvya, Samuel; Kataraihya, Johannes B.; Saleh, Ahmed M.; Obeid, Lama; Downs, Jennifer A.; Fitzgerald, Daniel W.; Peck, Robert N.

    2015-01-01

    Introduction Millions of HIV-infected Africans are living longer due to long-term antiretroviral therapy (ART), yet little is known about glucose metabolism disorders in this group. We aimed to compare the prevalence of glucose metabolism disorders among HIV-infected adults on long-term ART to ART-naïve adults and HIV-negative controls, hypothesizing that the odds of glucose metabolism disorders would be 2-fold greater even after adjusting for possible confounders. Methods In this cross-sectional study conducted between October 2012 and April 2013, consecutive adults (>18 years) attending an HIV clinic in Tanzania were enrolled in 3 groups: 153 HIV-negative controls, 151 HIV-infected, ART-naïve, and 150 HIV-infected on ART for ≥ 2 years. The primary outcome was the prevalence of glucose metabolism disorders as determined by oral glucose tolerance testing. We compared glucose metabolism disorder prevalence between each HIV group vs. the control group by Fisher’s exact test and used multivariable logistic regression to determine factors associated with glucose metabolism disorders. Results HIV-infected adults on ART had a higher prevalence of glucose metabolism disorders (49/150 (32.7%) vs.11/153 (7.2%), p<0.001) and frank diabetes mellitus (27/150 (18.0%) vs. 8/153 (5.2%), p = 0.001) than HIV-negative adults, which remained highly significant even after adjusting for age, gender, adiposity and socioeconomic status (OR = 5.72 (2.78–11.77), p<0.001). Glucose metabolism disorders were significantly associated with higher CD4+ T-cell counts. Awareness of diabetes mellitus was <25%. Conclusions HIV-infected adults on long-term ART had 5-fold greater odds of glucose metabolism disorders than HIV-negative controls but were rarely aware of their diagnosis. Intensive glucose metabolism disorder screening and education are needed in HIV clinics in sub-Saharan Africa. Further research should determine how glucose metabolism disorders might be related to immune

  19. Accessibility of antiretroviral therapy in Ghana: convenience of access.

    PubMed

    Addo-Atuah, Joyce; Gourley, Dick; Gourley, Greta; White-Means, Shelley I; Womeodu, Robin J; Faris, Richard J; Addo, Nii Akwei

    2012-01-01

    The convenience of accessing antiretroviral therapy (ART) is important for initial access to care and subsequent adherence to ART. We conducted a qualitative study of people living with HIV/AIDS (PLWHA) and ART healthcare providers in Ghana in 2005. The objective of this study was to explore the participants' perceived convenience of accessing ART by PLWHA in Ghana. The convenience of accessing ART was evaluated from the reported travel and waiting times to receive care, the availability, or otherwise, of special considerations, with respect to the waiting time to receive care, for those PLWHA who were in active employment in the formal sector, the frequency of clinic visits before and after initiating ART, and whether the PLWHA saw the same or different providers at each clinic visit (continuity of care). This qualitative study used in-depth interviews based on Yin's case-study research design to collect data from 20 PLWHA and 24 ART healthcare providers as study participants. • Reported travel time to receive ART services ranged from 2 to 12 h for 30% of the PLWHA. • Waiting time to receive care was from 4 to 9 h. • While known government workers, such as teachers, were attended to earlier in some of the centres, this was not a consistent practice in all the four ART centres studied. • The PLWHA corroborated the providers' description of the procedure for initiating and monitoring ART in Ghana. • PLWHA did not see the same provider every time, but they were assured that this did not compromise the continuity of their care. Our study suggests that convenience of accessing ART is important to both PLWHA and ART healthcare providers, but the participants alluded to other factors, including open provider-patient communication, which might explain the PLWHA's understanding of the constraints under which they were receiving care. The current nation-wide coverage of the ART programme in Ghana, however, calls for the replication of this study to identify

  20. Timing of Antiretroviral Therapy after Diagnosis of Cryptococcal Meningitis

    PubMed Central

    Boulware, David R.; Meya, David B.; Muzoora, Conrad; Rolfes, Melissa A.; Huppler Hullsiek, Katherine; Musubire, Abdu; Taseera, Kabanda; Nabeta, Henry W.; Schutz, Charlotte; Williams, Darlisha A.; Rajasingham, Radha; Rhein, Joshua; Thienemann, Friedrich; Lo, Melanie W.; Nielsen, Kirsten; Bergemann, Tracy L.; Kambugu, Andrew; Manabe, Yukari C.; Janoff, Edward N.; Bohjanen, Paul R.; Meintjes, Graeme

    2014-01-01

    Background Cryptococcal meningitis accounts for 20 to 25% of acquired immunodeficiency syndrome–related deaths in Africa. Antiretroviral therapy (ART) is essential for survival; however, the question of when ART should be initiated after diagnosis of cryptococcal meningitis remains unanswered. Methods We assessed survival at 26 weeks among 177 human immunodeficiency virus–infected adults in Uganda and South Africa who had cryptococcal meningitis and had not previously received ART. We randomly assigned study participants to undergo either earlier ART initiation (1 to 2 weeks after diagnosis) or deferred ART initiation (5 weeks after diagnosis). Participants received amphotericin B (0.7 to 1.0 mg per kilogram of body weight per day) and fluconazole (800 mg per day) for 14 days, followed by consolidation therapy with fluconazole. Results The 26-week mortality with earlier ART initiation was significantly higher than with deferred ART initiation (45% [40 of 88 patients] vs. 30% [27 of 89 patients]; hazard ratio for death, 1.73; 95% confidence interval [CI], 1.06 to 2.82; P = 0.03). The excess deaths associated with earlier ART initiation occurred 2 to 5 weeks after diagnosis (P = 0.007 for the comparison between groups); mortality was similar in the two groups thereafter. Among patients with few white cells in their cerebrospinal fluid (<5 per cubic millimeter) at randomization, mortality was particularly elevated with earlier ART as compared with deferred ART (hazard ratio, 3.87; 95% CI, 1.41 to 10.58; P = 0.008). The incidence of recognized cryptococcal immune reconstitution inflammatory syndrome did not differ significantly between the earlier-ART group and the deferred-ART group (20% and 13%, respectively; P = 0.32). All other clinical, immunologic, virologic, and microbiologic outcomes, as well as adverse events, were similar between the groups. Conclusions Deferring ART for 5 weeks after the diagnosis of cryptococcal meningitis was associated with

  1. Financing equitable access to antiretroviral treatment in South Africa

    PubMed Central

    2010-01-01

    Background While South Africa spends approximately 7.4% of GDP on healthcare, only 43% of these funds are spent in the public system, which is tasked with the provision of care to the majority of the population including a large proportion of those in need of antiretroviral treatment (ART). South Africa is currently debating the introduction of a National Health Insurance (NHI) system. Because such a universal health system could mean increased public healthcare funding and improved access to human resources, it could improve the sustainability of ART provision. This paper considers the minimum resources that would be required to achieve the proposed universal health system and contrasts these with the costs of scaled up access to ART between 2010 and 2020. Methods The costs of ART and universal coverage (UC) are assessed through multiplying unit costs, utilization and estimates of the population in need during each year of the planning cycle. Costs are from the provider’s perspective reflected in real 2007 prices. Results The annual costs of providing ART increase from US$1 billion in 2010 to US$3.6 billion in 2020. If increases in funding to public healthcare only keep pace with projected real GDP growth, then close to 30% of these resources would be required for ART by 2020. However, an increase in the public healthcare resource envelope from 3.2% to 5%-6% of GDP would be sufficient to finance both ART and other services under a universal system (if based on a largely public sector model) and the annual costs of ART would not exceed 15% of the universal health system budget. Conclusions Responding to the HIV-epidemic is one of the many challenges currently facing South Africa. Whether this response becomes a “resource for democracy” or whether it undermines social cohesiveness within poor communities and between rich and poor communities will be partially determined by the steps that are taken during the next ten years. While the introduction of a

  2. Maximizing the benefits of antiretroviral therapy for key affected populations

    PubMed Central

    Grubb, Ian R; Beckham, Sarah W; Kazatchkine, Michel; Thomas, Ruth M; Albers, Eliot R; Cabral, Mauro; Lange, Joep; Vella, Stefano; Kurian, Manoj; Beyrer, Chris

    2014-01-01

    Introduction Scientific research has demonstrated the clinical benefits of earlier initiation of antiretroviral treatment (ART), and that ART can markedly reduce HIV transmission to sexual partners. Ensuring universal access to ART for those who need it has long been a core principle of the HIV response, and extending the benefits of ART to key populations is critical to increasing the impact of ART and the overall effectiveness of the HIV response. However, this can only be achieved through coordinated efforts to address political, social, legal and economic barriers that key populations face in accessing HIV services. Discussion Recent analyses show that HIV prevalence levels among key populations are far higher than among the general population, and they experience a range of biological and behavioural factors, and social, legal and economic barriers that increase their vulnerability to HIV and have resulted in alarmingly low ART coverage. World Health Organization 2014 consolidated guidance on HIV among key populations offers the potential for increased access to ART by key populations, following the same principles as for the general adult population. However, it should not be assumed that key populations will achieve greater access to ART unless stigma, discrimination and punitive laws, policies and practices that limit access to ART and other HIV interventions in many countries are addressed. Conclusions Rights-based approaches and investments in critical enablers, such as supportive legal and policy environments, are essential to enable wider access to ART and other HIV interventions for key populations. The primary objective of ART should always be to treat the person living with HIV; prevention is an important, additional benefit. ART should be provided only with informed consent. The preventive benefits of treatment must not be used as a pretext for failure to provide other necessary HIV programming for key populations, including comprehensive harm

  3. Pharmacodynamic and Antiretroviral Activities of Combination Nanoformulated Antiretrovirals in HIV-1–Infected Human Peripheral Blood Lymphocyte–Reconstituted Mice

    PubMed Central

    Roy, Upal; McMillan, JoEllyn; Alnouti, Yazen; Gautum, Nagsen; Smith, Nathan; Balkundi, Shantanu; Dash, Prasanta; Gorantla, Santhi; Martinez-Skinner, Andrea; Meza, Jane; Kanmogne, Georgette; Swindells, Susan; Cohen, Samuel M.; Mosley, R. Lee; Poluektova, Larisa; Gendelman, Howard E.

    2012-01-01

    Lack of adherence, inaccessibility to viral reservoirs, long-term drug toxicities, and treatment failures are limitations of current antiretroviral therapy (ART). These limitations lead to increased viral loads, medicine resistance, immunocompromise, and comorbid conditions. To this end, we developed long-acting nanoformulated ART (nanoART) through modifications of existing atazanavir, ritonavir, and efavirenz suspensions in order to establish cell and tissue drug depots to achieve sustained antiretroviral responses. NanoART's abilities to affect immune and antiviral responses, before or following human immunodeficiency virus type 1 infection were tested in nonobese severe combined immune-deficient mice reconstituted with human peripheral blood lymphocytes. Weekly subcutaneous injections of drug nanoformulations at doses from 80 mg/kg to 250 mg/kg, 1 day before and/or 1 and 7 days after viral exposure, elicited drug levels that paralleled the human median effective concentration, and with limited toxicities. NanoART treatment attenuated viral replication and preserved CD4+ Tcell numbers beyond that seen with orally administered native drugs. These investigations bring us one step closer toward using long-acting antiretrovirals in humans. PMID:22811299

  4. Incidence and predictors of severe anemia in Asian HIV-infected children using first-line antiretroviral therapy

    PubMed Central

    Bunupuradah, Torsak; Kariminia, Azar; Chan, Kwai-Cheng; Ramautarsing, Reshmie; Huy, Bui Vu; Han, Ning; Nallusamy, Revathy; Hansudewechakul, Rawiwan; Saphonn, Vonthanak; Sirisanthana, Virat; Chokephaibulkit, Kulkanya; Kurniati, Nia; Kumarasamy, Nagalingeswaran; Yusoff, Nik Khairulddin Nik; Razali, Kamarul; Fong, Siew Moy; Sohn, Annette H.; Lumbiganon, Pagakrong

    2014-01-01

    Objective There are limited data on treatment-related anemia in Asian HIV-infected children. Methods Data from Asian HIV-infected children aged <18 years on first-line highly active antiretroviral therapy (HAART) were used. Children who had preexisting severe anemia at baseline were excluded. Anemia was graded by using the DAIDS 2004 table. Potential risk factors of severe anemia were assessed by logistic regression. Results Data from 1,648 children (51.9% female, 62.8% WHO stage 3/4) were analyzed. Median (IQR) age was 6.8 (3.7–9.6) years, CD4% was 9 (3–16)% and plasma HIV-RNA was 5.2 (4.7–5.6) log10 copies/ml at HAART initiation in those with available testing. The most common regimens were stavudine/lamivudine/nevirapine (42%) and zidovudine/lamivudine/nevirapine (25%). Severe anemia was identified in 47 (2.9%) children after a median time of 6 months after HAART initiation with an incidence rate of 5.4 per 100 child-years. Mild anemia or moderate anemia at baseline (p=0.024 and p=0.005, respectively), previous or current use of zidovudine (p<0.0001 and p=0.013, respectively), and male sex (p=0.008) were associated with severe anemia. Higher weight-for-age z-score (p=0.004) was protective. Conclusions The incidence of severe anemia in Asian HIV-infected children after HAART initiation was low and mainly occurred during the first few months after HAART initiation. Mild to moderate anemia at baseline and using AZT were independent risk factors of developing severe anemia. PMID:23764352

  5. Urinary albumin-to-creatinine ratio is associated with endothelial dysfunction in HIV-infected patients receiving antiretroviral therapy

    PubMed Central

    Pirro, Matteo; Mannarino, Massimo R.; Francisci, Daniela; Schiaroli, Elisabetta; Bianconi, Vanessa; Bagaglia, Francesco; Sahebkar, Amirhossein; Mannarino, Elmo; Baldelli, Franco

    2016-01-01

    Endothelial dysfunction, a marker of cardiovascular (CV) risk, is common in human immunodeficiency virus (HIV)-infected patients. Microalbuminuria is frequent in HIV-infected patients, and is a predictor of renal impairment and CV risk. We investigated the association between microalbuminuria and endothelial dysfunction among HIV-infected patients receiving highly-active antiretroviral therapy (HAART). Endothelial function, measured by brachial artery flow-mediated dilatation (bFMD), and urine albumin-to-creatinine ratio (UACR), were measured in 170 HAART-treated HIV-infected adults. The relationship between UACR and bFMD was evaluated. The prevalence of increased UACR, defined by two cut-off levels (20 mg/g and 30 mg/g), was 29% and 17%. UACR was significantly higher while bFMD was lower among patients with metabolic syndrome (MS). UACR was associated with bFMD (r = −0.31; p < 0.001). This association was stronger in MS-patients (r = −0.44; p = 0.003). UACR above 20 mg/g was associated with an increased risk (OR 2.37, 95% CI 1.15–4.89, p = 0.020) of severely impaired bFMD (bFMD ≤ 2.1%). Patients with MS and increased UACR had the lowest bFMD compared with those with none or one of the two conditions. Microalbuminuria and endothelial dysfunction are positively associated in HIV-infected patients regardless of known confounders. The coexistence of microalbuminuria and MS amplifies their deleterious influence on endothelial function. PMID:27353425

  6. Combination Antiretroviral Therapy Is Associated With Reduction in Liver Fibrosis Scores in HIV-1-Infected Subjects.

    PubMed

    Li, Yijia; Xie, Jing; Han, Yang; Wang, Huanling; Lv, Wei; Guo, Fuping; Qiu, Zhifeng; Li, Yanling; Du, Shanshan; Song, Xiaojing; Zhu, Ting; Thio, Chloe L; Li, Taisheng

    2016-02-01

    HIV increases the risk of liver disease as do two common coinfections, hepatitis B and C viruses (HBV and HCV). However, whether combination antiretroviral therapy (cART) reverses or exacerbates hepatic fibrosis remains unclear.This was an observational retrospective study. cART-naïve HIV-infected subjects without a history of substance abuse (including alcohol) had liver disease stage determined by aspartate aminotransferase-to-platelet ratio indices (APRIs) and fibrosis-4 (FIB-4) before and 24 and 48 weeks after cART. All the data were retrieved from previously established cohorts. Values before and after cART were compared using Wilcoxon test for paired samples. Regression analyses were used to determine factors associated with moderate-to-severe liver disease.Of the 1105 HIV-infected subjects, 120 were HBV coinfected and 64 were HCV coinfected. About 20% of HIV monoinfected participants had APRI and FIB-4 scores consistent with moderate-to-significant fibrosis compared to ∼36% of HIV-HBV coinfected and 67% to 77% of HIV-HCV coinfected participants. In adjusted analyses compared with HIV monoinfection, HBV coinfection was associated with 1.18-fold higher APRI (P < 0.001) and a 1.12-fold higher FIB-4 (P = 0.007) prior to cART; while HCV coinfection was associated with 1.94-fold higher APRI (P < 0.001) and a 1.43-fold higher FIB-4 (P < 0.001). After 48 weeks of cART, both fibrosis scores decreased in all subjects; however, HCV coinfection was still associated with higher fibrosis scores at week 48 compared to HIV monoinfection.cART was associated with improvement in hepatic fibrosis scores in the majority of HIV-hepatitis coinfected and HIV-monoinfected Chinese participants. PMID:26844493

  7. Combination Antiretroviral Therapy Is Associated With Reduction in Liver Fibrosis Scores in HIV-1-Infected Subjects

    PubMed Central

    Li, Yijia; Xie, Jing; Han, Yang; Wang, Huanling; Lv, Wei; Guo, Fuping; Qiu, Zhifeng; Li, Yanling; Du, Shanshan; Song, Xiaojing; Zhu, Ting; Thio, Chloe L.; Li, Taisheng

    2016-01-01

    Abstract HIV increases the risk of liver disease as do two common coinfections, hepatitis B and C viruses (HBV and HCV). However, wheth