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Sample records for observed highly-active antiretroviral

  1. Directly Observed Highly Active Antiretroviral Therapy for HIV-Infected Children in Cambodia

    PubMed Central

    Myung, Patricia; Pugatch, David; Brady, Mark F.; Many, Phok; Harwell, Joseph I.; Lurie, Mark; Tucker, John

    2007-01-01

    Antiretroviral medications are becoming available for HIV-infected children in resource-limited settings. Maryknoll, an international Catholic charity, provided directly observed antiretroviral therapy to HIV-infected children in Phnom Penh, Cambodia. Child care workers administered generic antiretroviral drugs twice daily to children, ensuring adherence. Treatment began with 117 late-stage HIV-infected children; 22 died of AIDS during the first 6 months. The rest were treated for at least 6 months and showed CD4 count increases comparable to those achieved in US and European children. Staffing cost for this program was approximately US $5 per child per month, or 15% more than the price of the medications. Drug toxicities were uncommon and easily managed. Directly observed antiretroviral therapy appears to be a promising, low-cost strategy for ensuring adherent treatment for HIV-infected children in a resource-limited setting. PMID:17463375

  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. Direct observation therapy-highly active antiretroviral therapy in a resource-limited setting: the use of community treatment support can be effective.

    PubMed

    Idoko, J A; Agbaji, O; Agaba, P; Akolo, C; Inuwa, B; Hassan, Zuweira; Akintunde, L; Badung, B; Muazu, M; Danang, M; Imade, G; Sankale, J Louis; Kanki, Phyllis

    2007-11-01

    This study examines the use of various direct observation therapy-HAART treatment support modalities in Jos, Nigeria. A 12-month observational study enrolling 175 antiretroviral naïve patients into four arms of direct observation therapy-HAART (highly active antiretroviral therapy); daily observed therapy (DOT), twice weekly observed therapy (TWOT), weekly observed therapy (WOT) and self-administered therapy (SAT), examined community treatment support using family and community members. Treatment outcomes were much better in the treatment-supported groups compared with the control self-therapy group. CD4 cell increases were 218/microL (DOT), 267/microL (TWOT), 205/microL (WOT) versus 224/microL (SAT), whereas plasma HIV-1 RNA reached undetectable levels (<400 copies/mL) in 91%, 88%, 84% versus 79% of patients in the DOT, TWOT, WOT versus SAT groups, respectively, at 48 weeks. We, therefore, strongly support the use of treatment support in our settings.

  4. 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

  5. Fibrinolytic changes in pregnant women on highly active antiretroviral therapy.

    PubMed

    Osime, Odaburhine E; Ese-Onakewhor, Joseph U; Kolade, Samson O

    2015-02-01

    To report on the changes in fibrinolytic activity in human immunodeficiency virus (HIV) infected pregnant women who are undergoing highly active antiretroviral therapy (HAART). Blood was collected from 50 HIV positive women on HAART (test subjects), and 50 HIV positive women not on HAART (controls). These women were attending the prevention of mother to child clinic (PMTCT) of the University of Benin Teaching Hospital, Benin City, Nigeria from January to June 2014. Standard manual techniques were used to estimate plasma fibrinogen concentration (PFC), euglobulin lysis time (ELT), packed cell volume (PCV), and plasma viscosity (PV). The mean ± standard error of mean (SEM) of PFC was 4.02±0.13 g/l and ELT from the test subjects was 378±15 mins was significantly higher (p<0.05) compared with the control subjects (PFC 3.46±0.12 g/l and ELT 267±9.0 mins). The PCV or hematocrit values in the test subject was 29.1±0.38%, which was significantly lower (p<0.05) compared with the control subject (31.3±0.43%). The PV in the test subject was 1.76±0.02 mPa/s, while the control subjects was higher (1.73±0.02 mPa/s). This increase was not statistically significant (p>0.05). There were differences in the various parameters investigated when the various trimesters were compared. These differences did not, however, follow a particular pattern. Highly active antiretroviral therapy can cause changes in fibrinolytic activity that may predispose pregnant women to hyperfibrinogenemia and anemia.

  6. Prevalence of oral candidiasis in HIV/AIDS children in highly active antiretroviral therapy era. A literature analysis.

    PubMed

    Gaitán-Cepeda, Luis Alberto; Sánchez-Vargas, Octavio; Castillo, Nydia

    2015-08-01

    SummaryHighly active antiretroviral therapy has decreased the morbidity and mortality related to HIV infection, including oral opportunistic infections. This paper offers an analysis of the scientific literature on the epidemiological aspects of oral candidiasis in HIV-positive children in the combination antiretroviral therapy era. An electronic databases search was made covering the highly active antiretroviral therapy era (1998 onwards). The terms used were oral lesions, oral candidiasis and their combination with highly active antiretroviral therapy and HIV/AIDS children. The following data were collected from each paper: year and country in which the investigation was conducted, antiretroviral treatment, oral candidiasis prevalence and diagnostic parameters (clinical or microbiological). Prevalence of oral candidiasis varied from 2.9% in American HIV-positive children undergoing highly active antiretroviral therapy to 88% in Chilean HIV-positive children without antiretroviral therapy. With respect to geographical location and antiretroviral treatment, higher oral candidiasis prevalence in HIV-positive children on combination antiretroviral therapy/antiretroviral therapy was reported in African children (79.1%) followed by 45.9% reported in Hindu children. In HIV-positive Chilean children on no antiretroviral therapy, high oral candidiasis prevalence was reported (88%) followed by Nigerian children (80%). Oral candidiasis is still frequent in HIV-positive children in the highly active antiretroviral therapy era irrespective of geographical location, race and use of antiretroviral therapy.

  7. Focal epithelial hyperplasia (Heck disease) related to highly active antiretroviral therapy in an HIV-seropositive child. A report of a case, and a review of the literature.

    PubMed

    Feller, L; Khammissa, R A G; Wood, N H; Malema, V; Meyerov, R; Lemmer, J

    2010-05-01

    Focal epithelial hyperplasia is increasingly frequently observed in rural South African communities. HIV-seropositive subjects have a higher prevalence of oral human papillomavirus (HPV) infections than immunocompetent subjects; and paradoxically, the introduction of highly active antiretroviral therapy for treatment of HIV-seropositive subjects is associated with increased frequency of focal epithelial hyperplasia. We describe a case of focal epithelial hyperplasia in an HIV-seropositive child receiving highly active antiretroviral therapy, who was successfully treated by using diode laser ablation.

  8. [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.

  9. Antiretroviral concentrations in breast-feeding infants of mothers receiving highly active antiretroviral therapy.

    PubMed

    Mirochnick, Mark; Thomas, Timothy; Capparelli, Edmund; Zeh, Clement; Holland, Diane; Masaba, Rose; Odhiambo, Prisca; Fowler, Mary Glenn; Weidle, Paul J; Thigpen, Michael C

    2009-03-01

    There are limited data describing the concentrations of zidovudine, lamivudine, and nevirapine in nursing infants as a result of transfer via breast milk. The Kisumu Breastfeeding Study is a phase IIb open-label trial of prenatal, intrapartum, and postpartum maternal treatment with zidovudine, lamivudine, and nevirapine from 34 weeks of gestation to 6 months postpartum. In a pharmacokinetic substudy, maternal plasma, breast milk, and infant dried blood spots were collected for drug assay on the day of delivery and at 2, 6, 14, and 24 weeks after delivery. Sixty-seven mother-infant pairs were enrolled. The median concentrations in breast milk of zidovudine, lamivudine, and nevirapine during the study period were 14 ng/ml, 1,214 ng/ml, and 4,546 ng/ml, respectively. Zidovudine was not detectable in any infant plasma samples obtained after the day of delivery, while the median concentrations in infant plasma samples from postpartum weeks 2, 6, and 14 were 67 ng/ml, 32 ng/ml, and 24 ng/ml for lamivudine and 987 ng/ml, 1,032 ng/ml, and 734 ng/ml for nevirapine, respectively. Therefore, lamivudine and nevirapine, but not zidovudine, are transferred to infants via breast milk in biologically significant concentrations. The extent and effect of infant drug exposure via breast milk must be well understood in order to evaluate the benefits and risks of maternal antiretroviral use during lactation.

  10. Impact of highly active antiretroviral therapy on organ-specific manifestations of HIV-1 infection.

    PubMed

    Torre, D; Speranza, F; Martegani, R

    2005-03-01

    In the last 10 years, interesting results have been reported concerning the impact of highly active antiretroviral therapy (HAART) on the changing pattern of organ-specific manifestations of HIV-1 infection. There has been a clear step-wise reduction in the incidence of several opportunistic infections (OIs), particularly Pneumocystis carinii pneumonia, whereas a nonsignificant reduction in incidence has been observed for other organ-specific diseases, including invasive cervical cancer and Hodgkin disease. In addition, several organ-specific manifestations, including HIV-associated nephropathy, wasting syndrome and cardiomyopathy, are a direct consequence of damage by HIV-1, and so HAART may have a therapeutic effect in improving or preventing these manifestations. Finally, the introduction of HAART has seen the emergence of several complications, termed immune reconstitution inflammatory syndrome, which includes OIs such as cytomegalovirus vitritis, Mycobacterium avium complex lymphadenitis, paradoxical responses to treatment for tuberculosis, and exacerbation of cryptococcosis. Because not all HIV-1 organ-specific manifestations are decreasing in the HAART era, this review will analyse the influence of HAART on several organ-specific manifestations, and in particular OIs related to several organs, cerebral disorders and HIV-1-related neoplasia.

  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. Body mass index changes during highly active antiretroviral therapy in Nigeria.

    PubMed

    Denue, B A; Ikunaiye, P N Y; Denue, C B A

    2014-01-09

    Wasting remains an important condition in HIV-infected patients receiving highly active antiretroviral therapy (HAART). In this study, 120 patients with newly diagnosed HIV infection were prospectively evaluated to determine the effect of HAART on body mass index (BMI). Eighty-nine (83.1%) patients gained weight, 5 (4.7%) had no weight change, and 13 (12.2%) lost weight. There was a significant increase in overweight and obese patients. On multivariate analysis, time-updated CD4 count and higher baseline BMI were associated with a greater increase in BMI. Anaemia at diagnosis was associated with a significant increase in BMI. There were no significant effects of age, sex, disease severity, viral load or educational status on BMI changes. About 27% of the HIV patients presented with weight loss, which emphasizes that weight loss and wasting remain important AIDS-defining conditions, despite the advent of HAART. A linear association was observed between time-updated CD4 count and increase in BMI. The association between time-updated CD4 count and greater increase in BMI suggests that BMI could be a surrogate for CD4 count in monitoring treatment response in resource-limited settings.

  13. Effect of highly active antiretroviral therapy on incident AIDS using calendar period as an instrumental variable.

    PubMed

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

    2009-05-01

    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 (>or=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.

  14. Vitamin E concentrations in adults with HIV/AIDS on highly active antiretroviral therapy.

    PubMed

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

    2014-09-15

    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.

  15. 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

  16. A pharmacovigilance study of adults on highly active antiretroviral therapy, South Africa: 2007 – 2011

    PubMed Central

    Dube, Nomathemba Michell; Summers, Robert; Tint, Khin-San; Mayayise, Guistee

    2012-01-01

    Background Of the 1.6 million South African people infected with human immunodeficiency virus (HIV), approximately 970,000 (55%) have been initiated on HAART. Despite these numbers, very little has been published about the safety profile of antiretroviral (ARV) medicines in the country. This study was performed at the Medunsa National Pharmacovigilance Centre and aimed to describe the demographic characteristics of patients enrolled in the pharmacovigilance surveillance study; highly active antiretroviral therapy (HAART) initiation regimen patterns; reasons for regimen changes; and adverse effects of ARV medicines. Methods A cohort study of HIV-infected individuals aged 15 years or older who were on ARV medicines was conducted at four sentinel sites. Results After HAART initiation, with an average lapse of 17.8 months (range: 0 – 83.8 months), 2,815 patients were enrolled into the study. Results show that patients were observed for 1,606.2 person-years for pharmacy visits (collection of ARV medicines) and 817.1 person-years for clinical visits (consultation with the doctor). Females constituted 69.6% (1,958/2,815) of the study population. Almost all patients initiated HAART on first-line regimens (2,801/2,815). Some patients (6.7%, 190/2,815) dropped out of the study after HAART initiation. Reasons for regimen changes were not recorded for 2.5% (22/891) of the patients who changed regimens. The primary reason for regimen changes was drug-related toxicity (76.1%, 678/891), mostly evident in patients taking first-line regimens. Adverse effects experienced by patients were polyneuropathy (24.0%, 163/678); lipodystrophy (23.9%, 162/678); neuropathy (10.6%, 72/678); and suspected lactic acidosis (3.8%, 26/678). Conclusion The majority of prescribers complied with the HAART guidelines and initiated most patients on first-line regimens. However, adverse effects are evident in patients taking first-line regimens. We recommend that the Department of Health should

  17. Mitochondrial DNA haplogroups and highly active antiretroviral therapy-related lipodystrophy.

    PubMed

    Nasi, Milena; Guaraldi, Giovanni; Orlando, Gabriella; Durante, Caterina; Pinti, Marcello; Nemes, Elisa; Nardini, Giulia; Passarino, Giuseppe; Cocchi, Marina; Esposito, Roberto; Mussini, Cristina; Cossarizza, Andrea

    2008-10-01

    The combination of different point mutations in mitochondrial DNA (mtDNA), which are defined as haplogroups, may cause modification in organelle function and may be involved in several pathologies. We analyzed the distribution of mtDNA polymorphisms in human immunodeficiency virus (HIV)-infected patients with lipodystrophy, a relevant adverse event caused by highly active antiretroviral therapy, and their correlation with metabolic and viroimmunologic parameters. The frequency of the 9 most common European haplogroups was investigated in 346 white, HIV-infected patients with lipodystrophy. Haplogroups were identified on the basis of classic methods. Statistical analysis was performed with use of 1-way analysis of variance, the chi(2) test, and principal-components analysis. The distribution of mtDNA haplogroups among patients with lipodystrophy was similar to that among the general European population. We found no differences between patients with different haplogroups with regard to viroimmunologic results (plasma HIV load, CD4(+) T cell count, and nadir CD4(+) T cell count), glucose data (glucose, insulin, C-peptide, and glycosylated hemoglobin concentrations and insulin resistance), lipid data (levels of triglycerides, total cholesterol, high- and low-density lipoproteins, and apolipoprotein A1 and B), acid-base balance parameters (lactate level and anion gap), or anthropometric measures (weight, body mass index, and waist-to-hip ratio). No differences were observed in trunk fat levels, leg-fat ratio (which was determined by dual-energy x-ray absorptiometry), or exposure to different drug classes. Principal-components analysis confirmed that the spatial distribution of patients belonging to a given haplogroup was not influenced by different clinical parameters. Our study indicates that, in HIV-infected patients with lipodystrophy, mtDNA haplogroups are not related to major metabolic changes or to particular viroimmunologic features.

  18. Incidence of cytomegalovirus retinitis in the era of highly active antiretroviral therapy.

    PubMed

    Sugar, Elizabeth A; Jabs, Douglas A; Ahuja, Alka; Thorne, Jennifer E; Danis, Ronald P; Meinert, Curtis L

    2012-06-01

    To estimate the incidence of cytomegalovirus (CMV) retinitis in the era of highly active antiretroviral therapy (HAART) and to characterize the factors associated with increased risk of CMV retinitis. Prospective cohort study. A total of 1600 participants with acquired immunodeficiency syndrome (AIDS) but without CMV retinitis at enrollment who completed at least 1 follow-up visit in the Longitudinal Study of the Ocular Complications of AIDS (LSOCA) were seen every 6 months to obtain disease and treatment history, ophthalmic examination, and laboratory testing. Incidence of CMV retinitis and risk factors for incident CMV retinitis were assessed. The incidence rate of CMV retinitis in individuals with AIDS was 0.36/100 person-years (PY) based upon 29 incident cases during 8134 PY of follow-up. The rate was higher for those with a CD4+ T cell count at the immediately prior visit below 50 cells/μL (3.89/100 PY, P < .01), whereas only 1 individual with a CD4+ T cell count of 50 to 99 cells/μL and 2 individuals with a CD4+ T cell count >100 cells/μL developed CMV retinitis. Having a CD4+ T cell count below 50 cells/μL at the clinical visit prior to CMV retinitis evaluation was the single most important risk factor (HR: 136, 95% CI: 30 to 605, P < .0001) for developing retinitis. Patients with AIDS, especially those with severely compromised immune systems, remain at risk for developing CMV retinitis in the HAART era, although the incidence rate is reduced from that observed in the pre-HAART era. Copyright © 2012 Elsevier Inc. All rights reserved.

  19. 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.

  20. Alternative therapy use in HIV-infected patients receiving highly active antiretroviral therapy.

    PubMed

    Risa, Kathleen J; Nepon, Lisa; Justis, Janice C; Panwalker, Anand; Berman, Stephen M; Cinti, Sandro; Wagener, Marilyn M; Singh, Nina

    2002-10-01

    The extent of use of alternative therapies, psychosocial and disease-specific variables predictive of alternative therapy use, and factors motivating the use of alternative therapies in HIV-infected patients receiving highly active antiretroviral therapy (HAART) have not been well defined. Types of alternative therapies used, demographic and medical data, coping (Billing and Moos inventory of coping with illness styles), social support (Irwing and Sarason questionnaire), sense of personal control (Pearlin's Mastery scale), quality of life (Medical Outcome Study scale), health beliefs, and adherence rate were prospectively assessed in 118 HIV-infected patients receiving HAART. Of 38% (45/118) of the patients who used alternative therapies, 56% (25/45) began using alternative therapies since the initiation of HAART. While Caucasian patients were more likely to use alternative therapies than all other patients (P = 0.015), new users of alternative therapies were more likely to be African-American (P = 0.022). Alternative therapy users reported less satisfaction with their emotional support (P = 0.027), and had greater psychological distress (P = 0.048), but were more likely to utilize problem-focused coping (P = 0.015). Patients who used alternative therapies were less likely to believe that HAART was beneficial (P = 0.06). Physicians were unaware of patients' alternative therapy use in 40% (18/45) of all patients who used alternative therapies, in 67% of herbal therapy users, and in 100% of dietary supplement users. Adherence to antiretroviral therapy, CD4 count, and HIV-RNA level were neither predictive nor affected by alternative therapy use. Despite scepticism about the benefits of HAART, resort to alternative therapies did not undermine adherence with antiretroviral therapy. Although able actively to cope with their illness, users of alternative therapies had greater psychological distress and were less satisfied with their emotional support. Interventions aimed

  1. 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.

  2. Course of cytomegalovirus retinitis in the era of highly active antiretroviral therapy: five-year outcomes.

    PubMed

    Jabs, Douglas A; Ahuja, Alka; Van Natta, Mark; Lyon, Alice; Srivastava, Sunil; Gangaputra, Sapna

    2010-11-01

    To describe the 5-year outcomes of patients with cytomegalovirus (CMV) retinitis and AIDS in the era of highly active antiretroviral therapy (HAART). Prospective, multicenter, observational study. A total of 503 patients with AIDS and CMV retinitis. Follow-up every 3 months with medical history, ophthalmologic examination, laboratory testing, and retinal photographs. Participants were classified as having previously diagnosed CMV retinitis and immune recovery (CD4+ T cells ≥ 100 cells/μl), previously diagnosed retinitis and immune compromise, and newly diagnosed CMV retinitis (diagnosis <45 days before enrollment). Mortality, retinitis progression (movement of the border of a CMV lesion ≥ ½ disc diameter or occurrence of a new lesion), retinal detachment, immune recovery uveitis (IRU), and visual loss (< 20/40 and ≥ 20/200). Overall mortality was 9.8 deaths/100 person-years (PY). Rates varied by group at enrollment from 3.0/100 PY for those with previously diagnosed retinitis and immune recovery to 26.1/100 PY for those with newly diagnosed retinitis. The rate of retinitis progression was 7.0/100 PY and varied from 1.4/100 PY for those with previously diagnosed retinitis and immune recovery to 28.0/100 PY for those with newly diagnosed retinitis. The rate of retinal detachment was 2.3/100 eye-years (EY) and varied from 1.2/100 EY for those with previously diagnosed retinitis and immune recovery to 4.9/100 EY for those with newly diagnosed retinitis. The rate of IRU was 1.7/100 PY and varied from 1.3/100 PY for those with previously diagnosed retinitis and immune recovery at enrollment to 3.6/100 PY for those with newly diagnosed retinitis who subsequently experienced immune recovery. The rates of visual loss to < 20/40 and to ≤ 20/200 were 7.9/100 EY and 3.4/100 EY, respectively; they varied from 6.1/100 EY and 2.7/100 EY for those with previously diagnosed retinitis and immune recovery to 11.8/100 EY and 5.1/100 EY for those with newly diagnosed

  3. 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.

  4. 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

  5. Human resources requirements for highly active antiretroviral therapy scale-up in Malawi

    PubMed Central

    Muula, Adamson S; Chipeta, John; Siziya, Seter; Rudatsikira, Emmanuel; Mataya, Ronald H; Kataika, Edward

    2007-01-01

    Background Twelve percent of the adult population in Malawi is estimated to be HIV infected. About 15% to 20% of these are in need of life saving antiretroviral therapy. The country has a public sector-led antiretroviral treatment program both in the private and public health sectors. Estimation of the clinical human resources needs is required to inform the planning and distribution of health professionals. Methods We obtained data on the total number of patients on highly active antiretroviral treatment program from the Malawi National AIDS Commission and Ministry of Health, HIV Unit, and the number of registered health professionals from the relevant regulatory bodies. We also estimated number of health professionals required to deliver highly active antiretroviral therapy (HAART) using estimates of human resources from the literature. We also obtained data from the Ministry of Health on the actual number of nurses, clinical officers and medical doctors providing services in HAART clinics. We then made comparisons between the human resources situation on the ground and the theoretical estimates based on explicit assumptions. Results There were 610 clinicians (396 clinical officers and 214 physicians), 44 pharmacists and 98 pharmacy technicians and 7264 nurses registered in Malawi. At the end of March 2007 there were 85 clinical officer and physician full-time equivalents (FTEs) and 91 nurse FTEs providing HAART to 95,674 patients. The human resources used for the delivery of HAART comprised 13.9% of all clinical officers and physicians and 1.1% of all nurses. Using the estimated numbers of health professionals from the literature required 15.7–31.4% of all physicians and clinical officers, 66.5–199.3% of all pharmacists and pharmacy technicians and 2.6 to 9.2% of all the available nurses. To provide HAART to all the 170,000 HIV infected persons estimated as clinically eligible would require 4.7% to 16.4% of the total number of nurses, 118.1% to 354.2% of all

  6. Human resources requirements for highly active antiretroviral therapy scale-up in Malawi.

    PubMed

    Muula, Adamson S; Chipeta, John; Siziya, Seter; Rudatsikira, Emmanuel; Mataya, Ronald H; Kataika, Edward

    2007-12-19

    Twelve percent of the adult population in Malawi is estimated to be HIV infected. About 15% to 20% of these are in need of life saving antiretroviral therapy. The country has a public sector-led antiretroviral treatment program both in the private and public health sectors. Estimation of the clinical human resources needs is required to inform the planning and distribution of health professionals. We obtained data on the total number of patients on highly active antiretroviral treatment program from the Malawi National AIDS Commission and Ministry of Health, HIV Unit, and the number of registered health professionals from the relevant regulatory bodies. We also estimated number of health professionals required to deliver highly active antiretroviral therapy (HAART) using estimates of human resources from the literature. We also obtained data from the Ministry of Health on the actual number of nurses, clinical officers and medical doctors providing services in HAART clinics. We then made comparisons between the human resources situation on the ground and the theoretical estimates based on explicit assumptions. There were 610 clinicians (396 clinical officers and 214 physicians), 44 pharmacists and 98 pharmacy technicians and 7264 nurses registered in Malawi. At the end of March 2007 there were 85 clinical officer and physician full-time equivalents (FTEs) and 91 nurse FTEs providing HAART to 95,674 patients. The human resources used for the delivery of HAART comprised 13.9% of all clinical officers and physicians and 1.1% of all nurses. Using the estimated numbers of health professionals from the literature required 15.7-31.4% of all physicians and clinical officers, 66.5-199.3% of all pharmacists and pharmacy technicians and 2.6 to 9.2% of all the available nurses. To provide HAART to all the 170,000 HIV infected persons estimated as clinically eligible would require 4.7% to 16.4% of the total number of nurses, 118.1% to 354.2% of all the available pharmacists and

  7. Maternal Highly Active Antiretroviral Therapy and Child HIV-Free Survival in Malawi, 2004-2009.

    PubMed

    Schwartz, Sheree R; Kumwenda, Newton; Kumwenda, Johnstone; Chen, Shu; Mofenson, Lynne M; Taylor, Allan W; Fowler, Mary Glenn; Taha, Taha E

    2016-03-01

    Highly active antiretroviral therapy (HAART) provision to eligible HIV-infected pregnant and post-partum women is critical for optimizing maternal health. We assessed the impact of maternal HAART on HIV-free survival of breastfed infants in Malawi. The post-exposure prophylaxis of infants-Malawi trial (2004-2009) enrolled mothers/infants during labor or immediately post-partum to evaluate 14-week extended infant antiretroviral prophylaxis for preventing HIV transmission through breastfeeding. Mothers meeting national HAART guidelines were referred for therapy. Child HIV-free survival-survival without HIV infection-was compared by maternal HAART status. Overall, 3022 mother-infant pairs contributed 4214 infant/person-years (PY) at-risk for HIV infection or death, with 532 events (incidence 12.6/100 PY, 95 % confidence interval [CI] 11.6-13.7). During follow-up, 349 mothers were HAART initiated; 581 remained HAART naïve with CD4 cell counts <250 cells/mm(3), and 2092 were never HAART-eligible. By 3 months, 11 % of infants with HAART naïve mothers (CD4 < 250) were infected with HIV or died versus 7 % of infants of HAART-initiated mothers and 4 % of infants of HAART-ineligible mothers. Maternal HAART was associated with a 46 % reduction in infant HIV infection or death as compared to infants with HAART naïve mothers (CD4 < 250) (adjusted hazards ratio 0.54, 95 % CI 0.36-0.81). Among HIV-exposed, uninfected infants, breastfeeding, but not HAART, was significantly associated with decreased child mortality. HIV infection and mortality are high during the first 3 months post-partum in infants of mothers with advanced HIV, and rapid maternal HAART initiation can significantly improve HIV-related infant outcomes. Clinical Trials Registration This study is registered at http://clinicaltrials.gov/ under trial number NCT00115648.

  8. Contraception choices in a cohort of HIV+ women in the era of highly active antiretroviral therapy.

    PubMed

    Ezeanolue, Echezona E; Stumpf, Paul G; Soliman, Evelen; Fernandez, George; Jack, Ineada

    2011-07-01

    The study was conducted to determine whether increased desire for fertility coupled with increased awareness of reduction in mother-to-child HIV transmission (MTCT) with increased availability and use of highly active antiretroviral therapy (HAART) has been associated with reduction in use of tubal sterilization as a form of contraception among women infected with HIV. One hundred HIV+ women, 18 to 45 years of age, receiving care at university-affiliated HIV facilities between October 2008 and February 2009, were surveyed about their contraceptive knowledge and practices. We performed descriptive analysis of population characteristics to determine contraception choices and fertility desires following initiation of HAART. The study group was composed of women with median age of 35 years, 55% African American, 18% Caucasians, 19% Hispanic and 8% "other". Most (63%) were single; 36% were married. Contraception choices were condom 61%, injectable contraceptive 7%, pills 6% and only 3% said they used female sterilization. Thirty-four percent of respondents said that their choice of contraception was based primarily on ease of use, 19% said that their choice was primarily based on convenience and only 9% said that their choice was primarily based on provider recommendation. Desire for future childbearing increased to 19% following knowledge that MTCT can be reduced by taking antiretroviral therapy (ARV) and to 22% following initiation of ARV. Initiation of ARV and awareness that maternal treatment can reduce MTCT may explain lower use of female sterilization as a form of contraception among a cohort of HIV+ women in the post HAART era. Copyright © 2011 Elsevier Inc. All rights reserved.

  9. 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

  10. Hypertension among HIV-infected adults receiving highly active antiretroviral therapy (HAART) in Malaysia.

    PubMed

    Hejazi, Nazisa; Huang, M S L; Lin, Khor Geok; Choong, Lee Christopher Kwok

    2013-12-01

    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.

  11. Failure of highly active antiretroviral therapy in reconstituting immune response to Clostridium tetani vaccine in aged AIDS patients.

    PubMed

    Andrade, Regis M; Andrade, Arnaldo F B; Lazaro, Marta A; Vieira, Morgana M M; Barros, Priscila O; Borner, Alice R S; Silva-Filho, Renato G; Santos, Juliana O; Brindeiro, Rodrigo M; Tanuri, Amilcar; Bento, Cleonice A M

    2010-05-01

    The purpose of this study was to evaluate the impact of age on tetanus-specific immune response in successfully highly active antiretroviral therapy-treated AIDS patients, using healthy age-matched individuals as controls. Whole Peripheral blood mononuclear cells or CD8(+) cell-depleted peripheral blood mononuclear cells from previously tetanus toxoid (TT)-immunized individuals were activated with TT plus IL-2, and cell proliferation, cytokine production, and in vitro HIV-1 replication were measured. The in vivo magnitude of the humoral immune response was also assessed by antibody measurements. Our results showed that, compared with other groups, both in vitro TT-specific lymphoproliferation and serum antibody concentration were lower in older AIDS patients. Although the IL-1beta and tumour necrosis factor alpha (TNF-alpha) production were higher in cultures from aged HIV-1-infected patients, a dramatic damage on the interferon gamma (IFN-gamma) release was observed, when compared with younger patients. CD8(+) T lymphocytes depletion reduced IL-1beta and TNF-alpha release in the older groups, however, it did not significantly alter their IFN-gamma production. Furthermore, the neutralization of endogenous IL-10 did not change the IFN-gamma deficiency in older AIDS patients. Finally, the lower cellular immune response in this patient group was not related to in vitro HIV-1 replication. The results suggest that successfully highly active antiretroviral therapy-treated aged AIDS patients do not reconstitute the immune response to TT, making them probably more susceptible to tetanus even after vaccination.

  12. The prevalence of antiretroviral multidrug resistance in highly active antiretroviral therapy-treated patients with HIV/AIDS between 2004 and 2009 in South Korea.

    PubMed

    Choi, Ju-yeon; Kwon, Oh-Kyung; Choi, Byeong-Sun; Kee, Mee-Kyung; Park, Mina; Kim, Sung Soon

    2014-06-01

    Highly active antiretroviral therapy (HAART) including protease inhibitors (PIs) has been used in South Korea since 1997. Currently, more than 20 types of antiretroviral drugs are used in the treatment of human immunodeficiency virus-infected/acquired immune deficiency syndrome patients in South Korea. Despite the rapid development of various antiretroviral drugs, many drug-resistant variants have been reported after initiating HAART, and the efficiency of HAART is limited by these variants. To investigate and estimate the annual antiretroviral drug resistance and prevalence of antiretroviral multi-class drug resistance in Korean patients with experience of treatment. The amplified HIV-1 pol gene in 535 patients requested for genotypic drug resistance testing from 2004 to 2009 by the Korea Centers for Disease Control and Prevention was sequenced and analyzed annually and totally. The prevalence of antiretroviral drug resistance was estimated based on "SIR" interpretation of the Stanford sequence database. Of viruses derived from 787 specimens, 380 samples (48.3%) showed at least one drug class-related resistance. Predicted NRTI drug resistance was highest at 41.9%. NNRTI showed 27.2% resistance with 23.3% for PI. The percent of annual drug resistance showed similar pattern and slightly declined except 2004 and 2005. The prevalence of multi-class drug resistance against each drug class was: NRTI/NNRTI/PI, 9.8%; NRTI/PI, 21.9%; NNRTI/PI, 10.4%; and NRTI/NNRTI, 21.5%. About 50% and less than 10% of patients infected with HIV-1 have multidrug and multiclass resistance linked to 16 antiretroviral drugs, respectively. The significance of this study lies in its larger-scale examination of the prevalence of drug-resistant variants and multidrug resistance in HAART-experienced patients in South Korea. Copyright © 2014 Elsevier B.V. All rights reserved.

  13. Rheumatic manifestations associated with HIV in the highly active antiretroviral therapy era.

    PubMed

    Nguyen, Binh Y; Reveille, John D

    2009-07-01

    To evaluate the rheumatic manifestations associated with HIV infection in the highly active antiretroviral therapy (HAART) era. The overall prevalence of rheumatic manifestations in HIV population is approximately 9% with various clinical features. Anti-TNF agents do not appear to adversely affect the CD4 cell counts or viral load if the HIV infection is well controlled prior to initiation of therapy. In the HAART era, HIV-infected individuals can be affected by various rheumatic syndromes including arthritis, spondyloarthritis, DILS, vasculitides, connective tissue disease, myopathies, and musculoskeletal diseases. With the use of HAART, the prevalence of spondyloarthritis and Diffuse Infiltrative Lymphocytosis Syndrome has decreased, whereas the musculoskeletal complications of HIV and HAART, such as osteopenia, osteonecrosis, and infection continue to be a concern. With immune restoration, various inflammatory and autoimmune diseases, such as SLE, rheumatoid arthritis, and polymyositis may occur de novo or exacerbate. Most antirheumatic therapies used in HIV-negative individuals appear to be safe and effective in the setting of HIV infection as long as prudent guidelines are followed.

  14. Examination of haematotoxicity of fixed-dose highly active antiretroviral drug in albino wistar rats.

    PubMed

    Nubila, Thomas; Ukaejiofo, Ernest O; Nubila, Nkoyo I; Okorie, Godfrey I

    2012-01-01

    Highly active antiretroviral therapy (HAART) is considered toxic and has other life-threatening side effects. Our aim was to evaluate the haematotoxic effects of lamivudine, zidovudine, and nevirapine fixed-dose combinations in Albino Wistar rats. Fifty (50) three (3) months old male Albino Wistar rats weighing between 200 and 250 g were randomly assigned to five (5) groups (A, B, C, D, and E). Group A served as control. Two (2 mLs) of venous blood was aseptically collected on Days 5, 10, 15, 20, and 25 of treatment. Red blood cell (RBC) mean value recorded statistically significant increase (P < 0.05) in groups B and C when compared with the control group on Day 5. However, there was a statistically significant decrease (P < 0.05) in RBC, haemoglobin concentration (Hb), packed cell volume (PCV), and some red cell indices on Day 10. In addition there was no statistically significant difference (P > 0.05) in all the parameters evaluated when the test group was compared with the control on Day 25. Furthermore, there was a time-related statistically significant increase (P < 0.05) in the two major blood cells-RBC and platelet counts. From the result of this present study, it can be concluded that HAART when administered in fixed-dose combinations have no subacute haematotoxic effects.

  15. 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

  16. Clinical challenges of thyroid eye disease in HIV-positive patients on highly active antiretroviral therapy.

    PubMed

    Edmunds, Matthew R; Mellington, Faye; Ford, Rebecca L; Torlinska, Barbara; Manavi, Kaveh; Boelaert, Kristien

    2015-03-01

    Graves' disease (GD) as an immune reconstitution inflammatory syndrome during highly active antiretroviral therapy (HAART) for HIV has previously been reported. However, clinical challenges associated with HIV in the context of thyroid eye disease (TED) are not as well-characterized. To determine the frequency of coexisting HIV and TED, describe TED presentation and course in the context of HIV, and evaluate management difficulties as well as potential solutions. Cross-sectional study of all patients with coexisting GD and HIV at University Hospitals Birmingham (2003-2014). Retrospective case note review to identify TED with particular reference to HAART regimen, CD4+ T-cell count, HIV viral load, and TED activity and severity. Of 783 subjects with GD and 1186 with HIV, 11 were identified with both GD and HIV. Of these, three had clinical features of TED; each was of Afro-Caribbean origin, was in their fourth decade, and initially presented with undetectable CD4 T cells and high HIV viral loads. All went on to develop GD >3 years after commencing HAART, with normal CD4 count and undetectable viral load at the time of GD diagnosis. The full spectrum of TED was represented, with two subjects requiring orbital decompression surgery. TED in the context of HIV is uncommon. Many challenges exist in such patients, particularly HAART drug interactions with antithyroid and immunosuppressant medications. To better understand TED in HIV and to counsel patients with this copathology most effectively, future multicenter surveillance is required.

  17. Acquired immunodeficiency syndrome-related malignancies in the era of highly active antiretroviral therapy.

    PubMed

    Bernstein, Wendy B; Little, Richard F; Wilson, Wyndham H; Yarchoan, Robert

    2006-07-01

    Since the beginning of the acquired immunodeficiency syndrome (AIDS) epidemic, malignancies have been an important feature of this disease. Several cancers, including Kaposi sarcoma (KS), certain aggressive B-cell lymphomas, and cervical cancer, are considered AIDS-defining when they occur in patients infected with human immunodeficiency virus. Most AIDS-defining tumors are associated with one of 3 DNA viruses: KS-associated herpesvirus, Epstein-Barr virus, or human papillomavirus. With the introduction of highly active antiretroviral therapy (HAART), the incidence of KS and certain lymphomas has decreased, whereas that of other tumors, such as cervical cancer, has undergone little change. Several new drugs and therapies have been developed for KS and AIDS-related lymphomas, and these treatments, plus the development of HAART, have contributed to improvements in morbidity and mortality. At the same time, the improved overall survival of patients with HAART has contributed to an increase in the number of patients living with AIDS in developed countries such as the United States. With the development of HAART and improved prevention and treatment of opportunistic infections, an increasing percentage of the deaths in AIDS patients have been from malignancies. Strategies for prevention, screening, and therapy remain important areas of research in this developing field.

  18. Cerebrovascular disease in HIV-infected individuals in the era of highly active antiretroviral therapy.

    PubMed

    Cruse, Belinda; Cysique, Lucette A; Markus, Romesh; Brew, Bruce J

    2012-08-01

    The widespread use of highly active antiretroviral therapy (HAART) in HIV-infected individuals mostly in developed countries has dramatically improved their prognosis. In such advantaged regions of the world, therefore, many patients are now transitioning from middle into older age, with altered patterns of disease. While previously a rare complication of HIV infection, cerebrovascular disease (particularly that associated with atherosclerosis) is becoming relatively more important in this treated group of individuals. This review summarises the evidence regarding the shifting epidemiology of cerebrovascular diseases affecting HIV-infected individuals. While outlining the association between HIV infection and AIDS and cerebrovascular disease, as well as opportunistic diseases and HIV-associated vasculopathies, the current evidence supporting an increase in atherosclerotic disease in treated HIV-infected individuals is emphasised and a management approach to ischaemic stroke in HIV-infected individuals is presented. Evidence supporting the important role of HAART and HIV infection itself in the pathogenesis of atherosclerotic disease is discussed, together with preventative approaches to this increasingly important disease process as the population ages. Finally, a discussion regarding the significant association between cerebrovascular disease and HIV-associated neurocognitive disorder is presented, together with possible mechanisms behind this relationship.

  19. Neurobehavioral Effects in HIV-Positive Individuals Receiving Highly Active Antiretroviral Therapy (HAART) in Gaborone, Botswana

    PubMed Central

    Lawler, Kathy; Jeremiah, Kealeboga; Mosepele, Mosepele; Ratcliffe, Sarah J.; Cherry, Catherine; Seloilwe, Esther; Steenhoff, Andrew P.

    2011-01-01

    Objective To explore the prevalence and features of HIV-associated neurocognitive disorders (HANDS) in Botswana, a sub-Saharan country at the center of the HIV epidemic. Design and Methods A cross sectional study of 60 HIV-positive individuals, all receiving highly active antiretroviral therapy (HAART), and 80 demographically matched HIV-seronegative control subjects. We administered a comprehensive neuropsychological test battery and structured psychiatric interview. The lowest 10th percentile of results achieved by control subjects was used to define the lower limit of normal performance on cognitive measures. Subjects who scored abnormal on three or more measures were classified as cognitively impaired. To determine the clinical significance of any cognitive impairment, we assessed medication adherence, employment, and independence in activities of daily living (ADL). Results HIV+ subjects were impaired for all cognitive-motor ability areas compared with matched, uninfected control subjects. Thirty seven percent of HIV+ patients met criteria for cognitive impairment. Conclusion These findings indicate that neurocognitive impairment is likely to be an important feature of HIV infection in resource-limited countries; underscoring the need to develop effective treatments for subjects with, or at risk of developing, cognitive impairment. PMID:21365002

  20. 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.

  1. Early initiation of highly active antiretroviral therapies for AIDS: dynamic choice with endogenous and exogenous learning.

    PubMed

    Lasserre, Pierre; Moatti, Jean-Paul; Soubeyran, Antoine

    2006-05-01

    Criteria for initiation of highly active antiretroviral treatments (HAART) in HIV-infected patients remain a matter of debate world-wide because short-term benefits have to be balanced with costs of these therapies, and restrictions placed on future treatment options if resistant viral strains develop. On the other hand, postponing the introduction of HAART may involve a therapeutic opportunity cost if a patient's health is allowed to deteriorate to such an extent of becoming unable to benefit from new treatments currently under development when they become available. We introduce a two period model where period one treatment adoption is an irreversible act with future, but uncertain, consequences. New information, both endogenous and exogenous, arises over time and shapes the conditions surrounding the second period therapeutic decision. A surprising result is that, under conditions that appear close to those surrounding the HAART debate, the magnitude of the feared resistance effect has no effect on leaves the optimal treatment decision as far as it is high enough.

  2. Dyslipidemia in a Cohort of HIV-infected Latin American Children Receiving Highly Active Antiretroviral Therapy*

    PubMed Central

    Brewinski, Margaret; Megazzini, Karen; Freimanis Hance, Laura; Cruz, Miguel Cashat; Pavia-Ruz, Noris; Della Negra, Marinella; Ferreira, Flavia Gomes Faleiro; Marques, Heloisa

    2011-01-01

    In order to describe the prevalence of hypercholesterolemia and hypertriglyceridemia in a cohort of HIV-infected children and adolescents in Latin America and to determine associations with highly active antiretroviral therapy (HAART), we performed this cross-sectional analysis within the NICHD International Site Development Initiative pediatric cohort study. Eligible children had to be at least 2 years of age and be on HAART. Among the 477 eligible HIV-infected youth, 98 (20.5%) had hypercholesterolemia and 140 (29.4%) had hypertriglyceridemia. In multivariable analyses, children receiving protease inhibitor (PI)-containing HAART were at increased risk for hypercholesterolemia [adjusted odds ratio (AOR) = 2.7, 95% confidence interval (CI) 1.3–5.6] and hypertriglyceridemia (AOR = 3.5, 95% CI 1.9–6.4) compared with children receiving non-nucleoside reverse transcriptase inhibitor (NNRTI)-containing HAART. In conclusion, HIV-infected youth receiving PI-containing HAART in this Latin American cohort were at increased risk for hypercholesterolemia and hypertriglyceridemia compared with those receiving NNRTI-containing HAART. PMID:20889625

  3. Dyslipidemia in a cohort of HIV-infected Latin American children receiving highly active antiretroviral therapy.

    PubMed

    Brewinski, Margaret; Megazzini, Karen; Hance, Laura Freimanis; Cruz, Miguel Cashat; Pavia-Ruz, Noris; Della Negra, Marinella; Ferreira, Flavia Gomes Faleiro; Marques, Heloisa; Hazra, Rohan

    2011-10-01

    In order to describe the prevalence of hypercholesterolemia and hypertriglyceridemia in a cohort of HIV-infected children and adolescents in Latin America and to determine associations with highly active antiretroviral therapy (HAART), we performed this cross-sectional analysis within the NICHD International Site Development Initiative pediatric cohort study. Eligible children had to be at least 2 years of age and be on HAART. Among the 477 eligible HIV-infected youth, 98 (20.5%) had hypercholesterolemia and 140 (29.4%) had hypertriglyceridemia. In multivariable analyses, children receiving protease inhibitor (PI)-containing HAART were at increased risk for hypercholesterolemia [adjusted odds ratio (AOR) =  2.7, 95% confidence interval (CI) 1.3-5.6] and hypertriglyceridemia (AOR = 3.5, 95% CI 1.9-6.4) compared with children receiving non-nucleoside reverse transcriptase inhibitor (NNRTI)-containing HAART. In conclusion, HIV-infected youth receiving PI-containing HAART in this Latin American cohort were at increased risk for hypercholesterolemia and hypertriglyceridemia compared with those receiving NNRTI-containing HAART.

  4. Characteristics and Outcomes of HIV-Infected Patients With Severe Sepsis: Continued Risk in the Post-Highly Active Antiretroviral Therapy Era.

    PubMed

    Cribbs, Sushma K; Tse, Caroline; Andrews, Joel; Shenvi, Neeta; Martin, Greg S

    2015-08-01

    Although highly active antiretroviral therapy has led to improved survival in HIV-infected individuals, outcomes for HIV-infected patients with sepsis in the post-highly active antiretroviral therapy era are conflicting. Access to highly active antiretroviral therapy and healthcare disparities continue to affect outcomes. We hypothesized that HIV-infected patients with severe sepsis would have worse outcomes compared with their HIV-uninfected counterparts in a large safety-net hospital where access to healthcare is low and delivery of critical care is delayed. Secondary analysis of an ongoing prospective observational study between 2006 and 2010. Three adult ICUs (medical ICU, surgical ICU, and neurologic ICU) at Grady Memorial Hospital, Atlanta, GA. Adult patients with severe sepsis in the ICU. Baseline patient characteristics and clinical outcomes were collected. HIV-infected and HIV-uninfected patients with sepsis were compared using t tests, chi-square tests, and logistic regression; p values less than 0.05 indicated significance. Of 1,095 patients with severe sepsis enrolled, 165 (15%) were positive for HIV, with a median CD4 count of 41 (8-167). Twenty-two percent of HIV-infected patients were on highly active antiretroviral therapy prior to admission, and 80% had a CD4 count less than 200. HIV-infected patients had a greater hospital mortality (50% vs 38%; p < 0.01). HIV infection (odds ratio = 1.78; p = 0.005) was an independent predictor of mortality by multivariate regression modeling after adjusting for age, history of pneumonia, history of hospital-acquired infection, and history of sepsis. HIV-infected patients with severe sepsis continue to suffer worse outcomes compared with HIV-uninfected patients in a large urban safety-net hospital caring for patients with limited access to medical care. Further studies need to be done to investigate the effect of socioeconomic status and mitigate healthcare disparities among critically ill HIV-infected patients.

  5. Changes to AIDS dementia complex in the era of highly active antiretroviral therapy.

    PubMed

    Dore, G J; Correll, P K; Li, Y; Kaldor, J M; Cooper, D A; Brew, B J

    1999-07-09

    To determine the protective efficacy of highly active antiretroviral therapy (HAART) against AIDS dementia complex (ADC) relative to other initial AIDS-defining illnesses (ADIs), Australian AIDS notification data over recent years were examined. All initial ADIs in Australia over the period 1992-1997 were included. Three initial ADI groups were established: ADC; other predominantly central nervous system (CNS) ADIs (toxoplasmosis and cryptococcosis); and non-CNS ADIs. For each ADI grouping, the proportion of total ADls, and median CD4 cell count in the pre-HAART era (1992-1995) were compared with the HAART era (1996 and 1997). Initial ADls peaked in Australia in 1994 (n = 1049), with a gradual decline to 1996 (n = 722), and a marked decline in 1997 (n = 367). ADC constituted 4.4% of initial ADIs over the period 1992-1995, but increased after the introduction of HAART to 6.0% in 1996 and 6.5% in 1997 (P = 0.02). In contrast, the proportion of other CNS ADIs (1992-1995, 8.1%; 1996, 6.0%; 1997, 8.2%; P = 0.41) was stable over the period 1992-1997. The median CD4 cell count at ADC diagnosis increased from 70/mm3 in 1992-1995 to 120/mm3 in 1996 and 170/mm3 in 1997 (P = 0.04). Although the median CD4 cell count also increased significantly over this period for both other CNS ADIs (40-60/mm3; P = 0.02), and non-CNS ADIs (60-70/mm3; P = 0.02), the increase was small. A proportional increase in ADC compared with other ADIs and a marked increase in the median CD4 cell count at ADC diagnosis have occurred since the introduction of HAART in Australia. These changes suggest that HAART has a lesser impact on ADC than on other ADIs, with the poor CNS penetration of many antiretroviral agents a possible explanation.

  6. Reconstitution of CD4 T Cells in Bronchoalveolar Lavage Fluid after Initiation of Highly Active Antiretroviral Therapy▿

    PubMed Central

    Knox, Kenneth S.; Vinton, Carol; Hage, Chadi A.; Kohli, Lisa M.; Twigg, Homer L.; Klatt, Nichole R.; Zwickl, Beth; Waltz, Jeffrey; Goldman, Mitchell; Douek, Daniel C.; Brenchley, Jason M.

    2010-01-01

    The massive depletion of gastrointestinal-tract CD4 T cells is a hallmark of the acute phase of HIV infection. In contrast, the depletion of the lower-respiratory-tract mucosal CD4 T cells as measured in bronchoalveolar lavage (BAL) fluid is more moderate and similar to the depletion of CD4 T cells observed in peripheral blood (PB). To understand better the dynamics of disease pathogenesis and the potential for the reconstitution of CD4 T cells in the lung and PB following the administration of effective antiretroviral therapy, we studied cell-associated viral loads, CD4 T-cell frequencies, and phenotypic and functional profiles of antigen-specific CD4 T cells from BAL fluid and blood before and after the initiation of highly active antiretroviral therapy (HAART). The major findings to emerge were the following: (i) BAL CD4 T cells are not massively depleted or preferentially infected by HIV compared to levels for PB; (ii) BAL CD4 T cells reconstitute after the initiation of HAART, and their infection frequencies decrease; (iii) BAL CD4 T-cell reconstitution appears to occur via the local proliferation of resident BAL CD4 T cells rather than redistribution; and (iv) BAL CD4 T cells are more polyfunctional than CD4 T cells in blood, and their functional profile is relatively unchanged after the initiation of HAART. Taken together, these data suggest mechanisms for mucosal CD4 T-cell depletion and interventions that might aid in the reconstitution of mucosal CD4 T cells. PMID:20610726

  7. [The clinical outcome and immune reconstitution in 45 advanced AIDS patients undergoing highly active antiretroviral therapy for 12 months].

    PubMed

    Ruan, Gui-ren; Qiu, Zhi-feng; Li, Tai-sheng; Han, Yang; Xie, Jing; Zuo, Ling-yan; Ma, Xiao-jun; Liu, Zheng-yin; Wang, Ai-xia

    2006-07-01

    To investigate the efficacy and side effects of highly active antiretroviral therapy (HAART) in Chinese AIDS patients. 45 antiretroviral drug-naive AIDS patients were enrolled and divided into two groups by their baseline CD(4) count < 100/microl or > or = 100/microl. Clinical, virological and immunological outcomes as well as side effects were followed at baseline and at the end of month 1, 3, 6, 9, 12 after receiving HAART. Among the 45 HIV/AIDS patients included, by the end of 12 months of HAART, the plasma viral load (VL) got a mean reduction by 2.8 lg copies/ml, CD(4) count had a mean gain of 187/microl, among which the naive phenotype increased by 68/microl and the memory phenotype by 119/microl. The CD(4)(+)CD(28)(+) T cell percentage went up from (62.5 +/- 25.8)% to (82.6 +/- 15.6)% (P < 0.001); and there was a significant reduction of CD(8)(+) T-cell activation. In the 31 patients with their baseline CD(4) count < 100/microl, 11 had a VL < 50 copies/ml, and 14 had fluctuations in their VL; while in 14 patients with their baseline CD(4) count > or = 100/microl, 10 had a VL < 50 copies/ml and 2 had fluctuations in their VL, respectively, with statistic significance between the two groups. CD(4) count showed a bi-phase increase during HAART and there was significant positive correlation between the change of CD(4) count and plasma VL. Throughout the 12 months of HAART, 39 patients had gastrointestinal side effects, 15 peripheral neuritis, 3 hepatic lesions, 4 hematological side effects and 1 renal calculus. 9 patients had adjustment of their initial therapy because of side effects. Immune reconstitution as well as significant therapeutic effect was observed in advanced Chinese AIDS patients after HAART. Side effects were common during HAART, so close clinical attention is needed.

  8. The Immune Pathogenesis of Immune Reconstitution Inflammatory Syndrome Associated with Highly Active Antiretroviral Therapy in AIDS

    PubMed Central

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

    2014-01-01

    Abstract 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

  9. Evaluation of adherence to highly active antiretroviral therapy in adults in Jamaica.

    PubMed

    Harvey, K M; Carrington, D; Duncan, J; Figueroa, J P; Hirschorn, L; Manning, D; Jackson, S

    2008-06-01

    Highly active antiretroviral therapy (HAART) has improved morbidity and mortality and quality of life, revitalized communities and transformed the perception of HIV/AIDS from being a "death sentence" to a chronic illness. Strict and sustained adherence to medication is essential long-term viral suppression. In April 2005, an Adherence Support Programme was introduced to Jamaica's HIV Programme, whereby Persons Living with HIV/AIDS (PLWHA) who had achieved high levels of adherence were trained to provide support to other PLWHA in order to increase their adherence to HAART regimens. A cross-sectional survey of 116 individuals with advanced HIV and on HAART was performed in June and July 2006. Many participants were unemployed, poor persons with limited education. Based on self-report of seven-day adherence, 54.8% of persons were 95-100% adherent, 37.5% were 80-94% adherent and 7.7% were < 80% adherent. Having interacted with an adherence counsellor was not associated with adherence levels. Factors associated with nonadherence were: being away from home (38%), sleeping through dose-time (37%), forgetfulness (37%) and running out of pills (31%). Having no food (26.9%), not wanting to be seen taking medication (200%) and intolerable side effects (18.8%) were also reasons given. Only 44% of persons used aids to remind them of dose times. Adherence in this study group is low and may have worsened since 2005. More emphasis must be placed on preparing adults to start HAART The use of pillboxes and other reminders such as alarm clocks and cell phones must be reinforced.

  10. [High activity antiretroviral therapy change associated to adverse drug reactions in a specialized center in Venezuela].

    PubMed

    Subiela, José D; Dapena, Elida

    2016-03-01

    Adverse drug reactions (ADRs) represent the first cause of change of the first-line highly active antiretroviral therapy (HAART) regimen, therefore, they constitute the main limiting factor in the long-term follow up of HIV patients in treatment. A retrospective study was carried out in a specialized center in Lara State, Venezuela, including 99 patients over 18 years of age who had change of first-line HAART regimen due to ADRs, between 2010 and 2013. The aims of this research were to describe the sociodemographic and clinical variables, frequency of ADRs related to change of HAART, duration of the first-line HAART regimen, to determine the drugs associated with ARVs and to identify the risk factors. The ADRs constituted 47.5% of all causes of change of first-line HAART regimen, the median duration was 1.08±0.28 years. The most frequent ADRs were anemia (34.3%), hypersensitivity reactions (20.2%) and gastrointestinal intolerance (13.1%). The most frequent ARV regimen type was the protease inhibitors-based regimen (59.6%), but zidovudine was the ARV most linked to ADRs (41.4%). The regression analysis showed increased risk of ADRs in singles and students in the univariate analysis and heterosexuals and homosexuals in multivariate analysis; and decreased risk in active workers. The present work shows the high prevalence of ADRs in the studied population and represents the first case-based study that describes the pharmacoepidemiology of a cohort of HIV-positive patients treated in Venezuela.

  11. 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.

  12. Has Highly Active Antiretroviral Therapy Increased the Time to Seroreversion in HIV Exposed but Uninfected Children?

    PubMed Central

    Gutierrez, Mavel; Ludwig, David A.; Khan, Safia S.; Chaparro, Aida A.; Rivera, Delia M.; Cotter, Amanda M.; Scott, Gwendolyn B.

    2012-01-01

    Background. Since the introduction of highly active antiretroviral therapy (HAART) for prevention of mother-to-child transmission of human immunodeficiency virus (HIV) in pregnancy in the United States, the time of seroreversion in infants born to HIV-infected mothers has not been documented. The objective of this study was to determine the timing of clearance of HIV antibodies and to identify any associated biological and clinical factors. Methods. A retrospective analysis of infants who remained uninfected after perinatal HIV exposure was performed. Infant and maternal medical records from January 2000 to December 2007 were reviewed and the time of seroreversion was estimated using methods for censored survival data. Results. In total, 744 infants were included in the study, with prenatal data available for 551 mothers. The median age of seroreversion was 13.9 months, and 14% of infants remained seropositive after 18 months, 4.3% after 21 months, and 1.2% after 24 months. Earlier age of seroreversion was associated with higher immunoglobulin G (IgG) levels at 3–7 months of age (P = .0029) and a higher rate of IgG change over the next 6 months of life (P = .003). Infants born by vaginal delivery were more likely to serorevert at a younger age (P = .0052), and maternal exposure to protease inhibitors was associated with a later age of seroreversion (P = .026). Conclusions. Clearance of HIV antibodies in uninfected infants was found to occur at a later age than has been previously reported. Fourteen percent of the infants had persistence of HIV antibodies at or beyond 18 months of age. PMID:22851494

  13. 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

  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. Prevalence of Depressive Symptoms Amongst Highly Active Antiretroviral Therapy (HAART) Patients in AIDSRelief Uganda

    PubMed Central

    Atukunda, Ruth; Imakit, Richard; Memiah, Peter

    2013-01-01

    There is limited data on the prevalence of depression in HIV and AIDS patients in Sub-Saharan Africa and little resources have been allocated to address this issue. Depression affects patient adherence to treatment and predisposes patients to resistance which poses a public health threat. It also affects quality of life and productivity of patients. From August 2008 to March 2009, 731 patient adherence surveys were administered to assess disease, treatment knowledge and services received. The primary variable of interest was patients’ level of depressive symptoms score, constructed using factor analysis from five survey questions relating to: sadness, need to be alone, hopelessness and confusion and was categorized as no depressive symptoms (score 0), low depressive symptoms (score 1-2), moderate depressive symptoms (score 3-4) and high depressive symptoms (score 5-10). Majority of the patients on highly active antiretroviral therapy (HAART) (59%) were found to have depressive symptoms and this was more among women than men (66% vs 43%). There was some association of depressive symptoms with non-disclosure (70% of those who had not disclosed had depressive symptoms compared to 53% among those who had disclosed). There is a high prevalence of depressive symptoms among adult patients on HAART. There is need for in-depth evaluation to find out the root causes of depressive symptoms among HAART patients in AIDSRelief clinics. There is need to integrate mental health management in HIV care and treatment as well as training the existing health workers on mental health management. PMID:28299108

  16. Cost-effectiveness of highly active antiretroviral therapy in South Africa.

    PubMed

    Badri, Motasim; Maartens, Gary; Mandalia, Sundhiya; Bekker, Linda-Gail; Penrod, John R; Platt, Robert W; Wood, Robin; Beck, Eduard J

    2006-01-01

    Little information exists on the impact of highly active antiretroviral therapy (HAART) on health-care provision in South Africa despite increasing scale-up of access to HAART and gradual reduction in HAART prices. Use and cost of services for 265 HIV-infected adults without AIDS (World Health Organization [WHO] stage 1, 2, or 3) and 27 with AIDS (WHO stage 4) receiving HAART between 1995 and 2000 in Cape Town were compared with HIV-infected controls matched for baseline WHO stage, CD4 count, age, and socioeconomic status, who did not receive antiretroviral therapy (ART; No-ART group). Costs of service provision (January 2004 prices, USD 1 = 7.6 Rand) included local unit costs, and two scenarios for HAART prices for WHO recommended first-line regimens: scenario 1 used current South African public-sector ART drug prices of $730 per patient-year (PPY), whereas scenario 2 was based on the anticipated public-sector price for locally manufactured drug of $181 PPY. All analyses are presented in terms of patients without AIDS and patients with AIDS. For patients without AIDS, the mean number of inpatient days PPY was 1.08 (95% confidence interval [CI]: 0.97-1.19) for the HAART group versus 3.73 (95% CI: 3.55-3.97) for the No-ART group, and 8.71 (95% CI: 8.40-9.03) versus 4.35 (95% CI: 4.12-5.61), respectively, for mean number of outpatient visits PPY. Average service provision PPY was $950 for the No-ART group versus $1,342 and $793 PPY for the HAART group for scenario 1 and 2, respectively, whereas the incremental cost per life-year gained (LYG) was $1,622 for scenario 1 and $675 for scenario 2. For patients with AIDS, mean inpatients days PPY was 2.04 (95% CI: 1.63-2.52) for the HAART versus 15.36 (95% CI: 13.97-16.85) for the No-ART group. Mean outpatient visits PPY was 7.62 (95% CI: 6.81-8.49) compared with 6.60 (95% CI: 5.69-7.62) respectively. Average service provision PPY was $3,520 for the No-ART group versus $1,513 and $964 for the HAART group for scenario 1 and

  17. The Effect of Individual Antiretroviral Drugs on Body Composition in HIV-Infected Persons Initiating Highly Active Antiretroviral Therapy

    PubMed Central

    Shlay, Judith C.; Sharma, Shweta; MS, Grace Peng; Gibert, Cynthia L.; Grunfeld, Carl

    2009-01-01

    Objectives To examine the long-term effects of individual antiretroviral drugs on body composition among 416 persons initiating antiretroviral therapy (ART). Methods In a substudy of a clinical trial of persons initiating ART, changes in body composition attributable to individual ART were examined. ART assessed were: indinavir, ritonavir, nelfinavir, efavirenz, nevirapine, stavudine (d4T), zidovudine (ZDV), lamivudine (3TC), didanosine (ddI), and abacavir (ABC). Skinfolds and circumferences were measured at baseline and every 4 months. Mid-arm, mid-thigh and waist subcutaneous tissue areas (STAs) and non-subcutaneous tissue areas (NSTAs) were calculated. Rates of change per year of exposure to each individual ART drug were determined using multivariate longitudinal regression. Results D4T and ZDV use were associated with losses in STA and skinfold thickness. 3TC use was associated with gains in all STAs and skinfold thickness, while ABC use was associated with an increase in waist STA. Indinavir was associated with gains in waist STA, while indinavir, efavirenz and nevirapine were associated with increases in upper back skinfolds. D4T use was also associated with increases in all NSTAs; 3TC use was associated with the greatest increase in waist NSTA. Conclusions In this prospective non-randomized evaluation, the NRTIs d4T and ZDV were associated with decreases in STAs, while 3TC use was associated with increased STAs and waist NSTA. PMID:19412117

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

    PubMed

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

    2012-05-01

    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). To identify the oral manifestations of HIV in children receiving HAART. 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 was done using Fisher's Chi-square test. Probability value (P value) was obtained for the three groups. 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. 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.

  19. Bone mineral density in human immunodeficiency virus-1 infected men with hypogonadism prior to highly-active-antiretroviral-therapy (HAART)

    PubMed Central

    2009-01-01

    Alterations of bone metabolism have been observed in numerous studies of HIV-infected patients. Sex steroids are known to profoundly influence bone mass and bone turnover. Hypogonadism is common in HIV-infection. Therefore, we performed a cross sectional study of 80 male HIV-infected patients without wasting syndrome, and 20 healthy male controls, in whom we analyzed urine and serum samples for both calciotropic hormones and markers of bone metabolism and of endocrine testicular function. Bone mineral density (BMD) was assessed by dual-energy X-ray absorptiometry both in the lumbar spine and Ward's triangle of the left hip. None of the patients received highly-active-antiretroviral-therapy (HAART). Compared to eugonadal HIV-infected patients, subjects with hypogonadism (n = 32; 40%) showed statistically significant decrease of serum osteocalcin (p < 0.05) and elevated urinary excretion of crosslinks (p < 0.05). However, we found 13 and 15, respectively, patients with osteopenia (t-score -1.0 to -2.5 SD below normal) of the lumbar spine. The dissociation between bone formation and resorption and the reduction of of BMD (p < 0.05) is stronger expressed in patients with hypogonadism. Habitual hypogonadism appears to be of additional relevance for bone metabolism of male HIV-positive patients prior to HAART. PMID:19258214

  20. 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.

  1. Immune recovery uveitis in AIDS patients with cytomegalovirus retinitis treated with highly active antiretroviral therapy in Venezuela.

    PubMed

    Arevalo, J Fernando; Mendoza, Aristides J; Ferretti, Yolanda

    2003-08-01

    To determine the characteristics of immune recovery uveitis (IRU) in acquired immunodeficiency syndrome (AIDS) patients with inactive cytomegalovirus (CMV) retinitis who responded to highly active antiretroviral therapy (HAART) in a Venezuelan population. We examined 34 patients (50 eyes) with AIDS (HAART responders) and healed CMV retinitis. Patients were observed for a median of 19.3 months following an increase in the CD4 cell count. Ten eyes were treated with sub-Tenon space corticosteroid injections. An age-matched control group of patients with healed CMV retinitis who did not have IRU (30 eyes of 20 patients) was included to compare CMV surface area and complications. We found that 12 (37.5%) of 32 HAART responders developed IRU (18 eyes). The clinical findings of these 18 eyes with IRU are presented. The clinical spectrum of inflammation included vitritis, macular edema, epiretinal membranes, anterior uveitis, macular hole, retinal detachment with proliferative vitreoretinopathy, and cataract. Eyes with IRU had a mean CMV surface area of 31.7%. However, eyes without IRU (control group) had a mean CMV surface area of 35% (P = 0.41). Periocular treatment resulted in vision improvement (in 90% of eyes) without reactivation of retinitis. Symptomatic IRU developed in a significant number of patients with CMV retinitis following successful HAART in a Venezuelan population. CMV surface area does not seem to be a risk factor for the development of IRU. Eyes with IRU respond favorably to antiinflammatory therapy without reactivation of retinitis.

  2. Association of HIV and highly active antiretroviral therapy with clinical and biochemical indices among women with pre-eclampsia.

    PubMed

    Maharaj, Niren R; Moodley, Jagidesa; Chuturgoon, Anil

    2016-09-01

    To determine whether clinical and biochemical features associated with pre-eclampsia are significantly altered among women with HIV infection taking highly active antiretroviral therapy (HAART). A prospective observational cohort study was conducted between July 2013 and September 2014 at Prince Mshiyeni Memorial Hospital, Durban, South Africa. Women with and without pre-eclampsia and HIV infection were enrolled at booking and followed up until delivery. Specific demographic data, clinical features, laboratory indices, and complications were analyzed. Of 193 participants, 98 had pre-eclampsia (45 [45.9%] with HIV infection). There were no significant differences in clinical features and laboratory indices among the study groups except for γ-glutamyl transferase levels, which were significantly higher among women with pre-eclampsia and HIV infection (26.9±40.9U/L) than among those with pre-eclampsia but no HIV infection (17.1±14.0U/L; P=0.001). Perinatal and maternal complications were similar, and there were no maternal deaths. Clinical features, laboratory indices, and complications among women with pre-eclampsia and HIV infection taking HAART were similar to those among women with pre-eclampsia without HIV infection. Current guidelines remain appropriate; however, frequent hepatic function tests should be conducted. Copyright © 2016 International Federation of Gynecology and Obstetrics. Published by Elsevier Ireland Ltd. All rights reserved.

  3. 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.

  4. National review of first treatment change after starting highly active antiretroviral therapy in antiretroviral-naïve patients.

    PubMed

    Hart, E; Curtis, H; Wilkins, E; Johnson, M

    2007-04-01

    The aim of the study was to explore the factors surrounding modification of the first antiretroviral (ARV) regimen where drug switch occurred 3 months or more after initiation. Reference was made to the British HIV Association (BHIVA) guidelines on HIV management. A case note and questionnaire-based audit was carried out. Toxicity was the single most important reason for ARV change and was the only, or a contributory, cause in over half the patients. Virological failure, adherence issues, requirement for treatment simplification, and patient request were other significant reasons cited. In one-third of those with virological failure, six or more months had elapsed between first detection and the time of switching to a new ARV regimen. This audit demonstrated broad adherence to the BHIVA guidelines, although the long time before switching ARVs in the setting of virological failure was of some concern, particularly given the continuing and significant occurrence of primary ARV resistance in the UK.

  5. Clinical outcomes and immune reconstitution in 103 advanced AIDS patients undergoing 12-month highly active antiretroviral therapy.

    PubMed

    Dai, Yi; Qiu, Zhi-feng; Li, Tai-sheng; Han, Yang; Zuo, Ling-yan; Xie, Jing; Ma, Xiao-jun; Liu, Zheng-yin; Wang, Ai-xia

    2006-10-20

    Highly active antiretroviral therapy (HAART) produces profound suppression of HIV replication, substantial increase in CD4(+) T cells, and partial reconstitution of the immune system. However, the numbers of subjects were small in previous Chinese studies. This study evaluated the efficacy and side effects of HAART in Chinese advanced AIDS patients. One hundred and three antiretroviral drug naive AIDS patients were enrolled in this study and were divided into two groups by their baseline CD4(+) count: < 100 cells/microl or > or = 100 cells/microl. Clinical, virological and immunological outcomes were monitored at baseline and at 1, 3, 6, 9 and 12 months during the course of treatment with HAART. One patient died and another was lost from the follow-up. For the remaining 101 HIV/AIDS patients at the 12th month during the HAART, the plasma viral load (VL) was reduced to (3.2 +/- 0.7) lg copies/ml, the CD4(+) count increased to (168 +/- 51) cells/microl [among which the naive phenotype (CD45RA(+)CD62L(+)) increased to (49 +/- 27) cells/microl and the memory phenotype (CD45RA(-)) increased to (119 +/- 55) cells/microl], and the percentage of CD4(+)CD28(+) cells increased. At the same time, there was a significant reduction of CD8(+) T cell activation. In the 69 patients with the baseline CD4(+) count < 100 cells/microl, 37 had a VL < 50 copies/ml; while in the 34 patients with the baseline CD4(+) count > or = 100 cells/microl, 25 had a VL < 50 copies/ml, the difference between the two groups was statistically significant. The CD4(+) T cell count showed a two-phase increase during HAART and a significant positive correlation was shown between the change of CD4(+) count and plasma VL. Over 12 months of HAART, 10 patients had gastrointestinal side effects, 13 peripheral neuritis, 7 hepatic lesions, 8 hematological side effects, 8 skin rashes, 10 lipodystrophy and 1 renal calculus. Immune reconstitution as well as the significantly improved clinical outcomes is observed in

  6. 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

  7. The impact of highly active antiretroviral therapy on obstetric conditions: A review.

    PubMed

    Sebitloane, Hannah M; Moodley, Dhayendre

    2017-03-01

    HIV is the leading cause of maternal and neonatal morbidity and mortality in resource constrained countries. Highly active antiretroviral treatment (HAART) initiated in pregnancy has now almost eliminated mother to child transmission of the virus, and is beginning to show the desired effect of reducing HIV related maternal mortality. By modulating host immunological responses HAART has the potential to alter infections during pregnancy, in addition to modifying clinical conditions such as preeclampsia. There is increasing evidence of the benefits of HAART given to pregnant women, however there is paucity of data that distinguishes HIV or HAART as the cause or exacerbation of pre-existing medical conditions or conditions specific to pregnancy. Anaemia is the commonest haematological disorder seen in HIV infected women and is more pronounced during pregnancy. The use of HAART has the potential to reduce the incidence and severity of the disease. Tuberculosis (TB) is the commonest chest infection amongst HIV infected people, being more common amongst pregnant than non-pregnant women. It is the leading cause of death from infectious diseases amongst women of reproductive age, and accounts for at least a quarter of all cases of maternal deaths associated with non-pregnancy related infections (NPRI). TB can manifest at any stage of the HIV infection, including during treatment with HAART. The latter (ie TB manifestation during HAART treatment) is thought to be the commonest manifestation of what is now known as immune reconstitution inflammatory syndrome (IRIS). In a South African report on maternal deaths, 55% of women who died of TB were on HAART, and a further 35% of women in the NPRI category died from other pneumoniae, notably pneumocystis jorevicci, which is also related to HIV infection. With regards to puerperal sepsis, studies are yet to show the impact of HAART independent of antibiotics in reducing infectious morbidity in HIV infected women. Preeclampsia has

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

    PubMed Central

    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/mm3 with comorbid conditions. PMID:22470896

  9. African Ancestry Influences CCR5 –2459G>A Genotype-Associated Virologic Success of Highly Active Antiretroviral Therapy

    PubMed Central

    Cheruvu, Vinay K.; Igo, Robert P.; Jurevic, Richard J.; Serre, David; Zimmerman, Peter A.; Rodriguez, Benigno; Mehlotra, Rajeev K.

    2014-01-01

    Introduction In a North American, HIV-positive, highly active antiretroviral therapy (HAART)-treated, adherent cohort of self-identified white and black patients, we previously observed that chemokine (C-C motif) receptor 5 (CCR5) –2459G>A genotype had a strong association with time to achieve virologic success (TVLS) in black but not in white patients. Methods Using 128 genome-wide ancestry informative markers, we performed a quantitative assessment of ancestry in these patients (n = 310) to determine (1) whether CCR5 –2459G>A genotype is still associated with TVLS of HAART when ancestry, not self-identified race, is considered and (2) whether this association is influenced by varying African ancestry. Results We found that the interaction between CCR5 –2459G>A genotype and African ancestry (≤0.125 vs. ≥0.425 and <0.71 vs. ≥0.71) was significantly associated with TVLS (GG compared with AA, P = 0.044 and 0.018, respectively). Furthermore, the association between CCR5 –2459G>A genotype and TVLS was stronger in patients with African ancestry ≥0.71 than in patients with African ancestry ≥0.452, in both Kaplan-Meier (log-rank P = 0.039 and 0.057, respectively, for AA, GA, and GG) and Cox proportional hazards regression (relative hazard for GG compared with AA 2.59 [95% CI, 1.27–5.22; P = 0.01] and 2.26 [95% CI, 1.18–4.32; P = 0.01], respectively) analyses. Conclusions We observed that the association between CCR5 –2459G>A genotype and TVLS of HAART increased with stronger African ancestry. Understanding the genomic mechanisms by which African ancestry influences this association is critical, and requires further studies. PMID:24714069

  10. Anal carcinomas in HIV-positive patients: high-dose chemoradiotherapy is feasible in the era of highly active antiretroviral therapy.

    PubMed

    Blazy, Anne; Hennequin, Christophe; Gornet, Jean-Marc; Furco, André; Gérard, Laurence; Lémann, Marc; Maylin, Claude

    2005-06-01

    Anal carcinoma, a common disease in HIV-positive patients, is usually treated with chemoradiotherapy. Generally tolerance was poor before the availability of highly active antiretroviral therapies. We report our experience of treating anal carcinoma in the era of new antiviral drugs. Between 1997 and 2001, nine men on highly active antiretroviral therapies with good immune status before chemoradiotherapy received concomitant chemoradiotherapy consisting of 5-fluorouracil and cisplatinum, and high-dose radiotherapy (60-70 Gy) for anal carcinoma. Six cancers were Stage I, two were Stage II, and one was Stage III. CD4+ cell counts were <200/ml for four patients, between 200/ml and 500/ml for four, and >500/ml for one. All patients received the planned dose of radiation (> or = 60 Gy). The chemotherapy dose was reduced 25 percent in six patients. Overall treatment time was 58 days. Grade 3 hematologic or skin toxicity occurred in four patients. No association was observed between high-grade toxicity and CD4+ cell count. None of the patients developed opportunistic infections during follow-up. Eight patients were disease-free after a median follow-up of 33 months. Among them, four had no or minor anal function impairment at the last follow-up visit. One patient with T4N2 disease relapsed locally one year after treatment and underwent salvage abdominoperineal excision. High-dose chemoradiotherapy for anal carcinomas is feasible with low toxicity in HIV-positive patients treated with highly active antiretroviral therapies. Local control is similar to that obtained for HIV-negative patients.

  11. Human immunodeficiency virus associated spondyloarthropathy: pathogenic insights based on imaging findings and response to highly active antiretroviral treatment

    PubMed Central

    McGonagle, D; Reade, S; Marzo-Ortega, H; Gibbon, W; O'Connor, P; Morgan, A; Melsom, R; Morgan, E; Emery, P

    2001-01-01

    The pathogenesis of human immunodeficiency virus (HIV) associated spondyloarthropathy (SpA) is poorly understood. In this case report a patient is described with severe HIV associated reactive arthritis, who on magnetic resonance imaging and sonographic imaging of inflamed knees had extensive polyenthesitis and adjacent osteitis. The arthritis deteriorated despite conventional antirheumatic treatment, but improved dramatically after highly active antiretroviral treatment, which was accompanied by a significant rise in CD4 T lymphocyte counts. The implications of the localisation of pathology and effect of treatment for pathogenic models of SpA and rheumatoid arthritis in the setting of HIV infection are discussed.

 PMID:11406526

  12. Care of the HIV-positive patient in the emergency department in the era of highly active antiretroviral therapy.

    PubMed

    Venkat, Arvind; Piontkowsky, David M; Cooney, Robert R; Srivastava, Adarsh K; Suares, Gregory A; Heidelberger, Cory P

    2008-09-01

    More than 1 million individuals in the United States are HIV positive, with greater than 40,000 new patients being diagnosed per year. With the advent of highly active antiretroviral therapy (HAART), HIV-infected patients in the United States are living longer. HIV-infected patients receiving HAART now more commonly have noninfectious and nonopportunistic complications of their disease. This review article will discuss the assessment and treatment of HIV-positive patients in the era of HAART, with an emphasis on the noninfectious and changing infectious complications that require emergency care.

  13. Complementary and alternative therapy (CAT) use and highly active antiretroviral therapy (HAART): current evidence in the literature, 2000-2009.

    PubMed

    Hoogbruin, Amandah

    2011-04-01

    To determine current evidence about the use of complementary and alternative medicine in the context of highly active antiretroviral therapy. The following objectives included identifying the risks and benefits of using complementary and alternative medicine when living with the human immunodeficiency virus (HIV) and taking such medications. In Canada and the USA, HIV/AIDS service organisations recognise that people affected or infected by HIV are increasingly choosing to use complementary and alternative medicine to cope with this disease. These same organisations advocate for increased access to complementary and alternative medicine and more information about the safe use of complementary and alternative medicine to make informed decisions. Based on the increased integral use of complementary and alternative medicine and conventional medicine in Canada and the USA, the literature review was limited to these two countries. Systematic review. Available full-text abstracts published in English from 2000-2009 were retrieved by electronic searches of selected databases, including the websites of Health Canada and American National Center for Complementary and Alternate Medicine (NCCAM). Forty studies were examined and were categorised by referring to the NCCAM (2007) four types of complementary and alternative medicine. Insufficient evidence exists to support the use of a particular complementary and alternate therapy to enhance the management of HIV disease. Decisions about using complementary and alternative medicine in conjunction with highly active antiretroviral therapy are often poorly informed. Safety risks and potential drug interactions are frequently ignored as people who use highly active antiretroviral therapy prefer to focus on the physical and mental benefits of using selected complementary and alternate therapies to promote their quality of life. As life expectancy increases, from the use of highly active antiretroviral therapy, it is important for

  14. Antiretroviral effect of lovastatin on HIV-1-infected individuals without highly active antiretroviral therapy (The LIVE study): a phase-II randomized clinical trial

    PubMed Central

    Montoya, Carlos J; Jaimes, Fabian; Higuita, Edwin A; Convers-Páez, Sandra; Estrada, Santiago; Gutierrez, Francisco; Amariles, Pedro; Giraldo, Newar; Peñaloza, Cristina; Rugeles, Maria T

    2009-01-01

    Background Highly active antiretroviral therapy produces a significant decrease in HIV-1 replication and allows an increase in the CD4 T-cell count, leading to a decrease in the incidence of opportunistic infections and mortality. However, the cost, side effects and complexity of antiretroviral regimens have underscored the immediate need for additional therapeutic approaches. Statins exert pleiotropic effects through a variety of mechanisms, among which there are several immunoregulatory effects, related and unrelated to their cholesterol-lowering activity that can be useful to control HIV-1 infection. Methods/design Randomized, double-blinded, placebo controlled, single-center, phase-II clinical trial. One hundred and ten chronically HIV-1-infected patients, older than 18 years and naïve for antirretroviral therapy (i.e., without prior or current management with antiretroviral drugs) will be enrolled at the outpatient services from the most important centres for health insurance care in Medellin-Colombia. The interventions will be lovastatin (40 mg/day, orally, for 12 months; 55 patients) or placebo (55 patients). Our primary aim will be to determine the effect of lovastatin on viral replication. The secondary aim will be to determine the effect of lovastatin on CD4+ T-cell count in peripheral blood. As tertiary aims we will explore differences in CD8+ T-cell count, expression of activation markers (CD38 and HLA-DR) on CD4 and CD8 T cells, cholesterol metabolism, LFA-1/ICAM-1 function, Rho GTPases function and clinical evolution between treated and not treated HIV-1-infected individuals. Discussion Preliminary descriptive studies have suggested that statins (lovastatin) may have anti HIV-1 activity and that their administration is safe, with the potential effect of controlling HIV-1 replication in chronically infected individuals who had not received antiretroviral medications. Considering that there is limited clinical data available on this topic, all these

  15. HIV/AIDS and Infertility: Emerging Problems in the Era of Highly Active Antiretrovirals

    PubMed Central

    Kushnir, Vitaly A.; Lewis, William

    2011-01-01

    Objective To review the effects of HIV/AIDS, associated co-morbid conditions, and side effects of antiretroviral treatment on fertility. Design A Pubmed computer search was performed to identify relevant articles. Setting Research institution. Intervention(s) None. Result(s) Biological alterations in reproductive physiology may account for sub-fertility in patients infected with HIV. Psychosocial factors in patients with HIV infection may affect reproductive desires and outcomes. Antiretroviral medications may have direct toxicity on gametes and embryos. Available evidence indicates that fertility treatments can be a safe option for HIV-discordant couples; although, potential risk of viral transmission cannot be completely eliminated. Conclusion(s) Reproductive desires are increasingly becoming prominent in the healthcare of young HIV-infected patients. Additional data is needed to address the effect of HIV and its treatments on fertility and reproductive outcomes. PMID:21722892

  16. Opportunistic Diseases in HIV-Infected Patients in Gabon following the Administration of Highly Active Antiretroviral Therapy: A Retrospective Study

    PubMed Central

    Okome-Nkoumou, Madeleine; Guiyedi, Vincent; Ondounda, Magloire; Efire, Nora; Clevenbergh, Philippe; Dibo, Mireille; Dzeing-Ella, Arnaud

    2014-01-01

    Opportunistic diseases cause substantial morbidity and mortality to human immunodeficiency virus (HIV)-infected patients. Highly active antiretroviral therapy (HAART) leading to immune reconstitution is the most effective treatment of preventing opportunistic diseases. This retrospective study established an epidemiologic profile of opportunistic diseases 10 years after the introduction of HAART. The HIV antiretroviral therapy-naive patients matching inclusion criteria were included. The primary outcome was the prevalence of opportunistic diseases. From January 1, 2002 to September 30, 2010, 654 opportunistic diseases were identified in 458 patients. Pulmonary tuberculosis, herpes zoster, cerebral toxoplasmosis, oral candidiasis, and severe pneumonia accounted for 22.05%, 15.94%, 14.19%, 14.19%, and 9.39%, respectively. Cryptococcal meningitis and pneumocystosis accounted for 0.44% and 0.21%, respectively. The prevalence of opportunistic diseases in Gabon remains high. New guidelines emphasize the importance of initiating antiretroviral therapy early to reconstitute the immune system, and reduce disease risk, and treat the primary opportunistic infection of pulmonary tuberculosis. PMID:24323514

  17. Decreasing incidence of cryptococcal meningitis in West Africa in the era of highly active antiretroviral therapy.

    PubMed

    Bamba, Sanata; Lortholary, Olivier; Sawadogo, Adrien; Millogo, Athanase; Guiguemdé, Robert T; Bretagne, Stéphane

    2012-05-15

    Cryptococcosis remains a major opportunistic infection in AIDS in sub-Saharan Africa, but few data exist from its western part. We report data from Bobo Dioulasso University Hospital, Bobo-Dioulasso, Burkina Faso, with a steady decline from 14 to two cases per year from 2002 to 2010 which contrasts with the increase (from 147 to 3940) of patients on antiretroviral therapy (ART). Better ART availability decreases the incidence of cryptococcosis in Burkina Faso.

  18. Acute kidney injury in HIV-infected children: comparison of patients according to the use of highly active antiretroviral therapy.

    PubMed

    Soares, Douglas de Sousa; Cavalcante, Malena Gadelha; Ribeiro, Samille Maria Vasconcelos; Leitão, Rayana Café; Vieira, Ana Patrícia Freitas; Pires Neto, Roberto da Justa; Silva Junior, Geraldo Bezerra da; Daher, Elizabeth de Francesco

    To assess clinical and laboratory data, and acute kidney injury (AKI) in HIV-infected children using and not using highly active antiretroviral therapy (HAART) prior to admission. A retrospective study was conducted with HIV-infected pediatric patients (<16 years). Children who were using and not using HAART prior to admission were compared. Sixty-three patients were included. Mean age was 5.3±4.27 years; 55.6% were females. AKI was observed in 33 (52.3%) children. Patients on HAART presented lower levels of potassium (3.9±0.8 vs. 4.5±0.7mEq/L, p=0.019) and bicarbonate (19.1±4.9 vs. 23.5±2.2mEq/L, p=0.013) and had a higher estimated glomerular filtration rate (102.2±36.7 vs. 77.0±32.8mL/min/1.73m(2), p=0.011) than those not on HAART. In the multivariate analysis, the use of HAART prior to the admission was a protective factor for AKI (p=0.036; OR=0.30; 95% CI=0.097-0.926). AKI is a common complication of pediatric HIV infection. Use of HAART prior to the admission preserved glomerular filtration and was a protective factor for AKI, but increased medication side effects, such as hypokalemia and renal metabolic acidosis. Copyright © 2016 Sociedade Brasileira de Pediatria. Published by Elsevier Editora Ltda. All rights reserved.

  19. Oral Candida colonization and its relation with predisposing factors in HIV-infected children and their uninfected siblings in Brazil: the era of highly active antiretroviral therapy.

    PubMed

    Cerqueira, Daniella Ferraz; Portela, Maristela Barbosa; Pomarico, Luciana; de Araújo Soares, Rosangela Maria; de Souza, Ivete Pomarico Ribeiro; Castro, Glória Fernanda

    2010-02-01

    To evaluate predisposing factors such as orofacial manifestations, immunosuppression status and antiretroviral therapy in relation to oral colonization by Candida spp. in Brazilian HIV-infected children and their uninfected siblings in the era of highly active antiretroviral therapy (HAART). Whole stimulated saliva was collected from 65 HIV-infected children (HIV+) and 40 uninfected siblings (HIV-), followed by assessment of orofacial manifestation, caries indexes and the number of cavitated dentinal carious teeth (CDT). The salivary samples were cultured and the colonies were counted. After which they were identified by sugar assimilation and fermentation (API 20C). Data was analyzed using chi-square, Mann-Whitney, Spearman tests and logistic regression. Regarding positive growth, HIV+ presented 80% (52/65) and HIV- 57.5% (23/40) (P = 0.013). Absence of antiretroviral therapy and HAART increased the probability of Candida isolation (P < 0.05). Mean CD4%, immune-status and history of recurrent oral candidiasis (OC) had no influence on Candida isolation. Mixed Candida spp. cultures were observed in HIV+ (40%) and HIV- (52%): C. albicans was more frequently found in both groups, with a higher prevalence in HIV+ (P = 0.05); other non-albicans species were isolated in HIV+ and HIV-. Low prevalence of orofacial manifestations was observed in HIV+ (10.7% of OC). There was an association between means of CDT and Candida growth (P < 0.05) and a positive correlation between number of CDT and Candida cfu-counts in HIV+ and HIV-. Mean CD4% and immune-status had no influence on Candida isolation. Absence of antiretroviral therapy and HAART increased the probability of Candida isolation (P < 0.05). The HIV infected children had a significantly higher prevalence of oral Candida spp. compared to their uninfected siblings. Absence of HAART and presence of dentinal carious teeth increased significantly Candida spp. colonization in these children.

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

    PubMed

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

    2011-07-01

    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. 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. 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. 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.

  1. 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

  2. RITONAVIR-ASSOCIATED TOXICITY MIMICKING RETINITIS PIGMENTOSA IN AN HIV-INFECTED PATIENT ON HIGHLY ACTIVE ANTIRETROVIRAL THERAPY.

    PubMed

    Papavasileiou, Evangelia; Younis, Saad; Zygoura, Vasiliki; Quijano, Claudia; Jackson, Timothy L

    2017-01-01

    To report ritonavir-associated retinal pigment epithelium toxicity in a patient infected with the HIV on highly active antiretroviral therapy including ritonavir. Retrospective single case report. The authors describe a case of gradual onset of blurry vision in both eyes in an HIV-positive male. Visual acuity, clinical examination findings, and functional testing (electroretinogram and Goldmann perimetry) were reviewed. Diagnostic imaging, including fundus photography, spectral domain optical coherence tomography, fluorescein angiography, and fundus autofluorescence were assessed. 59-year-old HIV-infected male, treated with ritonavir for eight years, presented with a history of decreased night vision and peripheral field loss. Ophthalmologic examination confirmed the diagnosis of retinal toxicity. Goldmann perimetry showed areas of central and para-central scotomas. Electroretinograms demonstrated mild to moderate photoreceptor dysfunction. Fundus examination revealed a diffuse pattern of retinal pigment epithelium mottling in both eyes. Spectral domain optical coherence tomography confirmed the presence of choroidal thinning, whereas fundus autofluorescence showed mottled hypoautofluorescence. Although ritonavir-associated retinal toxicity is clinically uncommon, the clinical features of our findings support this diagnosis. Consideration of highly active antiretroviral therapy-associated retinal toxicity should be given to the differential diagnosis in HIV-positive patients with retinopathy of unclear etiology. This report also highlights the need for constant monitoring of patients using the ritonavir for early detection of possible retinal toxicity.

  3. Treatment intensification does not reduce residual HIV-1 viremia in patients on highly active antiretroviral therapy.

    PubMed

    Dinoso, J B; Kim, S Y; Wiegand, A M; Palmer, S E; Gange, S J; Cranmer, L; O'Shea, A; Callender, M; Spivak, A; Brennan, T; Kearney, M F; Proschan, M A; Mican, J M; Rehm, C A; Coffin, J M; Mellors, J W; Siliciano, R F; Maldarelli, F

    2009-06-09

    In HIV-1-infected individuals on currently recommended antiretroviral therapy (ART), viremia is reduced to <50 copies of HIV-1 RNA per milliliter, but low-level residual viremia appears to persist over the lifetimes of most infected individuals. There is controversy over whether the residual viremia results from ongoing cycles of viral replication. To address this question, we conducted 2 prospective studies to assess the effect of ART intensification with an additional potent drug on residual viremia in 9 HIV-1-infected individuals on successful ART. By using an HIV-1 RNA assay with single-copy sensitivity, we found that levels of viremia were not reduced by ART intensification with any of 3 different antiretroviral drugs (efavirenz, lopinavir/ritonavir, or atazanavir/ritonavir). The lack of response was not associated with the presence of drug-resistant virus or suboptimal drug concentrations. Our results suggest that residual viremia is not the product of ongoing, complete cycles of viral replication, but rather of virus output from stable reservoirs of infection.

  4. [Successful treatment of HIV-associated chronic inflammatory demyelinating polyneuropathy by early initiation of highly active anti-retroviral therapy].

    PubMed

    Kume, Kodai; Ikeda, Kazuyo; Kamada, Masaki; Touge, Tetsuo; Deguchi, Kazushi; Masaki, Tsutomu

    2013-01-01

    A 47-year-old man with HIV infection presented with lower leg dominant dysesthesia, muscle weakness and sensory ataxia of 3 month's duration. Nerve conduction studies (NCS) showed demyelination change in the median and tibial nerves and sensory nerve action potential (SNAP) in the sural nerve was not evoked. Somatosensory evoked potential (SEP) showed the delayed N9 latency. Diagnose of HIV-associated chronic inflammatory demyelinating polyneuropathy (CIDP) was made. Although the CD4 lymphocyte counts were relatively preserved (466/μl), highly active anti-retroviral therapy (HAART) was started according to a new guideline for the use of antiretroviral agents in HIV-1-infected adults and adolescents recommending early initiation of treatment. After six months, HIV1-RNA was not detected and the CD4 lymphocyte counts showed a recovering trend (585/μl). His symptoms had disappeared, except for dysesthesia in the tip of a toe. Repeated NCS demonstrated full recovery from the demyelination and appearance of SNAP in the sural nerve. The improvement of his symptoms and NCS findings has been maintained for two years. Although effectiveness of immunotherapies such as oral prednisone, high-dose immunoglobulins and plasmapheresis have been reported in HIV-associated CIDP, early initiation of HAART may be also important for favorable prognosis in HIV-associated CIDP.

  5. Cervical Shedding of HIV-1 RNA Among Women With Low Levels of Viremia While Receiving Highly Active Antiretroviral Therapy

    PubMed Central

    Neely, Michael N.; Benning, Lorie; Xu, Jiaao; Strickler, Howard D.; Greenblatt, Ruth M.; Minkoff, Howard; Young, Mary; Bremer, James; Levine, Alexandra M.; Kovacs, Andrea

    2011-01-01

    Background Among women with low o r undetectable quantities of HIV-1 RNA in plasma, factors associated with genital HIV-1 RNA shedding, including choice of treatment regimen, are poorly characterized. Methods We measured HIV-1 RNA in cervical swab specimens obtained from participants in the Women’s Interagency HIV Study who had concurrent plasma viral RNA levels <500 copies/mL, and we assessed factors associated with genital HIV shedding. The study was powered to determine the relative effects of antiretroviral protease inhibitors (PIs) versus nonnucleoside reverse transcriptase inhibitors (NNRTIs) on viral RNA shedding. Results Overall, 44 (15%) of 290 women had detectable HIV-1 RNA in cervical specimens. In the final multivariate model, shedding was independently associated with NNRTI (vs. PI) use (odds ratio [OR], 95% confidence interval [CI]: 2.24, 1.13 to 4.45) and illicit drug use (OR, 95% CI: 2.41, 0.96 to 5.69). Conclusions This is the largest study to define risks for genital HIV-1 RNA shedding in women with low/undetectable plasma virus. Shedding in this population was common, and NNRTI-based highly active antiretroviral therapy (HAART) (vs. PI-based HAART) was associated with genital HIV shedding. Further study is required to determine the impact of these findings on transmission of HIV from mother to child or to sexual partners. PMID:17106279

  6. The potential impact of highly active antiretroviral therapy on the treatment and epidemiology of ranula in human immunodeficiency virus-positive patients.

    PubMed

    Syebele, Kabunda; Munzhelele, Thifhelimbilu I

    2013-07-01

    The study's aim was to assess the potential therapeutic effect of highly active antiretroviral therapy (HAART) on ranulas in human immunodeficiency virus (HIV)-positive patients. The study includes a retrospective observation of 3 patients who were initially part of a prospective study on the comparative effect of HAART on ranulas in 14 HIV-positive patients. These patients were clinically monitored while pursuing the medical treatment with HAART. Neither a fine needle aspiration nor a surgical procedure was performed. Clinical photographs were used for monitoring of any reduction in the ranula size. The effect of HAART on ranula was assessed at 3, 6 and 12 month. A complete resolution of the ranula lesion was noticed in the 3 HIV-positive selected patients. These results were observed between 6 and 12 months period. This study suggests that HAART might present a potential therapeutic effect on ranula in HIV-positive patients. Copyright © 2013 Elsevier Inc. All rights reserved.

  7. Highly Active Antiretroviral Therapy versus Zidovudine for Prevention of Mother-to-Child Transmission in a Programmatic Setting, Botswana

    PubMed Central

    Dryden-Peterson, Scott; Jayeoba, Oluwemimo; Hughes, Michael D.; Jibril, Haruna; Keapoletswe, Koona; Tlale, Josephine; Modise, Taolo A.; Asmelash, Aida; Moyo, Sikhulile; van Widenfelt, Erik; Makhema, Joseph; Essex, Max; Shapiro, Roger L.; Lockman, Shahin

    2011-01-01

    Few studies have compared the programmatic effectiveness of the recommended strategies of antenatal highly-active antiretroviral therapy (HAART) and zidovudine for prevention of mother-to-child transmission (MTCT). We prospectively followed infants (93% formula-fed) whose mothers who took either HAART (258 infants) or zidovudine (170 infants) during pregnancy in the Botswana national program. Overall, 10 infants (2.5%) acquired HIV— 9 infants in the zidovudine group (5.5%, 95%CI 2.6-10.2%) and 1 infant in the HAART group (0.4%, 95%CI 0.0-2.2%). Maternal HAART was associated with decreased MTCT (P=0.001) and improved HIV-free survival (P=0.040) compared with zidovudine (with or without single-dose nevirapine) in a programmatic setting. PMID:21792062

  8. Use of atomic force microscopy to reveal sperm ultrastructure in HIV-patients on highly active antiretroviral therapy.

    PubMed

    Barboza, J M; Medina, H; Doria, M; Rivero, L; Hernandez, L; Joshi, N V

    2004-01-01

    Atomic force microscopy (AFM) has been employed to examine morphological and topographical changes caused by human immunodeficiency virus (HIV) and the effects of highly active antiretroviral therapy (HAART) on spermatozoon of HIV infected patients. This powerful technique has allowed us to visualize morphological alterations present in the spermatozoa of patients either with or without treatment. In addition to this, even the minute details, such as viral particles, located on the membrane of the spermatozoa, and the merging of such particles on the surface of the spermatozoa were detected with precision. The most important aspect is that AFM, unlike electron microscopy, permits to image virions in their nearly natural environment. Excess of damage of spermatozoon is due to the chemicals involved in HAART rather than the damage made by virus.

  9. Etiology and pharmacologic management of noninfectious diarrhea in HIV-infected individuals in the highly active antiretroviral therapy era.

    PubMed

    MacArthur, Rodger D; DuPont, Herbert L

    2012-09-01

    Diarrhea remains a common problem for patients with human immunodeficiency virus (HIV) infection despite highly active antiretroviral therapies (HAART) and can negatively affect patient quality of life and lead to discontinuation or switching of HAART regimens. In the era of HAART, diarrhea from opportunistic infections is uncommon, and HIV-associated diarrhea often has noninfectious causes, including HAART-related adverse events and HIV enteropathy. Diarrhea associated with HAART is typically caused by protease inhibitors (eg, ritonavir), which may damage the intestinal epithelial barrier (leaky-flux diarrhea) and/or alter chloride ion secretion (secretory diarrhea). HIV enteropathy may result from direct effects of HIV on gastrointestinal tract cells and on the gastrointestinal immune system and gut-associated lymphoid tissue, which may be active sites of HIV infection and ongoing inflammation and mucosal damage. New therapies targeting the pathogenic mechanisms of noninfectious diarrheas are needed.

  10. Prevalence of Anemia and Immunological Markers in HIV-Infected Patients on Highly Active Antiretroviral Therapy in Northeastern Nigeria

    PubMed Central

    Denue, Ballah Akawu; Kida, Ibrahim Musa; Hammagabdo, Ahmed; Dayar, Ayuba; Sahabi, Mohammed Abubakar

    2013-01-01

    Background There are conflicting reports on the impact of highly active antiretroviral therapy (HAART) in resolving hematological complications. Whereas some studies have reported improvements in hemoglobin and other hematological parameters resulting in reduction in morbidity and mortality of HIV patients, others have reported no improvement in hematocrit values of HAART-treated HIV patients compared with HAART-naïve patients. Objective This current study was designed to assess the impact of HAART in resolving immunological and hematological complications in HIV patients by comparatively analyzing the results (immunological and hematological) of HAART-naive patients and those on HAART in our environment. Methods A total of 500 patients participated, consisting of 315 HAART-naive (119 males and 196 females) patients and 185 HAART-experienced (67 males and 118 females) patients. Hemoglobin (Hb), CD4+ T-cell count, total white blood count (WBC), lymphocyte percentage, plateletes, and plasma HIV RNA were determined. Results HAART-experienced patients were older than their HAART-naive counterparts. In HAART-naive patients, the incidence of anemia (packed cell volume [PCV] <30%) was 57.5%, leukopenia (WBC < 2.5), 6.1%, and thrombocytopenia < 150, 9.6%; it was, significantly higher compared with their counterparts on HAART (24.3%, 1.7%, and 1.2%, respectively). The use of HAART was not associated with severe anemia. Of HAART-naive patients, 57.5% had a CD4 count < 200 cells/μL in comparison with 20.4% of HAART-experienced patients (P < 0.001). The mean viral load log10 was significantly higher in HAART-naive than in HAART-experienced patients (P < 0.001). Total lymphocyte count < 1.0 was a significant predictor of observed in HAART-experienced patients. Conclusion HAART has the capability of reducing the incidence of anemia, other deranged hematological and immunological parameters

  11. Effectiveness of highly active antiretroviral therapy among HIV-1 infected women

    PubMed Central

    Gange, S; Barron, Y; Greenblatt, R; Anastos, K; Minkoff, H; Young, M; Kovacs, A; Cohen, M; Meyer, W; Munoz, A

    2002-01-01

    Design: Data collected from the Women's Interagency HIV Study, a prospective cohort study that enrolled women between October 1994 and November 1995. Setting: Six clinical consortia based in five cities in the United States (New York, NY; Washington, DC; Los Angeles, CA; San Francisco, CA; and Chicago, IL). Participants: A total of 1691 HIV seropositive women with a study visit after April 1996. Main results: Beginning in April 1996, the self reported use of HAART increased over time, with more than 50% of the cohort reporting HAART use in 1999. There was a 23% decline per semester in the incidence of AIDS from April 1996 (95% confidence intervals (CI) -29% to -16%). Furthermore, there was a 21% decline of the semiannual mortality rates among those with AIDS at baseline (95% CI -27% to -14%) and an 11% decline among those AIDS free at baseline (95% CI -3% to -18%). CD4+ lymphocyte counts either increased (women with baseline AIDS) or stabilised (women without baseline AIDS) after April 1996, and HIV RNA levels dramatically declined in both groups, although the percentage of women with HIV RNA above 4000 cps/ml remained stable at approximately 40% since mid-1997. Conclusions: Despite concerns regarding the use of antiretroviral therapies in this population, the use of therapies led to improved immunological function, suppressed HIV disease activity, and dramatic declines in morbidity and mortality. PMID:11812817

  12. Disease-modifying therapeutic concepts for HIV in the era of highly active antiretroviral therapy.

    PubMed

    Butler, Scott L; Valdez, Hernan; Westby, Michael; Perros, Manos; June, Carl H; Jacobson, Jeffrey M; Levy, Yves; Cooper, David A; Douek, Daniel; Lederman, Michael M; Tebas, Pablo

    2011-11-01

    Chronic HIV infection is associated with persistent immune activation and inflammation even among patients virologically suppressed on antiretroviral therapy for years. Chronic immune activation has been associated with poor outcomes--both AIDS-defining and non-AIDS-defining clinical events--and persistent CD4 T-cell depletion. The cause of chronic immune activation in well-controlled HIV infection is unknown. Proposed drivers include residual viral replication, microbial translocation, and coinfecting pathogens. Therapeutic interventions targeting immune activation are emerging, from approaches that interfere directly with activation and inflammatory pathways to those that prevent microbial translocation or decrease the availability of host target cells for the virus. In the context of the disappointing results of the interleukin-2 trials, the main challenges to developing these disease-modifying therapies include identifying an adequate target population and choosing surrogate endpoints that will provide positive proof-of-concept that the interventions will translate into long-term clinical benefit before embarking on large clinical endpoint trials.

  13. Recognizing cognitive and psychiatric changes in the post-highly active antiretroviral therapy era

    PubMed Central

    Carvalhal, Adriana; Baril, Jean-Guy; Crouzat, Frederic; De Wet, Joss; Junod, Patrice; Kovacs, Colin; Sheehan, Nancy

    2012-01-01

    Amid numerous complications that plague the health and quality of life of people living with HIV, neurocognitive and psychiatric illnesses pose unique challenges. While there remains uncertainty with respect to the pathophysiology surrounding these disorders, their adverse implications are increasingly recognized. Left undetected, they have the potential to significantly impact patient well being, adherence to antiretroviral treatment and overall health outcomes. As such, early identification of HIV-associated neurocognitive disorders (HAND) and psychiatric illnesses will be paramount in the proactive management of affected patients. The present review focuses on strategies to ensure optimal screening and detection of HAND, depression and substance abuse in routine practice. For each topic, currently available screening methods are discussed. These include identification of risk factors, recognition of relevant symptomatology and an update on validated screening tools that can be efficiently implemented in the clinical setting. Specifically addressed in the present review are the International HIV Dementia Scale, a novel screening equation and algorithm for HAND, as well as brief, validated, verbal questionnaires for detection of depression and substance abuse. Adequate understanding and usage of these screening mechanisms can ensure effective use of resources by distinguishing patients who require referral for more extensive diagnostic procedures from those who likely do not. PMID:24294277

  14. Relationship of Postprandial Nonesterified Fatty Acids, Adipokines, and Insulin Across Gender in Human Immunodeficiency Virus–Positive Patients Undergoing Highly Active Antiretroviral Therapy

    PubMed Central

    Lu, Guijing; Thomas-Geevarghese, Asha; Anuurad, Erdembileg; Raghavan, Subhashree; Minolfo, Robert; Ormsby, Bernard; Karmally, Wahida; El-Sadr, Wafaa M.; Albu, Jeanine

    2009-01-01

    Abstract Background Metabolic derangements are common in human immunodeficiency virus (HIV)-positive subjects undergoing antiretroviral therapy, but little is known about postprandial conditions. Methods We investigated the relationship between leptin, adiponectin, nonesterified fatty acids (NEFA), and insulin in response to a day-long meal pattern and evaluated gender differences in HIV-positive men (n = 12) and women (n = 13) undergoing highly active antiretroviral therapy (HAART). Results For both men and women, a significant decrease in postprandial NEFA levels was observed following breakfast (0.53 vs. 0.22 mmol/L, P < 0.001, baseline and at 3 hours, respectively), whereas day-long postprandial leptin and adiponectin levels showed small nonsignificant oscillations. In contrast to NEFA and adiponectin, postprandial leptin levels were significantly higher among women compared to men (P < 0.05). Postprandial NEFA levels correlated positively with fasting insulin levels (r2 = 0.25, P = 0.016), and the postbreakfast decrease in NEFA levels correlated significantly with the postbreakfast increase in insulin levels (r2 = 0.17, P = 0.038). No significant association between postprandial adipokines and insulin was observed. Conclusions In HAART-treated, HIV-infected men and women, levels of NEFA, but not adipokines, showed significant postprandial variation. Furthermore, food intake resulted in significant NEFA suppression in proportion to the food-stimulated insulin increase. PMID:19320559

  15. 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

  16. Renal manifestations of HIV infected highly active antiretroviral therapy naive children in India.

    PubMed

    Shah, Ira; Gupta, Shradha; Shah, Dhaval M; Dhabe, Harshal; Lala, Mamatha

    2012-08-01

    There are several studies on renal manifestations in human immunodeficiency virus (HIV) infected children from American and African regions, but similar studies from India are lacking. A cross-sectional study was carried out in 28 HIV infected antiretroviral therapy (ART) naïve children coming to the pediatric HIV clinic. Demographic data of the children, clinical presentations including blood pressure, detailed laboratory investigations (serum creatinine, glomerular filtration rate), urine analysis (urine morphology, urine albumin, pus cells, and red blood cells), and CD4 counts were collected. Of the 28 children, 15 (53.6%) had renal manifestations with a male to female ratio of 1:1.5. The most common renal manifestation in our study was abnormal glomerular filtration rate (GFR) in 11 (44.0%) of 25 children. This was followed by pus cells in urine in 6 (21.4%) of the 28 children while 3 (10.7%) of them had proteinuria. The mean age of children with renal manifestations was 5.04±2.75 years as compared to those without renal manifestations who had a mean age of 7.38±2.95 years (P=0.0390). CDC class and sex were not associated with renal manifestations. Our study suggests that reduced GFR is the common renal manifestation, particularly in younger children. Other renal manifestations are related to proteinuria. The lack of correlation of CDC classification with renal manifestations mandates screening of children with HIV for renal disease. A more detailed study of renal manifestations in HIV-infected children is needed.

  17. Successful administration of aggressive chemotherapy concomitant to tuberculostatic and highly active antiretroviral therapy in a patient with AIDS-related Burkitt's lymphoma.

    PubMed

    Lehmann, C; Wyen, C; Hoffmann, C; Fätkenheuer, G

    2005-01-01

    Treatment of AIDS-related malignant lymphoma (ARL) remains a therapeutic challenge. There are concerns not only about infectious and haematological complications in HIV-infected patients during intensive chemotherapy, but also about potential interactions between chemotherapy and highly active antiretroviral therapy (HAART). Current data on patients treated concomitantly with intensive chemotherapy and HAART are limited, and no data exist on patients with ARL suffering from active opportunistic infections. We report the case of a 38-year-old man with advanced HIV-1 infection, pulmonary tuberculosis and Burkitt's lymphoma. Intensive chemotherapy was administered in parallel with tuberculostatic therapy and HAART. Six months later, the patient achieved not only a complete remission of Burkitt's lymphoma and sustained viral suppression, but also a full recovery from tuberculosis. This case report provides some useful observations on the successful application of intensive chemotherapy in addition to tuberculostatic therapy and HAART in HIV-infected patients.

  18. Effects of highly active antiretroviral therapy with nelfinavir in vertically HIV-1 infected children: 3 years of follow-up. Long-term response to nelfinavir in children

    PubMed Central

    Resino, Salvador; Larrú, Beatriz; Ma Bellón, Jose; Resino, Rosa; de José, Ma Isabel; Navarro, Marisa; Léon, Juan Antonio; Ramos, José Tomás; Mellado, Ma José; Muñoz-Fernández, Ma Ángeles

    2006-01-01

    Background Antiretroviral treatment (ART) in children has special features and consequently, results obtained from clinical trials with antiretroviral drugs in adults may not be representative of children. Nelfinavir (NFV) is an HIV-1 Protease Inhibitor (PI) which has become as one of the first choices of PI for ART in children. We studied during a 3-year follow-up period the effects of highly active antiretroviral therapy with nelfinavir in vertically HIV-1 infected children. Methods Forty-two vertically HIV-infected children on HAART with NFV were involved in a multicentre prospective study. The children were monitored at least every 3 months with physical examinations, and blood sample collection to measure viral load (VL) and CD4+ cell count. We performed a logistic regression analysis to determinate the odds ratio of baseline characteristics on therapeutic failure. Results Very important increase in CD4+ was observed and VL decreased quickly and it remained low during the follow-up study. Children with CD4+ <25% at baseline achieved CD4+ >25% at 9 months of follow-up. HIV-infected children who achieved undetectable viral load (uVL) were less than 40% in each visit during follow-up. Nevertheless, HIV-infected children with VL >5000 copies/ml were less than 50% during the follow-up study. Only baseline VL was an important factor to predict VL control during follow-up. Virological failure at defined end-point was confirmed in 30/42 patients. Along the whole of follow-up, 16/42 children stopped HAART with NFV. Baseline characteristics were not associated with therapeutic change. Conclusion NFV is a safe drug with a good profile and able to achieve an adequate response in children. PMID:16834769

  19. Decreased Specificity of an Assay for Recent Infection in HIV-1-Infected Patients on Highly Active Antiretroviral Treatment: Implications for Incidence Estimates

    PubMed Central

    Chaillon, Antoine; Le Vu, Stéphane; Brunet, Sylvie; Gras, Guillaume; Bastides, Frédéric; Bernard, Louis; Meyer, Laurence

    2012-01-01

    The aim of this study was to estimate the rate of misclassification in treated HIV patients who initiated treatment at the chronic stage of HIV infection using an enzyme immunoassay (EIA) that discriminates between recent infection (RI; within 6 months) and established infection. The performance of EIA-RI was evaluated in 96 HIV-1 chronically infected patients on highly active antiretroviral therapy (HAART) with an undetectable viral load (VL) for at least 3 years. Demographic data, HIV-1 viral load, CD4+ T-cell count, viral subtype, and treatment duration were collected. The subset of misclassified patients was further analyzed using samples collected annually. The impact on incidence estimates was evaluated by simulation. The specificity in treated patients was significantly lower (70.8 to 77.1%) than that observed in untreated patients (93.3 to 99.3%, P < 0.001). Patients falsely classified as recently infected had been treated for a longer period and had longer-term viral suppression than those correctly classified. The loss of specificity of the test due to treatment may have a dramatic impact on the accuracy of the incidence estimates, with a major impact when HIV prevalence is high. The cross-sectional studies intended to derive HIV incidence must collect information on treatment or, alternatively, should include detection of antiretroviral drugs in blood specimens to rule out treated patients from the calculations. PMID:22718132

  20. Predictors of Suboptimal Virologic Response to Highly Active Antiretroviral Therapy Among Human Immunodeficiency Virus-Infected Adolescents

    PubMed Central

    Ding, Helen; Wilson, Craig M.; Modjarrad, Kayvon; McGwin, Gerald; Tang, Jianming; Vermund, Sten H.

    2013-01-01

    Objective To examine the prevalence and biopsychosocial predictors of sub-optimal virologic response to highly active antiretroviral therapy (HAART) among human immunodeficiency virus (HIV)-infected adolescents. Design Population-based cohort study. Setting Sixteen academic medical centers across thirteen cities in the United States. Participants One hundred and fifty four HIV-infected adolescents who presented for at least two consecutive visits after initiation of HAART. Main Outcome Measures Viral load (plasma concentration of HIV RNA), CD4+ T-lymphocyte count. Results Of the 154 adolescents enrolled in the study, 50 (32.5%) demonstrated early and sustained virologic suppression while receiving HAART. The remaining 104 adolescents (67.5%) had a poor virologic response. Adequate adherence (>50%) to HAART—reported by 70.8% of respondents—was associated with a 60% reduced odds of suboptimal virologic suppression in a multivariable logistic regression model (adjusted odds ratio = 0.4; 95% confidence interval : 0.2 – 1.0). Exposure to sub-optimal antiretroviral therapy (ART) prior to HAART, on the other hand, was associated with more than a two-fold increased odds of sub-optimal virologic response (adjusted odds ratio = 2.6; 95% confidence interval: 1.1 – 5.7). Conclusions Fully two-thirds of HIV-infected adolescents in the current study demonstrated a sub-optimal virologic response to HAART. Non-adherence and prior single or dual ART were associated with subsequent poor virologic responses to HAART. These predictors of HAART failure echo findings in pediatric and adult populations. Given the unique developmental stage of adolescence, age-specific interventions are indicated to address high rates of non-adherence and therapeutic failure. PMID:19996046

  1. Maternal Highly Active Antiretroviral Therapy Reduces Vertical Cytomegalovirus Transmission But Does Not Reduce Breast Milk Cytomegalovirus Levels.

    PubMed

    Slyker, Jennifer A; Richardson, Barbra; Chung, Michael H; Atkinson, Claire; Ásbjörnsdóttir, Kristjana H; Lehman, Dara A; Boeckh, Michael; Emery, Vincent; Kiarie, James; John-Stewart, Grace

    2017-04-01

    To evaluate the impact of highly active antiretroviral therapy (HAART) on CMV transmission and breast milk level in the context of maternal HIV. Specimens from a randomized trial conducted in Nairobi, Kenya between 2003-2005 were used to compare CMV transmission and breast milk levels between mother-infant pairs randomized to HAART versus short-course antenatal zidovudine plus single-dose nevirapine (ZDV/sdNVP) for prevention of mother-to-child HIV transmission (PMTCT). Fifty-one antiretroviral-naïve women ≤32 weeks gestation, and CD4 between 200-500 cells/mm(3) were randomized at 34 weeks to begin either antenatal ZDV/sdNVP, or HAART through 6 months postpartum. Mean breast milk CMV levels and transmission were compared between arms. Age, sociodemographics, CD4%, and HIV plasma RNA viral load were similar between arms at baseline. CMV viral loads were measured from 243 infant plasma and 185 breast milk specimens during the first year postpartum. The probability of infant CMV infection at 12 months was 19% lower in the HAART arm compared to ZDV/sdNVP (75% vs. 94%, p = .04). All women had CMV detected in breast milk, with 72%, 98%, and 97% testing positive during the first, second, and third weeks postpartum, respectively. There was a trend for early higher mean breast milk CMV level in the HAART arm at 1 week (p = .08), and there was significantly slower decline in breast milk CMV levels (area under the curve, p = .01). HAART started during the third trimester may decrease infant CMV infections, by mechanisms independent of breast milk CMV levels.

  2. Quality of life of people living with HIV/AIDS and on highly active antiretroviral therapy in Ethiopia.

    PubMed

    Abera, Kebede; Gedif, Teferi; Engidawork, Ephrem; Gebre-Mariam, Tsige

    2010-04-01

    The Amharic version of the Short Form-36 Health Survey (SF-36) was used to measure quality of life among patients on highly active antiretroviral therapy (HAART) at selected governmental hospitals in central and southern Ethiopia. The study was cross-sectional and used SF-36-specific software for automatic scoring of the form's scales and dimensions. Pearson bivariate correlations showed moderate correlation between the SF-36 scales, ranging from 0.2673 between 'general health' and 'vitality,' to 0.8583 between 'role physical' and 'role emotional.' Cronbach's-αwas >0.70 for six out of eight multi-item scales, with values ranging from 0.6500 to 0.8860 for all scales, thus indicating good internal reliability of the Amharic version of the SF-36. The independent variables shown to positively affect mean scores were: duration of treatment, CD4 cell count, and adherence to doses of antiretrovirals. Participants treated for >12 months had higher mean scores for all domains than those who had been treated for ≤12 months. Likewise, those with a CD4 cell count >200 cells/mm(3) had better mean scores for all scales except 'social functioning' and 'mental health' than those with counts ≤200. Participants adhering to treatment (in the last 15 days, according to self-report) had better mean scores for all scales except 'role physical,' 'bodily pain' and 'vitality' in comparison to those who were not adherent. The findings suggest that the Amharic version of the SF-36 is a valid and reliable health survey instrument for use in Ethiopia to assess the quality of life of people living with HIV/AIDS on HAART.

  3. A therapeutic HIV-1 vaccine enhances anti-HIV-1 immune responses in patients under highly active antiretroviral therapy.

    PubMed

    Tung, Frank Y; Tung, Jack K; Pallikkuth, Suresh; Pahwa, Savita; Fischl, Margaret A

    2016-04-27

    HIV-1 specific cellular immunity plays an important role in controlling viral replication. In this first-in-human therapeutic vaccination study, a replication-defective HIV-1 vaccine (HIVAX) was tested in HIV-1 infected participants undergoing highly active antiretroviral therapy (HAART) to enhance anti-HIV immunity (Clinicaltrials.gov, identifier NCT01428596). A010 was a randomized, placebo-controlled trial to evaluate the safety and the immunogenicity of a replication defective HIV-1 vaccine (HIVAX) given as a subcutaneous injection to HIV-1 infected participants who were receiving HAART with HIV-1 viral load <50 copies/ml and CD4 cell count >500 cells/mm(3). HIV-1 specific immune responses were monitored by INF-γ enzyme linked immunospot (Elispot) and intracellular cytokine staining (ICS) assay after vaccination. Following the randomized placebo-controlled vaccination phase, subjects who received HIVAX vaccine and who met eligibility underwent a 12-week analytical antiretroviral treatment interruption (ATI). Viral load was monitored throughout the study. HIVAX was well tolerated in trial participants. Transient grade 1 to 2 (mild to moderate) injection site reactions occurred in 8 of 10 vaccinated participants. HIVAX was immunogenic in all vaccinated participants. The functionality of T cells was significantly enhanced after vaccination. Median viral load (3.45 log10 copies/ml, range of 96-12,830 copies/ml) at the end of the 12-week treatment interruption in HIVAX vaccinated group was significantly lower than the pre-treatment levels. Three vaccinated participants extended ATI for up to 2 years with stable CD4 cells and low viral loads. HIVAX vaccine is generally safe, elicits strong anti-HIV-1 immune responses, and may play an important role in controlling viral load during treatment interruption in HIV-1 infected participants. Copyright © 2016 Elsevier Ltd. All rights reserved.

  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. 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…

  6. Immunoglobulin G(κ) [IgG(κ)] and IgG(λ) Paraproteinemia in a Child with AIDS and Response to Highly Active Antiretroviral Therapy

    PubMed Central

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

    2005-01-01

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

  7. Evaluation of incidence of zidovudine induced anemia in Indian human immunodeficiency virus positive patients in comparison with stavudine based highly active antiretroviral therapy.

    PubMed

    Rajesh, Radhakrishnan; Vidyasagar, Sudha; Varma, Danturulu Muralidhar; Mohiuddin, Shabaz; Noorunnisa

    2011-01-01

    In patients infected with human immunodeficiency virus (HIV), zidovudine has been known to cause a severe anemia that resolves promptly when the drug is stopped. The study was aimed to assess the incidence, the pattern of occurrence of zidovudine induced anemia, causality, severity, predictability, preventability and to identify risk factors for zidovudine induced anemia in Indian HIV positive patients in comparision with stavudine based highly active antiretroviral therapy (HAART). This was a prospective observational study conducted over a period of 6 months by clinical pharmacists. Enrolled HIV positive patients were intensively monitored for zidovudine and stavudine induced anemia. zidovudine and stavudine fixed dose drug combinations of antiretroviral therapy (ART) were only included. The World Health Organization (WHO)/AIDS Clinical Trials Group (ACTG) definition of a severity grading of anemia was adopted. Each reported case of zidovudine and stavudine induced anemia was assessed for its causality by using the WHO probability scale and also with Naranjo's algorithm. Preventability was assessed using Schumock and Thornton criteria and severity was assessed using the modified Hartwig and Siegel scale. Multivariate logistic regression was used to evaluate the influence of zidovudine induced anemia. P-value < 0.05 was considered as statistically significant. Monitoring of ninety eight HIV positive patients with fixed dose highly active antiretroviral therapy identified 19 cases of zidovudine induced anemia and 2 cases of stavudine induced anemia from 55 and 43 patients respectively. Incidence of zidovudine induced anemia in intensively monitored HIV positive patients was found to be 34.5%. Chi Square tests identified statistically significant incidence differences of anemia (p < 0.05) between the zidovudine group and the stavudine group. Grade 2 and grade 4 anemia accounted for 42.1%. Causality was 'probable' by WHO probability scale and 'definite' and 'probable

  8. 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

  9. Imported Acquired Immunodeficiency Syndrome–Related Histoplasmosis in Metropolitan France: A Comparison of Pre–Highly Active Anti-Retroviral Therapy and Highly Active Anti-Retroviral Therapy Eras

    PubMed Central

    Peigne, Vincent; Dromer, Françoise; Elie, Caroline; Lidove, Olivier; Lortholary, Olivier

    2011-01-01

    Histoplasma capsulatum var. capsulatum infection is rare outside disease-endemic areas. Clinical presentation and outcome of acquired immunodeficiency syndrome–related histoplasmosis are unknown in non-endemic areas with wide access to highly active anti-retroviral therapy (HAART). Retrospective analysis of cases recorded at the French National Reference Center for Mycoses and Antifungals during two decades: pre-HAART (1985–1994) and HAART (1997–2006). Clinical features and outcome of all adults with proven acquired immunodeficiency syndrome–related histoplasmosis were compared between the two periods. One hundred four patients were included (40 during the pre-HAART era and 64 during the HAART era). Diagnosis was established a mean of 62 days after onset of symptoms. One-year overall mortality rates decreased from 53% (pre-HAART era) to 22% (HAART era). Diagnosis during the pre-HAART era and an older age were the only independent factors associated with death. Histoplasmosis is a rare invasive fungal infection outside disease-endemic areas. Its prognosis improved significantly during the HAART era. PMID:22049053

  10. Imported acquired immunodeficiency syndrome-related histoplasmosis in metropolitan France: a comparison of pre-highly active anti-retroviral therapy and highly active anti-retroviral therapy eras.

    PubMed

    Peigne, Vincent; Dromer, Françoise; Elie, Caroline; Lidove, Olivier; Lortholary, Olivier

    2011-11-01

    Histoplasma capsulatum var. capsulatum infection is rare outside disease-endemic areas. Clinical presentation and outcome of acquired immunodeficiency syndrome-related histoplasmosis are unknown in non-endemic areas with wide access to highly active anti-retroviral therapy (HAART). Retrospective analysis of cases recorded at the French National Reference Center for Mycoses and Antifungals during two decades: pre-HAART (1985-1994) and HAART (1997-2006). Clinical features and outcome of all adults with proven acquired immunodeficiency syndrome-related histoplasmosis were compared between the two periods. One hundred four patients were included (40 during the pre-HAART era and 64 during the HAART era). Diagnosis was established a mean of 62 days after onset of symptoms. One-year overall mortality rates decreased from 53% (pre-HAART era) to 22% (HAART era). Diagnosis during the pre-HAART era and an older age were the only independent factors associated with death. Histoplasmosis is a rare invasive fungal infection outside disease-endemic areas. Its prognosis improved significantly during the HAART era.

  11. Safety and Effectiveness of Highly Active Antiretroviral Therapy in Treatment-Naïve HIV Patients: Preliminary Findings of a Cohort Event Monitoring Study in Belarus.

    PubMed

    Setkina, Svetlana; Dotsenko, Marina; Bondar, Sviatlana; Charnysh, Iryna; Kuchko, Alla; Kaznacheeva, Alena; Kozorez, Elena; Dodaleva, Alena; Rossa, Natalia

    2015-04-01

    Antiretroviral drugs have well-documented evidence-based favorable benefit-risk ratios. Although various studies have investigated and characterized the safety profile of antiretroviral medicines, there are a limited number of studies evaluating the safety of first-line antiretroviral therapy (ART) in patients with a specific co-morbidity. A cohort event monitoring (CEM) study of the safety and effectiveness of antiretroviral medicines in a target population that has a significant level of co-morbidities (chronic infectious diseases, peripheral blood cytopenias) was implemented. The aim was to evaluate the safety profile of the highly active ART (HAART) in the target population and subpopulations with risk factors, to optimize the monitoring and decision-making procedure for subgroups of patients with specific types of co-morbidity, and to implement a more vigilant approach to therapy management in risk groups of patients. Prospective observational CEM was implemented among HAART-naïve HIV-positive patients at four clinical sites from December 2012. Eligible patients were those starting first-line HAART. Close medical supervision of all enrolled patients, with regular clinical and laboratory monitoring, was provided by healthcare professionals within 1 year after commencement of therapy. Standardized forms were used for data collection on initial and subsequent visits. All objective or subjective deviations in condition (events) were assessed for a causal relationship with ART, and for severity, seriousness, reversibility, preventability, and pre-existing risk factors in the case of adverse drug reactions (ADRs). A total of 518 HAART-naïve HIV-positive patients were enrolled in the CEM study. Of these patients, 65% (337) experienced one or several ADRs related to one or more components of HAART. Most of the ADRs reported were non-serious, expected, common (very common), transient (correctable), or reversible. The most common were hematotoxic, hepatotoxic, and

  12. Prevalence of lipodystrophy and metabolic syndrome among HIV positive individuals on Highly Active Anti-Retroviral treatment in Jimma, South West Ethiopia

    PubMed Central

    Berhane, Tsegay; Yami, Alemishet; Alemseged, Fessahaye; Yemane, Tilahun; Hamza, Leja; Kassim, Mehedi; Deribe, Kebede

    2012-01-01

    Introduction Use of highly active antiretroviral therapy has led to significant reductions in morbidity and mortality rates. However, these agents had also given rise to the metabolic and morphologic abnormalities which are modifiable risk factors for cardiovascular diseases. Evidences elsewhere indicate growing in prevalence of these problems but studies are lacking in Ethiopia. This study was conducted to determine the prevalence of HIV-associated lipodystrophy and metabolic syndrome in patients taking highly active antiretroviral therapy. Methods A cross-sectional study was conducted in 2010 on a sample of 313 patients taking highly active antiretroviral therapy in Jimma University specialized hospital. Structured questionnaire was used to assess patients’ sociodemographic characteristics and clinical manifestations of metabolic abnormalities. Checklists were used for reviewing charts about clinical manifestations of metabolic abnormalities and immunologic profile of patients. Data was cleaned, entered in and analyzed using SPSS for windows version 16.0. Results Metabolic syndrome was detected in 21.1% and HIV-lipodystrophy was detected 12.1% of patients. The factors found to be independently associated with metabolic syndrome were taking the antiretroviral therapy for more than 12 months (AOR=4.2; 95% CI=1.24–14.23) and female sex (AOR=2.30; 95% CI=1.0–5.27) and the factor found to be independently associated with HIV-lipodystrophy was taking the antiretroviral therapy (AOR=3.59; 95% CI=1.03–12.54) for more than 12 months. Conclusion Metabolic abnormalities were relatively common in the study population. The problems were higher among those who took anti-retroviral treatment for longer duration. Therefore, regular screening for and taking action against the metabolic abnormalities is mandatory. PMID:23330034

  13. Reaping the prevention benefits of highly active antiretroviral treatment: policy implications of HIV Prevention Trials Network 052.

    PubMed

    Forsyth, Andrew D; Valdiserri, Ronald O

    2012-03-01

    This review explores the policy implications of findings from the HIV Prevention Trials Network (HPTN 052) treatment as prevention (TasP) study. To date, the potential of antiretrovirals to prevent sexual transmission of HIV by infected persons has been grounded in observational cohort, ecological, mathematical modeling, and meta-analytic studies. HPTN 052 represents the first randomized controlled trial to test the secondary prevention benefit of HIV transmission using antiretroviral treatment in largely asymptomatic persons with high CD4 cell counts. The US National HIV/AIDS Strategy has among its key goals the reduction of incident HIV infections, improved access to quality care and associated outcomes, and the reduction in HIV-associated health disparities and inequities. HPTN 052 demonstrates that providing TasP, in combination with other effective prevention strategies offers the promise of achieving these life-saving goals. But HPTN 052 also highlights the need for cautious optimism and underscores the importance of addressing current gaps in the HIV prevention, treatment, and care continuum in order for 'TasP' strategies to achieve their full potential. Among these are necessary improvements in the capacity to expand HIV testing, facilitate effective linkage and retention in care, and improve treatment initiation, maintenance, and virus suppression.

  14. Toxoplasmic encephalitis in an AIDS cohort at Puerto Rico before and after highly active antiretroviral therapy (HAART).

    PubMed

    Mayor, Angel M; Fernández Santos, Diana M; Dworkin, Mark S; Ríos-Olivares, Eddy; Hunter-Mellado, Robert F

    2011-05-01

    Highly active antiretroviral therapy (HAART) significantly reduced the toxoplasmic encephalitis (TE) incidence in acquired immunodeficiency syndrome (AIDS) patients. The TE incidence and mortality were evaluated in an AIDS cohort followed in Puerto Rico before, during, and after HAART implementation in the Island. Of the 2,431 AIDS studied patients 10.9% had TE diagnosis, with an incidence density that decreased from 5.9/100 person-years to 1.1/100 person-years after HAART. Cox proportional hazard analysis showed substantial mortality reduction among TE cases who received HAART. No mortality reduction was seen in those cases who received TE prophylaxis. Although this study shows a TE incidence and mortality reduction in the AIDS cohort after HAART, the incidence was higher than those reported in the United States AIDS patients. Poor TE prophylaxis compliance might explain the lack of impact of this intervention. Strengthening the diagnostic and opportune TE diagnosis and prompt initiation of HAART in susceptible patients is important to control this opportunistic infection.

  15. Prolonged control of replication-competent dual- tropic human immunodeficiency virus-1 following cessation of highly active antiretroviral therapy.

    PubMed

    Salgado, Maria; Rabi, S Alireza; O'Connell, Karen A; Buckheit, Robert W; Bailey, Justin R; Chaudhry, Amina A; Breaud, Autumn R; Marzinke, Mark A; Clarke, William; Margolick, Joseph B; Siliciano, Robert F; Blankson, Joel N

    2011-12-05

    While initiation of highly active antiretroviral therapy (HAART) during primary HIV-1 infection occasionally results in transient control of viral replication after treatment interruption, the vast majority of patients eventually experience a rebound in plasma viremia. Here we report a case of a patient who was started on HAART during symptomatic primary infection and who has subsequently maintained viral loads of < 50 copies/mL for more than nine years after the cessation of treatment. This patient had a high baseline viral load and has maintained a relatively high frequency of latently infected CD4(+) T cells. In addition, he does not have any known protective HLA alleles. Thus it is unlikely that he was destined to become a natural elite controller or suppressor. The mechanism of control of viral replication is unclear; he is infected with a CCR5/CXCR4 dual-tropic virus that is fully replication-competent in vitro. In addition, his spouse, who transmitted the virus to him, developed AIDS. The patient's CD4(+) T cells are fully susceptible to HIV-1 infection, and he has low titers of neutralizing antibodies to heterologous and autologous HIV-1 isolates. Furthermore, his CD8(+) T cells do not have potent HIV suppressive activity. This report suggests that some patients may be capable of controlling pathogenic HIV-1 isolates for extended periods of time after the cessation of HAART through a mechanism that is distinct from the potent cytotoxic T lymphocyte (CTL) mediated suppression that has been reported in many elite suppressors.

  16. Could low level laser therapy and highly active antiretroviral therapy lead to complete eradication of HIV-1 in vitro?

    NASA Astrophysics Data System (ADS)

    Lugongolo, Masixole Yvonne; Manoto, Sello Lebohang; Ombinda-Lemboumba, Saturnin; Maaza, Malik; Mthunzi-Kufa, Patience

    2017-02-01

    Human immunodeficiency virus (HIV-1) infection remains a major health problem despite the use of highly active antiretroviral therapy (HAART), which has greatly reduced mortality rates. Due to the unavailability of an effective vaccine or a treatment that would completely eradicate the virus, the quest for new and combination therapies continues. In this study we explored the influence of Low Level Laser Therapy (LLLT) in HIV-1 infected and uninfected cells. Literature reports LLLT as widely used to treat different medical conditions such as diabetic wounds, sports injuries and others. The technique involves exposure of cells or tissue to low levels of red and near infrared laser light. Both HIV infected and uninfected cells were laser irradiated at a wavelength of 640 nm with fluencies ranging from 2 to 10 J/cm2 and cellular responses were assessed 24 hours post laser treatment. In our studies, laser therapy had no inhibitory effects in HIV-1 uninfected cells as was indicated by the cell morphology and proliferation results. However, laser irradiation enhanced cell apoptosis in HIV-1 infected cells as the laser fluencies increased. This led to further studies in which laser irradiation would be conducted in the presence of HAART to determine whether HAART would minimise the detrimental effects of laser irradiation in infected cells.

  17. [Successful treatment with hyper-CVAD and highly active anti-retroviral therapy (HAART) for AIDS-related Burkitt lymphoma].

    PubMed

    Suzuki, Kazuhito; Nakazato, Tomonori; Sanada, Yukinari; Mihara, Ai; Tachikawa, Natsuo; Kurai, Hanako; Yoshimura, Yukihiro; Hayashi, Hiroyuki; Yoshida, Sachiko; Kakimoto, Tsunayuki

    2010-03-01

    A 38-year-old man was admitted to our hospital because of continuous fever and right facial palsy. He was diagnosed as HIV positive. Abdominal CT scan showed a large mass in the ascending colon. Gallium scintigraphy demonstrated increased uptake in the ascending colon. Colonoscopy was performed and histological examination of the colon tumor revealed Burkitt's lymphoma (BL). He received highly active anti-retroviral therapy (HAART) and his facial palsy improved. Because CD4 count was significantly low at 31/microl, he was treated with dose-adjusted EPOCH (DA-EPOCH) combined with HAART. Although the tumor was decreased in size by DA-EPOCH, we changed to the combination of hyper-CVAD/MTX-Ara-C alternating therapy with HAART in order to increase dose intensity. Six cycles of hyper-CVAD/MTX-Ara-C were performed and complete remission was obtained. In the HAART era, the survival of patients with AIDS-related diffuse large cell lymphoma (DLCL) improved dramatically, whereas the survival of similarly treated patients with AIDS-related BL remained poor. Our case suggests that intensive chemotherapy with hyper-CVAD/MTX-Ara-C combined with HAART may be well tolerated and effective in AIDS-related BL.

  18. Immunogenicity and immunologic memory after hepatitis B virus booster vaccination in HIV-infected children receiving highly active antiretroviral therapy.

    PubMed

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

    2009-09-15

    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. 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. 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. 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.

  19. Immunogenicity, immunologic memory, and safety following measles revaccination in HIV-infected children receiving highly active antiretroviral therapy.

    PubMed

    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

    2012-08-15

    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). 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. 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. Measles revaccination induced high rates of seroprotection and memory in children receiving HAART. Both endpoints were associated with HIV viral load suppression. NCT00013871 (www.clinicaltrials.gov).

  20. Toxoplasmic Encephalitis in an AIDS Cohort at Puerto Rico before and after Highly Active Antiretroviral Therapy (HAART)

    PubMed Central

    Mayor, Angel M.; Fernández Santos, Diana M.; Dworkin, Mark S.; Ríos-Olivares, Eddy; Hunter-Mellado, Robert F.

    2011-01-01

    Highly active antiretroviral therapy (HAART) significantly reduced the toxoplasmic encephalitis (TE) incidence in acquired immunodeficiency syndrome (AIDS) patients. The TE incidence and mortality were evaluated in an AIDS cohort followed in Puerto Rico before, during, and after HAART implementation in the Island. Of the 2,431 AIDS studied patients 10.9% had TE diagnosis, with an incidence density that decreased from 5.9/100 person-years to 1.1/100 person-years after HAART. Cox proportional hazard analysis showed substantial mortality reduction among TE cases who received HAART. No mortality reduction was seen in those cases who received TE prophylaxis. Although this study shows a TE incidence and mortality reduction in the AIDS cohort after HAART, the incidence was higher than those reported in the United States AIDS patients. Poor TE prophylaxis compliance might explain the lack of impact of this intervention. Strengthening the diagnostic and opportune TE diagnosis and prompt initiation of HAART in susceptible patients is important to control this opportunistic infection. PMID:21540399

  1. Anemia and Red Blood Cell Indices Predict HIV-Associated Neurocognitive Impairment in the Highly Active Antiretroviral Therapy Era

    PubMed Central

    Kallianpur, Asha R.; Wang, Quan; Jia, Peilin; Hulgan, Todd; Zhao, Zhongming; Letendre, Scott L.; Ellis, Ronald J.; Heaton, Robert K.; Franklin, Donald R.; Barnholtz-Sloan, Jill; Collier, Ann C.; Marra, Christina M.; Clifford, David B.; Gelman, Benjamin B.; McArthur, Justin C.; Morgello, Susan; Simpson, David M.; McCutchan, J. A.; Grant, Igor

    2016-01-01

    Background. Anemia has been linked to adverse human immunodeficiency virus (HIV) outcomes, including dementia, in the era before highly active antiretroviral therapy (HAART). Milder forms of HIV-associated neurocognitive disorder (HAND) remain common in HIV-infected persons, despite HAART, but whether anemia predicts HAND in the HAART era is unknown. Methods. We evaluated time-dependent associations of anemia and cross-sectional associations of red blood cell indices with neurocognitive impairment in a multicenter, HAART-era HIV cohort study (N = 1261), adjusting for potential confounders, including age, nadir CD4+ T-cell count, zidovudine use, and comorbid conditions. Subjects underwent comprehensive neuropsychiatric and neuromedical assessments. Results. HAND, defined according to standardized criteria, occurred in 595 subjects (47%) at entry. Mean corpuscular volume and mean corpuscular hemoglobin were positively associated with the global deficit score, a continuous measure of neurocognitive impairment (both P < .01), as well as with all HAND, milder forms of HAND, and HIV-associated dementia in multivariable analyses (all P < .05). Anemia independently predicted development of HAND during a median follow-up of 72 months (adjusted hazard ratio, 1.55; P < .01). Conclusions. Anemia and red blood cell indices predict HAND in the HAART era and may contribute to risk assessment. Future studies should address whether treating anemia may help to prevent HAND or improve cognitive function in HIV-infected persons. PMID:26690344

  2. Risk factors for tuberculosis after highly active antiretroviral therapy initiation in the United States and Canada: implications for tuberculosis screening.

    PubMed

    Sterling, Timothy R; Lau, Bryan; Zhang, Jinbing; Freeman, Aimee; Bosch, Ronald J; Brooks, John T; Deeks, Steven G; French, Audrey; Gange, Stephen; Gebo, Kelly A; John Gill, M; Horberg, Michael A; Jacobson, Lisa P; Kirk, Gregory D; Kitahata, Mari M; Klein, Marina B; Martin, Jeffrey N; Rodriguez, Benigno; Silverberg, Michael J; Willig, James H; Eron, Joseph J; Goedert, James J; Hogg, Robert S; Justice, Amy C; McKaig, Rosemary G; Napravnik, Sonia; Thorne, Jennifer; Moore, Richard D

    2011-09-15

    Screening for tuberculosis prior to highly active antiretroviral therapy (HAART) initiation is not routinely performed in low-incidence settings. Identifying factors associated with developing tuberculosis after HAART initiation could focus screening efforts. Sixteen cohorts in the United States and Canada contributed data on persons infected with human immunodeficiency virus (HIV) who initiated HAART December 1995-August 2009. Parametric survival models identified factors associated with tuberculosis occurrence. Of 37845 persons in the study, 145 were diagnosed with tuberculosis after HAART initiation. Tuberculosis risk was highest in the first 3 months of HAART (20 cases; 215 cases per 100000 person-years; 95% confidence interval [CI]: 131-333 per 100000 person-years). In a multivariate Weibull proportional hazards model, baseline CD4+ lymphocyte count <200, black race, other nonwhite race, Hispanic ethnicity, and history of injection drug use were independently associated with tuberculosis risk. In addition, in a piece-wise Weibull model, increased baseline HIV-1 RNA was associated with increased tuberculosis risk in the first 3 months; male sex tended to be associated with increased risk. Screening for active tuberculosis prior to HAART initiation should be targeted to persons with baseline CD4 <200 lymphocytes/mm³ or increased HIV-1 RNA, persons of nonwhite race or Hispanic ethnicity, history of injection drug use, and possibly male sex.

  3. Virologic response differences between African Americans and European Americans initiating highly active antiretroviral therapy with equal access to care.

    PubMed

    Weintrob, Amy C; Grandits, Greg A; Agan, Brian K; Ganesan, Anuradha; Landrum, Michael L; Crum-Cianflone, Nancy F; Johnson, Erica N; Ordóñez, Claudia E; Wortmann, Glenn W; Marconi, Vincent C

    2009-12-01

    Studies comparing virologic response to highly active antiretroviral therapy (HAART) between African Americans (AA) and European Americans (EA) have been confounded by differences in duration of HIV infection and access to health care. We evaluated virologic response to HAART between ethnicities in a large cohort with fewer confounders. The odds of attaining viral suppression at 6- and 12-months post-HAART were determined by multivariate logistic regression for HIV-infected AA and EA prospectively followed in a large US military cohort. Time-to-event methods were used to compare maintenance of suppression. A total of 1363 subjects (51% AA, 92% men) with viral load results available 6 months after HAART initiation were included. There was no difference between ethnicities in time from seroconversion to HIV diagnosis or HAART initiation or in HAART regimens. Adjusted for multiple demographic and HIV-related factors, AA had significantly lower odds of obtaining undetectable viral loads after 6 (odds ratio 0.6, 95% confidence interval 0.4-0.8, P < 0.001) and 12 months (odds ratio 0.6, 95% confidence interval 0.4-0.8, P = 0.002) of HAART. Once undetectable, there was no difference in time to virologic failure between AA and EA. Despite similar durations of HIV infection and equal access to health care, AAs were significantly less likely to achieve viral suppression compared with EA.

  4. Prevalence and Persistence of Cervical Human Papillomavirus Infection In HIV-Positive Women Initiating Highly-Active Antiretroviral Therapy

    PubMed Central

    Fife, Kenneth H.; Wu, Julia W.; Squires, Kathleen E.; Watts, D. Heather; Andersen, Janet W.; Brown, Darron R.

    2009-01-01

    Objective To determine the prevalence of HPV DNA in cervical specimens from treatment-naïve women initiating highly active antiretroviral therapy (HAART) and explore the longitudinal association of HPV DNA with CD4 count and HIV viral load (VL). Methods Women enrolled prior to HAART were evaluated at baseline, weeks 24, 48, and 96 with CD4 count, VL, and cervical swab for HPV DNA. Results The 146 subjects had a median CD4 count of 238 cells/μL and VL of 13,894 copies/mL. Ninety-seven (66%) subjects had HPV DNA detected in the baseline specimen including 90 subjects (62%) positive for one or more high risk HPV types. HPV DNA detection declined to 49% at week 96, and that of a high risk HPV type to 39%. The duration of follow-up was associated with decreased detection of HPV DNA of any type (p=0.045) and of high risk HPV types (p=0.003). There was at most a marginal association between HAART response and loss of detection of cervical HPV DNA. Conclusions Women initiating HAART had a high prevalence of cervical HPV DNA that declined over 96 weeks of HAART. The relationship of CD4 count and VL response to the decline of cervical HPV DNA was not strong. PMID:19387354

  5. Increased resting energy expenditure, fat oxidation, and food intake in patients with highly active antiretroviral therapy-associated lipodystrophy.

    PubMed

    Sutinen, Jussi; Yki-Järvinen, Hannele

    2007-03-01

    Highly active antiretroviral therapy (HAART) is associated with metabolic adverse events such as lipodystrophy in human immunodeficiency virus (HIV)-infected patients. The objective of the present study was to evaluate the effects of HAART-associated lipodystrophy on resting energy expenditure and caloric intake. In this cross-sectional study we compared resting energy expenditure (REE) and energy intake in 30 HAART-treated patients with lipodystrophy (HAART+LD+) with 13 HAART-treated patients without lipodystrophy (HAART+LD-). REE was measured using indirect calorimetry, and energy intake was recorded as a 3-day diary of food intake. REE (5,180+/-160 vs. 4,260+/-150 J/min, P<0.01) and also REE expressed per fat-free mass (86+/-1 vs. 78+/-2 J.kg fat-free mass-1.min-1, P<0.01) were significantly higher in the HAART+LD+ than the HAART+LD- group. Rate of lipid oxidation was significantly higher in the HAART+LD+ than the HAART+LD- group. Total energy and fat intakes were significantly increased in the HAART+LD+ compared with the HAART+LD- group. These results imply that HAART-associated lipodystrophy is associated with increased REE and lipid oxidation and with increased caloric and fat intake.

  6. Difficulty swallowing and lack of receipt of highly active antiretroviral therapy predict acute weight loss in human immunodeficiency virus disease.

    PubMed

    Jacobson, Denise L; Bica, Ioana; Knox, Tamsin A; Wanke, Christine; Tchetgen, Eric; Spiegelman, Donna; Silva, Marisela; Gorbach, Sherwood; Wilson, Ira B

    2003-11-15

    In human immunodeficiency virus (HIV) disease, symptoms of underlying illness may promote weight loss through decreased caloric intake, increased metabolic needs, or nutrient malabsorption. We evaluated disease symptoms as predictors of acute weight loss (i.e., loss of > or =5% of weight). HIV-infected men and women (n=415) were telephoned every 5 weeks to obtain information about weight and recent symptoms. Weight change between each pair of consecutive calls (telephone intervals, 2814) was calculated. Acute weight loss occurred across 4.5% of intervals and among 24% of individuals. Patients reported > or =1 symptom before 58% of telephone intervals. The most common symptoms or symptom complexes before intervals were diarrhea (21% of patients), anorexia (17%), upper respiratory symptoms (16%), skin symptoms (12%), and abdominal pain (12%). Trouble swallowing (6%) and oral symptoms (7%) were less common. Risk of acute weight loss was significantly increased when oral symptoms or trouble swallowing were present, and it was decreased when highly active antiretroviral therapy (HAART) was used or when diarrhea was not present. Even when HAART is being administered, clinicians should remain vigilant regarding weight loss, oral symptoms, and trouble swallowing.

  7. Immunological response to hepatitis B vaccination in patients with AIDS and virological response to highly active antiretroviral therapy.

    PubMed

    Paitoonpong, Leilani; Suankratay, Chusana

    2008-01-01

    Previous studies showed that an immunological response to hepatitis B virus (HBV) vaccination in patients with AIDS was lower than in the normal population. However, those with virological response to highly active antiretroviral therapy (HAART) may have a normal immunological response to HBV vaccination. In our study, patients with AIDS who had a virological response to HAART and no immunity to HBV received 3 doses of HBV vaccine (20 microg of Engerix-B(R)) on d 0, 30, and 180. Anti-HBs level was measured 1 month after complete vaccination. Of 28 patients, overall response rate to vaccination was 71.4%. The responder group had a significantly higher CD4 count at 1 month after complete vaccination than the non-responder group (466.95+/-146.94 and 335+/-112.62 cells/microl, p =0.035). The patients receiving efavirenz-containing HAART had better response than those without efavirenz-containing HAART (p =0.030). The responder group had received a longer duration of HAART. In conclusion , to our knowledge, ours is the first prospective study to determine the immunological response to HBV vaccination in all patients with AIDS who had maintained the virological response after receiving HAART throughout the study period. Patients with AIDS and virological response to HAART have a good immunological response to HBV vaccination.

  8. Impact of Highly Active Antiretroviral Treatment on HIV Seroincidence Among Men Who Have Sex With Men: San Francisco

    PubMed Central

    Katz, Mitchell H.; Schwarcz, Sandra K.; Kellogg, Timothy A.; Klausner, Jeffrey D.; Dilley, James W.; Gibson, Steven; McFarland, William

    2002-01-01

    Objectives. This study assessed the countervailing effects on HIV incidence of highly active antiretroviral treatment (HAART) among San Francisco men who have sex with men (MSM). Methods. Behavioral risk was determined on the basis of responses to cross-sectional community interviews. HIV incidence was assessed through application of an enzyme-linked immunoassay testing strategy. Results. Use of HAART among MSM living with AIDS increased from 4% in 1995 to 54% in 1999. The percentage of MSM who reported both unprotected anal intercourse and multiple sexual partners increased from 24% in 1994 to 45% in 1999. The annual HIV incidence rate increased from 2.1% in 1996 to 4.2% in 1999 among MSM who sought anonymous HIV testing, and the rate was high (5.3%) but stable in a blinded survey of MSM seeking sexually transmitted disease services. Conclusions. Any decrease in per contact risk of HIV transmission due to HAART use appears to have been counterbalanced or overwhelmed by increases in the number of unsafe sexual episodes. (Am J Public Health. 2002;92:388–394) PMID:11867317

  9. 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

  10. Initial response to highly active antiretroviral therapy in HIV-1C-infected adults in a public sector treatment program in Botswana.

    PubMed

    Wester, C William; Kim, Soyeon; Bussmann, Hermann; Avalos, Ava; Ndwapi, Ndwapi; Peter, Trevor F; Gaolathe, Tendani; Mujugira, Andrew; Busang, Lesego; Vanderwarker, Chris; Cardiello, Peter; Johnson, Onalethata; Thior, Ibou; Mazonde, Patson; Moffat, Howard; Essex, Max; Marlink, Richard

    2005-11-01

    To describe the response to highly active antiretroviral treatment (HAART) in a public sector pilot antiretroviral (ARV) treatment program in Botswana. The response to HAART is described in adult HIV-infected ARV-naive patients initiating treatment from April 2001 to January 2002 at Princess Marina Hospital in Gaborone, Botswana. Patients had medical and laboratory evaluations before initiating ARV treatment and were followed longitudinally. For analysis, data were collected from charts and patient management records. One hundred fifty-three ARV-naive patients initiated HAART. Most received didanosine plus stavudine (ddI + d4T) with efavirenz or nevirapine. The mean CD4 cell count increase was 149 cells/mm at 24 weeks and 204 cells/mm at 48 weeks. The percentage of patients with an HIV-1 RNA level < or =400 copies/mL was 87.0% at 24 weeks and 78.8% at 48 weeks. The Kaplan-Meier 1-year survival estimate was 84.7% (79.0%, 90.8%), with a 3.2-fold increased risk (P = 0.004) of mortality among patients with a CD4 cell count <50 cells/mm. The 1-year Kaplan-Meier estimate of toxicity-related drug switches was 32.2% (20.3%, 40.4%). The most common toxicity was peripheral neuropathy, occurring more frequently in patients with a preexisting diagnosis of peripheral neuropathy and among those placed on ddI + d4T-containing regimens. An excellent response to HAART was observed among HIV-1C-infected patients, paralleling those seen elsewhere. Despite excellent responses, high rates of toxicity were observed for ddI + d4T-containing regimens.

  11. Factors associated with syphilis incidence in the HIV-infected in the era of highly active antiretrovirals.

    PubMed

    Shilaih, Mohaned; Marzel, Alex; Braun, Dominique L; Scherrer, Alexandra U; Kovari, Helen; Young, Jim; Calmy, Alexandra; Darling, Katharine; Battegay, Manuel; Hoffmann, Matthias; Bernasconi, Enos; Thurnheer, Maria C; Günthard, Huldrych F; Kouyos, Roger D

    2017-01-01

    After several years of steady decline, syphilis is reemerging globally as a public health hazard, especially among people living with human immunodeficiency virus (HIV). Syphilis resurgence is observed mainly in men who have sex with men (MSM), yet other transmission groups are affected too. In this manuscript, we study the factors associated with syphilis incidence in the Swiss HIV cohort study in the era of highly effective antiretrovirals. Using parametric interval censored models with fixed and time-varying covariates, we studied the immunological, behavioral, and treatment-related elements associated with syphilis incidence in 3 transmission groups: MSM, heterosexuals, and intravenous drug users. Syphilis incidence has been increasing annually since 2005, with up to 74 incident cases per 1000 person-years in 2013, with MSM being the population with the highest burden (92% of cases). While antiretroviral treatment (ART) in general did not affect syphilis incidence, nevirapine (NVP) was associated with a lower hazard of syphilis incidence (multivariable hazard ratio 0.5, 95% confidence interval 0.2-1.0). We observed that condomless sex and younger age were associated with higher syphilis incidence. Moreover, time-updated CD4, nadir CD4, and CD8 cell counts were not associated with syphilis incidence. Finally, testing frequency higher than the recommended once a year routine testing was associated with a 2-fold higher risk of acquiring syphilis. Condomless sex is the main driver of syphilis resurgence in the Swiss HIV Cohort study; ART and immune reconstitution provide no protection against syphilis. This entails targeted interventions and frequent screening of high-risk populations. There is no known effect of NVP on syphilis; therefore, further clinical, epidemiological, and microbiological investigation is necessary to validate our observation.

  12. Factors associated with syphilis incidence in the HIV-infected in the era of highly active antiretrovirals

    PubMed Central

    Shilaih, Mohaned; Marzel, Alex; Braun, Dominique L.; Scherrer, Alexandra U.; Kovari, Helen; Young, Jim; Calmy, Alexandra; Darling, Katharine; Battegay, Manuel; Hoffmann, Matthias; Bernasconi, Enos; Thurnheer, Maria C.; Günthard, Huldrych F.; Kouyos, Roger D.

    2017-01-01

    Abstract After several years of steady decline, syphilis is reemerging globally as a public health hazard, especially among people living with human immunodeficiency virus (HIV). Syphilis resurgence is observed mainly in men who have sex with men (MSM), yet other transmission groups are affected too. In this manuscript, we study the factors associated with syphilis incidence in the Swiss HIV cohort study in the era of highly effective antiretrovirals. Using parametric interval censored models with fixed and time-varying covariates, we studied the immunological, behavioral, and treatment-related elements associated with syphilis incidence in 3 transmission groups: MSM, heterosexuals, and intravenous drug users. Syphilis incidence has been increasing annually since 2005, with up to 74 incident cases per 1000 person-years in 2013, with MSM being the population with the highest burden (92% of cases). While antiretroviral treatment (ART) in general did not affect syphilis incidence, nevirapine (NVP) was associated with a lower hazard of syphilis incidence (multivariable hazard ratio 0.5, 95% confidence interval 0.2–1.0). We observed that condomless sex and younger age were associated with higher syphilis incidence. Moreover, time-updated CD4, nadir CD4, and CD8 cell counts were not associated with syphilis incidence. Finally, testing frequency higher than the recommended once a year routine testing was associated with a 2-fold higher risk of acquiring syphilis. Condomless sex is the main driver of syphilis resurgence in the Swiss HIV Cohort study; ART and immune reconstitution provide no protection against syphilis. This entails targeted interventions and frequent screening of high-risk populations. There is no known effect of NVP on syphilis; therefore, further clinical, epidemiological, and microbiological investigation is necessary to validate our observation. PMID:28079818

  13. Preliminary outcomes of a paediatric highly active antiretroviral therapy cohort from KwaZulu-Natal, South Africa

    PubMed Central

    Reddi, Anand; Leeper, Sarah C; Grobler, Anneke C; Geddes, Rosemary; France, K Holly; Dorse, Gillian L; Vlok, Willem J; Mntambo, Mbali; Thomas, Monty; Nixon, Kristy; Holst, Helga L; Karim, Quarraisha Abdool; Rollins, Nigel C; Coovadia, Hoosen M; Giddy, Janet

    2007-01-01

    Background Few studies address the use of paediatric highly active antiretroviral therapy (HAART) in Africa. Methods We performed a retrospective cohort study to investigate preliminary outcomes of all children eligible for HAART at Sinikithemba HIV/AIDS clinic in KwaZulu-Natal, South Africa. Immunologic, virologic, clinical, mortality, primary caregiver, and psychosocial variables were collected and analyzed. Results From August 31, 2003 until October 31, 2005, 151 children initiated HAART. The median age at HAART initiation was 5.7 years (range 0.3–15.4). Median follow-up time of the cohort after HAART initiation was 8 months (IQR 3.5–13.5). The median change in CD4% from baseline (p < 0.001) was 10.2 (IQR 5.0–13.8) at 6 months (n = 90), and 16.2 (IQR 9.6–20.3) at 12 months (n = 59). Viral loads (VLs) were available for 100 children at 6 months of which 84% had HIV-1 RNA levels ≤ 50 copies/mL. At 12 months, 80.3% (n = 61) had undetectable VLs. Sixty-five out of 88 children (73.8%) reported a significant increase (p < 0.001) in weight after the first month. Eighty-nine percent of the cohort (n = 132) reported ≤ 2 missed doses during any given treatment month (> 95%adherence). Seventeen patients (11.3%) had a regimen change; two (1.3%) were due to antiretroviral toxicity. The Kaplan-Meier one year survival estimate was 90.9% (95%confidence interval (CI) 84.8–94.6). Thirteen children died during follow-up (8.6%), one changed service provider, and no children were lost to follow-up. All 13 deaths occurred in children with advanced HIV disease within 5 months of treatment initiation. In multivariate analysis of baseline variables against mortality using Cox proportional-hazards model, chronic gastroenteritis was associated with death [hazard ratio (HR), 12.34; 95%CI, 1.27–119.71) and an HIV-positive primary caregiver was found to be protective against mortality [HR, 0.12; 95%CI, 0.02–0.88). Age, orphanhood, baseline CD4%, and hemoglobin were not

  14. Parametric modelling of survival following HIV and AIDS in the era of highly active antiretroviral therapy: data from Australia.

    PubMed

    Nakhaee, F; Law, M

    2011-03-01

    Parametric survival models have not previously been applied to survival following a diagnosis of HIV/AIDS in Australia. Four different parametric models--exponential, Weibull, log-normal and log-logistic--were applied to data both on HIV-positive cases and on cases diagnosed with AIDS collected through the national HIV/AIDS surveillance system. Using likelihood based goodness-of-fit criteria the Weibull model was found to be the best-fitted model for predicting survival following a diagnosis of HIV infection without and with a diagnosis of AIDS. Several covariates-age, sex, combined HIV exposure category, CD4 cell counts, antiretroviral treatment and AIDS-defining illnesses--were included in the parametric model to predict factors associated with future mortality. Predicted deaths were in agreement with the observed deaths following HIV infection and AIDS. The Weibull model will be applied for future projections of deaths from HIV/AIDS.

  15. Abnormal humoral immune response to influenza vaccination in pediatric type-1 human immunodeficiency virus infected patients receiving highly active antiretroviral therapy.

    PubMed

    Montoya, Carlos J; Toro, Maria F; Aguirre, Carlos; Bustamante, Alberto; Hernandez, Mariluz; Arango, Liliana P; Echeverry, Marta; Arango, Ana E; Prada, Maria C; Alarcon, Herminia del P; Rojas, Mauricio

    2007-06-01

    Given that highly active antiretroviral therapy (HAART) has been demonstrated useful to restore immune competence in type-1 human immunodeficiency virus (HIV-1)-infected subjects, we evaluated the specific antibody response to influenza vaccine in a cohort of HIV-1-infected children on HAART so as to analyze the quality of this immune response in patients under antiretroviral therapy. Sixteen HIV-1-infected children and 10 HIV-1 seronegative controls were immunized with a commercially available trivalent inactivated influenza vaccine containing the strains A/H1N1, A/H3N2, and B. Serum hemagglutinin inhibition (HI) antibody titers were determined for the three viral strains at the time of vaccination and 1 month later. Immunization induced a significantly increased humoral response against the three influenza virus strains in controls, and only against A/H3N2 in HIV-1-infected children. The comparison of post-vaccination HI titers between HIV-1+ patients and HIV-1 negative controls showed significantly higher HI titers against the three strains in controls. In addition, post vaccination protective HI titers (defined as equal to or higher than 1:40) against the strains A/H3N2 and B were observed in a lower proportion of HIV-1+ children than in controls, while a similar proportion of individuals from each group achieved protective HI titers against the A/H1N1 strain. The CD4+ T cell count, CD4/CD8 T cells ratio, and serum viral load were not affected by influenza virus vaccination when pre- vs post-vaccination values were compared. These findings suggest that despite the fact that HAART is efficient in controlling HIV-1 replication and in increasing CD4+ T cell count in HIV-1-infected children, restoration of immune competence and response to cognate antigens remain incomplete, indicating that additional therapeutic strategies are required to achieve a full reconstitution of immune functions.

  16. A relationship between CD4 count and oral manifestations of human immunodeficiency virus-infected patients on highly active antiretroviral therapy in urban population.

    PubMed

    Satyakiran, Gadavalli Vera Venkata; Bavle, Radhika Manoj; Alexander, Glory; Rao, Saritha; Venugopal, Reshma; Hosthor, Sreelatha S

    2016-01-01

    Human immunodeficiency virus (HIV) infection gradually destroys the body's immune system, which makes it harder for the body to fight infections. HIV infection causes a quantitative and qualitative depletion of CD4 lymphocyte count, which increases the risk of opportunistic infections. Thus, CD4 count is one of the key factors in determining both the urgency of highly active antiretroviral therapy (HAART) initiation and the need of prophylaxis for opportunistic infections. This study aims to evaluate the prevalence and variations in the oral manifestations of HIV/acquired immune deficiency syndrome patients on HAART therapy in urban population and their association with CD4 count. A study was conducted by screening eighty patients who were HIV positive in an urban location. Both adult and pediatric patients were screened for oral manifestations and simultaneously CD4 count was also evaluated. Patients with HIV infection for variable time period who are under HAART were considered. Measures of central tendency were used to analyse the data. HIV infection destroys the immune system of an individual, making the patient susceptible to various infections and malignancies. With the advent of antiretroviral therapy, the scenario has changed drastically. We have observed that patients with CD4 counts between 164 and 1286 show relatively few oral manifestations. Long-term HAART therapy causes pigmentation, xerostomia and angular cheilitis but is taken up quite well by the patients. In this study, eighty patients with HAART from urban population showed very minimal oral findings because of good accessibility for treatment and awareness about HIV infections. The patients who were on long-standing HAART treatment also showed minimal oral manifestation such as pigmentation and xerostomia. Hence, we conclude that recognition, significance and treatment of these lesions in patients with HIV infection do not require elaborate setup and can be treated with basic primary health care.

  17. A relationship between CD4 count and oral manifestations of human immunodeficiency virus-infected patients on highly active antiretroviral therapy in urban population

    PubMed Central

    Satyakiran, Gadavalli Vera Venkata; Bavle, Radhika Manoj; Alexander, Glory; Rao, Saritha; Venugopal, Reshma; Hosthor, Sreelatha S

    2016-01-01

    Introduction: Human immunodeficiency virus (HIV) infection gradually destroys the body's immune system, which makes it harder for the body to fight infections. HIV infection causes a quantitative and qualitative depletion of CD4 lymphocyte count, which increases the risk of opportunistic infections. Thus, CD4 count is one of the key factors in determining both the urgency of highly active antiretroviral therapy (HAART) initiation and the need of prophylaxis for opportunistic infections. Aim: This study aims to evaluate the prevalence and variations in the oral manifestations of HIV/acquired immune deficiency syndrome patients on HAART therapy in urban population and their association with CD4 count. Materials and Methods: A study was conducted by screening eighty patients who were HIV positive in an urban location. Both adult and pediatric patients were screened for oral manifestations and simultaneously CD4 count was also evaluated. Patients with HIV infection for variable time period who are under HAART were considered. Statistical Analysis: Measures of central tendency were used to analyse the data. Results: HIV infection destroys the immune system of an individual, making the patient susceptible to various infections and malignancies. With the advent of antiretroviral therapy, the scenario has changed drastically. We have observed that patients with CD4 counts between 164 and 1286 show relatively few oral manifestations. Long-term HAART therapy causes pigmentation, xerostomia and angular cheilitis but is taken up quite well by the patients. Conclusion: In this study, eighty patients with HAART from urban population showed very minimal oral findings because of good accessibility for treatment and awareness about HIV infections. The patients who were on long-standing HAART treatment also showed minimal oral manifestation such as pigmentation and xerostomia. Hence, we conclude that recognition, significance and treatment of these lesions in patients with HIV

  18. Anemia and Red Blood Cell Indices Predict HIV-Associated Neurocognitive Impairment in the Highly Active Antiretroviral Therapy Era.

    PubMed

    Kallianpur, Asha R; Wang, Quan; Jia, Peilin; Hulgan, Todd; Zhao, Zhongming; Letendre, Scott L; Ellis, Ronald J; Heaton, Robert K; Franklin, Donald R; Barnholtz-Sloan, Jill; Collier, Ann C; Marra, Christina M; Clifford, David B; Gelman, Benjamin B; McArthur, Justin C; Morgello, Susan; Simpson, David M; McCutchan, J A; Grant, Igor

    2016-04-01

    Anemia has been linked to adverse human immunodeficiency virus (HIV) outcomes, including dementia, in the era before highly active antiretroviral therapy (HAART). Milder forms of HIV-associated neurocognitive disorder (HAND) remain common in HIV-infected persons, despite HAART, but whether anemia predicts HAND in the HAART era is unknown. We evaluated time-dependent associations of anemia and cross-sectional associations of red blood cell indices with neurocognitive impairment in a multicenter, HAART-era HIV cohort study (N = 1261), adjusting for potential confounders, including age, nadir CD4(+) T-cell count, zidovudine use, and comorbid conditions. Subjects underwent comprehensive neuropsychiatric and neuromedical assessments. HAND, defined according to standardized criteria, occurred in 595 subjects (47%) at entry. Mean corpuscular volume and mean corpuscular hemoglobin were positively associated with the global deficit score, a continuous measure of neurocognitive impairment (both P < .01), as well as with all HAND, milder forms of HAND, and HIV-associated dementia in multivariable analyses (all P < .05). Anemia independently predicted development of HAND during a median follow-up of 72 months (adjusted hazard ratio, 1.55; P < .01). Anemia and red blood cell indices predict HAND in the HAART era and may contribute to risk assessment. Future studies should address whether treating anemia may help to prevent HAND or improve cognitive function in HIV-infected persons. © The Author 2015. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com.

  19. Highly active antiretroviral therapy is associated with decreased incidence of sexually transmitted diseases in a Taiwanese HIV-positive population.

    PubMed

    Cheng, Shu-Hsing; Yang, Chin-Hui; Hsueh, Yu-Mei

    2013-03-01

    There are reports of increased sexual risk behaviors in the HIV-positive population since the introduction of highly active antiretroviral therapy (HAART). Little is known about the effects of the case management (CM) program and HAART on sexually transmitted diseases (STDs) in Taiwan. HIV-positive subjects, who visited the outpatient clinics of Taoyuan General Hospital between 2007 and 2010, were enrolled. A total of 574 subjects and 14,462 person-months were reviewed. Incident STDs occurred in 104 (18.1%) subjects, and the incidence rate was 8.6 (95% confidence interval [CI], 7.1-10.5) per 100 person-years (PY). For men who have sex with men (MSM), heterosexual men and women, and injection drug users (IDU), 19.4 per 100 PY(95% CI, 15.7-24.0), 3.5 per 100 PY (95% CI, 1.4-7.3), and 1.1 per 100 PY (95% CI, 0.4-2.4) of STDs were noted, respectively; (MSM versus IDU and MSM versus heterosexual subjects, p<0.000001; heterosexual subjects versus IDU, p=0.061). Syphilis (59.6%) was the most common STD. Regular CM and no HAART (hazard ratio, 2.58; 95% CI, 1.14-5.84; p=0.02) was significantly associated with STDs in MSM. Though this retrospective study might underestimate the incidence of STDs and not draw the conclusion of causality, we concluded that the CM program and HAART are associated with lower acquisition of STDs in the Taiwanese HIV-positive population.

  20. 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

  1. 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

  2. Acupuncture and the relaxation response for treating gastrointestinal symptoms in HIV patients on highly active antiretroviral therapy.

    PubMed

    Chang, Bei-Hung; Sommers, Elizabeth

    2011-09-01

    To examine the effect of acupuncture and the relaxation response (RR) for treating gastrointestinal (GI) symptoms in HIV patients who are using highly active antiretroviral therapy (HAART). The authors conducted a 4-arm 2×2 double-blind randomised controlled trial in an acupuncture clinic in the USA. Sham acupuncture and health education were used as the control conditions of real acupuncture and RR elicitation, respectively. Enrolled patients were randomised to real acupuncture+RR (AR), sham acupuncture+RR (SR), real acupuncture+health education (AE) or sham acupuncture+health education (SE) study arm. Participants listened to CDs with RR-eliciting instructions or health education while receiving acupuncture intervention. Interventions were provided twice weekly for 4 weeks and once weekly for another 4 weeks. Participants used daily diaries to record GI symptom severity ratings (0-10). The authors estimated the intervention effect as the changes in symptom rating per intervention session increase using a mixed-effects regression model. A total of 130 people with HIV/AIDS who were on HAART and had persistent GI symptoms were enrolled and 115 started the study intervention. The AR group had greater intervention effects for loose stools symptoms than the other three groups (β=-0.149, -0.151 and -0.144, p value=0.013, 0.013 and 0.018 comparing AR to AE, SR and SE, respectively). The AR group also had significant intervention effects on reducing nausea symptoms when the intervention was given twice per week (β=-0.218, p=0.001). Our trial provided preliminary data demonstrating the potential synergistic effects of acupuncture and RR for treating GI symptoms in HIV patients on HAART.

  3. AIDS defining neoplasms prevalence in a cohort of HIV infected patients, before and after highly active antiretroviral therapy

    PubMed Central

    Mayor, Angel M.; Gómez, María A.; Ríos-Olivares, Eddy; Hunter-Mellado, Robert F.

    2012-01-01

    Introduction Malignant disorders have been linked to HIV epidemic from its onset. Implementation of highly active antiretroviral therapy (HAART) has resulted in a dramatic reduction in the HIV/AIDS morbidity and mortality. The present study evaluates the neoplasm prevalence before and after the implementation of HAART. Methods A cross-sectional study was performed in 171 adults HIV infected persons followed in Puerto Rico, between May 1992 and December 2005. Neoplasm prevalence was measured and the difference in AIDS and non-AIDS defining neoplasms was analyzed before and after the HAART era. Chi-square, Fisher exact test, ANOVA and student t test were used to explore differences between groups. Results Malignant neoplasms were detected in 171 patients (4.8%). Of these, 51.5% were AIDS defining neoplasms and 68% were established before HAART. AIDS defining neoplasms accounted for 62.4% of the neoplasms before the availability of HAART and 25.9% after HAART. Except for cervical carcinoma, the prevalence of AIDS defining neoplasms was decreased after HAART. Non-AIDS lymphomas and prostate neoplasms were more frequent after HAART. Discussion: Our study finds a significant reduction of Kaposi's sarcoma and AIDS related lymphoma in the HAART era of the epidemic. A higher prevalence of non-AIDS defining lymphomas, prostate and cervical carcinoma were seen in the HAART era. These findings suggest that factors other than severe immunosuppression are involved in the neoplasms' pathogenesis. Preventive strategies that include screening tests, vaccination and life style modification should be routinely applied in the HIV infected patients. PMID:18646347

  4. Palliative care for AIDS: challenges and opportunities in the era of highly active anti-retroviral therapy.

    PubMed

    Selwyn, Peter A; Rivard, Mimi

    2003-06-01

    In contrast to the first decade of the AIDS epidemic, the past decade has seen an increasing separation between AIDS care and palliative care services. While this may be due in part to the perception that AIDS is no longer a uniformly fatal illness, AIDS in fact remains an important cause of morbidity and mortality for young adult populations in the United States, particularly among certain racial-ethnic minorities. Death rates have remained steady since the dramatic decreases noted in the mid-1990s, and causes of death now increasingly include co-morbidities such as hepatitis B, C, end-organ failure, and various malignancies. Moreover, as AIDS has been transformed into a more manageable, chronic disease in the era of 'highly active antiretroviral therapy' (HAART), the opportunities for palliative care interventions have only increased. Patients with AIDS continue to experience a high burden of pain and other chronic symptoms, over a longer period of time, with a disease course marked by more cumulative exacerbations and remissions than when AIDS was a stereotypic, rapidly fatal illness. Advance care planning and discussions of goals of care are more complex and involve more uncertainty than was the case when prognosis was clear-cut and treatment options were more limited. For all of these reasons, it is important for the distance which has developed between HIV and palliative care providers to be bridged. Contrary to popular perceptions, palliative medicine continues to have much to offer in the HAART era for the care of patients and families with HIV/AIDS, for whom treatment outcomes will only benefit from greater integration of disease-specific and palliative interventions. The challenge for care providers is now to implement successful strategies for integrating AIDS and palliative care services in all relevant clinical environments.

  5. Impact of highly active antiretroviral therapy on individual AIDS-defining illness incidence and survival in Australia.

    PubMed

    Dore, Gregory J; Li, Yueming; McDonald, Ann; Ree, Hugo; Kaldor, John M; Kaldo, John M

    2002-04-01

    To determine the effect of highly active antiretroviral therapy (HAART) on incidence of initial AIDS-defining illnesses (ADIs) and survival after individual ADIs. Australian AIDS notification data over the period 1993 to 2000 were examined. Analyses were based on all initial ADIs. To examine the impact of HAART, two periods of AIDS diagnosis were chosen: pre-HAART (1993-1995) and HAART (1996-2000). Comparisons between these two periods included proportion of individual ADIs, median CD4 lymphocyte counts at and survival following AIDS and individual ADIs. Median survival was based on Kaplan-Meier estimates, with examination of factors influencing survival in a Cox proportional hazards model. Over the period 1993 to 2000 in Australia, 5017 initial ADIs were diagnosed among 4351 AIDS cases. At AIDS diagnosis, changes from the pre-HAART (1993-1995) to HAART (1996-2000) periods included an increased proportion of Pneumocystis carinii pneumonia (PCP) (25.9% to 30.4%; p =.001), AIDS dementia complex (5.2% to 6.8%; p = 0.029), non-Hodgkin lymphoma (NHL) (4.4% to 6.3%; p =.005), and tuberculosis (0.5% to 2.7%; p <.0005). Median survival following AIDS increased from 19.6 months for AIDS cases diagnosed in 1993 to 1995 to 39.6 months for AIDS cases diagnosed in 1996 to 2000 (p <.0005). Median survival was stable for NHL (7.5-8.8 months; p =.26), but increased significantly for almost all other ADIs. An increased proportion of PCP relative to other ADIs suggests an increasing proportion of AIDS patients not receiving specific prophylaxis, presumably because of "late" HIV diagnosis. Survival following almost all ADIs has increased in the era of HAART, although the prognosis after NHL remains extremely poor.

  6. Increased lipodystrophy is associated with increased exposure to highly active antiretroviral therapy in HIV-infected children.

    PubMed

    Viganò, Alessandra; Mora, Stefano; Testolin, Corrado; Beccio, Sabrina; Schneider, Laura; Bricalli, Dorella; Vanzulli, Angelo; Manzoni, Paola; Brambilla, Paolo

    2003-04-15

    To assess body composition changes in HIV-infected children receiving highly active antiretroviral therapy (HAART). Thirty-seven HIV-positive children were enrolled. Dual-energy X-ray absorptiometry (DXA) scans were performed in all HIV-infected children at baseline and after an additional 12 months of HAART and in 54 matched (for sex, age, body mass index [BMI], and pubertal stage) healthy controls. Abdominal MRI was performed in 14 of 37 HIV-positive children at baseline and in 28 of 37 HIV-positive children after additional 12 months of HAART. During the study period, mean HAART exposure increased from 39.3 to 50.9 months and the number of HIV-infected children with clinical lipodystrophy (LD) increased from 6 to 8, whereas mean BMI, CD4 percentage, and percentage of HIV-infected children with HIV RNA <50 copies/mL did not change. DXA scans showed an increase in lean mass, peripheral fat loss, and central fat accumulation in all HIV-infected children. As compared with controls, 70% and 84% of HIV-infected children showed DXA-detectable LD at baseline and at 12 months of follow-up, respectively. Mixed LD and central fat accumulation were the most common LD phenotype. At baseline and at 12 months of follow-up, intra-abdominal adipose tissue (IAT) was greater than in controls in 33% and 35% of HIV-infected children, and it was greater in those with LD than in those without. Peripheral fat loss and IAT content were associated with duration of HAART and were independent of immunologic stage of disease and immunologic response. Changes in body composition related to LD in HAART-treated children are frequent, precocious, and progressive. Duration of HAART negatively influences visceral adiposity and peripheral fat loss.

  7. Relationship of ethnicity and CD4 Count with glucose metabolism among HIV patients on Highly-Active Antiretroviral Therapy (HAART)

    PubMed Central

    2013-01-01

    Background HIV patients on HAART are prone to metabolic abnormalities, including insulin resistance, lipodystrophy and diabetes. This study purports to investigate the relationship of ethnicity and CD4+ T cell count attained after stable highly-active antiretroviral treatment (HAART) with glucose metabolism in hyperrtriglyceridemic HIV patients without a history of diabetes. Methods Demographic, anthropometric, clinical, endocrinologic, energy expenditure and metabolic measures were obtained in 199 multiethnic, healthy but hypertriglyceridemic HIV-infected patients [46% Hispanic, 17% African-American, 37% Non-Hispanic White (NHW)] on stable HAART without a history of diabetes. The relationship of glucose and insulin responses to ethnicity, CD4 strata (low (<300/cc) or moderate-to-high (≥ 300/cc)), and their interaction was determined. Results African-Americans had significantly greater impairment of glucose tolerance (P < 0.05) and HbA1c levels (P < .001) than either Hispanics or NHWs. In multivariate models, after adjusting for confounders (age, sex, HIV/HAART duration, smoking, obesity, glucose, insulin and lipids), African-Americans and Hispanics had significantly higher HbA1c and 2-hour glucose levels than NHW’s. Demonstrating a significant interaction between ethnicity and CD4 count (P = 0.023), African Americans with CD4 <300/cc and Hispanics with CD4 ≥300/cc had the most impaired glucose response following oral glucose challenge. Conclusions Among hypertriglyceridemic HIV patients on HAART, African-Americans and Hispanics are at increased risk of developing diabetes. Ethnicity also interacts with CD4+ T cell count attained on stable HAART to affect post-challenge glycemic response. PMID:23607267

  8. Acupuncture and the relaxation response for treating gastrointestinal symptoms in HIV patients on highly active antiretroviral therapy

    PubMed Central

    Chang, Bei-Hung; Sommers, Elizabeth

    2011-01-01

    Objectives To examine the effect of acupuncture and the relaxation response (RR) for treating gastrointestinal (GI) symptoms in HIV patients who are using highly active antiretroviral therapy (HAART). Methods The authors conducted a 4-arm 2×2 double-blind randomised controlled trial in an acupuncture clinic in the USA. Sham acupuncture and health education were used as the control conditions of real acupuncture and RR elicitation, respectively. Enrolled patients were randomised to real acupuncture+RR (AR), sham acupuncture+RR (SR), real acupuncture+health education (AE) or sham acupuncture+health education (SE) study arm. Participants listened to CDs with RR-eliciting instructions or health education while receiving acupuncture intervention. Interventions were provided twice weekly for 4 weeks and once weekly for another 4 weeks. Participants used daily diaries to record GI symptom severity ratings (0–10). The authors estimated the intervention effect as the changes in symptom rating per intervention session increase using a mixed-effects regression model. Results A total of 130 people with HIV/AIDS who were on HAART and had persistent GI symptoms were enrolled and 115 started the study intervention. The AR group had greater intervention effects for loose stools symptoms than the other three groups (β=−0.149, −0.151 and −0.144, p value=0.013, 0.013 and 0.018 comparing AR to AE, SR and SE, respectively). The AR group also had significant intervention effects on reducing nausea symptoms when the intervention was given twice per week (β=−0.218, p=0.001). Conclusions Our trial provided preliminary data demonstrating the potential synergistic effects of acupuncture and RR for treating GI symptoms in HIV patients on HAART. PMID:21705396

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

    PubMed

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

    2010-10-15

    Excess mortality has decreased among human immunodeficiency virus (HIV)-infected patients but without evidence of a decrease among 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). We included 1188 patients of the Longitudinal Study of Ocular Complications in AIDS who were aged 25-64 years at enrollment and who received a diagnosis of 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 during the period 1999-2007. We used a relative survival model to identify risk factors for excess mortality. There were a mean of 50 excess deaths per 1000 person-years (95% confidence interval [CI], 44-57 excess deaths per 1000 person-years) during 1999-2007. Excess mortality almost halved, with an annual decrease of 8.0% per year (95% CI, 3.0%-12.7%; P = .002) but remained high at 36 excess deaths per 1000 person-years in 2007. Viral load >400 copies/mL (compared with or= 200 cells/μL; risk ratio, 2.7; 95% CI, 1.9-3.9), and cytomegalovirus retinitis (risk ratio, 1.6; 95% CI, 1.2-2.1) were the strongest risk factors for excess mortality. 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 ∼5 times higher in patients with AIDS than in HIV-infected patients without AIDS.

  10. 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

  11. Virulence factors and genetic variability of vaginal Candida albicans isolates from HIV-infected women in the post-highly active antiretroviral era.

    PubMed

    Zanni, Pâmela Cristina Mastellaro Delvas; Bonfim-Mendonça, Patrícia de Souza; Negri, Melyssa; Nakamura, Sandra Sayuri; Donatti, Lucélia; Svidzinski, Terezinha Inez Estivalet; Consolaro, Márcia Edilaine Lopes

    2017-01-01

    Vulvovaginal candidiasis (VVC) in HIV-infected (HIV+) women is a serious public health problem. However, little is known about the virulence mechanisms of vaginal Candida albicans from HIV+ women in the post-highly active antiretroviral therapy (HAART) era. Here, we report a comparative analysis of the expression of key virulence factors and genetic variability of 26 vaginal C. albicans strains isolated from HIV+ women undergoing HAART and 18 from HIV-uninfected (HIV-) women. In general, we observed that C. albicans from HIV+ women receiving HAART showed lower expression of virulence factors compared with C. albicans from HIV- women, except for the proteinase activity which is highly expressed. The results in HIV-women further suggest that virulence factors appear to be expressed in response to the yeast stress, in the presence of an adequate immune response. Furthermore, the RAPD results showed a high heterogeneity among isolates from both groups of women. These findings in HIV+ women using HAART will help to improve the monitoring of vaginal yeast infections and the quality of life of patients.

  12. [Prevalence and factors associated with the adhesion of children in highly active antiretroviral therapy in three urban centers in Southern Brazil].

    PubMed

    Trombini, Eliana Silva; Schermann, Lígia Braun

    2010-03-01

    This study verified the prevalence and associated factors to the adhesion of children in Highly Active Antiretroviral Therapy (HAART), in three urban centers in Southern Brazil: Passo Fundo, Canoas and Cachoeira do Sul. The population of the study consisted of 44 children, between 18 months to 13 years old, in HAART. Data was collected by applying a socio-demographic questionnaire with the caregivers, aiming to know the children's sex, age, schooling, treatment type and clinical state, as well as the caregiver's income, age and schooling. Adhesion was considered when the effectiveness of the HAART was at least 95% of the prescribed regimen. The design of the study was analytical and transversal. Data analysis was performed by descriptive analysis (frequency, percentage) and bivariate analysis (chi-square test), crossing the outcome variable (adhesion to HAART) and the independent variables (sociodemographic, clinical state, treatment type, caregiver's age and schooling). The results showed 82% of adhesion in the studied children. The bivariate analysis did not point out significant associations between adhesion and independent variables. A possible linear tendency to increase the adhesion as a function of the improvement of the physical state was observed.

  13. Associations between HIV, highly active anti-retroviral therapy, and hypertensive disorders of pregnancy among maternal deaths in South Africa 2011-2013.

    PubMed

    Sebitloane, Hannah M; Moodley, Jagidesa; Sartorius, Benn

    2017-02-01

    To explore potential relationships between HIV and highly active anti-retroviral therapy (HAART), and hypertensive disorders of pregnancy (HDP). A retrospective secondary analysis of maternal-deaths data from the 2011-2013 Saving Mothers Report from South Africa. The incidence of HIV infection amongst individuals who died owing to HDP was determined and comparisons were made based on HIV status and the use of HAART. Among 4452 maternal deaths recorded in the Saving Mothers report, a lower risk of a maternal deaths being due to HDP was observed among women who had HIV infections compared with women who did not have HIV (relative risk [RR] 0.57, 95% confidence interval [CI] 0.51-0.64). Further, reduced odds of death being due to HDP were recorded among women with AIDS not undergoing HAART compared with women with HIV who did not require treatment (RR 0.42, 95% CI 0.3-0.58). Notably, among all women with AIDS, a greater risk of death due to HDP was demonstrated among those who received HAART compared with those who did not (RR 1.15, 95% CI 1.02-1.29). HIV and AIDS were associated with a decreased risk of HDP being the primary cause of death; the use of HAART increased this risk. © 2016 International Federation of Gynecology and Obstetrics.

  14. Highly Active Antiretroviral Therapy (HAART)-Related Hypertriglyceridemia Is Associated With Failure of Recovery of CD14lowCD16+ Monocyte Subsets in AIDS Patients.

    PubMed

    Han, Junyan; Zhao, Hongxin; Ma, Yaluan; Zhou, Haiwei; Hao, Yu; Li, Yanmei; Song, Chuan; Han, Ning; Liu, Xiangyi; Zeng, Hui; Qin, Mingzhao

    2015-07-01

    As cellular reservoirs, CD16 monocyte subsets play important roles in the progression of HIV infection. Previous studies have shown that highly active antiretroviral therapy (HAART) reduced the percentages of CD14CD16 monocyte subsets, but did not recover the percentages of CD14CD16 subsets. Eighty-four chronic HIV-infected, HAART-naïve individuals and 55 HIV-negative subjects (31 without hyperlipidemia and 24 with hypertriglyceridemia) were enrolled. Plasma HIV-1 RNA levels, CD4 T-cell counts, triglycerides, total cholesterol, high-density lipoprotein, and low-density lipoprotein were followed up for 48 weeks during HAART treatment in the longitudinal study. We found that mild hypertriglyceridemia in HIV-negative subjects and HIV-infected patients, naïve to HAART, did not affect the percentage of monocyte subsets. However, a failure of CD14CD16 subset recovery was observed in patients with HAART-related hypertriglyceridemia at 48 weeks. Thus, HAART-related hypertriglyceridemia altered homeostasis of monocyte subsets to antiviral therapy, which might further affect immune reconstitution.

  15. Diagnostic yield of fine-needle aspiration cytology in HIV-infected patients with lymphadenopathy in the era of highly active antiretroviral therapy.

    PubMed

    Lowe, S M; Kocjan, G I; Edwards, S G; Miller, R F

    2008-08-01

    Fine-needle aspiration (FNA) cytology has an established role in the investigation of lymphadenopathy in HIV-infected patients. However, changes in the spectrum of disease have been observed since the introduction of highly active antiretroviral therapy (HAART). The aim of the study was to establish whether FNA cytology remains a useful investigative tool in the post-HAART era and to determine whether the cytology results reflect the changing patterns of disease. Retrospective search of the cytopathology database at University College London Hospitals identified 73 FNA cytology procedures performed in 62 patients between January 1998 and December 2006. FNA cytology showed significant disease in 90% of adequate samples. The most common diagnoses were persistent generalized lymphadenopathy (PGL, 50%), infection (22%) and malignancy (18%). Diagnoses could not be made in 31% of patients because of inadequate sampling. An open lymph node biopsy was subsequently performed in 27% of patients. FNA cytology remains an important initial investigation in the post-HAART era, particularly in the diagnosis of PGL, infection and malignancy. Difficulties in diagnosis of Castleman disease and Hodgkin's lymphoma by FNA cytology are recognized.

  16. Highly Active Antiretroviral Therapy (HAART)-Related Hypertriglyceridemia Is Associated With Failure of Recovery of CD14lowCD16+ Monocyte Subsets in AIDS Patients

    PubMed Central

    Han, Junyan; Zhao, Hongxin; Ma, Yaluan; Zhou, Haiwei; Hao, Yu; Li, Yanmei; Song, Chuan; Han, Ning; Liu, Xiangyi; Zeng, Hui; Qin, Mingzhao

    2015-01-01

    Abstract As cellular reservoirs, CD16+ monocyte subsets play important roles in the progression of HIV infection. Previous studies have shown that highly active antiretroviral therapy (HAART) reduced the percentages of CD14highCD16+ monocyte subsets, but did not recover the percentages of CD14lowCD16+ subsets. Eighty-four chronic HIV-infected, HAART-naïve individuals and 55 HIV-negative subjects (31 without hyperlipidemia and 24 with hypertriglyceridemia) were enrolled. Plasma HIV-1 RNA levels, CD4+ T-cell counts, triglycerides, total cholesterol, high-density lipoprotein, and low-density lipoprotein were followed up for 48 weeks during HAART treatment in the longitudinal study. We found that mild hypertriglyceridemia in HIV-negative subjects and HIV-infected patients, naïve to HAART, did not affect the percentage of monocyte subsets. However, a failure of CD14lowCD16+ subset recovery was observed in patients with HAART-related hypertriglyceridemia at 48 weeks. Thus, HAART-related hypertriglyceridemia altered homeostasis of monocyte subsets to antiviral therapy, which might further affect immune reconstitution. PMID:26166108

  17. Hyperinsulinemia induced by highly active antiretroviral therapy in an adolescent with polycystic ovary syndrome who was infected with human immunodeficiency virus.

    PubMed

    Viganò, Alessandra; Manzoni, Paola; Riva, Silvia; Brambilla, Paolo; Ferrazzi, Enrico; Marzi, Marco M

    2003-02-01

    To report a case of polycystic ovary syndrome (PCOS) in an adolescent infected with human immunodeficiency virus (HIV) and lipodystrophy whose insulin resistance was induced by highly active antiretroviral therapy (HAART). Case report. Academic department of pediatrics. A 14-year-old vertically HIV-infected adolescent receiving HAART. Clinical observation, metabolic and endocrinologic assessment, imaging of ovaries by ultrasound, and of intra-abdominal adipose tissue content by magnetic resonance imaging. Lipodystrophy, insulin resistance, PCOS. After 34 months of HAART this adolescent showed lipodystrophy with central obesity and insulin resistance after oral glucose tolerance test (OGTT). Ovaries were normal at ultrasonography. After 56 weeks of HAART, the adolescent showed more severe evidence of lipodystrophy and insulin resistance, and she developed acne, hirsutism, and amenorrhea. The following hormone levels were elevated: FSH 5.9 mUI/mL, LH 15.4 mUI/mL, LH/FSH ratio >2.5, free T 5.6 pg/mL, DHEAS 2,070 ng/mL, androstenedione (A) 3.42 ng/mL; whereas 17-beta-E(2), P, PRL, and free T(4) values were within the normal range. Ultrasonography demonstrated a typical polycystic echographic architecture of the ovaries. Lipodystrophy and insulin resistance are well-recognized side effects of HAART. Polycystic ovary syndrome might be an additional side effect secondary to insulin resistance and lipodystrophy.

  18. Factors associated with late initiation of highly active antiretroviral therapy among young HIV-positive men and women aged 18 to 29 years in Canada.

    PubMed

    Palmer, Alexis K; Cescon, Angela; Chan, Keith; Cooper, Curtis; Raboud, Janet M; Miller, Caroline L; Burchell, Ann N; Klein, Marina B; Machouf, Nima; Montaner, Julio S G; Tsoukas, Chris; Hogg, Robert S; Loutfy, Mona R

    2014-01-01

    Initiating highly active antiretroviral therapy (HAART) with low CD4 counts or AIDS-defining illnesses (ADIs) increases risk of treatment failure and death. We examined factors associated with late initiation among 18- to 29-year-olds within the Canadian Observational Cohort (CANOC) collaboration, a multi-site study of HIV-positive persons who initiated HAART after 2000. Late initiation was defined as beginning HAART with a CD4 count <200 cells/mm(3) and/or having a baseline ADI. Multivariable logistic regression was used to identify independent correlates of late initiation. In total, 1026 individuals (422 from British Columbia, 400 from Ontario, and 204 from Quebec) met our age criteria. At HAART initiation, median age was 27 years (interquartile range, 24, 28 years). A total of 412 individuals (40%) identified as late initiators. Late initiation was associated with female gender, age >25 years at initiation, initiating treatment in earlier years, and having higher baseline viral load. The high number of young adults in our cohort starting HAART late indicates important target populations for specialized services, increased testing, and linkages to care.

  19. Efficacy of interventions in improving highly active antiretroviral therapy adherence and HIV-1 RNA viral load. A meta-analytic review of randomized controlled trials.

    PubMed

    Simoni, Jane M; Pearson, Cynthia R; Pantalone, David W; Marks, Gary; Crepaz, Nicole

    2006-12-01

    Adherence to highly active antiretroviral therapy (HAART) is generally suboptimal, limiting the effectiveness of HAART. This meta-analytic review examined whether behavioral interventions addressing HAART adherence are successful in increasing the likelihood of a patient attaining 95% adherence or an undetectable HIV-1 RNA viral load (VL). We searched electronic databases from January 1996 to September 2005, consulted with experts in the field, and hand searched reference sections from relevant articles. Nineteen studies (with a total of 1839 participants) met the selection criteria of describing a randomized controlled trial among adults evaluating a behavioral intervention with HAART adherence or VL as an outcome. Random-effects models indicated that across studies, participants in the intervention arm were more likely than those in the control arm to achieve 95% adherence (odds ratio [OR] = 1.50, 95% confidence interval [CI]: 1.16 to 1.94); the effect was nearly significant for undetectable VL (OR = 1.25; 95% CI: 0.99 to 1.59). The intervention effect for 95% adherence was significantly stronger in studies that used recall periods of 2 weeks or 1 month (vs. observed. In sum, various HAART adherence intervention strategies were shown to be successful, but more research is needed to identify the most efficacious intervention components and the best methods for implementing them in real-world settings with limited resources.

  20. Persistence of HIV-1 structural proteins and glycoproteins in lymph nodes of patients under highly active antiretroviral therapy.

    PubMed

    Popovic, Mikulas; Tenner-Racz, Klara; Pelser, Colleen; Stellbrink, Hans-Jurgen; van Lunzen, Jan; Lewis, George; Kalyanaraman, Vaniambadi S; Gallo, Robert C; Racz, Paul

    2005-10-11

    Here we report a long-term persistence of HIV-1 structural proteins and glycoproteins in germinal centers (GCs) of lymph nodes (LNs) in the absence of detectable virus replication in patients under highly active antiretroviral therapy (HAART). The persistence of viral structural proteins and glycoproteins in GCs was accompanied by specific antibody responses to HIV-1. Seven patients during the chronic phase of HIV-1 infection were analyzed for the presence of the capsid protein (HIV-1p24), matrix protein (HIV-1p17), and envelope glycoproteins (HIV-1gp120/gp41), as well as for viral RNA (vRNA) in biopsy specimens from LNs obtained before initiation of therapy and during HAART that lasted from 5 to 13 months. In parallel, these patients were also monitored for viremia and specific anti-HIV-1 antibody responses to structural proteins and glycoproteins both before and during treatment. Before-therapy viral levels, as determined by RT-PCR, ranged from 3 x 10(3) to 6.3 x 10(5) copies of vRNA per ml, whereas during treatment, vRNA was under detectable levels (<25 copies per ml). The pattern of vRNA detection in peripheral blood was concordant with in situ hybridization results of LN specimens. Before treatment, vRNA associated with follicular dendritic cells (FDCs) was readily detected in GCs of LNs of the patients, whereas during therapy, vRNA was consistently absent in the GCs of LN biopsies of treated patients. In contrast to vRNA hybridization results, viral structural proteins and glycoproteins, evaluated by immunohistochemical staining, were present and persisted in the GC light zone of LNs in abundant amounts not only before initiation of therapy but also during HAART, when no vRNA was detected in GCs. Consistent with immunohistochemical findings, specific antibody responses to HIV-1p17, -p24, and -gp120/gp41, as evaluated by ELISA and virus neutralization, persisted in patients under therapy for up to 13 months of follow-up. The implications of these findings are

  1. Smear positive pulmonary tuberculosis among HIV patients receiving highly active antiretroviral therapy in Dar es Salaam, Tanzania.

    PubMed

    Bwana, Veneranda; Tenu, Filemoni; Magesa, Stephen M; Mfinanga, Sayoki G

    2011-01-01

    Globally, tuberculosis-HIV co-infections are on the increase. In 2007, 15% (1.37 million) of the tuberculosis cases were HIV-positive tuberculosis (TB). This cross-sectional study was conducted in February 2009 to assess the effect of the level of CD4 lymphocyte counts on the development of smear positive pulmonary TB (PTB) among HIV patients before and after initiation of highly active antiretroviral therapy (HAART). A total of 155 HIV patients who were on HAART programme were enrolled and out of these 42 (27.1%) were smear positive PTB. Of the 42 PTB patients, 38 (90.5%) were also infected with HIV and were already at initiation of HAART. There was no association between the development of smear positive PTB and socio-demographic characteristics among HIV patients before and after HAART initiation (P>0.05). A larger proportion of HIV+PTB patients diagnosed before and after HAART initiation was found with CD4 lymphocyte count <200cells/microl. However, the difference was not statistically significant (P =0.092). Among HIV patients who were diagnosed to be smear positive PTB after HAART initiation, their CD4 lymphocyte counts at time of TB diagnosis was lower than their CD4 lymphocyte counts at time of HAART initiation. The four patients diagnosed with PTB after HAART initiation had mean CD4 lymphocyte counts at HAART initiation not statistically different from that at TB diagnosis (t=0.715, P=0.526). The median time period within which the diagnosis of smear positive PTB was made after HAART initiation was 22 weeks and the mean time was 66.75 weeks. These findings provide evidence that development of smear positive PTB after HAART initiation may occur at any level of CD4 lymphocyte count (P<0.05). This study was limited by the relatively small sample size, we therefore recommend more studies involving a larger sample size in order to estimate more accurately the effect of both level of CD4 lymphocyte count and HAART on the development of smear positive PTB among

  2. Oral lesions as clinical markers of highly active antiretroviral therapy failure: a nested case-control study in Mexico City.

    PubMed

    Ramírez-Amador, Velia; Ponce-de-León, Sergio; Anaya-Saavedra, Gabriela; Crabtree Ramírez, Brenda; Sierra-Madero, Juan

    2007-10-01

    Clinical markers that may predict virological failure during highly active antiretroviral therapy (HAART) have not been evaluated adequately. The aim of the present study was to evaluate the usefulness of human immunodeficiency virus (HIV)-related oral lesions as clinical predictors of virological failure in HIV-infected patients receiving HAART. A nested case-control study was conducted within a cohort of 1134 HIV-infected patients receiving HAART who attended the AIDS Clinic of the Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán in Mexico City during the period 1997-2005. Case patients were patients who, after achieving an undetectable viral load, had at least 1 viral load determination > or = 2000 copies/mL while receiving treatment. Control subjects were patients who, after achieving an undetectable viral load, continued to have undetectable viral loads during the follow-up period. There were 2-3 control subjects for each case patient, matched according to duration of follow-up. Oral examinations were blinded to viral loads and CD4+ lymphocyte counts. Analyses were performed with multivariate conditional logistic regression models, and associations were shown as odds ratios (ORs) with 95% confidence intervals (CI). Positive predictive values were calculated. The target cohort consisted of 431 HIV-infected individuals; 47 case patients and 132 control subjects underwent complete oral examinations and formed the basis of the analysis. At the visit at which an undetectable viral load was determined, case patients and control subjects showed a similar frequency of HIV-related oral lesions (21.3% vs. 17.4%) (OR, 1.39; 95% CI, 0.57-3.38; P=.47). At the visit at which virological failure was determined, case patients showed a higher risk for HIV-related oral lesions (OR, 14.5; 95% CI, 4.21-49.94; P<.001) and oral candidosis (OR, 26.2; 95% CI, 3.34-205.9; P<.001) than did control subjects. The positive predictive value of HIV-related oral lesions

  3. A double-edged sword: does highly active antiretroviral therapy contribute to syphilis incidence by impairing immunity to Treponema pallidum?

    PubMed

    Rekart, Michael L; Ndifon, Wilfred; Brunham, Robert C; Dushoff, Jonathan; Park, Sang Woo; Rawat, Sanjana; Cameron, Caroline E

    2017-08-01

    Recently, the world has experienced a rapidly escalating outbreak of infectious syphilis primarily affecting men who have sex with men (MSM); many are taking highly active antiretroviral therapy (HAART) for HIV-1 infection. The prevailing hypothesis is that HAART availability and effectiveness have led to the perception among both individuals who are HIV-1 infected and those who are uninfected that HIV-1 transmission has become much less likely, and the effects of HIV-1 infection less deadly. This is expected to result in increased sexual risk-taking, especially unprotected anal intercourse, leading to more non-HIV-1 STDs, including gonorrhoea, chlamydia and syphilis. However, syphilis incidence has increased more rapidly than other STDs. We hypothesise that HAART downregulates the innate and acquired immune responses to Treponema pallidum and that this biological explanation plays an important role in the syphilis epidemic. We performed a literature search and developed a mathematical model of HIV-1 and T. pallidum confection in a population with two risk groups with assortative mixing to explore the consequence on syphilis prevalence of HAART-induced changes in behaviour versus HAART-induced biological effects. Since rising syphilis incidence appears to have outpaced gonorrhoea and chlamydia, predominantly affecting HIV-1 positive MSM, behavioural factors alone may be insufficient to explain the unique, sharp increase in syphilis incidence. HAART agents have the potential to alter the innate and acquired immune responses in ways that may enhance susceptibility to T. pallidum. This raises the possibility that therapeutic and preventative HAART may inadvertently increase the incidence of syphilis, a situation that would have significant and global public health implications. We propose that additional studies investigating the interplay between HAART and enhanced T. pallidum susceptibility are needed. If our hypothesis is correct, HAART should be combined with

  4. Comparison of treatment regimens for cytomegalovirus retinitis in patients with AIDS in the era of highly active antiretroviral therapy.

    PubMed

    Jabs, Douglas A; Ahuja, Alka; Van Natta, Mark; Dunn, J P; Yeh, Steven

    2013-06-01

    To describe the outcomes of different treatment approaches for cytomegalovirus (CMV) retinitis in the era of highly active antiretroviral therapy (HAART). Prospective cohort study, the Longitudinal Study of the Ocular Complications of AIDS. A total of 250 patients with CMV retinitis and a CD4+ T-cell count <100 cells/μl (n = 221) at enrollment or incident retinitis (n = 29) during cohort follow-up. The effects of systemic therapy (vs. intraocular therapy only) on systemic outcomes and the effect of intraocular therapies (ganciclovir implants, intravitreal injections) on ocular outcomes were evaluated. Mortality, CMV dissemination, retinitis progression, and treatment side effects. Regimens containing systemic anti-CMV therapy were associated with a 50% reduction in mortality (adjusted hazard ratio [HR], 0.5; 95% confidence interval [CI], 0.3-0.7; P = 0.006), a 90% reduction in new visceral CMV disease (adjusted HR, 0.1; 95% CI, 0.04-0.4; P = 0.004), and among those with unilateral CMV retinitis at presentation, an 80% reduction in second eye disease (adjusted HR, 0.2; 95% CI, 0.1-0.5; P = 0.0005) when compared with those using only intraocular therapy (implants or injections). Compared with systemic treatment only, regimens containing intravitreal injections had greater rates of retinitis progression (adjusted HR, 3.4; P = 0.004) and greater visual field loss (for loss of one half of the normal field, adjusted HR, 5.5; P < 0.01). Intravitreal implants were not significantly better than systemic therapy (adjusted HR for progression, 0.5; P = 0.26; adjusted HR for loss of one half of the visual field, 0.5; P = 0.45), but the sample size was small. Hematologic and renal side effect rates were similar between those groups with and without systemic anti-CMV therapy. The rate of endophthalmitis was 0.017 per eye-year (EY) (95% CI, 0.006-0.05) among those treated with intravitreal injections and 0.01 per EY (95% CI, 0.002-0.04) among those treated with an implant. In the

  5. 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

  6. Gender differences in health related quality of life among people living with HIV on highly active antiretroviral therapy in Mekelle Town, Northern Ethiopia.

    PubMed

    Tesfay, Amanuel; Gebremariam, Abebe; Gerbaba, Mulusew; Abrha, Hailay

    2015-01-01

    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. 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. 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. 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.

  7. Eruptive cheilitis: a new adverse effect in reactive HIV-positive patients subjected to high activity antiretroviral therapy (HAART). Presentation of six clinical cases.

    PubMed

    Casariego, Z; Pombo, T; Pérez, H; Patterson, P

    2001-01-01

    A variety of exfoliative cheilitis has been observed in reactive HIV-1 patients subjected to high activity antiretroviral therapy (HAART). The lesions exhibit exfoliation, crater formation, fissuring, erosions and/or the formation of papules, vesicles and blisters associated to erythema and edema. The condition is not included in the 1993 EEC Clearinghouse classification (1) of oral lesions associated with HIV infection. In an earlier series of 1899 patients (2), we failed to observe this pathology and have only found one similar case described in the literature to date (3). We present a series of 6 patients with HIV infection and morpho-histological alterations of the labial semimucosa, subjected to HAART. The 6 patients were selected from among 20 HIV-positive individuals treated in our Infectious Diseases Unit with a combination of nucleoside and non-nucleoside reverse transcriptase inhibitors and protease inhibitors requiring stomatological care for painful lesions of the lips and oral cavity. The study was conducted over a 6-month period between May and October 1998. An analysis was made of the case histories, CD4-positive cell counts and viral load. The stomatological explorations were completed with biopsies, hematoxylin-eosin staining and immunohistochemical studies involving AE1 and AE3 monoclonal antibodies, vimentin, protein S-100, carcinoembryonic antigen (CEA), laminin, CD8, HLA-DR, BM-1 and CD31 markers. At the time of detection of the oral lesions, the patients had received different combinations of the following antiretroviral treatments: stavudine (D4T), zalcitabine (DDC), didanosine (DDI), zidovudine (AZT), lamivudine (3TC), nelfinavir (NFV), saquinavir (SQV), ritonavir (RTV), hydroxyurea (HU), indinavir (IDN) and efavirenz (EFV). There were four males and two females (age range 31-42 years). The CD4-positive and viral load ranges were 70-330 cells/mm3 and 200-500,200 copies, respectively. Stomatologic manifestations: The oral clinical

  8. 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

  9. Long-term effects of highly active antiretroviral therapy on CD4+ cell evolution among children and adolescents infected with HIV: 5 years and counting.

    PubMed

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

    2008-06-01

    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. 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. 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. 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.

  10. 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.

  11. The impact of highly active antiretroviral therapy (HAART) on visceral leishmaniasis in Spanish patients who are co-infected with HIV.

    PubMed

    López-Vélez, R

    2003-10-01

    Clinicians in Madrid have been observing and treating HIV-positive patients with visceral leishmaniasis (VL) for over a decade. As their records cover some of the co-infection cases that occurred before and after highly active antiretroviral therapy (HAART) was introduced into Spain, retrospective analysis of the records has allowed some of the effects of HAART on local VL to be determined. Encouragingly, HAART appears to have decreased the annual incidence of VL among local AIDS cases, from 4.81 cases/100 to just 0.8 case/100 (P <0.0005), a first episode of VL now appearing only when there is obvious HAART failure. Unfortunately, it does not seem to be very good at preventing VL relapses; within 24 months of antileishmanial treatment, 70% of patients who were receiving HAART had such relapses. The mean time between antileishmanial treatment and VL relapse was, however, longer when HAART was used than when it was not (20 v. 13 months). In those receiving HAART, relapses of the VL often occurred despite increasing CD4+ cell counts and undetectable HIV loads, indicating that successful treatment of the viral infection is insufficient to prevent the relapse of the leishmaniasis. These results are in general agreement with other observations made in Spain. VL relapses are possible and even frequent in HIV-positives who have no more than 200 CD4+ cells/microl, but secondary prophylaxis to prevent VL relapses may be safely suspended if a CD4+ count of >200 cells/microl can be maintained using HAART. VL also seems to hamper the immunological recovery of the HIV-positive, although HAART appears to have little effect on the clinical manifestations of VL.

  12. 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

  13. 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.

  14. Low immunologic response to highly active antiretroviral therapy in naive vertically human immunodeficiency virus type 1-infected children with severe immunodeficiency.

    PubMed

    Resino, Salvador; Alvaro-Meca, Alejandro; de José, Maria Isabel; Martin-Fontelos, Pablo; Gutiérrez, Maria Dolores Gurbindo; Léon, Juan Antonio; Ramos, José Tomás; Ciria, Luis; Muñoz-Fernández, Maria Angeles

    2006-04-01

    We conducted a retrospective study to analyze the CD4 recovery of naive vertically human immunodeficiency virus-infected children with severe immunodeficiency who were followed up during at least 4 years of receiving highly active antiretroviral therapy (HAART). Children with baseline CD4 of <15% did not reach a mean CD4 of > or =25% after the 4th year on HAART. We conclude that starting HAART after severe immunosuppression of naive HIV-infected children may not be effective for recovery of normal %CD4.

  15. Cardiac function in vertically HIV-infected children and adolescents in the era of highly active antiretroviral therapy.

    PubMed

    Sainz, Talía; Álvarez-Fuente, María; Fernández-Jiménez, Rodrigo; González-Tomé, María Isabel; de José, María Isabel; Ramos, José Tomás; Navarro, María Luisa; Martínez, Jorge; García-Hortelano, Milagros; Medrano, Constancio; Muñoz-Fernández, María Ángeles; Mellado, María José

    2015-05-01

    Previous studies have demonstrated increased risk of adverse cardiac outcomes in adults with HIV infection. However, few studies have addressed this problem in vertically HIV-infected children and adolescents, and the long-term cardiac health of this unique population in the antiretroviral therapy era is still unknown. Ventricular function was evaluated cross-sectionally in a group of HIV-infected children and adolescents and healthy controls, using conventional echocardiography along with tissue Doppler imaging and strain analysis by speckle tracking. Simultaneously, measurements of carotid intima-media thickness were performed. A total of 64 cases and 58 controls were included, mean age was 13.6 ± 5.4 years and 64% were females. All but 2 patients were on antiretroviral treatment, and 64% had undetectable viral load. HIV-infected patients showed higher intima-media thickness (0.425 ± 0.019 vs. 0.415 ± 0.019 mm, P = 0.003). Statistically significant differences were found between groups in ejection fraction and fractional shortening (66.1% and 36.2% in the HIV-infected group vs. 71.5% and 40.8% in the control group, respectively, P = 0.001), although individual values fell within or near normal ranges. There were no significant differences in diastolic function, tissue Doppler imaging or cardiac strain (longitudinal and rotational) between both groups. No associations were identified between echocardiographic parameters and current CD4+ T-lymphocyte counts, CD4+ T-lymphocyte nadir, HIV viral load, duration or type of antiretroviral treatment regimens. In a context of highly effective antiretroviral treatment, no differences were found regarding cardiac abnormalities using conventional and advanced ultrasound imaging techniques in this cohort of vertically HIV-infected children and adolescents, when compared with healthy controls.

  16. Adherence to highly active antiretroviral therapy in depressed patients with HIV/AIDS attending a Nigerian university teaching hospital clinic.

    PubMed

    Olisah, V O; Baiyewu, O; Sheikh, T L

    2010-09-01

    To determine the prevalence of depressive disorder in patients with HIV/AIDS receiving HAART; to determine the effect of depressive disorder on adherence to antiretroviral therapy; and to determine the significance of the association. The study was conducted amongst outpatients of Ahmadu Bello University Teaching Hospital, Zaria. A sociodemographic and drug adherence questionnaire was administered. The Centre for Epidemiological Studies Depression Scale (CES-D) was used to screen for depressive symptoms while the Schedule for Clinical Assessment in Neuropsychiatry (SCAN) was used to confirm the diagnosis of depressive disorder. A total of 310 patients with HIV/AIDS receiving HAART participated in the study. 68.4% were female and the mean age was 35.5 (± 8.97 years). 37.4% had secondary education, while 27.1% had tertiary education. Sixty-six participants (21.3%) had significant depressive symptoms while 14.2% met ICD-10 diagnostic criteria for depressive disorder. Overall, 73% of participants had good adherence to HAART. 63.6% of participants with depressive disorder had poor adherence to HAART compared to 21.1% of participants without depressive disorder (p<0.05). Depressive disorder in patients with HIV/AIDS is associated with poor adherence to antiretroviral medication. Early identification and treatment of depression in such patients may improve antiretroviral medication adherence and treatment outcomes.

  17. Outcomes of highly active antiretroviral therapy in the context of universal access to healthcare: the U.S. Military HIV Natural History Study

    PubMed Central

    2010-01-01

    Background To examine the outcomes of highly-active antiretroviral therapy (HAART) for individuals with free access to healthcare, we evaluated 2327 patients in a cohort study composed of military personnel and beneficiaries with HIV infection who initiated HAART from 1996 to the end of 2007. Methods Outcomes analyzed were virologic suppression (VS) and failure (VF), CD4 count changes, AIDS and death. VF was defined as never suppressing or having at least one rebound event. Multivariate (MV) analyses stratified by the HAART initiation year (before or after 2000) were performed to identify risk factors associated with these outcomes. Results Among patients who started HAART after 2000, 81% had VS at 1 year (N = 1,759), 85% at 5 years (N = 1,061), and 82% at 8 years (N = 735). Five years post-HAART, the median CD4 increase was 247 cells/ml and 34% experienced VF. AIDS and mortality rates at 5 years were 2% and 0.3%, respectively. In a MV model adjusted for known risk factors associated with treatment response, being on active duty (versus retired) at HAART initiation was associated with a decreased risk of AIDS (HR = 0.6, 95% CI 0.4-1.0) and mortality (0.6, 0.3-0.9), an increased probability of CD4 increase ≥ 50% (1.2, 1.0-1.4), but was not significant for VF. Conclusions In this observational cohort, VS rates approach those described in clinical trials. Initiating HAART on active duty was associated with even better outcomes. These findings support the notion that free access to healthcare likely improves the response to HAART thereby reducing HIV-related morbidity and mortality. PMID:20507622

  18. The effect of depressive symptoms and CD4 count on adherence to highly active antiretroviral therapy in sub-Saharan Africa.

    PubMed

    Memiah, Peter; Shumba, Constance; Etienne-Mesubi, Martine; Agbor, Solomon; Hossain, Mian B; Komba, Patience; Niyang, Mercy; Biadgilign, Sibhatu

    2014-01-01

    Studies have identified several programmatic and nonprogrammatic indicators that affect adherence to highly active antiretroviral therapy (HAART). Depression has been shown to impact adherence to HAART. This cross-sectional analysis of data collected from Nigeria, Uganda, Zambia, and Tanzania in 2008 examined the relationship between levels of depressive symptoms, clinical progression, and adherence to HAART. A multinational, multicenter, observational, retrospective cross-sectional evaluation of a population of focus comprised randomly selected patients on HAART. The dependent variable was adherence to HAART. The primary variable of interest to be assessed was patients' level of depressive symptom score. A multivariable logistic regression model was used to examine the relationship between explanatory variables and adherence to HAART. A total of 2344 patients were recruited for adherence survey. About 70% of the study sample reported having some level of depression. Logistic regression results show that patients who reported, respectively, low, moderate, and high levels of depressive symptoms are 35% (P < .001), 56% (P < .001), and 64% (P < .001) less likely to adhere to HAART than those who reported having no depressive symptoms. At multivariate analysis, adherence to HAART was independently associated with the levels of depressive symptoms, older age, CD4 count >200 cells/mm3, Truvada (tenofovir [TDF]/emtricitabine [FTC])-based regimens, good knowledge about HAART, and longer period on therapy. These results indicate that mental health and clinical parameters are significant factors in determining patients' adherence to their HAART, which need to be more aggressively addressed as a critical component of care and treatment support.

  19. The effect of mental illness, substance use, and treatment for depression on the initiation of highly active antiretroviral therapy among HIV-infected individuals.

    PubMed

    Tegger, Mary K; Crane, Heidi M; Tapia, Kenneth A; Uldall, Karina K; Holte, Sarah E; Kitahata, Mari M

    2008-03-01

    Information regarding the prevalence of mental illness and substance use among HIV-infected patients and the effect of these problems on HIV treatment is needed. We conducted an observational study of patients in the University of Washington (UW) HIV Cohort to determine prevalence rates for mental illness and substance use. Cox regression analyses were used to examine the relationship between mental illness and substance use, pharmacologic treatment for depression/anxiety, and initiation of highly active antiretroviral therapy (HAART) within 9 months of becoming eligible for HAART. Among 1774 patients in the UW HIV cohort during 2004, 63% had a mental illness (including mood, anxiety, psychotic, or personality disorders), 45% had a substance use disorder, and 38% had both. There were 278 patients who met criteria for HAART eligibility. After controlling for other factors, patients with depression and/or anxiety were significantly less likely to initiate HAART compared with patients without a mental illness (hazard ratio [HR] 0.4, p = 0.02). However, patients with depression/anxiety who received antidepressant/antianxiety medications were equally likely to initiate HAART as patients without a mental illness (HR 0.9, p = 0.5). We found that patients with mental illness or substance use disorders receive HAART at lower CD4+ cell counts and higher HIV-1 RNA levels than patients without these disorders. However, HAART initiation among patients who receive treatment for depression/anxiety is associated with no delay. Screening for these disorders in primary care settings and access to appropriate treatment are increasingly important components of providing care to HIV-infected patients.

  20. The use of cell phone reminder calls for assisting HIV-infected adolescents and young adults to adhere to highly active antiretroviral therapy: a pilot study.

    PubMed

    Puccio, Joseph A; Belzer, Marvin; Olson, Johanna; Martinez, Miguel; Salata, Cathy; Tucker, Diane; Tanaka, Diane

    2006-06-01

    Long-term medication regimen adherence is challenging in all populations, but in the HIV-infected adolescent population the frequency of poverty, homelessness, substance abuse, and mental illness make highly active antiretroviral therapy (HAART) adherence even more challenging. In 2003, we developed a pilot program for HIV-infected adolescents and young adults between the ages of 16 and 24 who were either going to begin a HAART regimen for the first time or begin a new HAART regimen. Participants received a free cell phone with a local service plan for approximately 6 months. Participants received phone call reminders for 12 weeks. Call frequency was tapered at 4-week intervals. Patients were assessed at 4-week intervals to determine the perceived intrusiveness or helpfulness of receiving calls, and missed medication doses. Eight consecutive patients were recruited for the study, and five were able to complete it through the 24 weeks. Most participants found the calls to be helpful and the level of intrusion into their daily lives acceptable. Using cell phone reminders to assist patients does not require an extensive amount of daily staff time. Tapering calls rapidly over 3 months, followed by discontinuation of calls provided inadequate support for subjects, especially those with significant psychosocial issues such as substance abuse. Use of cell phone reminders to assist adolescents adhere with HIV medications was practical and acceptable to pilot study participants. Viral suppression waned for all but two patients after termination of cell phone reminders and suggests that a 12-week intervention was not adequate for most subjects. Larger prospective studies of cell phone observation of therapy will be needed to determine if this intervention can improve long-term adherence and health outcomes.

  1. Early and late effects of highly active antiretroviral therapy: a 2 year follow-up of antiviral-treated and antiviral-naive chronically HIV-infected patients.

    PubMed

    Clerici, Mario; Seminari, Elena; Maggiolo, Franco; Pan, Angelo; Migliorino, Marco; Trabattoni, Daria; Castelli, Francesco; Suter, Fredy; Fusi, Maria Luisa; Minoli, Lorenzo; Carosi, Giampiero; Maserati, Renato

    2002-09-06

    Control of HIV replication can be observed in highly active antiretroviral therapy (HAART)-treated and, occasionally, in HAART-naive patients. The immunological correlates of these situations were examined in a longitudinal study. A prospective study. Immunovirological analyses in 16 chronically HIV-infected, HAART-naive patients (time 0) who started HAART. Fifteen patients (short-term HAART) were re-evaluated after 24 months (time 1). Results were compared with those of 30 patients who received HAART for more than 12 months before the study period (long-term HAART) and were analysed at the same timepoints. Fifteen patients who were antiviral therapy naive (naive) at both timepoints were also studied. Over a 24-month period CD4 and CD8 cell counts and viraemia remained unchanged in naive and long-term HAART patients; CD4 cell counts increased and viraemia diminished in short-term HAART individuals. Antigen-stimulated proliferation was unmodified in naive and short-term HAART patients, but improved in long-term HAART individuals. Gp160-stimulated IL-2 and IFN-gamma production was augmented in long-term HAART patients and marginally modified in other patients. IL-7 production was unmodified in naive individuals, augmented in short-term HAART patients, and diminished in long-term HAART patients. Chemokine production was similar in all patients. Naive patients showed the highest CD8 cell counts at both timepoints. HAART has a major impact on the outcome of HIV infection, even if functional immune modulation in HAART-treated patients is evident only after long periods of therapy. Low but detectable HIV replication in HAART-naive patients with preserved immune functions might not be associated with CD4 cell reduction, functional immune defects, or changes in viraemia. Copyright 2002 Lippincott Williams & Wilkins

  2. Association between highly active antiretroviral therapy and selected cardiovascular disease risk factors in sub-Saharan Africa: a systematic review and meta-analysis protocol

    PubMed Central

    Dimala, Christian Akem; Blencowe, Hannah

    2017-01-01

    Introduction The increasing highly active antiretroviral therapy (HAART) coverage in sub-Saharan Africa (SSA) has been associated with increasing cardiovascular disease (CVD) incidence. However, the epidemiology of the association between HAART and CVD risk factors in SSA is sparse. We aim to assess the extent to which HAART is associated with selected cardiovascular risk factors (hypertension, diabetes, dyslipidaemia and metabolic syndrome) in SSA. Methods and analysis This will be a systematic review and meta-analysis of published studies on the association between HAART and CVD risk factors retrieved from Medline, Embase, Popline, Africa-Wide Information, African Index Medicus and the Cochrane library databases. Studies will be screened for eligibility according to the selection criteria by two independent reviewers. Eligible studies will be assessed for the quality of their evidence and risk of bias using the Quality Assessment Tool for Observational Cohort and Cross-Sectional Studies of the National Health Institute and the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach, with respect to the measured outcomes (hypertension, diabetes, dyslipidaemia and metabolic syndrome). A data abstraction form will be produced on Epi info V.7 and data analysis done on STATA V.14 statistical software. Summary estimates of measures of effects for the association between HAART use and the outcomes will be derived. Random effects meta-analyses will be performed and I2 statistic used to assess for heterogeneity between studies with respect to measured parameters. Qualitative synthesis will be used where data is insufficient to produce quantitative synthesis. Ethics and dissemination The protocol has been reviewed by the Research Governance & Integrity Office of the Research Ethics Committee of the London School of Hygiene and Tropical Medicine and confirmed as not requiring ethical approval. The findings of this study will be made widely

  3. 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

  4. Mortality trends of HIV-infected patients after the introduction of highly active antiretroviral therapy: analysis of a cohort of 3,322 HIV-infected persons.

    PubMed

    Mayor, Angel M; Gómez, María A; Ríos-Oliveras, Eddy; Hunter-Mellado, Robert F

    2005-01-01

    The implementation of highly active antiretroviral therapies (HAART) has reduced the mortality attributed to the human immunodeficiency virus (HIV) infection. Variation in the specific causes of death has also changed since the implementation of these therapies. A prospective study was performed in 3322 HIV-infected persons enrolled in Puerto Rico between 1992 and 2003. We measured the mortality rates and the causes of death as listed in the death certificate and analyzed the variation as a function of the antiretroviral therapy (ART) use. Statistical analyses were performed to evaluate differences. The study found that persons treated with HAART had significantly lower mortality risk than ART-naïve persons, regardless of gender and the use of injecting drugs. AIDS-defining conditions as a cause of demise were less frequently reported in patients with HAART. Gastrointestinal dysfunction, sepsis, metabolic abnormalities, and non-Kaposi neoplasms were more frequently reported as causes of death in patients treated with HAART. Hepatic failure as cause of death was also more frequent in these patients. The variation in the mortality trends was similar in both genders and according to the presence or absence of intravenous drug use. Highly active antiretroviral therapies (HAART) is associated with significant reduction in mortality and an increment in gastrointestinal dysfunction, sepsis, non-Kaposi neoplasms, and metabolic disorders as listed causes of death. Adverse and toxic profile of ART, along with the potential synergy of concomitant conditions, may accelerate these trends. Continued mortality surveillance of HIV/AIDS is imperative to follow the epidemic changes.

  5. 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.

  6. Impact of gender on response to highly active antiretroviral therapy in HIV-1 infected patients: a nationwide population-based cohort study

    PubMed Central

    2012-01-01

    Background Impact of gender on time to initiation, response to and risk of modification of highly active antiretroviral therapy (HAART) in HIV-1 infected individuals is still controversial. Methods From a nationwide cohort of Danish HIV infected individuals we identified all heterosexually infected women (N=587) and heterosexually infected men (N=583) with no record of Hepatitis C infection diagnosed with HIV after 1 January 1997. Among these subjects, 473 women (81%) and 435 men (75%) initiated HAART from 1 January 1997 to 31 December 2009. We used Cox regression to calculate hazard ratio (HR) for time to initiation of HAART, Poisson regression to assess incidence rate ratios (IRR) of risk of treatment modification the first year, logistic regression to estimate differences in the proportion with an undetectable viral load, and linear regression to detect differences in CD4 count at year 1, 3 and 6 after start of HAART. Results At initiation of HAART, women were younger, predominantly of Black ethnicity and had a higher CD4 count (adjusted p=0.026) and lower viral load (adjusted p=0.0003). When repeating the analysis excluding pregnant women no difference was seen in CD4 counts (adjusted p=0.21). We observed no delay in time to initiation of HAART in women compared to men (HR 0.91, 95% CI 0.79-1.06). There were no gender differences in risk of treatment modification of the original HAART regimen during the first year of therapy for either toxicity (IRR 0.97 95% CI 0.66-1.44) or other/unknown reasons (IRR 1.18 95% CI 0.76-1.82). Finally, CD4 counts and the risk of having a detectable viral load at 1, 3 and 6 years did not differ between genders. Conclusions In a setting with free access to healthcare and HAART, gender does neither affect time from eligibility to HAART, modification of therapy nor virological and immunological response to HAART. Differences observed between genders are mainly attributable to initiation of HAART in pregnant women. PMID:23140254

  7. Prevalence, Correlates and Under-Diagnosis of Clinical Depression among Adults on Highly Active Antiretroviral Therapy in a Tertiary Health Institution in Northeastern Nigeria

    PubMed Central

    Jidda, Mohammed Said; Wakil, Musa Abba; Rabbebe, Isa Bukar; Omeiza, Asuku Beida; Yusuph, Haruna; Ogunlesi, Adegboyega; Suleiman, Umar Garba

    2014-01-01

    Clinical depression is a highly debilitating illness, which is often under-diagnosed and negatively impacts on the quality of life of its sufferers. When it co-exists with other medical conditions, its effect is even more incapacitating. Undiagnosed depression in the context of HIV infection leads to accelerated decline in CD4+ cell counts with concomitant increase in the viral load and poor adherence to the antiretroviral medications which lead to viral mutation and the evolution of resistant strains. This study examined the prevalence of depression, its correlates and the frequency of the diagnosis of the condition among HIV+ subjects on highly active antiretroviral therapy (HAART) by the internists and general physicians at the University of Maiduguri Teaching Hospital in Northeastern Nigeria. Three hundred and fifty representative samples of HIV+ adults on HAART were drawn from the Antiretroviral Therapy Clinic of the Institution. Diagnosis of depression was made using the International Classification of Diseases-10 criteria based on Composite International Diagnostic Interview generated data. Socio-demographic and clinical variables were also analyzed for their correlation with depression in the subjects. About 20% of the respondents were diagnosed with clinical depression and no diagnosis of the condition was hitherto entertained in all the respondents. The independent determinants of depression in the participants were: female gender [odds ratio (OR)=3.87 (95% confidence interval, CI: 2.089-7.183)], past history of psychiatric illness [OR=43.81 (95% CI: 9.731-197.30)] and family history of psychiatric illness in first-degree relatives of the subjects [OR=14.364 (95% CI=5.327-38.729)]. Depression is a relatively common psychiatric condition among adults on HAART, there is therefore the need for routine screening of this condition among HIV+ subjects in order to optimize patient care and improve clinical outcomes.

  8. [Prevalence of oral lesions by Candida sp.: Their varieties and serotypes in a population of patients with AIDS under a highly active antiretroviral therapy.].

    PubMed

    Ceballos Salobreña, A; Gaitán Cepeda, L A; Ruesga, M T; Ceballos García, L; Quindós, G

    1998-09-01

    The aim of this study has been to determine the prevalence of oral candidiasis and oral Candida carriers in an AIDS population under highly active antiretroviral therapy. Eighty-six AIDS patients treated with an antiretroviral combination (indinavir o ritonavir o saquinavir + zidovudine [AZT] + lamivudine [3TC]). Patients were grouped attending the predisposing factors for HIV infection in: intravenous drug users (IDU), heterosexuals, homosexuals, patients using hematological products or having unknown factors. Oral cavity was examined and an oral specimen was inoculated in a chromogenic culture medium (Albicans ID, bioMérieux, France). The prevalence of oral Candida lesions was 30.2% and Candida was isolated from 54.7% of patients. The predominant species was C. albicans serotype A in all the groups with the exception of homosexual patients, were C. albicans serotype B was the predominant. The IDU group showed the higher prevalence of Candida lesions and oral yeasts colonization, followed by the group of heterosexuals and homosexuals. An association was found between the presence of lesions and/or Candida spp. and the clinical stage or the viral concentration. The species Candida dubliniensis was isolated in the oral samples of two patients with candidosis and in two individuals without oral candidosis. The finding of this species in Spanish patients can be added to the data obtained in epidemiological studies in other countries.

  9. Human immunodeficiency virus serodiscordant couples on highly active antiretroviral therapies with undetectable viral load: conception by unprotected sexual intercourse or by assisted reproduction techniques?

    PubMed

    Vandermaelen, Aline; Englert, Yvon

    2010-02-01

    Until recently, only assisted reproduction was proposed to serodiscordant couples wishing to conceive. Nevertheless, recent publications have proposed unprotected sexual intercourse, targeting fertile days, for couples where antiretroviral treatment has lowered blood viral load to an undetectable level. Available data and the arguments for and against conception by safe sex versus the use of a strategy of unprotected sexual intercourse targeting fertile days are reviewed and analyzed. Although the rate of transmission of human immunodeficiency virus in serodiscordant couples in precise conditions (such as an undetectable viral load on treatment by highly active antiretroviral therapies and sexual intercourse limited to the fertile days) is very low, not zero, here we stress the various factors which can increase the risk of seroconversion in this particular population. In this context, it seems less cautious to abandon the recommendations of safe sex in serodiscordant couples desiring a child. The recourse to medically assisted procreation is advised, as long as evidence from further studies does not show that unprotected sexual intercourse, targeted to fertile days, does not have unexpected harmful consequences.

  10. Failure to restore the Vgamma2-Jgamma1.2 repertoire in HIV-infected men receiving highly active antiretroviral therapy (HAART).

    PubMed

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

    2008-09-01

    Gammadelta (gammadelta) T cells expressing the Vgamma2-Jgamma1.2Vdelta2 (Vgamma9-JPVdelta2, alternate nomenclature) T cell receptor (TCR) constitute the major peripheral blood population of gammadelta T cells in adult humans and are specifically depleted during human immunodeficiency virus (HIV) disease. Vgamma2-Jgamma1.2Vdelta2 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 enrolled in the Multicenter AIDS Cohort Study (MACS) and were starting highly active antiretroviral therapy (HAART). Vgamma2-Jgamma1.2Vdelta2 T cells were depleted in these individuals as a result of HIV infection. Despite evidence for clinical benefits of HAART, the Vgamma2-Jgamma1.2Vdelta2 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.

  11. 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

  12. 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

  13. Efficacy of non-nucleoside reverse transcriptase inhibitor-based highly active antiretroviral therapy in Thai HIV-infected children aged two years or less.

    PubMed

    Puthanakit, Thanyawee; Aurpibul, Linda; Sirisanthana, Thira; Sirisanthana, Virat

    2009-03-01

    Twenty-six Thai HIV-infected children, aged 2 years or less were prospectively enrolled to receive non-nucleoside reverse transcription inhibitor-based highly active antiretroviral therapy (HAART). Twenty-two children (85%) had World Health Organization clinical stage 3 or 4. The median baseline CD4 cell percentage and plasma HIV RNA were 17% and 5.9 log 10 copies/mL, respectively. The median age at HAART initiation was 9.8 months (range, 1.5-24.0). One child died. The mean CD4 cell percentages at 24, 48, and 96 weeks of treatment were 26%, 31%, and 37%, respectively. The proportions of children with virologic suppression (<400 copies/mL) at week 24 and 48 were 14/26 (54%) and 19/26 (73%), respectively. Non-nucleoside reverse transcription inhibitor-based HAART is safe and effective in HIV-infected young children in a resource-limited setting.

  14. Stage IV advanced diffuse large B-cell lymphoma in human immunodeficiency virus infection with achieving cure by using highly active antiretroviral therapy alone: a case report.

    PubMed

    Lim, Do Hyoung; Rhee, Ji-Young; Park, Keon Woo

    2017-08-01

    After the introduction of highly active antiretroviral therapy (HAART), there has been a decrease in the incidence of lymphoma among the HIV-infected population and also significantly improved survival rates. We describe a remarkable case of an HIV-infected patient with advanced stage IV diffuse large B-cell lymphoma (DLBCL), completely regressed with the use of HAART alone. He remained disease-free for 6 years and he achieved cure without chemotherapy. Although several cases of low-grade lymphoma with complete regression were reported, we could not find any case of stage IV high-grade malignant lymphoma with HAART alone in complete remission for over 5 years from our review of the literature. This unique case shows the importance of HAART in improving survival and achieving cure in HIV-high-grade malignant lymphoma.

  15. Evidence for a change in AIDS dementia complex in the era of highly active antiretroviral therapy and the possibility of new forms of AIDS dementia complex.

    PubMed

    Brew, Bruce J

    2004-01-01

    This review will discuss emerging evidence for the possibility that AIDS dementia complex (ADC) has changed in the era of highly active antiretroviral therapy (HAART). The consequences of not considering these possibilities at the patient level and at the level of research are considerable. Data will be discussed that are derived from epidemiological studies, neuropsychological and positron emission tomography studies, as well as analyses from the abacavir ADC trial. These will then be assessed to develop the concept that there are now different forms of ADC: an inactive form, a chronic variety and a 'transformed' variant. Whereas the latter relates to the compounding influence of a number of other processes on ADC, such as hepatitis C, particular discussion will focus upon Alzheimer's disease and whether HIV may lead to Alzheimer-like changes. It is certainly recognized that some of the concepts discussed here are highly speculative.

  16. The physical activity levels among people living with human immunodeficiency virus/acquired immunodeficiency syndrome receiving high active antiretroviral therapy in Rwanda.

    PubMed

    Frantz, J M; Murenzi, A

    2013-01-01

    The accessibility of high active antiretroviral therapy (HAART) for local human immunodeficiency virus (HIV) patients is improving in Rwanda. It is well known that this therapy is associated with serious adverse effects, such as metabolic and morphologic changes. One of the recommended preventive modalities for these complications is participation in physical activity. The current study aims to determine the anthropometric profile and physical activity levels among people living with HIV and receiving HAART in Kigali, Rwanda. The study was a cross-sectional, descriptive quantitative survey. The participant's levels of physical activity participation and their association with anthropometric profiles were measured, using a structured self-administered questionnaire for 407 clients passing through the clinics. Of the participants, approximately 70% were inactive and in addition, 40% were obese and 43% overweight. Obesity was found to be strongly associated with inactivity. Lack of motivation, and time as well as fear of worsening the disease were found to be barriers to participation in physical activity.

  17. Highly active antiretroviral therapy and outcome of AIDS-related Burkitt's lymphoma or leukemia. Results of the PETHEMA-LAL3/97 study.

    PubMed

    Oriol, Albert; Ribera, Josep-Maria; Brunet, Salut; del Potro, Eloy; Abella, Eugènia; Esteve, Jordi

    2005-07-01

    Short, intensive cycles of chemotherapy have resulted in improved survival in BurkittOs lymphoma/leukemia (BL) in adults. The prognosis of patients with immunodeficiency virus (HIV)-associated BL is considered to be poor, but these patients have seldom been treated with BL-specific protocols. However, a study (PETHEMA-LAL3/97) in which patients with BL were treated regardless of their HIV status failed to find differences between HIV-infected and immunocompetent individuals. Furthermore, patients who received highly active antiretroviral therapy (HAART) seemed to have a slightly better disease-free survival than those who did not (p=0.051). We extended the follow-up analysis to elucidate the role of HAART in the survival of HIV-infected patients included in the PETHEMA-LAL3/97 protocol.

  18. 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.

  19. Hepatic histomorphological and biochemical changes following highly active antiretroviral therapy in an experimental animal model: Does Hypoxis hemerocallidea exacerbate hepatic injury?

    PubMed

    Azu, Onyemaechi Okpara; Jegede, Ayoola Isaac; Ugochukwu, Offor; Onanuga, Ismail Olasile; Kharwa, Salem; Naidu, Edwin Coleridge

    2016-01-01

    As the roll-out of antiretroviral therapy continues to drive downwards morbidity and mortality in people living with HIV/AIDS (PLWHAs), organ toxicities (especially the liver) are frequently becoming a major concern for researchers, scientists and healthcare planners. This study was conducted to investigate the possible protective effect of Hypoxis hemerocallidea (AP) against highly active antiretroviral therapy (HAART)-induced hepatotoxicity. A total of 63 pathogen-free adult male Sprague-Dawley rats were divided into 9 groups and treated according to protocols. While no mortality was reported, animals treated with adjuvant HAART and AP recorded least% body weight gain. Significant derangements in serum lipid profiles were exacerbated by treatment of with AP as LDL (increased p < 0.03), triglycerides (increased p < 0.03) with no change in total cholesterol levels. Adjuvant AP with HAART caused reduction in LDL (p < 0.05 and 0.03), increased HDL (p < 0.05) and TG (p < 0.05 and 0.001 for AP100 and AP200 doses respectively). Markers of liver injury assayed showed significant increase (p < 0.003, 0.001) in AST in AP alone as well as HAART+ vitamins C and E groups respectively. Adjuvant HAART and AP and vitamins C and E also caused significant declines in ALT and ALP levels. Serum GGT was not markedly altered. Disturbances in histopathology ranged from severe hepatocellular distortions, necrosis and massive fibrosis following co-treatment of HAART with vitamins C and E as well as HAART alone. These results warrant caution on the adjuvant use of AP with HAART by PLWHAs as implications for hepatocellular injuries are suspect with untoward cardiometabolic changes.

  20. Stochastic modelling of the eradication of the HIV-1 infection by stimulation of latently infected cells in patients under highly active anti-retroviral therapy.

    PubMed

    Sánchez-Taltavull, Daniel; Vieiro, Arturo; Alarcón, Tomás

    2016-10-01

    HIV-1 infected patients are effectively treated with highly active anti-retroviral therapy (HAART). Whilst HAART is successful in keeping the disease at bay with average levels of viral load well below the detection threshold of standard clinical assays, it fails to completely eradicate the infection, which persists due to the emergence of a latent reservoir with a half-life time of years and is immune to HAART. This implies that life-long administration of HAART is, at the moment, necessary for HIV-1-infected patients, which is prone to drug resistance and cumulative side effects as well as imposing a considerable financial burden on developing countries, those more afflicted by HIV, and public health systems. The development of therapies which specifically aim at the removal of this latent reservoir has become a focus of much research. A proposal for such therapy consists of elevating the rate of activation of the latently infected cells: by transferring cells from the latently infected reservoir to the active infected compartment, more cells are exposed to the anti-retroviral drugs thus increasing their effectiveness. In this paper, we present a stochastic model of the dynamics of the HIV-1 infection and study the effect of the rate of latently infected cell activation on the average extinction time of the infection. By analysing the model by means of an asymptotic approximation using the semi-classical quasi steady state approximation (QSS), we ascertain that this therapy reduces the average life-time of the infection by many orders of magnitudes. We test the accuracy of our asymptotic results by means of direct simulation of the stochastic process using a hybrid multi-scale Monte Carlo scheme.

  1. The associations between age and the development of laboratory abnormalities and treatment discontinuation for reasons other than virological failure in the first year of highly active antiretroviral therapy.

    PubMed

    Sabin, C A; Smith, C J; Delpech, V; Anderson, J; Bansi, L; Gilson, R; Schwenk, A; Leen, C; Gazzard, B; Porter, K; Mackie, N; Fisher, M; Orkin, C; Johnson, M; Easterbrook, P; Hill, T; Phillips, A N

    2009-01-01

    The aim of this study was to describe the relationship between age and the time to treatment discontinuation in the absence of virological failure as well as the development of specific laboratory abnormalities, in patients starting highly active antiretroviral therapy (HAART) for the first time. Analyses included 8708 antiretroviral-naïve patients from the UK Collaborative HIV Cohort (CHIC) study who started HAART from 1998 onwards. We considered time to the first discontinuation of any drug in the initial HAART regimen for reasons other than virological failure; the association between this and age at the start of HAART was determined using proportional hazards regression after adjustment for potential confounders. The incidence of specific laboratory abnormalities in the first year after starting HAART was compared in those of different ages using multiple logistic regression. A total of 2650 patients discontinued at least one drug in their HAART regimen in the first year for reasons other than virological failure; after controlling for confounders, those aged < 30 years at the time of starting HAART were more likely to discontinue than those aged 30-39 years [relative hazard (RH) 1.12; 95% confidence interval (CI) 1.01, 1.24] as were those aged > or = 50 years (RH 1.14; 95% CI 1.00, 1.31). There were strong associations between greater age and raised total cholesterol, decreased haemoglobin and raised triglycerides over the first year, although the latter disappeared after adjustment for pre-HAART levels, suggesting that this finding reflected higher pre-HAART triglyceride levels in older individuals. Continued attempts to improve the tolerability of HAART regimens may help to sustain the good outcomes in all age groups over the longer term.

  2. Pulmonary Kaposi Sarcoma with Osseous Metastases in an Human Immunodeficiency Virus (HIV) Patient: A Remarkable Response to Highly Active Antiretroviral Therapy

    PubMed Central

    Dirweesh, Ahmed; Khan, Muhammad Yasir; Hamiz, Shaikh Fawad; Karabulut, Nigahus

    2017-01-01

    Patient: Male, 34 Final Diagnosis: Pulmonary Kaposi’s sarcoma with bony metastatses Symptoms: Cough • weight loss Medication: — Clinical Procedure: — Specialty: Infectious Diseases Objective: Rare disease Background: Kaposi sarcoma (KS) is known to involve the mucocutaneous tissues and the aero-digestive tracts. In acquired immune deficiency syndrome (AIDS) patients, KS has an aggressive course and carries poor prognosis. We present a case of pulmonary KS with osseous metastases as the first presentation of human immunodeficiency virus (HIV) infection in a young male. The lesions impressively decreased in size and numbers following initiation of highly active antiretroviral therapy (HAART). Case Report: A 34-year-old heterosexual male presented with a one month history of cough and 15–20 pound weight loss within six months. Examination revealed oral thrush, decreased breath sounds and crackles on the right lower lung base. Imaging showed a large right perihilar mass with multiple lytic lesions involving thoracic and lumber vertebrae, ribs, sternum, and clavicles. Blood and sputum cultures, smears for acid fast bacilli, and a QUANTIferon gold test were all negative. He tested positive for HIV and his CD4 count was 7 cells/uL. Bronchoscopy with biopsy was unrevealing. Pathology of the right hilar mass was diagnostic of KS. Following initiation of antiretroviral therapy his condition dramatically improved; repeat chest CT scan showed marked regression of the bony and pulmonary lesions. Conclusions: The dual action of HAART on the recovery of the immune system and against human herpes virus 8 (HHV-8) may essentially cause regression of KS lesions. PMID:28216610

  3. Postpartum viral load rebound in HIV-1-infected women treated with highly active antiretroviral therapy: AIDS Clinical Trials Group Protocol A5150.

    PubMed

    Sha, Beverly E; Tierney, Camlin; Cohn, Susan E; Sun, Xin; Coombs, Robert W; Frenkel, Lisa M; Kalams, Spyros A; Aweeka, Francesca T; Bastow, Barbara; Bardeguez, Arlene; Kmack, Anne; Stek, Alice

    2011-01-01

    Pregnancy may lead to increases in HIV-1 RNA levels postpartum. The AIDS Clinical Trials Group (ACTG) A5150 study was designed to characterize the incidence of viral load rebound during the immediate 24 weeks postpartum and explore factors associated with viral load rebound. We enrolled pregnant women in the United States who were ≥13 years of age, between 22 to 30 weeks gestation, and who planned to be on stable highly active antiretroviral therapy (HAART) for ≥8 weeks predelivery and to continue this therapy after delivery for the duration of the study. Choice of antiretrovirals (ARVs) was determined by the primary HIV provider. Viral load rebound was defined as an increase of ≥0.7 log10 (5-fold) from the average of the weeks 34 and 36 gestation viral loads to week 24 postpartum or an absolute increase to ≯500 copies/mL for those with viral load <50 copies/mL. Eighty-four women enrolled for postpartum follow-up. Sixty-three had follow-up and viral load obtained through week 24 postpartum. Overall, 18/63 (28.6%; 95% confidence interval [CI], 17.9-41.4) met criteria for viral load rebound. Nineteen of the 63 women made changes or discontinued their ARV regimen prior to week 24 postpartum. For those who remained on stable ARVs, rebound occurred in 8/44 (18.2%; 95% CI, 8.2-32.7) compared with 10/19 (52.6%; 95% CI, 28.9-75.5) who did not remain on a stable ARV regimen. In the early postpartum period, HIV-1-infected women commonly have increases in viral load. Unplanned changes in ARV regimens and discontinuations of treatment are frequent.

  4. Short-term garlic supplementation and highly active antiretroviral treatment adherence, CD4+ cell counts, and human immunodeficiency virus viral load.

    PubMed

    Liu, Chenglong; Wang, Cuiwei; Robison, Esther; Levine, Alexandra M; Gandhi, Monica; Schwartz, Rebecca; Weber, Kathleen M; Merenstein, Daniel

    2012-01-01

    Human immunodeficiency virus (HIV)-infected individuals frequently have consumed garlic, a popular complementary supplement. Researchers rarely have studied garlic's association with antiretroviral therapies, however, even though that association is very relevant clinically. To examine associations of supplemental use of garlic with highly active antiretroviral treatment (HAART) adherence level and HAART effectiveness (HIV viral load and CD4+ cell counts) in HIV-infected women. The research team carried out a self-controlled, longitudinal study nested within the Women's Interagency HIV Study (WIHS). The team used a paired study design that allowed participants to serve as their own controls. The team first identified all of the studies visits in which the participant self-reported the use of a garlic supplement since her last visit (index visit). Then for each index visit, the team identified a matching visit (a control visit) using the following criteria: (a) the visit must be one for the same participant in which that participant reported no garlic supplementation; (b) the visit must immediately precede the index visit (less than 1 year apart); and (c) at the time of the control visit, the participant must have been using antiretroviral therapy identical to that used at the time of the index visit. Participants were persons using garlic supplementation who already were participants in the WIHS. The research team used a logistic regression model to examine the association between garlic supplementation and HAART adherence level. The team used a mixed linear model to examine the association of garlic supplementation with HIV viral load and CD4+ cell counts. From October 1994 to April 2009, 390 HIV-infected women in the WIHS made 1112 visits at which they reported using garlic supplements. Seventy-seven HIV-infected women using HAART met the research teams selection criteria and contributed 99 pairs of visits for the study. Among the women who used garlic

  5. Short-term Garlic Supplementation and Highly Active Antiretroviral Treatment Adherence, CD4+ Cell Counts, and Human Immunodeficiency Virus Viral Load

    PubMed Central

    Liu, Chenglong; Wang, Cuiwei; Robison, Esther; Levine, Alexandra M.; Gandhi, Monica; Schwartz, Rebecca; Weber, Kathleen M.; Merenstein, Daniel

    2012-01-01

    Context Human immunodeficiency virus (HIV)–infected individuals frequently have consumed garlic, a popular complementary supplement. Researchers rarely have studied garlic’s association with antiretroviral therapies, however, even though that association is very relevant clinically. Objective To examine associations of supplemental use of garlic with highly active antiretroviral treatment (HAART) adherence level and HAART effectiveness (HIV viral load and CD4+ cell counts) in HIV-infected women. Design The research team carried out a self-controlled, longitudinal study nested within the Women’s Interagency HIV Study (WIHS). The team used a paired study design that allowed participants to serve as their own controls. The team first identified all of the study’s visits in which the participant self-reported the use of a garlic supplement since her last visit (index visit). Then for each index visit, the team identified a matching visit (a control visit) using the following criteria: (a) the visit must be one for the same participant in which that participant reported no garlic supplementation; (b) the visit must immediately precede the index visit (less than 1 year apart); and (c) at the time of the control visit, the participant must have been using antiretroviral therapy identical to that used at the time of the index visit. Participants Participants were persons using garlic supplementation who already were participants in the WIHS. Outcome Measures The research team used a logistic regression model to examine the association between garlic supplementation and HAART adherence level. The team used a mixed linear model to examine the association of garlic supplementation with HIV viral load and CD4+ cell counts. Results From October 1994 to April 2009, 390 HIV-infected women in the WIHS made 1112 visits at which they reported using garlic supplements. Seventy-seven HIV-infected women using HAART met the research team’s selection criteria and contributed 99

  6. 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

  7. New Highly Active Antiretroviral drugs and generic drugs for the treatment of HIV infection: a budget impact analysis on the Italian National Health Service (Lombardy Region, Northern Italy).

    PubMed

    Restelli, Umberto; Scolari, Francesca; Bonfanti, Paolo; Croce, Davide; Rizzardini, Giuliano

    2015-08-11

    In the healthcare sector, it is crucial to identify sustainable strategies in order to allow the introduction and use of innovative technologies. Now, and over the next few years, the expiry of patents for different antiretroviral drugs offers an opportunity to increase the efficiency of resources allocation. The aim of the present study was to assess the impact, on the budget of the Italian National Healthcare Service, of generic antiretroviral drugs and of new antiretroviral drugs entering the market from 2015 to 2019. A budget impact model was developed in order to forecast the rate of use of ARTs, based on trends observed within the Lombardy Region (Italy), on clinical experts' opinion, and the consequent impact on the Italian NHS budget in a five year time horizon. Different scenarios were developed, considering the sole introduction of generic drugs, of new drugs, and their cumulative effects. A multivariate sensitivity analysis was also performed. The cumulative use of generic drugs and new drugs would lead to annual savings of 4.6 million € (-0.6 %) in 2015; 16.9 million € (-2.1 %) in 2016; 19.4 million € (-2.4 %) in 2017; 51.1 million € (-6.1 %) in 2018 and -110.3 million € (-12.8 %) in 2019. The impact of new drugs in percentage terms is +2.0 % in 2015, +3.4 % in 2016, +3.9 % in 2017, +5.7 % in 2018 and +7.7 % in 2019. The impact of generic drugs would lead to savings of 4.9 million € in 2015, 18.6 million € in 2016, 22.8 million € in 2017, 76.5 million € in 2018 and 187.4 million € in 2019. The sensitivity analysis showed annual mean savings for the Italian NHS ranging from 12.6 million €, -1.5 % compared to the base case scenario (decreasing all the rates of transition used in the simulation, and increasing the cost of generic drugs) to 76.0 million €, -9.1 % (increasing all the rates of transition used in the simulation, and decreasing the cost of generic and new drugs). The use of antiretroviral generic drugs may lead to

  8. [Effect of highly active anti-retroviral therapy on prevention of mother to child transmission of HIV and on infant growth and development].

    PubMed

    He, Yan; Luo, Yan; Ding, Yi-ling; Zheng, Yu-huang; Li, Jing; Huang, Jian; Li, Jie-min

    2011-10-01

    To identify the effect of highly active anti-retroviral therapy (HAART) on prevention of mother to child transmission (PMTCT) of HIV and on infant growth and development. A total of 16 HIV-infected women or pregnant women selected in this study received HAART before or 18 - 24 weeks after pregnancy. The treatment included taking Zidovudine (AZT) 0.3 g each time, twice a day, Lamivudine (3TC) 0.3 g each time, once a day and Nevirapine (NVP) 0.2 g each time, twice a day or Efavirenz (EFV) 0.6 g each time, once a day, as well as labor intervention and artificial feeding. The growth index for 17 infants from HIV-infected mothers (experimental group) and 16 normal infants (control group) were observed for 18 months. Neonatal hemoglobin (Hb), liver and kidney function, serum iron and calcium were detected at neonatal period and at 12(th) month, respectively. All the pregnant women were in good conditions and had tolerance with HAART. The birth weight, length and Apgar score of the newborns in the experimental group were (3.5 ± 0.9) kg, (54.2 ± 3.8) cm and 7 - 10 scores respectively, however those in the control group were (3.6 ± 0.8) kg, (55.6 ± 3.6) cm and 8 - 10 scores (t(weight) = 1.01, t(length) = 6.98, P > 0.05). Weight and length of infants in experimental group were (9.36 ± 1.8) kg and (76.3 ± 2.7) cm at 12(th) month, while those in control group were (9.86 ± 2.5) kg and (76.8 ± 2.9) cm (t(weight) = 0.83, t(length) = 1.00, P > 0.05). The level of Hb in experimental group was (126.2 ± 16.7) g/L, and was (148.6 ± 20.5) g/L in control group (t = -5.89, P = 0.11). At 12(th) month, the levels of Hb and the total bilirubin (TB) were (125.9 ± 19.8) g/L and (11.7 ± 3.5) µmol/L in experimental group; and those in the control group were (130.1 ± 18.7) g/L and (13.2 ± 3.7) µmol/L (t(Hb) = -3.82, t(TB) = -2.14, P > 0.05). Serum iron and calcium were (25.4 ± 5.7) µmol/L and (26.4 ± 7.2) µmol/L at neonatal period and were (2.3 ± 0.6) mol/L and (2.8 ± 0

  9. Prevalence of ocular manifestations of HIV/AIDS in the highly active antiretroviral therapy (HAART) era: a different spectrum in Central South China.

    PubMed

    Luo, Jing; Jing, Deng; Kozak, Igor; Huiming, Zhang; Siying, Chen; Yezhen, Yang; Xin, Qi; Luosheng, Tang; Adelman, Ron A; Forster, Susan H

    2013-06-01

    To investigate ocular manifestations of human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS) in a population in central south China during a time of highly active antiretroviral therapy (HAART). A cross-sectional study in central south China was performed between June 2009 and April 2010. Ocular examinations were performed on recruited patients with HIV/AIDS. Systemic information (including CD4+ T cell count) was also collected where possible. Among 1041 patients (2082 eyes) with HIV/AIDS enrolled in our study, we found a broad spectrum of ocular manifestations related to HIV/AIDS. The prevalence of HIV-associated ocular disease was 23.73% (247 patients). Of those with ocular complications, 87.85% had CD4 counts <200 cells/µL. HIV retinopathy (12.68%) was the most common HIV-associated ocular finding, followed by cytomegalovirus retinitis (6.72%). Prevalences of visual impairment and blindness were 7.59% and 0.77%, respectively. This epidemiologic study shows the spectrum of ocular lesions associated with HIV/AIDS in central south China. Our findings highlight the need for routine ophthalmic examinations in this population, even in patients who are asymptomatic, especially those at high risk, in the era of HAART.

  10. Impact of highly active antiretroviral therapy on the prevalence of oral lesions in HIV-positive patients: a systematic review and meta-analysis.

    PubMed

    de Almeida, V L; Lima, I F P; Ziegelmann, P K; Paranhos, L R; de Matos, F R

    2017-11-01

    The aim of this study was to determine whether highly active antiretroviral therapy (HAART) is associated with the prevalence of oral lesions in HIV-positive patients. This systematic review and meta-analysis was performed in accordance with the PRISMA guidelines (Preferred Reporting Items for Systematic Reviews and Meta-Analyses). The search was conducted in seven electronic databases (PubMed, Scopus, SciELO, LILACS, Embase, Web of Science, and OpenGrey), without restriction on publication period or language. Studies that showed the prevalence of oral lesions manifested in adult HIV-positive patients, subjected or not to HAART, were selected. The meta-analysis estimate of relative risk was calculated using the Mantel-Haenszel method and DerSimonian and Laird estimator to determine the variance between studies in the random-effects model. The meta-analysis showed significant results in favour of the group on HAART, with lower prevalence for angular cheilitis, erythematous candidiasis, oral herpes, pseudomembranous candidiasis, Kaposi sarcoma, and oral hairy leukoplakia. The prevalence of oral mucosal hyperpigmentation was higher in patients on HAART. These results suggest that the prevalence of oral lesions in HIV-positive patients is lower for those on HAART, which might occur because of the improvement in immunity provided by the therapy. Copyright © 2017 International Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.

  11. 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

  12. Mother-to-child transmission (MTCT) of HIV and drugs of abuse in post-highly active antiretroviral therapy (HAART) era.

    PubMed

    Purohit, Vishnudutt; Rapaka, Rao S; Shurtleff, David

    2010-12-01

    In the pre-highly active antiretroviral therapy (HAART) era, prenatal "vertical" mother-to-child transmission (MTCT) of HIV was about 25% and exposure of pregnant mothers to drugs of abuse (illicit drugs and tobacco smoking) was a significant contributory factor of MTCT. However, with the introduction of HAART, the rate of MTCT of HIV has decreased to less that 2%. But, it is estimated that currently about 5.1% of pregnant women use illicit drugs and 16.4% smoke tobacco. The residual prevalence of MTCT is of concern and may be related to this continued prevalence of substance use among pregnant mothers. In this report, we review and present evidence that supports the hypothesis that drugs of abuse do have the potential to increase MTCT of HIV in the presence of HAART. Exposure to drugs of abuse during pregnancy may increase MTCT of HIV through a variety of mechanisms that are addressed in detail including possible damage to the placenta, induction of preterm birth, and increasing maternal plasma viral load though a variety of putative mechanisms such as: (a) promoting HIV replication in monocyte/macrophages; (b) increasing the expression of CCR5 receptors; (c) decreasing the expression of CCR5 receptor ligands; (d) increasing the expression of CXCR4 receptors; (e) increasing the expression of DC-SIGN; (f) impairing the efficacy of HAART through drug-drug interaction; and (g) promoting HIV mutation and replication through non-adherence to HAART.

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

    PubMed

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

    2015-01-01

    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. The aim was to document and compare oral lesions in HIV-seropositive patients before and after HAART. 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. 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. 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.

  14. [Information about the medicines and adherence to high activity antiretroviral treatment in patients with HIV/AIDS in a hospital of Lima, Peru].

    PubMed

    Pacífico, Juana; Gutiérrez, César

    2015-01-01

    Determine the association between the information received on high activity antiretroviral treatment (HAART) and the adherence to this treatment in patients with HIV / AIDS of a hospital of Lima, Peru. Cross-sectional analytical study. Through interviews were applied the questionnaire SIMS (Satisfaction with Information about Medicines Scale) to measure satisfaction with information received about medications and SMAQ (Simplified Medication Adherence Questionnaire) to determine adherence to HAART. By reviewing medical records sociodemographic and clinical data were collected. 364 patients were interviewed. Satisfaction with the information received about drugs was not associated with adherence to HAART (p = 0.611). Factors associated with the satisfaction with information were: female (ORa = 0.52; 95% CI 0.30 to 0.90); level of higher education (ORa = 0.45; 95% CI 0.27 to 0.75) and age (ORa = 1.05; 95% CI 1.02 to 1.08). There were more satisfaction with the information received on the action and drug use compared with information about potential adverse events (48.9% vs. 43.1%; p = 0.0291). Satisfaction with information received about drugs was not associated with adherence to HAART. This satisfaction increases with age and is lower in females and in the degree of higher education. There are desires for further information on the potential adverse reactions to HAART.

  15. Evaluation of viral load thresholds for predicting new WHO Stage 3 and 4 events in HIV-infected children receiving highly active antiretroviral therapy

    PubMed Central

    Siberry, George K; Harris, D. Robert; Oliveira, Ricardo Hugo; Krauss, Margot R.; Hofer, Cristina B.; Tiraboschi, Adriana Aparecida; Marques, Heloisa; Succi, Regina C.; Abreu, Thalita; Negra, Marinella Della; Mofenson, Lynne M.; Hazra, Rohan

    2012-01-01

    Background This study evaluated a wide range of viral load (VL) thresholds to identify a cut-point that best predicts new clinical events in children on stable highly-active antiretroviral therapy (HAART). Methods Cox proportional hazards modeling was used to assess the adjusted risk of World Health Organization stage 3 or 4 clinical events (WHO events) as a function of time-varying CD4, VL, and hemoglobin values in a cohort study of Latin American children on HAART ≥ 6 months. Models were fit using different VL cut-points between 400 and 50,000 copies/mL, with model fit evaluated on the basis of the minimum Akaike Information Criterion (AIC) value, a standard model fit statistic. Results Models were based on 67 subjects with WHO events out of 550 subjects on study. The VL cutpoints of > 2600 copies/mL and > 32,000 copies/mL corresponded to the lowest AIC values and were associated with the highest hazard ratios [2.0 (p = 0.015) and 2.1 (p = 0.0058), respectively] for WHO events. Conclusions In HIV-infected Latin American children on stable HAART, two distinct VL thresholds (> 2,600 copies/mL and > 32,000 copies/mL) were identified for predicting children at significantly increased risk of HIV-related clinical illness, after accounting for CD4 level, hemoglobin level, and other significant factors. PMID:22343177

  16. Roles of family dynamics on adherence to highly active antiretroviral therapy among people living with HIV/AIDS at a tertiary hospital in Osogbo, south-west Nigeria.

    PubMed

    Afolabi, B A; Afolabi, M O; Afolabi, A A; Odewale, M A; Olowookere, S A

    2013-12-01

    Adherence to highly active antiretroviral therapy (HAART) has been proven to be the only effective treatment for HIV/AIDS worldwide. Good adherence to HAART might require good family support. To determine the family dynamics and social support of people living with HIV/AIDS (PLWHA) and its roles on HAART adherence at an ARV treatment clinic in Osogbo, Nigeria. Descriptive cross-sectional study. Consenting PLWHA on HAART were interviewed using pre-tested semistructured questionnaire incorporating Perceived Social Support- Family Scale and Family APGAR. HAART adherence was measured using patient self report. A total of 379 PLWHA were interviewed. Their mean age was 40.8 (SD=9.9) years. Most (60.7%) were females. More than half (55.7%) were currently married and the majority (72.1%) had secondary education and were Yoruba (86.3%). Most respondents (95.5%) were adherent to HAART. Over 90% were satisfied with support received from their family while 82.3% were treated like other family members. Most attributed their HAART adherence to the care and support received from their family. Most PLWHA had good social support and were adherent to HAART.

  17. Pulmonary Kaposi Sarcoma: An Uncommon Cause of Respiratory Failure in the Era of Highly Active Antiretroviral Therapy—Case Report and Review of the Literature

    PubMed Central

    Hemmings, Stefan; Paul, Yonette; Habtegebriel, Yordanis; Polk, Octavius

    2016-01-01

    Kaposi Sarcoma (KS) is the most common malignancy associated with Acquired Immune Deficiency Syndrome (AIDS) and is caused by Human Herpesvirus 8 (HHV 8) or Kaposi Sarcoma Herpesvirus (KSHV). In about 90% of cases Kaposi Sarcoma is associated with cutaneous lesions; however visceral disease can occur in the absence of cutaneous involvement. In the era of Highly Active Antiretroviral Therapy (HAART), the incidence of KS has declined. Clinical features of pulmonary KS might be difficult to distinguish from pneumonia in the immunocompromised patients and could lead to diagnostic challenges. First-line treatment of KS is with HAART and the incidence has declined with its use. Systemic chemotherapy may play a role depending on the extent of the disease. We report the case of a young man who presented with pulmonary symptoms and was later found to have pulmonary KS. Interestingly this diagnosis was made in the absence of the classic skin lesions. His disease was complicated by progressive respiratory failure and he eventually died. PMID:27872774

  18. Does discordancy between the CD4 count and CD4 percentage in HIV-positive individuals influence outcomes on highly active antiretroviral therapy?

    PubMed

    Gompels, Mark; Dunn, David T; Phillips, Andrew; Dooley, Debbie; De Burgh Thomas, Andrew; Anderson, Jane; Post, Frank; Pillay, Deenan; Gazzard, Brian; Hill, Teresa; Johnson, Margaret; Gilson, Richard; Bansi, Loveleen; Easterbrook, Philippa; Fisher, Martin; Walsh, John; Orkin, Chloe; Ainsworth, Jonathan; Leen, Clifford; Sabin, Caroline

    2012-02-15

    The CD4 count and CD4 percentage (CD4%) are both strong predictors of clinical disease progression in human immunodeficiency virus (HIV). Although individuals may show discordancy between their CD4 count and CD4%, the clinical relevance of this is unclear. Discordancy was defined where the CD4% was ≤10th percentile for a selected CD4 count range (referred to as low discordancy), within the central 80% range (concordant), or ≥90th percentile (high discordancy). Regression methods identified factors associated with low and high discordancy in untreated individuals and assessed the impact of discordancy on treatment responses to highly active antiretroviral therapy (HAART). High discordancy was associated with female sex, low viral load, and white ethnicity; low discordancy was associated with black or nonwhite ethnicity, older age, and injection drug use. Clinical event rates were higher in individuals with high discordancy starting HAART, but there was no association with subsequent HIV progression by 6 months after starting HAART. CD4 count increases remained lower, by 20 cells/mm(3), in individuals with low discordancy, and higher, by 27 cells/mm(3), in those with high discordancy. Overall discrepancies between the CD4/CD4% are small, confirming the use of absolute CD4 counts as a monitoring tool.

  19. Cervical cancer screening practices, knowledge of screening and risk, and highly active antiretroviral therapy adherence among women living with human immunodeficiency virus in Lima, Peru.

    PubMed

    Delgado, Jeanne R; Menacho, Luis; Segura, Eddy R; Roman, Fernando; Cabello, Robinson

    2017-03-01

    Cervical cancer (CC) is the leading cause of cancer death among Peruvian women. Awareness shown by women living with HIV (WLHIV) of their increased risk and Papanicoloau (Pap) smear frequency is understudied, particularly in Peru. We assessed the uptake of guidelines-based CC screening practices and its associations with two predictors, knowledge of CC screening and risk and highly active antiretroviral therapy (HAART) adherence, among WLHIV. Collected by self-administered questionnaires from 2014 to 2016, we analyzed the data of 71 WLHIV. Most WLHIV (77.5%, n = 55/71) were overdue to CC screening by not having a Pap smear within the prior 12 months. WLHIV who had on-time Pap smears had a higher median composite 'knowledge' score of 3.0 ([interquartile range] 1.5-4) compared to 2.0 (IQR 1-3) for overdue WLHIV. On-time and overdue WLHIV had the same median composite 'HAART adherence' score of 3.0 (IQR 2-4). Bivariate analysis found no association between knowledge nor adherence with on-time Pap smears. Although on-time WLHIV were more knowledgeable about CC screening and risk, overall CC screening uptake was poor. Larger studies of this population are needed to assess the educational, social, and structural barriers contributing to this low prevalence of screening.

  20. Longitudinal assessment of changes in HIV-specific effector activity in HIV-infected patients starting highly active antiretroviral therapy in primary infection.

    PubMed

    Alter, G; Hatzakis, G; Tsoukas, C M; Pelley, K; Rouleau, D; LeBlanc, R; Baril, J G; Dion, H; Lefebvre, E; Thomas, R; Côté, P; Lapointe, N; Routy, J P; Sékaly, R P; Conway, B; Bernard, N F

    2003-07-01

    Both the magnitude and breadth of HIV-specific immunity were evaluated longitudinally on samples collected from six subjects starting highly active antiretroviral therapy (HAART) preseroconversion (group 1), 11 recently infected subjects starting HAART postseroconversion (group 2), five subjects starting HAART in the second half of the first year of infection (group 3), and six persons starting treatment in the chronic phase of infection (group 4). HIV-specific immunity was measured by IFN-gamma ELISPOT, detecting the frequency of cells responding to a panel of HLA-restricted HIV-1 peptides. Intracellular cytokine staining was used to detect the frequency of HIV-1 Gag p55-specific CD4(+) and CD8(+) T cells in a subset of participants. The magnitude and breadth of HIV-specific responses persisted in all group 1 subjects and in 5 of 11 (45%) group 2 subjects. Both of these parameters declined in 6 of 11 (55%) group 2 and in all group 3 and 4 individuals. All persons who maintained detectable numbers of HIV-1 Gag p55-specific CD4(+) and CD8(+) T cells after starting HAART preserved the intensity and breadth of their HIV-specific effector response. Our results show that HIV-specific immunity can be preserved even if HAART is initiated beyond the acute phase of infection.

  1. Poor health-related quality of life and abnormal psychosocial adjustment in Italian children with perinatal HIV infection receiving highly active antiretroviral treatment.

    PubMed

    Bomba, Monica; Nacinovich, Renata; Oggiano, Silvia; Cassani, Morena; Baushi, Liliana; Bertulli, Cristina; Longhi, Daniela; Coppini, Simonetta; Parrinello, Giovanni; Plebani, Alessandro; Badolato, Raffaele

    2010-07-01

    To evaluate health-related quality of life (HRQL), social competence, and behavioral problems in children with perinatal HIV infection receiving highly active antiretroviral therapy (HAART), a cross-sectional study was performed at the Department of Pediatrics, University of Brescia. We evaluated HRQL, social competence, and behavioral problems in 27 HIV-infected children compared with age and sex-matched control subjects using the Pediatric Quality of Life Inventory (PedsQL) and the Child Behavior Checklist (CBCL), respectively. On the PedsQL 4.0 Generic Core Scale, HIV-infected subjects displayed significantly reduced physical (p=0.043) and psychosocial health (p=0.021) functioning, particularly at school (p=0.000), compared with healthy subjects, resulting in a significantly reduced total score (p=0.013). Assessment of social competence and the behavioral features of HIV-infected children by means of the CBCL revealed severe limitations of functioning in HIV-infected children who had impaired social ability. Children with HIV-RNA above the threshold level of 50 had higher scores on the CBCL delinquent behavior (p=0.021) and school competence (p=0.025) subsets. Although the introduction of HAART regimens has prolonged the survival of HIV-infected children, other factors, including disease morbidity and familial and environmental conditions, negatively affect their quality of life, thereby contributing to increased risk for behavioral problems.

  2. Black–White Mortality From HIV in the United States Before and After Introduction of Highly Active Antiretroviral Therapy in 1996

    PubMed Central

    Levine, Robert S.; Briggs, Nathaniel C.; Kilbourne, Barbara S.; King, William D.; Fry-Johnson, Yvonne; Baltrus, Peter T.; Husaini, Baqar A.; Rust, George S.

    2007-01-01

    Objectives. We sought to describe Black–White differences in HIV disease mortality before and after the introduction of highly active antiretroviral treatment (HAART). Methods. Black–White mortality from HIV is described for the nation as a whole. We performed regression analyses to predict county-level mortality for Black men aged 25–84 years and the corresponding Black:White male mortality ratios (disparities) in 140 counties with reliable Black mortality for 1999–2002. Results. National Black–White disparities widened significantly after the introduction of HAART, especially among women and the elderly. In county regression analyses, contextual socioeconomic status (SES) was not a significant predictor of Black:White mortality rate ratio after we controlled for percentage of the population who were Black and percentage of the population who were Hispanic, and neither contextual SES nor race/ethnicity were significant predictors after we controlled for pre-HAART mortality. Contextual SES, race, and pre-HAART mortality were all significant and independent predictors of mortality among Black men. Conclusions. Although nearly all segments of the Black population experienced widened post-HAART disparities, disparities were not inevitable and tended to reflect pre-HAART levels. Public health policymakers should consider the hypothesis of unequal diffusion of the HAART innovation, with place effects rendering some communities more vulnerable than others to this potential problem. PMID:17761583

  3. Evaluation of viral load thresholds for predicting new World Health Organization stage 3 and 4 events in HIV-infected children receiving highly active antiretroviral therapy.

    PubMed

    Siberry, George K; Harris, D Robert; Oliveira, Ricardo Hugo; Krauss, Margot R; Hofer, Cristina B; Tiraboschi, Adriana Aparecida; Marques, Heloisa; Succi, Regina C; Abreu, Thalita; Della Negra, Marinella; Mofenson, Lynne M; Hazra, Rohan

    2012-06-01

    This study evaluated a wide range of viral load (VL) thresholds to identify a cut-point that best predicts new clinical events in children on stable highly active antiretroviral therapy (HAART). Cox proportional hazards modeling was used to assess the adjusted risk for World Health Organization stage 3 or 4 clinical events (WHO events) as a function of time-varying CD4, VL, and hemoglobin values in a cohort study of Latin American children on HAART ≥6 months. Models were fit using different VL cut-points between 400 and 50,000 copies per milliliter, with model fit evaluated on the basis of the minimum Akaike information criterion value, a standard model fit statistic. Models were based on 67 subjects with WHO events out of 550 subjects on study. The VL cut-points of >2600 and >32,000 copies per milliliter corresponded to the lowest Akaike information criterion values and were associated with the highest hazard ratios (2.0, P = 0.015; and 2.1, P = 0.0058, respectively) for WHO events. In HIV-infected Latin American children on stable HAART, 2 distinct VL thresholds (>2600 and >32,000 copies/mL) were identified for predicting children at significantly increased risk for HIV-related clinical illness, after accounting for CD4 level, hemoglobin level, and other significant factors.

  4. The Impact of Comorbid Clinical Depression on The Health-Related Quality of Life of Adults on Highly Active Antiretroviral Therapy in Maiduguri, Northeastern Nigeria

    PubMed Central

    Wakawa, Ibrahim Abdu; Said, Jidda Mohammed; Abba, Wakil Musa; Shehu, Saleh; Rabbebe, Isa Bukar; Beida, Omeiza

    2014-01-01

    Background: Globally, depression compromises the quality of life (QOL) of people suffering from it. We assessed the impact of comorbid depression on the health-related quality of life (HRQOL) of adults on highly active antiretroviral therapy (HAART) in northeastern Nigeria in this study. Materials and Methods: Three hundred and three adults on HAART were recruited for this study from the ART clinic of the University of Maiduguri Teaching Hospital in northeastern Nigeria. The depressive disorder module of the Composite international diagnostic interview (CIDI version 3.0) and the WHO quality of life instrument (WHOQOL-BREF) were used for the evaluation of depression and quality of life respectively. Results: The prevalence of depression in this study was 19.8%. The depressed respondents rated their HRQOL poorer than their nondepressed counterparts on the physical, psychological, social relationships and environmental domains as well as the global outcome, as shown by these statistically significant findings (T = 9.739, P = <0.001), (T = 8.972, P = <0.001), (T = 6.533, P = <0.001), (T = 8.913, P = <0.001), and (T = 10.018, P = <0.001), respectively. Female gender, CD4 counts <200/mm3 and diagnosis of depression were significant predictors poor QOL. Conclusion: Depression has a negative impact on the QOL of the respondents. We therefore recommend incorporation of the routine screening of this important psychiatric comorbidity into the care of this vulnerable group in order to optimize patient care. PMID:25336775

  5. The physical activity levels among people living with human immunodeficiency virus/acquired immunodeficiency syndrome receiving high active antiretroviral therapy in Rwanda

    PubMed Central

    Frantz, J.M.; Murenzi, A.

    2014-01-01

    The accessibility of high active antiretroviral therapy (HAART) for local human immunodeficiency virus (HIV) patients is improving in Rwanda. It is well known that this therapy is associated with serious adverse effects, such as metabolic and morphologic changes. One of the recommended preventive modalities for these complications is participation in physical activity. The current study aims to determine the anthropometric profile and physical activity levels among people living with HIV and receiving HAART in Kigali, Rwanda. The study was a cross-sectional, descriptive quantitative survey. The participant's levels of physical activity participation and their association with anthropometric profiles were measured, using a structured self-administered questionnaire for 407 clients passing through the clinics. Of the participants, approximately 70% were inactive and in addition, 40% were obese and 43% overweight. Obesity was found to be strongly associated with inactivity. Lack of motivation, and time as well as fear of worsening the disease were found to be barriers to participation in physical activity. PMID:24521093

  6. Level of adherence and HIV RNA suppression in the current era of Highly Active Antiretroviral Therapy (HAART)

    PubMed Central

    Viswanathan, Shilpa; Detels, Roger; Mehta, Shruti H.; Macatangay, Bernard J.C.; Kirk, Gregory D.; Jacobson, Lisa P.

    2014-01-01

    The need to achieve ≥95% adherence to HAART for treatment effectiveness may be a barrier for universal initiation at early stages of HIV. Using longitudinal data collected from 2006-2011 from cohort studies of MSM (MACS) and IDUs (ALIVE study), we estimated the minimum adherence needed to achieve HIV RNA suppression (<50 copies/mL), defined as the level at which at least 80% were virally suppressed, and the odds of suppression was not significantly different than that observed with ≥95% adherence. In the MACS, ≥80% suppression was observed with 80-84% adherence and the odds ratio for suppression (vs.≥95% adherence) was 1.43 (0.61, 3.33). In the ALIVE study where <35% were on newer drugs, only 71.4% were suppressed among those who reported ≥95% adherence. Although IDUs on older HAART regimens may need to be ≥95% adherent, concerns related to non-adherence may be less of a barrier to initiation of modern HAART regimens. PMID:25342151

  7. [Factors associated with immunovirologic dissociation in HIV-1-infected patients under highly active antiretroviral therapy in the Ambulatory Treatment Center (ATC) in Dakar].

    PubMed

    Kà, Daye; Manga, Noël Magloire; Ngom-Guéye, Ndéye Fatou; Ndiaga, Diop; Diop, Moustapha; Cisse-Diallo, Viviane Marie Pierre; Diallo-Mbaye, Khardiata; Lakhe, Ndèye Aissatou; Fortès-Déguenonvo, Louise; Ndour, Cheikh Tidiane; Diop-Nyafouna, Sylvie Audrey; Seydi, Moussa

    2017-01-01

    The objective of this work is to evaluate the different factors associated with immunovirologic dissociation despite highly active and effective antiretroviral treatment. We conducted a retrospective, cohort, descriptive and analytical study of the medical records of HIV-1 infected patients having received at least 12 months of antiretroviral therapy, followed in the ATC cohort from 2001 to 2011 and with undetectable viral load in the last 6 months. During this 10-year study period, the prevalence of IVD was 19.3%. Female sex was predominant, with a sex ratio of 1.9. Immunovirologic dissociation was more frequent in male patients (29.7% vs 14.1%) with a statistically significant difference (p = 0,00006). The average age was 44 years ± 10 years. A history of tuberculosis was found in about a third of the cases (31.4%). Immunovirologic dissociation was significantly more frequent in patients with a history of tuberculosis (p = 0.00005). Most patients (68%) had AIDS at WHO clinical stages 3 or 4. Patients with immunovirologic dissociation were more often in WHO clinical stages 3 and 4 (p = 0.0001). More than half of the cases (56.2%) were found to be malnourished and immunovirologic dissociation was prevalent in malnourished patients (p=0.005). The mean CD4+ T lymphocytes counts was 86.7± 83 cells / mm(3). Immunovirologic dissociation was more frequent in patients with initial low CD4+ T lymphocyte counts and with a statistically significant difference (p = 0.00000). By multivariate analysis, only age greater than or equal to 43 years, CD4 initial counts < 100 c/mm(3) and male sex were significantly associated with this immunovirologic dissociation. Our study assessed the main factors associated with immunovirologic dissociation. Other studies of this nature would also merit consideration in order to highlight the impact of this partial immune response on the emergence of opportunistic infections or the implementation of a specific tritherapy for the sole purpose of

  8. Factors associated with virological suppression among HIV-positive individuals on highly active antiretroviral therapy in a multi-site Canadian cohort.

    PubMed

    Cescon, A M; Cooper, C; Chan, K; Palmer, A K; Klein, M B; Machouf, N; Loutfy, M R; Raboud, J; Rachlis, A; Ding, E; Lima, V D; Montaner, J S G; Rourke, S B; Smieja, M; Tsoukas, C; Hogg, R S

    2011-07-01

    The aim of the study was to evaluate time to virological suppression in a cohort of individuals who started highly active antiretroviral therapy (HAART), and to explore the factors associated with suppression. Eligible participants were HIV-positive individuals from a multi-site Canadian cohort of antiretroviral-naïve patients initiating HAART on or after 1 January 2000. Viral load and CD4 measurements within 6 months prior to HAART initiation were assessed. Univariate and multivariate analyses were conducted using piecewise survival exponential models where time scale was divided into intervals (<10 months; ≥10 months). Virological suppression was defined as the time to the first of at least two consecutive viral load measurements <50 HIV-1 RNA copies/mL. A total of 3555 individuals were included in the study, of median age 40 years [interquartile range (IQR) 34-47 years]. Eighty per cent were male, 18% had a history of injecting drug use (IDU), and 13% presented with an AIDS-defining illness at baseline. The median time to suppression was 4.55 months (IQR 2.99-7.89 months). In multivariate analyses, older age, male sex, treatment in Ontario rather than British Columbia, non-IDU history, and having an AIDS diagnosis at baseline predicted increased likelihood of suppression. Patients with low baseline viral load were more likely to have suppression [4-5 log(10) copies/mL, hazard ratio (HR) 1.27, 95% confidence interval (CI) 1.18-1.38; <4 log(10) copies/mL, HR 1.49, 95% CI 1.32-1.68] than patients with baseline viral load ≥5 log(10) copies/mL; however, this effect ceased after 18 months of follow-up. Suppression was more likely with nonnucleoside reverse transcriptase inhibitors and ritonavir-boosted HAART. Identification of patients at risk for diminished likelihood of virological suppression will allow focusing of efforts and the utilization of resources to maximize the benefits of HAART. © 2010 British HIV Association.

  9. Impact of highly active antiretroviral therapy on nutritional and immunologic status in HIV-infected children in the low-income country of Ethiopia.

    PubMed

    Ebissa, Getachew; Deyessa, Negusse; Biadgilign, Sibhatu

    2016-06-01

    HIV/AIDS and malnutrition combine to undermine the immunity of individuals and are inextricably interrelated. Although the effect of highly active antiretroviral therapy (HAART) on growth in HIV-infected children is well known, the influence of prior nutritional and immunologic status on the response to HAART is not well documented. The aim of the present study was to determine the effects of HAART on nutritional and immunological status in HIV-infected children in the low-income country of Ethiopia. A multicenter, retrospective cohort study was conducted on HIV-infected children receiving antiretroviral therapy at the pediatric units of public hospitals in Addis Ababa (Black Lion, Zewditu, Yekatit 12 and ALERT hospitals), Ethiopia. Nutritional status was defined as stunting (height-for-age Z score [HAZ] <-2), wasting (weight-for-height Z score [WHZ] <-2), and underweight (weight-for-age Z score [WAZ] <-2). Multivariable logistic regression was used to analyze factors associated with treatment success and to establish whether growth (baseline nutritional status) in children predicts immunologic outcomes. In all, 556 HIV-infected children receiving HAART from January 2008 to December 2009 were included in this study. Over the 24-mo follow-up period, the study showed that the immunologic recovery of stunted and underweight children, regardless of their baseline nutritional status, responded equally to treatment. However, wasted children showed less immunologic recovery at the different follow-up visits. Predictors of positive shift in WHZ after 24 mo of follow-up were advanced disease stage (World Health Organization clinical stages 3 and 4) with odds ratio (OR), 0.25 (95% confidence interval [CI], 0.34-0.99; P = 0.045) and baseline severe underweight OR, 0.19 (95% CI, 0.09-0.56; P = 0.003). The independent predictors of positive shift of growth shift in WAZ over 24 mo were lower baseline age (<36 mo) with OR, 0.21 (95% CI, 0.04-0.90; P = 0.036) and baseline

  10. Viremia and HIV-1 drug resistance mutations among patients receiving second-line highly active antiretroviral therapy in Chennai, Southern India.

    PubMed

    Saravanan, Shanmugam; Vidya, Madhavan; Balakrishnan, Pachamuthu; Kantor, Rami; Solomon, Sunil S; Katzenstein, David; Kumarasamy, Nagalingeswaran; Yeptomi, Tokugha; Sivamalar, Sathasivam; Rifkin, Samara; Mayer, Kenneth H; Solomon, Suniti

    2012-04-01

    A cross-sectional study among individuals receiving second-line antiretroviral treatment was conducted to report on the level of detectable viremia and the types of drug resistance mutations among those with detectable human immunodeficiency virus (HIV) type 1 plasma viral loads (PVLs). PVLs were measured using Abbott m2000rt real-time polymerase chain reaction, and genotyping was performed with the ViroSeq genotyping system, version 2.0, and ViroSeq analysis software, version 2.8. Of 107 patient plasma specimens consecutively analyzed, 30 (28%) had undetectable PVLs (<150 copies/mL), and 77 (72%) were viremic with a median PVL of 5450 copies/mL (interquartile range, 169-1 997 967). Sequencing was done for 107 samples with PVLs >2000 copies/mL: 33 patients (73%) had 1 of the protease (PR) inhibitor mutations; 41 (91%) had nucleoside reverse-transcriptase inhibitor (NRTI) mutations; 33 (73%) had non-NRTI (NNRTI) mutations; and 30 (66.7%) had both NRTI and NNRTI mutations. Triple-class resistance to NRTIs, NNRTIs, and PR inhibitors was observed in 24 (53%) patients. Based on the mutational profiles observed, all 45 sequences were susceptible to darunavir and tipranavir, whereas 47% showed resistance to lopinavir, 58% showed resistance to atazanavir, and >60% showed resistance to saquinavir, indinavir, nelfinavir, and fosamprenavir. The results of the study showed that the majority of patients receiving second-line antiretroviral therapy started to accumulate PR resistance mutations, and the mutation profiles suggest that darunavir might be the drug of choice for third-line regimens in India.

  11. Viremia and HIV-1 Drug Resistance Mutations Among Patients Receiving Second-Line Highly Active Antiretroviral Therapy in Chennai, Southern India

    PubMed Central

    Vidya, Madhavan; Balakrishnan, Pachamuthu; Kantor, Rami; Solomon, Sunil S.; Katzenstein, David; Kumarasamy, Nagalingeswaran; Yeptomi, Tokugha; Sivamalar, Sathasivam; Rifkin, Samara; Mayer, Kenneth H.; Solomon, Suniti

    2012-01-01

    Background. A cross-sectional study among individuals receiving second-line antiretroviral treatment was conducted to report on the level of detectable viremia and the types of drug resistance mutations among those with detectable human immunodeficiency virus (HIV) type 1 plasma viral loads (PVLs). Methods. PVLs were measured using Abbott m2000rt real-time polymerase chain reaction, and genotyping was performed with the ViroSeq genotyping system, version 2.0, and ViroSeq analysis software, version 2.8. Results. Of 107 patient plasma specimens consecutively analyzed, 30 (28%) had undetectable PVLs (<150 copies/mL), and 77 (72%) were viremic with a median PVL of 5450 copies/mL (interquartile range, 169–1 997 967). Sequencing was done for 107 samples with PVLs >2000 copies/mL: 33 patients (73%) had 1 of the protease (PR) inhibitor mutations; 41 (91%) had nucleoside reverse-transcriptase inhibitor (NRTI) mutations; 33 (73%) had non-NRTI (NNRTI) mutations; and 30 (66.7%) had both NRTI and NNRTI mutations. Triple-class resistance to NRTIs, NNRTIs, and PR inhibitors was observed in 24 (53%) patients. Based on the mutational profiles observed, all 45 sequences were susceptible to darunavir and tipranavir, whereas 47% showed resistance to lopinavir, 58% showed resistance to atazanavir, and >60% showed resistance to saquinavir, indinavir, nelfinavir, and fosamprenavir. Conclusions. The results of the study showed that the majority of patients receiving second-line antiretroviral therapy started to accumulate PR resistance mutations, and the mutation profiles suggest that darunavir might be the drug of choice for third-line regimens in India. PMID:22323567

  12. In-house human immunodeficiency virus-1 genotype resistance testing to determine highly active antiretroviral therapy resistance mutations in Hong Kong.

    PubMed

    Chen, Jonathan H K; Wong, K H; Li, Patrick C K; Chan, Kenny K C; Lee, M P; To, Sabrina W C; Yam, W C

    2012-02-01

    To determine the frequency of highly active antiretroviral therapy resistance mutations in the viral pol gene of human immunodeficiency virus-1 (HIV-1) genotypes that circulate in Hong Kong, by means of an in-house HIV-1 genotyping system. Retrospective study. Two HIV clinics in Hong Kong. A modified in-house genotyping resistance test was used to sequence the partial pol gene in 1165 plasma samples from 965 patients. The performance of our test was cross-compared with the US Food and Drug Administration-approved ViroSeq HIV-1 genotyping system. The results of genotyping were submitted to the Stanford HIV-1 drug resistance database for analysis. The cost-effective in-house genotypic resistance test (US$40) demonstrated comparable performance to the US Food and Drug Administration-approved ViroSeq system. The detection limit of this in-house genotypic resistance test could reach 400 copies/mL for both HIV-1 subtype B and CRF01_AE, which were the predominant genotypes in Hong Kong. Drug resistance mutations were detected only in post-treatment samples from treatment-failure patients. However, there was no significant difference in the frequency of drug resistance mutations between subtype B and CRF01_AE. Our cost-effective in-house genotypic resistance test detected no significant difference in drug resistance-related mutations frequencies between HIV-1 subtype B and CRF01_AE in Hong Kong. A drug resistance-related mutations database for different HIV-1 genotypes should be established in Hong Kong to augment guidance for HIV treatment.

  13. The effect of highly active antiretroviral therapy on the prevalence of oral manifestation in human immunodeficiency virus-infected patients in Karnataka, India

    PubMed Central

    Patil, Neelkant; Chaurasia, Vishwajit Rampratap; Babaji, Prashant; Ramesh, Dnsv; Jhamb, Kshitij; Sharma, Akanksha Manmohan

    2015-01-01

    Objectives: Acquired Immunodeficiency Syndrome (AIDS) is a highly lethal, progressively epidemic viral infection characterized by profound impairment of the immune system. Oral manifestations are common in Human Immunodeficiency Virus (HIV) infected AIDS patients, and are usually the first indicator of symptom and disease progression. The main objective of the current study was to compare the prevalence of oral manifestations in HIV patients on Highly Active Antiretroviral Therapy (HAART) with those, not on HAART therapies. Materials and Methods: A cross sectional study was conducted among 100 patients diagnosed as human immune virus sero-positive. These patients were divided equally into two groups (50 each); Group I patients on HAART and Group II patients who were not on HAART. Information regarding age, sex and cluster of differentiation 4 cell count was obtained from the medical records. Oral examination was done, and findings were recorded by using internationally accepted presumptive clinical criteria. Statistical analysis was performed using Chi-square statistical test. Results: The presence of oral manifestations was significantly decreased in subjects on HAART (32%) compared to those who are not on HAART (56%). The most common oral lesions detected in patients on HAART were increased oral hyper-pigmentation (14%), recurrent aphthous stomatitis (8%), non-specific ulcerations (4%), pseudo-membranous candidiasis (2%), periodontitis (2%) and xerostomia (2%), whereas in non HAART oral hyperpigmentation (10%), pseudo-membranous candidiasis (8%), angular cheilitis (4%), and erythematous candidiasis (4%) and Periodontitis (14%) were more prevalent. Conclusion: The number and severity of oral manifestation decreased, and even there was a change in the type of oral manifestations on HAART, which may be because of the improvement in immunity gained by the therapy. PMID:25713484

  14. New subtypes and genetic recombination in HIV type 1-infecting patients with highly active antiretroviral therapy in Peru (2008-2010).

    PubMed

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

    2012-12-01

    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.

  15. Restoration of anti-tetanus toxoid responses in patients initiating highly active antiretroviral therapy with or without a boost immunization: an INITIO substudy

    PubMed Central

    Burton, C T; Goodall, R L; Samri, A; Autran, B; Kelleher, A D; Poli, G; Pantaleo, G; Gotch, F M; Imami, N; Imami, N

    2008-01-01

    INITIO is an open-labelled randomized trial evaluating first-line therapeutic strategies for human immunodeficiency virus-1 (HIV-1) infection. In an immunology substudy a tetanus toxoid booster (TTB) immunization was planned for 24 weeks after initiation of highly active antiretroviral therapy (HAART). All patients had received tetanus toxoid immunization in childhood. Generation of proliferative responses to tetanus toxoid was compared in two groups of patients, those receiving a protease inhibitor (PI)-sparing regimen (n = 21) and those receiving a PI-containing (n = 54) regimen. Fifty-two participants received a TTB immunization [PI-sparing (n = 15), PI-containing (n = 37)] and 23 participants did not [PI-sparing (n = 6) or PI-containing (n = 17)]. Cellular responses to tetanus antigen were monitored by lymphoproliferation at time of immunization and every 24 weeks to week 156. Proportions with a positive response (defined as stimulation index ≥ 3 and Δ counts per minute ≥ 3000) were compared at weeks 96 and 156. All analyses were intent-to-treat. Fifty-two participants had a TTB immunization at median 25 weeks; 23 patients did not. At weeks 96 and 156 there was no evidence of a difference in tetanus-specific responses, between those with or without TTB immunization (P = 0·2, P = 0·4). There was no difference in the proportion with response between those with PI-sparing or PI-containing regimens at both time-points (P = 0·8, P = 0·7). The proliferative response to tetanus toxoid was unaffected by initial HAART regimen. Anti-tetanus responses appear to reconstitute eventually in most patients over 156 weeks when treated successfully with HAART, irrespective of whether or not a TTB immunization has been administered. PMID:18410636

  16. Restoration of anti-tetanus toxoid responses in patients initiating highly active antiretroviral therapy with or without a boost immunization: an INITIO substudy.

    PubMed

    Burton, C T; Goodall, R L; Samri, A; Autran, B; Kelleher, A D; Poli, G; Pantaleo, G; Gotch, F M; Imami, N

    2008-05-01

    INITIO is an open-labelled randomized trial evaluating first-line therapeutic strategies for human immunodeficiency virus-1 (HIV-1) infection. In an immunology substudy a tetanus toxoid booster (TTB) immunization was planned for 24 weeks after initiation of highly active antiretroviral therapy (HAART). All patients had received tetanus toxoid immunization in childhood. Generation of proliferative responses to tetanus toxoid was compared in two groups of patients, those receiving a protease inhibitor (PI)-sparing regimen (n = 21) and those receiving a PI-containing (n = 54) regimen. Fifty-two participants received a TTB immunization [PI-sparing (n = 15), PI-containing (n = 37)] and 23 participants did not [PI-sparing (n = 6) or PI-containing (n = 17)]. Cellular responses to tetanus antigen were monitored by lymphoproliferation at time of immunization and every 24 weeks to week 156. Proportions with a positive response (defined as stimulation index > or = 3 and Delta counts per minute > or = 3000) were compared at weeks 96 and 156. All analyses were intent-to-treat. Fifty-two participants had a TTB immunization at median 25 weeks; 23 patients did not. At weeks 96 and 156 there was no evidence of a difference in tetanus-specific responses, between those with or without TTB immunization (P = 0.2, P = 0.4). There was no difference in the proportion with response between those with PI-sparing or PI-containing regimens at both time-points (P = 0.8, P = 0.7). The proliferative response to tetanus toxoid was unaffected by initial HAART regimen. Anti-tetanus responses appear to reconstitute eventually in most patients over 156 weeks when treated successfully with HAART, irrespective of whether or not a TTB immunization has been administered.

  17. Cellular immune responses in human immunodeficiency virus (HIV)-1-infected children: is immune restoration by highly active anti-retroviral therapy comparable to non-progression?

    PubMed

    Hainaut, M; Verscheure, V; Ducarme, M; Schandené, L; Levy, J; Mascart, F

    2011-07-01

    The objective of this study was to investigate whether the restored immune functions of vertically human immunodeficiency virus (HIV)-infected children who were severely immunodeficient before the initiation of highly active anti-retroviral therapy (HAART) are comparable to those of untreated slow progressors. We therefore assessed T cell proliferation and cytokine [interferon (IFN)-γ, interleukin (IL)-5 and IL-13] secretions after mitogen, recall antigens and HIV-1-specific stimulation in 12 untreated slow progressors, 16 untreated progressors and 18 treated patients. Treated children were profoundly immunodeficient before the initiation of HAART and had long-lasting suppression of viral replication on treatment. We demonstrated that slow progressors are characterized not only by the preservation of HIV-1-specific lymphoproliferative responses but also by the fact that these responses are clearly T helper type 1 (Th1)-polarized. Children on HAART had proliferative responses to HIV-1 p24 antigen, purified protein derivative (PPD) and tetanus antigen similar to slow progressors and higher than those of progressors. However, in contrast to slow progressors, most treated children exhibited a release of Th2 cytokines accompanying the IFN-γ secretion in response to the HIV-1 p24 antigen. Moreover, despite higher proliferative responses to phytohaemagglutinin (PHA) than the two groups of untreated children, treated children had lower levels of IFN-γ secretion in response to PHA than slow progressors. These data show that in severely immunodeficient vertically HIV-infected children, a long-lasting HAART allows recovering lymphoproliferative responses similar to untreated slow progressors. However, alterations in IFN-γ secretion in response to the mitogen PHA persisted, and their cytokine release after HIV-specific stimulation was biased towards a Th2 response. © 2011 The Authors. Clinical and Experimental Immunology © 2011 British Society for Immunology.

  18. 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.

  19. Hepatobiliary diseases in patients with human immunodeficiency virus (HIV) treated with non highly active anti-retroviral therapy: frequency and clinical manifestations.

    PubMed

    Lizardi-Cervera, Javier; Soto Ramírez, Luis E; Poo, Jorge Luis; Uribe, Misael

    2005-01-01

    To evaluate the frequency of hepatobiliary diseases and the clinical manifestations in patients with HIV treated with non highly active anti-retroviral therapy. Seven hundred clinical records of patients with HIV infection who entered the Instituto Nacional de Ciencias Médicas y de la Nutrición Salvador Zubirán from January 1987 to December 1996 were reviewed. All patients with alterations associated to hepatobiliary disease and/or liver function tests derangement throughout the clinical development of their disease were included. Demographic variables, date of diagnosis and clinical stage of the disease, as well as the presentation forms, diagnostic approach and image studies were analyzed. One hundred and sixty-one patients (22.8%) with hepatobiliary manifestations were found. The average time between the HIV diagnosis and the presentation of hepatic manifestations was 2-12 years. The majority of patients 124/161 (77%) did not show clinical signs of liver damage. The diagnostic suspicion was established by the presence of alkaline phosphatase above normal in 29% and alkaline phosphatase plus aminotransferases above normal in 45%. Hepatomegaly and jaundice were present in 18% and 4% of the patients, respectively. The most frequent ultrasonographic diagnosis were hepatomegaly (40%) and steatosis (30%). Liver biopsies were performed in 85 (51%) of the patients. The main histologic diagnoses were granulomatous hepatitis (29%), steatosis plus granulomatous hepatitis (19.5%), and steatosis alone (14.6%). Microorganisms were isolated in 27.9% being the most frequent Mycobacterium tuberculosis (26.6%), Histoplasma capsulatum (20%), Cytomegalovirus (13.3%), and Mycobacterium avium intracellulare (11%). The HBsAg was positive in 21 of the 69 patients (30.4%). The clinical presentation was asymptomatic in most of cases and the main etiology could be explained by the presence of associated infections, granulomatoses and liver steatosis.

  20. Relationship of chronic hepatitis C infection to rates of AIDS-defining illnesses in a Canadian cohort of HIV seropositive individuals receiving highly active antiretroviral therapy.

    PubMed

    Raboud, J; Anema, A; Su, D; Klein, M B; Zakaryan, A; Swan, T; Palmer, A; Hosein, S; Loutfy, M R; Machouf, N; Montaner, J S G; Rourke, S B; Tsoukas, C; Hogg, R S; Cooper, C

    2012-01-01

    The influence of chronic hepatitis C virus (HCV) infection on the risk, timing, and type of AIDS-defining illnesses (ADIs) is not well described. To this end, rates of ADIs were evaluated in a Canadian cohort of HIV seropositive individuals receiving highly active antiretroviral therapy (HAART). ADIs were classified into 6 Centers for Disease Control and Prevention (CDC)-defined etiological subgroups: non-Hodgkin lymphoma, viral infection, bacterial infection, HIV-related disease, protozoal infection, and mycotic infection. Generalized estimating equation (GEE) Poisson regression models were used to estimate the effect of HCV on rates of ADIs after adjusting for covariates. Among 2,706 HAART recipients, 768 (28%) were HCV coinfected. Rates of all ADIs combined and of bacterial infection, HIV-related disease, and mycotic infection were increased in HCV-coinfected persons and among those with CD4 counts <200 cells/mm3 HCV was associated with an increased risk of ADIs (rate ratio [RR], 1.38; 95% CI, 1.01-1.88) and a 2-fold increased risk of mycotic infections (RR, 2.21; 95% CI, 1.35-3.62) in univariate analyses and after adjusting for age, baseline viral load, baseline CD4 count, and region of Canada. However, after further adjustment for HAART interruptions, HCV was no longer associated with an increased rate of ADIs overall (RR, 1.13; 95% CI, 0.80-1.59), but remained associated with an increased rate of mycotic infections (RR, 1.97, 95% CI, 1.08-3.61). Although HCV coin-fected individuals are at increased risk of developing ADIs overall, our analysis suggests that behavioral variables associated with HCV (including rates of retention on HAART), and not biological interactions with HCV itself, are primarily responsible.

  1. Cancer incidence and all-cause mortality in HIV-positive patients in Northeastern Algeria before and during the era of highly active antiretroviral therapy.

    PubMed

    Chaabna, Karima; Newton, Robert; Vanhems, Philippe; Laouar, Maamar; Forman, David; Boudiaf, Zahira; Soerjomataram, Isabelle

    2016-01-01

    To assess cancer incidence and all-cause mortality trends in HIV-positive patients in Algeria before and during the highly active antiretroviral therapy (HAART) era. Cross-sectional study. We used hospital-based data of patients with HIV/AIDS between January 1988 and December 2010. Cancer incidence, standardized mortality ratios (SMRs), risk of death, and proportion of HIV-positive patients treated before and during the HAART era were calculated. The joinpoint model was used to assess the magnitude of changes in SMRs. In 1988-2010, 156 patients were diagnosed as HIV-positive. During pre-HAART era, Kaposi sarcoma (KS) incidence was 5%. After the introduction of HAART, KS incidence decreased to 2%. No other AIDS-related cancer was diagnosed during the study. One-third died (52/156), of which 83.6% died in the same year as or in the year after HIV diagnosis; median age at death (interquartile range) was 34.5 (11.8) years. Yearly risk of death declined from 100% in 1998 to 8% in 2010; percentage of patients treated with HAART increased from 13% in 1998 to >80% after 2002. Overall SMR decreased from 200.2 (95% confidence interval [95% CI], 123.2-325.2) before the HAART era to 91.4 (95% CI, 66.0-126.6) thereafter. From 2003, yearly SMRs decreased significantly by 66.1% (P < 0.05) until 2006 but not thereafter. Since 1998, the proportion of HIV-positive patients treated with HAART increased, reaching 84% in 2010, all-cause mortality decreased, and cancer remained rare. However, almost all patients who died during the study seemed to be diagnosed at a late stage of the disease, emphasizing the need for earlier diagnosis of HIV in Algeria.

  2. Discordant responses on starting highly active antiretroviral therapy: suboptimal CD4 increases despite early viral suppression in the UK Collaborative HIV Cohort (UK CHIC) Study.

    PubMed

    Gilson, R J C; Man, S-L; Copas, A; Rider, A; Forsyth, S; Hill, T; Bansi, L; Porter, K; Gazzard, B; Orkin, C; Pillay, D; Schwenk, A; Johnson, M; Easterbook, P; Walsh, J; Fisher, M; Leen, C; Anderson, J; Sabin, C A

    2010-02-01

    Patients starting highly active antiretroviral therapy (HAART) may have a suboptimal CD4 increase despite rapid virological suppression. The frequency and the significance for patient care of this discordant response are uncertain. This study was designed to determine the incidence of a discordant response at two time-points, soon after 6 months and at 12 months, and to determine the relationship with clinical outcomes. Data obtained in the UK Collaborative HIV Cohort Study were analysed. A total of 2584 treatment-naïve patients starting HAART with HIV viral load (VL) > 1000 HIV-1 RNA copies/mL at baseline and < 50 copies/mL within 6 months were included in the analysis. Patients were classified at either 6-10 (midpoint 8) months or 10-14 (midpoint 12) months as having a discordant (CD4 count increase < 100 cells/microL from baseline) or concordant response (CD4 count increase >or= 100 cells/microL). Discordant responses occurred in 32.1% of patients at 8 months and in 24.2% at 12 months; 35% of those discordant at 8 months were concordant at 12 months. A discordant response was associated with older age, lower baseline VL, and (at 12 months) higher baseline CD4 cell count. In a multivariate analysis it was associated with an increased risk of death, more strongly at 12 months [incidence rate ratio (IRR) 3.35, 95% confidence interval (CI) 1.73-6.47, P < 0.001] than at 8 months (IRR 2.08, 95% CI 1.19-3.64, P = 0.010), but not with new AIDS events. Discordant responders have a worse outcome, but assessment at 12 months may be preferred, given the number of 'slow' responders. Management strategies to improve outcomes for discordant responders need to be investigated.

  3. Effect of hepatitis C virus on immunological and virological responses in HIV-infected patients initiating highly active antiretroviral therapy: a meta-analysis.

    PubMed

    Tsiara, C G; Nikolopoulos, G K; Dimou, N L; Bagos, P G; Saroglou, G; Velonakis, E; Hatzakis, A

    2013-10-01

    Co-infection of human immunodeficiency virus (HIV) with hepatitis C virus (HCV) is rather common. In the era of highly active antiretroviral therapy (HAART), viral hepatitis could result in adverse outcomes in HIV+ patients. The current meta-analysis aims to evaluate the impact of HCV on immunological and virological responses after HAART initiation in HIV/HCV co-infected individuals by synthesizing the existing scientific evidence. A comprehensive search of electronic databases was performed. Eligible studies were analysed using univariate and multivariate meta-analytic methods. Totally, 21 studies involving 22533 individuals were eligible. The estimated summary difference in CD4 cell counts increase between HIV and HIV/HCV co-infected subjects after 3-12 months on HAART was 34.86 cells/mm(3) [95% confidence interval (CI): 16.82-52.89]. The difference was more prominent in patients with baseline CD4 counts below 350 cells/mm(3) (38.97, 95% CI: 20.00-57.93) and attenuated 2 years later (13.43, 95% CI: 0.83-26.04). The analysis of ratio measures yielded similar findings. The virological control remained unaffected by the presence of HCV (adjusted Hazard Ratio for co-infected patients vs those with HIV alone: 0.99, 95% CI: 0.91-1.07). The bivariate meta-analytic method confirmed the results of the univariate approaches. This meta-analysis supports the adverse effect of HCV on immune recovery of HIV+ patients initiating HAART, especially of those with initially impaired immunologic status. Although this effect diminishes over time, early administration of HAART in the setting of co-infection seems to be justified.

  4. Drug use and receipt of highly active antiretroviral therapy among HIV-infected persons in two U.S. clinic cohorts.

    PubMed

    McGowan, Catherine C; Weinstein, David D; Samenow, Charles P; Stinnette, Samuel E; Barkanic, Gema; Rebeiro, Peter F; Sterling, Timothy R; Moore, Richard D; Hulgan, Todd

    2011-04-25

    Drug use and receipt of highly active antiretroviral therapy (HAART) were assessed in HIV-infected persons from the Comprehensive Care Center (CCC; Nashville, TN) and Johns Hopkins University HIV Clinic (JHU; Baltimore, MD) between 1999 and 2005. Participants with and without injection drug use (IDU) history in the CCC and JHU cohorts were evaluated. Additional analysis of persons with history of IDU, non-injection drug use (NIDU), and no drug use from CCC were performed. Activity of IDU and NIDU also was assessed for the CCC cohort. HAART use and time on HAART were analyzed according to drug use category and site of care. 1745 persons were included from CCC: 268 (15%) with IDU history and 796 (46%) with NIDU history. 1977 persons were included from JHU: 731 (35%) with IDU history. Overall, the cohorts differed in IDU risk factor rates, age, race, sex, and time in follow-up. In multivariate analyses, IDU was associated with decreased HAART receipt overall (OR = 0.61, 95% CI: [0.45-0.84] and OR = 0.58, 95% CI: [0.46-0.73], respectively for CCC and JHU) and less time on HAART at JHU (0.70, [0.55-0.88]), but not statistically associated with time on HAART at CCC (0.78, [0.56-1.09]). NIDU was independently associated with decreased HAART receipt (0.62, [0.47-0.81]) and less time on HAART (0.66, [0.52-0.85]) at CCC. These associations were not altered significantly whether patients at CCC were categorized according to historical drug use or drug use during the study period. Persons with IDU history from both clinic populations were less likely to receive HAART and tended to have less cumulative time on HAART. Effects of NIDU were similar to IDU at CCC. NIDU without IDU is an important contributor to HAART utilization.

  5. 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

  6. HIV Status Does Not Influence Outcome in Patients With Classical Hodgkin Lymphoma Treated With Chemotherapy Using Doxorubicin, Bleomycin, Vinblastine, and Dacarbazine in the Highly Active Antiretroviral Therapy Era

    PubMed Central

    Montoto, Silvia; Shaw, Kate; Okosun, Jessica; Gandhi, Shreyans; Fields, Paul; Wilson, Andrew; Shanyinde, Milensu; Cwynarski, Kate; Marcus, Robert; de Vos, Johannes; Young, Anna Marie; Tenant-Flowers, Melinda; Orkin, Chloe; Johnson, Margaret; Chilton, Daniella; Gribben, John G.; Bower, Mark

    2012-01-01

    Purpose The prognosis of HIV-infected patients with non-Hodgkin lymphoma in the highly active antiretroviral therapy (HAART) era approaches that of the general population when they are treated with the same protocols. We analyzed the outcome of patients with Hodgkin lymphoma (HL) treated with doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) in the HAART era according to HIV serostatus to establish whether this also holds true for HL. Patients and Methods From 1997 to 2010, 224 patients newly diagnosed with HL, of whom 93 were HIV positive, were consecutively treated with ABVD chemotherapy. HIV-positive patients had more high-risk disease according to the International Prognostic Score (IPS) than HIV-negative patients (IPS ≥ 3: 68% v 26%, respectively; P < .001). Forty-seven HIV-positive patients had a CD4 count less than 200/μL, and 92 patients received HAART during chemotherapy. Results The complete response rate was 74% for HIV-positive patients and 79% for HIV-negative patients (P = not significant). After a median follow-up of 60 months (range, 8 to 174 months), 23 patients (16 HIV-negative and seven HIV-positive patients) have experienced relapse at a median time of 6 months (range, 1 to 106 months). Five-year event-free survival (EFS) was 59% (95% CI, 47% to 70%) for HIV-positive patients and 66% (95% CI, 57% to 74%) for HIV-negative patients (P = not significant). Five-year overall survival (OS) was 81% (95% CI, 69% to 89%) and 88% (95% CI, 80% to 93%) for HIV-positive and HIV-negative patients, respectively (P = not significant). HIV status did not predict OS or EFS on multivariate analysis including IPS and HIV status. Conclusion This mature study demonstrates that HIV-positive patients with HL have more extensive disease with more adverse prognostic factors than HIV-negative patients, but when treated with ABVD, HIV infection does not adversely affect OS or EFS. PMID:23045581

  7. Differences in serum IgA responses to HIV-1 gp41 in elite controllers compared to viral suppressors on highly active antiretroviral therapy.

    PubMed

    Nabi, Rafiq; Moldoveanu, Zina; Wei, Qing; Golub, Elizabeth T; Durkin, Helen G; Greenblatt, Ruth M; Herold, Betsy C; Nowicki, Marek J; Kassaye, Seble; Cho, Michael W; Pinter, Abraham; Landay, Alan L; Mestecky, Jiri; Kozlowski, Pamela A

    2017-01-01

    Mechanisms responsible for natural control of human immunodeficiency type 1 (HIV) replication in elite controllers (EC) remain incompletely defined. To determine if EC generate high quality HIV-specific IgA responses, we used Western blotting to compare the specificities and frequencies of IgA to HIV antigens in serum of gender-, age- and race-matched EC and aviremic controllers (HC) and viremic noncontrollers (HN) on highly active antiretroviral therapy (HAART). Concentrations and avidity of IgA to HIV antigens were measured using ELISA or multiplex assays. Measurements for IgG were performed in parallel. EC were found to have stronger p24- and V1V2-specific IgG responses than HN, but there were no IgG differences for EC and HC. In contrast, IgA in EC serum bound more frequently to gp160 and gag proteins than IgA in HC or HN. The avidity of anti-gp41 IgA was also greater in EC, and these subjects had stronger IgA responses to the gp41 heptad repeat region 1 (HR1), a reported target of anti-bacterial RNA polymerase antibodies that cross react with gp41. However, EC did not demonstrate greater IgA responses to E. coli RNA polymerase or to peptides containing the shared LRAI sequence, suggesting that most of their HR1-specific IgA antibodies were not induced by intestinal microbiota. In both EC and HAART recipients, the concentrations of HIV-specific IgG were greater than HIV-specific IgA, but their avidities were comparable, implying that they could compete for antigen. Exceptions were C1 peptides and V1V2 loops. IgG and IgA responses to these antigens were discordant, with IgG reacting to V1V2, and IgA reacting to C1, especially in EC. Interestingly, EC with IgG hypergammaglobulinemia had greater HIV-specific IgA and IgG responses than EC with normal total IgG levels. Heterogeneity in EC antibody responses may therefore be due to a more focused HIV-specific B cell response in some of these individuals. Overall, these data suggest that development of HIV-specific Ig

  8. Differences in serum IgA responses to HIV-1 gp41 in elite controllers compared to viral suppressors on highly active antiretroviral therapy

    PubMed Central

    Nabi, Rafiq; Moldoveanu, Zina; Wei, Qing; Golub, Elizabeth T.; Durkin, Helen G.; Greenblatt, Ruth M.; Herold, Betsy C.; Nowicki, Marek J.; Kassaye, Seble; Cho, Michael W.; Pinter, Abraham; Landay, Alan L.; Mestecky, Jiri

    2017-01-01

    Mechanisms responsible for natural control of human immunodeficiency type 1 (HIV) replication in elite controllers (EC) remain incompletely defined. To determine if EC generate high quality HIV-specific IgA responses, we used Western blotting to compare the specificities and frequencies of IgA to HIV antigens in serum of gender-, age- and race-matched EC and aviremic controllers (HC) and viremic noncontrollers (HN) on highly active antiretroviral therapy (HAART). Concentrations and avidity of IgA to HIV antigens were measured using ELISA or multiplex assays. Measurements for IgG were performed in parallel. EC were found to have stronger p24- and V1V2-specific IgG responses than HN, but there were no IgG differences for EC and HC. In contrast, IgA in EC serum bound more frequently to gp160 and gag proteins than IgA in HC or HN. The avidity of anti-gp41 IgA was also greater in EC, and these subjects had stronger IgA responses to the gp41 heptad repeat region 1 (HR1), a reported target of anti-bacterial RNA polymerase antibodies that cross react with gp41. However, EC did not demonstrate greater IgA responses to E. coli RNA polymerase or to peptides containing the shared LRAI sequence, suggesting that most of their HR1-specific IgA antibodies were not induced by intestinal microbiota. In both EC and HAART recipients, the concentrations of HIV-specific IgG were greater than HIV-specific IgA, but their avidities were comparable, implying that they could compete for antigen. Exceptions were C1 peptides and V1V2 loops. IgG and IgA responses to these antigens were discordant, with IgG reacting to V1V2, and IgA reacting to C1, especially in EC. Interestingly, EC with IgG hypergammaglobulinemia had greater HIV-specific IgA and IgG responses than EC with normal total IgG levels. Heterogeneity in EC antibody responses may therefore be due to a more focused HIV-specific B cell response in some of these individuals. Overall, these data suggest that development of HIV-specific Ig

  9. High-dose (5000-microg) intravitreal ganciclovir combined with highly active antiretroviral therapy for cytomegalovirus retinitis in HIV-infected patients in Venezuela.

    PubMed

    Arevalo, J F; Garcia, R A; Mendoza, A J

    2005-01-01

    To describe the use of high doses of intravitreal ganciclovir combined with highly active antiretroviral therapy (HAART) for the treatment of cytomegalovirus (CMV) retinitis in human immunodeficiency virus (HIV)-infected patients. Thirteen HIV-infected patients (18 eyes) with active CMV retinitis (83.3% in zone 1 and 38.4% resistant) participated in this prospective interventional case series. Patients were treated with high dose intravitreal ganciclovir (5.0 mg/0.1 mL once a week) in combination with HAART therapy. Intravitreal injections were discontinued once CMV retinitis healed if there was a significant increase in CD4+ count (any increase of > or 50 cells/microL to levels over 100 cells/microL sustained for at least 3 months). Mean follow-up was 15.6 months. Main outcome measures included assessment of visual acuity and retinal inflammation (CMV retinitis activity). A matched historical control group of 20 eyes (15 patients) with CMV retinitis treated with systemic ganciclovir (intravenous [induction] and oral [maintenance]) was included. Complete regression of the retinitis was obtained with high doses of intravitreal ganciclovir in 88.8% of eyes (two patients died during follow-up) at a mean of 4.5 weeks (2 to 8 weeks). Visual acuity improved two or more lines in 61.1% of eyes. No ganciclovir retinal toxicity was identified. Three eyes presented CMV retinitis reactivation at a mean of 25.6 days after their last injection. Complications (33.3%) included retinal detachment (RD; 3 eyes), immune recovery uveitis (IRU; 2 eyes), and endophthalmitis (1 eye). In our control group complete regression of the retinitis was obtained in 100% of eyes at a mean of 4 weeks (3 to 7 weeks). However, 12 eyes (60%) presented with CMV retinitis relapse at a mean of 29 days (21 to 32 days) after initiating oral ganciclovir (maintenance). Complications included RD (7 eyes, 35%) and IRU (3 eyes, 15%). Severe neutropenia occurred in 2 patients (13%). High doses of intravitreal

  10. Prevalence of renal disease in Nigerian children infected with the human immunodeficiency virus and on highly active anti-retroviral therapy.

    PubMed

    Iduoriyekemwen, Nosakhare J; Sadoh, Wilson E; Sadoh, Ayebo E

    2013-01-01

    Access to highly active anti-retroviral therapy (HAART) has improved the prognosis of Nigerian children infected with the human immunodeficiency virus (HIV); thus, more children are surviving. Long-term exposure to HAART is potentially nephrotoxic. We therefore aimed at assessing the prevalence of renal disease in Nigerian children infected with HIV, who are on HAART. In this cross-sectional study, we studied children, aged ten months to 17 years, infected with HIV, attending the pediatric HIV clinics of the University of Benin Teaching Hospital. Demographic and clinical data were obtained by parental interview as well as from the medical records. Each child's urine was tested for albumin and microalbuminuria using multi test strips and mitral test strips, respectively. The serum creatinine level of each child was also estimated and used in calculating the glomerular filtration rate (GFR). Renal disease was defined as the presence of significant proteinuria of 1+ and above on dipstick or the presence of microalbuminuria of ≥20 mg and/or GFR <60 mL/min/1.73 m 2 . Of the 99 children recruited, 60 were males and 39 were females. The mean age of the children was 6.6 ± 3.5 years. All the children were on HAART and 85% had acquired the HIV infection by vertical transmission. The overall prevalence of renal disease was 16.2%. Microalbuminuria was seen in 11 children with renal disease (11.1%); 3 of them had significant proteinuria. GFR of less than 60 mL/min/1.73 m 2 was seen in five children (5.1%) with renal disease, but none had end-stage renal disease (GFR less than 15 mL/min/1.73 m 2 ). Renal disease was found to be significantly associated with advanced stage of HIV infection (P < 0.049). Our study showed that t he prevalence of renal disease in HAART-treated Nigerian children is high and majority of them are asymptomatic of renal disease, but in the advanced stages of HIV infection.

  11. Drug Use and Receipt of Highly Active Antiretroviral Therapy among HIV-Infected Persons in Two U.S. Clinic Cohorts

    PubMed Central

    McGowan, Catherine C.; Weinstein, David D.; Samenow, Charles P.; Stinnette, Samuel E.; Barkanic, Gema; Rebeiro, Peter F.; Sterling, Timothy R.; Moore, Richard D.; Hulgan, Todd

    2011-01-01

    Objective Drug use and receipt of highly active antiretroviral therapy (HAART) were assessed in HIV-infected persons from the Comprehensive Care Center (CCC; Nashville, TN) and Johns Hopkins University HIV Clinic (JHU; Baltimore, MD) between 1999 and 2005. Methods Participants with and without injection drug use (IDU) history in the CCC and JHU cohorts were evaluated. Additional analysis of persons with history of IDU, non-injection drug use (NIDU), and no drug use from CCC were performed. Activity of IDU and NIDU also was assessed for the CCC cohort. HAART use and time on HAART were analyzed according to drug use category and site of care. Results 1745 persons were included from CCC: 268 (15%) with IDU history and 796 (46%) with NIDU history. 1977 persons were included from JHU: 731 (35%) with IDU history. Overall, the cohorts differed in IDU risk factor rates, age, race, sex, and time in follow-up. In multivariate analyses, IDU was associated with decreased HAART receipt overall (OR = 0.61, 95% CI: [0.45–0.84] and OR = 0.58, 95% CI: [0.46–0.73], respectively for CCC and JHU) and less time on HAART at JHU (0.70, [0.55–0.88]), but not statistically associated with time on HAART at CCC (0.78, [0.56–1.09]). NIDU was independently associated with decreased HAART receipt (0.62, [0.47–0.81]) and less time on HAART (0.66, [0.52–0.85]) at CCC. These associations were not altered significantly whether patients at CCC were categorized according to historical drug use or drug use during the study period. Conclusions Persons with IDU history from both clinic populations were less likely to receive HAART and tended to have less cumulative time on HAART. Effects of NIDU were similar to IDU at CCC. NIDU without IDU is an important contributor to HAART utilization. PMID:21541016

  12. 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

    2016-02-16

    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

  13. Rate of candidiasis among HIV-infected children in Spain in the era of highly active antiretroviral therapy (1997–2008)

    PubMed Central

    2013-01-01

    Background Candidiasis is the most common opportunistic infection seen in human immunodeficiency virus (HIV)-infected individuals. The aim of our study was to estimate the candidiasis rate and evaluate its trend in HIV-infected children in Spain during the era of highly active antiretroviral therapy (HAART) compared to HIV-uninfected children. Methods We carried out a retrospective study. Data were obtained from the records of the Minimum Basic Data Set from hospitals in Spain. All HIV-infected children were under 17 years of age, and a group of HIV-uninfected children with hospital admissions matching the study group by gender and age were randomly selected. The follow-up period (1997–2008) was divided into three calendar periods: a) From 1997 to 1999 for early-period HAART; b) from 2000 to 2002 for mid-period HAART; and c) from 2003 to 2008 for late-period HAART. Results Among children with hospital admissions, HIV-infected children had much higher values than HIV-uninfected children during each of the three calendar periods for overall candidiasis rates (150.0 versus 6.1 events per 1,000 child hospital admissions/year (p < 0.001), 90.3 versus 3.1 (p < 0.001), and 79.3 versus 10.7 (p < 0.001), respectively) and for non-invasive Candida mycosis (ICM) rates (118.5 versus 3.8 (p < 0.001), 85.3 versus 2.3 (p < 0.001), and 80.6 versus 6.0 (p < 0.001), respectively). In addition, HIV-infected children also had higher values of ICM rates than HIV-uninfected children, except during the last calendar period when no significant difference was found (32.4 versus 1.2 (p < 0.001), 11.6 versus 0.4 (p < 0.001), and 4.6 versus 2.3 (p = 0.387), respectively). For all children living with HIV/AIDS, the overall candidiasis rate (events per 1,000 HIV-infected children/year) decreased from 1997–1999 to 2000–2002 (18.8 to 10.6; p < 0.001) and from 2000–2002 to 2003–2008 (10.6 to 5.7; p = 0.060). Within each category of candidiasis

  14. The cameroon mobile phone sms (CAMPS) trial: a protocol for a randomized controlled trial of mobile phone text messaging versus usual care for improving adherence to highly active anti-retroviral therapy

    PubMed Central

    2011-01-01

    Background This trial aims at testing the efficacy of weekly reminder and motivational text messages, compared to usual care in improving adherence to Highly Active Antiretroviral Treatment in patients attending a clinic in Yaoundé, Cameroon. Methods and Design This is a single-centered randomized controlled single-blinded trial. A central computer generated randomization list will be generated using random block sizes. Allocation will be determined by sequentially numbered sealed opaque envelopes. 198 participants will either receive the mobile phone text message or usual care. Our hypothesis is that weekly motivational text messages can improve adherence to Highly Active Antiretroviral Treatment and other clinical outcomes in the control group by acting as a reminder, a cue to action and opening communication channels. Data will be collected at baseline, three months and six months. A blinded program secretary will send out text messages and record delivery. Our primary outcomes are adherence measured by the visual analogue scale, self report, and pharmacy refill data. Our secondary outcomes are clinical: weight, body mass index, opportunistic infections, all cause mortality and retention; biological: Cluster Designation 4 count and viral load; and quality of life. Analysis will be by intention-to-treat. Covariates and subgroups will be taken into account. Discussion This trial investigates the potential of SMS motivational reminders to improve adherence to Highly Active Antiretroviral Treatment in Cameroon. The intervention targets non-adherence due to forgetfulness and other forms of non-adherence. Trial Registration Pan-African Clinical Trials Registry PACTR201011000261458 http://clinicaltrials.gov/ NCT01247181 PMID:21211064

  15. [Treatment of opportunistic infections in adolescent and adult patients infected with the human immunodeficiency virus during the era of highly active antiretroviral therapy. AIDS Study Group (GESIDA) and National AIDS Plan Expert Committee].

    PubMed

    2008-01-01

    Despite the huge advance that highly active antiretroviral therapy has represented for the prognosis of infection by human immunodeficiency virus (HIV), opportunistic infections continue to be a cause of morbidity and mortality in HIV-infected patients. This is often the case because of severe immunodepression, poor adherence to antiretroviral therapy, failure of therapy, or the fact that patients are unaware of their HIV-positive status and debut with an opportunistic infection. This article updates the guidelines on treatment of acute episodes of various opportunistic infections in HIV-infected patients, including infections due to parasites, fungi, viruses, mycobacteria, and bacteria. This edition has a new chapter on imported parasite infections as well as additional information on endemic mycoses in the chapter on fungal infections, taking into account the growing number of immigrants in our setting. Lastly, the chapter on the immune reconstitution syndrome has also been updated, providing relevant data on a phenomenon that has clinical and diagnostic repercussions in patients who start antiretroviral therapy while they are severely immunodepressed (English version available at http://www.gesida.seimc.org).

  16. Outcomes of Highly Active Antiretroviral Therapy in the Context of Universal Access to Healthcare: The U.S. Military HIV Natural History Study

    DTIC Science & Technology

    2010-05-27

    Hepatitis C virus ( HCV ) co- infection was defined as having at least one positive HCV antibody test. ARV use referred to any antiretroviral ther...Factors associated with higher mor- tality included non-active duty status, lower CD4 count at HAART initiation, higher VL at HAART initiation, HCV ...clinical and immunologic outcomes as well as a higher likelihood of VS (data not shown), no difference was found with time to VF. Marconi et al. AIDS

  17. Low Prevalence of Varicella Zoster Virus and Herpes Simplex Virus Type 2 in Saliva from Human Immunodeficiency Virus-Infected Persons in the Era of Highly Active Antiretroviral Therapy

    PubMed Central

    Wang, Chunmei C.; Yepes, Luis C.; Danaher, Robert J.; Berger, Joseph R.; Mootoor, Yunanan; Kryscio, Richard J.; Miller, Craig S.

    2009-01-01

    Objectives Human herpesviruses (HHVs), e.g. herpes simplex virus (HSV) type 1, Epstein-Barr virus and cytomegalovirus, appear in saliva at greater frequency in persons infected with human immunodeficiency virus (HIV) than healthy individuals. However, it is not known if varicella zoster virus (VZV) and HSV-2 appear simultaneously during HIV infection at greater frequency in saliva during this era of highly active antiretroviral therapy (HAART). The aim of this study was to investigate the prevalence and amounts of VZV and HSV-2 in the saliva of HIV-infected, orally asymptomatic patients. Study Design Quantitative polymerase chain reaction was used to investigate the prevalence, quantity, risk, and correlates of salivary VZV and HSV-2 from 59 HIV-seropositive individuals and 53 healthy controls in a case-control, cross-sectional study. Seventy-eight percent of the HIV-seropositive patients (46/59) were taking HAART. Results VZV DNA was detected in the saliva of 5.1% (3/59) of the HIV-positive group and in only one healthy control 1.9% (1/53; P = 0.62). The amount of VZV DNA in the expressors was low, generally less than 1,100 copies/mL with no observed difference between the HIV-positive group and the controls (P= 1.0). HSV-2 DNA was not detected in either group. In the HIV-infected group, VZV shedding occurred in those on HAART, but was not associated with oral lesions, specific CD4+ or CD8+ T-cell levels, or demographic factors. Conclusions VZV was detected at low prevalence in the saliva of HIV-infected persons whereas HSV-2 was not detected in the saliva of this cohort. HAART does not appear to diminish the risk for asymptomatic VZV shedding. PMID:20123407

  18. A phase I/pharmacokinetic study of sunitinib in combination with highly active antiretroviral therapy (HAART) in HIV-positive patients with cancer: AIDS Malignancy Consortium Trial AMC 061

    PubMed Central

    Rudek, Michelle A; Moore, Page C.; Mitsuyasu, Ronald T.; Dezube, Bruce J.; Aboulafia, David; Gerecitano, John; Sullivan, Ryan; Cianfrocca, Mary E.; Henry, David H.; Ratner, Lee; Haigentz, Missak; Dowlati, Afshin; Little, Richard F.; Ivy, S. Percy; Deeken, John F.

    2014-01-01

    Background Treatment of non-AIDS defining cancers (NADCs) may be complicated by drug interactions between highly active antiretroviral therapy (HAART) and chemotherapy. This trial is the first by the AIDS Malignancy Consortium assessing targeted therapies and HAART in HIV+ cancer patients (ClinicalTrials.gov NCT00890747). Methods Patients were stratified into two arms based on whether they were taking ritonavir, a potent CYP3A4 inhibitor, in a modified phase I study of sunitinib. Patients in arm 1 (non-ritonavir HAART) received standard sunitinib dosing (50mg/day). Arm 2 (ritonavir-based HAART) used a phase I, 3+3 dose escalation design (from 25 to 50mg/day). Cycles were with four weeks on treatment followed by a two week break (6 weeks total). Pharmacokinetics of sunitinib and its active metabolite (N-desethyl sunitinib) were assessed. Results Nineteen patients were enrolled and evaluable. Patients on Arm 1 tolerated treatment with one observed dose limiting toxicity (DLT). In Arm 2, a DLT was experienced at 37.5mg, and an additional 3 of 5 patients experienced grade 3 neutropenia, an uncommon toxicity of sunitinib. No patient had a response, but 10 had stable disease, including 8 with prolonged disease stability. Efavirenz, a potent inducer of CYP3A4, resulted in increased exposure of N-desethyl sunitinib, whereas ritonavir caused decreased exposure of the metabolite. Hand-foot syndrome was associated with higher steady-state trough concentrations of sunitinib. Conclusions Patients on non-ritonavir based HAART regimens tolerated standard dosing of sunitinib. Patients on ritonavir-based therapy treated with 37.5mg/day experienced higher toxicities. Dose reduction of sunitinib to 37.5mg may be warranted in patients on ritonavir. PMID:24474568

  19. Viral Load Predicts New World Health Organization Stage 3 and 4 Events in HIV-Infected Children Receiving Highly Active Antiretroviral Therapy, Independent of CD4 T Lymphocyte Value

    PubMed Central

    Oliveira, Ricardo; Krauss, Margot; Essama-Bibi, Suzanne; Hofer, Cristina; Harris, D. Robert; Tiraboschi, Adriana; de Souza, Ricardo; Marques, Heloisa; Succi, Regina; Abreu, Thalita; Della Negra, Marinella; Hazra, Rohan; Mofenson, Lynne M.; Siberry, George K.

    2010-01-01

    Background. Many resource-limited countries rely on clinical and immunological monitoring without routine virological monitoring for human immunodeficiency virus (HIV)-infected children receiving highly active antiretroviral therapy (HAART). We assessed whether HIV load had independent predictive value in the presence of immunological and clinical data for the occurrence of new World Health Organization (WHO) stage 3 or 4 events (hereafter, WHO events) among HIV-infected children receiving HAART in Latin America. Methods. The NISDI (Eunice Kennedy Shriver National Institute of Child Health and Human Development International Site Development Initiative) Pediatric Protocol is an observational cohort study designed to describe HIV-related outcomes among infected children. Eligibility criteria for this analysis included perinatal infection, age <15 years, and continuous HAART for ≥6 months. Cox proportional hazards modeling was used to assess time to new WHO events as a function of immunological status, viral load, hemoglobin level, and potential confounding variables; laboratory tests repeated during the study were treated as time-varying predictors. Results. The mean duration of follow-up was 2.5 years; new WHO events occurred in 92 (15.8%) of 584 children. In proportional hazards modeling, most recent viral load >5000 copies/mL was associated with a nearly doubled risk of developing a WHO event (adjusted hazard ratio, 1.81; 95% confidence interval, 1.05–3.11; P = .033), even after adjustment for immunological status defined on the basis of CD4 T lymphocyte value, hemoglobin level, age, and body mass index. Conclusions. Routine virological monitoring using the WHO virological failure threshold of 5000 copies/mL adds independent predictive value to immunological and clinical assessments for identification of children receiving HAART who are at risk for significant HIV-related illness. To provide optimal care, periodic virological monitoring should be considered

  20. Impact of antiretroviral therapy on opportunistic infections of HIV-infected children in the therapeutic research, education and AIDS training asia pediatric HIV observational database.

    PubMed

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

    2014-07-01

    There are limited data on opportunistic infections (OIs) 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. Retrospective and prospectively collected data from the Therapeutic Research, Education and AIDS Training Asia Pediatric HIV Observational Database cohort study from March 1993 to March 2009 were analyzed. OIs were defined according to World Health Organization clinical staging criteria and incidence rates calculated. Factors associated with the incidence of severe OIs were analyzed using random effects Poisson regression modeling. Of 2280 children in the cohort, 1752 were ever reported to have received antiretroviral therapy, of whom 1480 (84%) started on HAART. Before commencing any antiretroviral therapy, 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 antiretroviral therapy initiation were recurrent upper respiratory tract infections, persistent oral candidiasis and pulmonary tuberculosis. The incidence rates of World Health Organization 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 % <15%, and World Health Organization stage 3 at HAART initiation. 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.

  1. Neuropathology of AIDS: An Autopsy Review of 284 Cases from Brazil Comparing the Findings Pre- and Post-HAART (Highly Active Antiretroviral Therapy) and Pre- and Postmortem Correlation.

    PubMed

    Silva, Ana Cristina Araújo Lemos; Rodrigues, Blenda Sousa Carli; Micheletti, Adilha Misson Rua; Tostes, Sebastião; Meneses, Antonio Carlos Oliveira; Silva-Vergara, Mário Leon; Adad, Sheila Jorge

    2012-01-01

    A retrospective study of central nervous system (CNS) in 284 autopsy AIDS cases in Brazil (1989-2008) divided into 3 groups: A (without antiretroviral treatment: 163 cases); B (other antiretroviral therapies: 76 cases); C (HAART for 3 months or more: 45 cases). In 165 (58.1%) cases, relevant lesions were found, predominantly infections (54.2%); the most frequent was toxoplasmosis (29.9%) followed by cryptococcosis (15.8%), purulent bacterial infections (3.9%), and HIV encephalitis (2.8%); non-Hodgkin lymphomas occurred in 1.4% and vascular lesions in 1.1%. There was no difference when compared the frequency of lesion among the groups; however, toxoplasmosis was less common while HIV encephalitis was more frequent in group C related to A. CNS lesions remain a frequent cause of death in AIDS; however, the mean survival time was four times greater in group C than in A. In 91 (55.1%) of 165 cases with relevant brain lesions (or 32% of the total 284 cases), there was discordance between pre- and postmortem diagnosis; disagreement type 1 (important disease that if diagnosed in life could change the patient prognosis) occurred in 49 (53.8%) of 91 discordant cases (17.6% of the total 284) indicating the autopsy importance, even with HAART and advanced diagnostics technologies.

  2. Neuropathology of AIDS: An Autopsy Review of 284 Cases from Brazil Comparing the Findings Pre- and Post-HAART (Highly Active Antiretroviral Therapy) and Pre- and Postmortem Correlation

    PubMed Central

    Silva, Ana Cristina Araújo Lemos; Rodrigues, Blenda Sousa Carli; Micheletti, Adilha Misson Rua; Tostes, Sebastião; Meneses, Antonio Carlos Oliveira; Silva-Vergara, Mário Leon; Adad, Sheila Jorge

    2012-01-01

    A retrospective study of central nervous system (CNS) in 284 autopsy AIDS cases in Brazil (1989–2008) divided into 3 groups: A (without antiretroviral treatment: 163 cases); B (other antiretroviral therapies: 76 cases); C (HAART for 3 months or more: 45 cases). In 165 (58.1%) cases, relevant lesions were found, predominantly infections (54.2%); the most frequent was toxoplasmosis (29.9%) followed by cryptococcosis (15.8%), purulent bacterial infections (3.9%), and HIV encephalitis (2.8%); non-Hodgkin lymphomas occurred in 1.4% and vascular lesions in 1.1%. There was no difference when compared the frequency of lesion among the groups; however, toxoplasmosis was less common while HIV encephalitis was more frequent in group C related to A. CNS lesions remain a frequent cause of death in AIDS; however, the mean survival time was four times greater in group C than in A. In 91 (55.1%) of 165 cases with relevant brain lesions (or 32% of the total 284 cases), there was discordance between pre- and postmortem diagnosis; disagreement type 1 (important disease that if diagnosed in life could change the patient prognosis) occurred in 49 (53.8%) of 91 discordant cases (17.6% of the total 284) indicating the autopsy importance, even with HAART and advanced diagnostics technologies. PMID:22461978

  3. Morphological changes in the digestive system of 322 necropsies of patients with acquired immune deficiency syndrome: comparison of findings pre- and post-HAART (Highly Active Antiretroviral Therapy)

    PubMed Central

    Guimarães, Lucinda Calheiros; da Silva, Ana Cristina Araújo Lemos; Micheletti, Adilha Misson Rua; Moura, Everton Nunes Melo; Silva-Vergara, Mario Léon; Tostes, Sebastião; Adad, Sheila Jorge

    2017-01-01

    ABSTRACT Involvement of the digestive system in AIDS pathologies or injuries is frequent. Aiming at comparing the frequency, the importance that these lesions have for death and the survival time in patients using or not using HAART, we studied 322 necropsies classified as follows: Group A - without antiretroviral drugs (185 cases); B - one or two antiretroviral drugs or HAART for less than six months (83 cases); C - HAART for six months or longer (54 cases). In the overall analysis of the digestive system, changes were present in 73.6% of cases. The most frequent was Candida infection (22.7%), followed by cytomegalovirus (19.2%), Histoplasma capsulatum (6.5%), mycobacteria (5.6%), and Toxoplasma gondii (4.3%). T. gondii infection was more frequent in group A compared with group C, and cytomegalovirus (CMV) was more frequent in group A compared with groups B and C (p < 0.05); 2.2% of the deaths were due to gastrointestinal bleeding. Regarding the segments, only in the large intestine, and only cytomegalovirus, were more frequent in group A compared with group C. We conclude that digestive system infections are still frequent, even with the use of HAART. However, the average survival time in group C was more than three times greater than the one in group A and nearly double that of group B, demonstrating the clear benefit of this therapy. PMID:28380114

  4. Morphological changes in the digestive system of 322 necropsies of patients with acquired immune deficiency syndrome: comparison of findings pre- and post-HAART (Highly Active Antiretroviral Therapy).

    PubMed

    Guimarães, Lucinda Calheiros; Silva, Ana Cristina Araújo Lemos da; Micheletti, Adilha Misson Rua; Moura, Everton Nunes Melo; Silva-Vergara, Mario Léon; Tostes, Sebastião; Adad, Sheila Jorge

    2017-04-03

    Involvement of the digestive system in AIDS pathologies or injuries is frequent. Aiming at comparing the frequency, the importance that these lesions have for death and the survival time in patients using or not using HAART, we studied 322 necropsies classified as follows: Group A - without antiretroviral drugs (185 cases); B - one or two antiretroviral drugs or HAART for less than six months (83 cases); C - HAART for six months or longer (54 cases). In the overall analysis of the digestive system, changes were present in 73.6% of cases. The most frequent was Candida infection (22.7%), followed by cytomegalovirus (19.2%), Histoplasma capsulatum (6.5%), mycobacteria (5.6%), and Toxoplasma gondii (4.3%). T. gondii infection was more frequent in group A compared with group C, and cytomegalovirus (CMV) was more frequent in group A compared with groups B and C (p < 0.05); 2.2% of the deaths were due to gastrointestinal bleeding. Regarding the segments, only in the large intestine, and only cytomegalovirus, were more frequent in group A compared with group C. We conclude that digestive system infections are still frequent, even with the use of HAART. However, the average survival time in group C was more than three times greater than the one in group A and nearly double that of group B, demonstrating the clear benefit of this therapy.

  5. Introduction: Linkage, engagement, and retention in HIV care: essential for optimal individual- and community-level outcomes in the era of highly active antiretroviral therapy.

    PubMed

    Mayer, Kenneth Hugh

    2011-01-15

    Engagement in medical care after a diagnosis of human immunodeficiency virus (HIV) infection is essential to initiate lifesaving antiretroviral therapy and facilitate the delivery of important prevention messages for reducing HIV transmission. Failure to engage and be retained in HIV care can be associated with negative outcomes for both the individual and the community. However, many Americans living with HIV infection are, for a variety of reasons, undiagnosed, not in medical care, or not receiving HIV treatment. The articles in this supplement describe the barriers, challenges, and successes in linking HIV-infected patients to expert care in the United States, with a focus on the unique issues faced by specific populations of men who have sex with men, heterosexual men, and women, and the role of the health care system and other structural factors in facilitating or impeding engagement in care.

  6. Virologic response and safety of the abacavir/lamivudine fixed-dose formulation as part of highly active antiretroviral therapy: analyses of six clinical studies.

    PubMed

    Ha, Belinda; Liao, Qiming M; Dix, Lynn P; Pappa, Keith A

    2009-01-01

    We analyzed virologic response and safety data from six recent clinical studies conducted in antiretroviral-naïve subjects treated with ABC/3TC or its components to assess the impact of baseline viral load on efficacy and safety endpoints used in the ACTG5202 protocol. Primary endpoints were time to virologic failure (confirmed HIV-1 RNA > or = 1,000 copies/mL at 16-24 weeks or > or = 200 copies/mL at > or = 24 weeks) and time to first grade 3 or 4 adverse event or laboratory abnormality that was at least one grade higher than at baseline. The survival distributions of both endpoints were estimated using the Kaplan-Meier method overall and by baseline viral load (<100,000 vs. 100,000 copies/mL). A weighted mean of the virologic response and 95% confidence intervals (CI) were calculated by inverse-variance weighting for baseline viral load 100,000 copies/mL across studies. For subjects with baseline HIV-1 RNA 100,000 copies/mL, the rate of virologic survival ranged from 87% to 95% by 48 weeks. Few subjects treated with ABC/3TC developed grade 3 or 4 adverse events, laboratory toxicities, or changes in lipid levels. The weighted mean (CI) for the pooled virologic response was 91% (87%-96%). Based on the A5202 endpoints, ABC/3TC-containing regimens in this analysis had a high rate of virologic survival and were generally well tolerated in antiretroviral-naïve subjects regardless of baseline viral load. The pooled virologic response for ABC/3TC in our analysis is higher than the A5202 estimate.

  7. Determinants of Highly Active Antiretroviral Therapy Duration in HIV-1-Infected Children and Adolescents in Madrid, Spain, from 1996 to 2012

    PubMed Central

    Palladino, Claudia; Briz, Verónica; Bellón, José María; Climent, Francisco J.; de Ory, Santiago J.; Mellado, María José; Navarro, María Luisa; Ramos, José T.; Taveira, Nuno; de José, María Isabel; Muñoz-Fernández, María Ángeles

    2014-01-01

    Objectives To investigate the duration of sequential HAART regimens and predictors of first-line regimen discontinuation among HIV-1 vertically infected children and adolescents. Design Multicentre survey of antiretroviral-naïve patients enrolled in the HIV-Paediatric Cohor,t CoRISpeS-Madrid Cohort, Spain. Methods Patients with a follow-up of ≥1 month spent on HAART, with available baseline CD4 count and HIV-viral load (VL) were included. Time spent on sequential HAART regimens was estimated and multivariable regression was used to identify predictors of time to first-line regimen discontinuation. Results 104 patients were followed for a median 8 years after starting HAART among 1996–2012; baseline %CD4 was 21.5 (12.3–34.0)and viral load was 5.1 (4.6–5.6) log10 copies/mL. Patients received a mean of 1.9 regimens. Median time on first-line HAART (n = 104) was 64.5 months; second HAART (n = 56) 69.8 months; and third HAART (n = 21) 66.5 months. Eleven (11%) patients were lost to follow-up while on first-line HAART and 54% discontinued (cumulative incidence of 16% and 38% by 1 and 3-year, respectively). The main predictor of first-line regimen discontinuation was suboptimal adherence to antiretrovirals (AHR: 2.60; 95% CI: 1.44–4.70). Conclusions Adherence to therapy was the main determinant of the duration of the first-line HAART regimen in children. It is important to identify patients at high risk for non-adherence, such as very young children and adolescents, in provide special care and support to those patients. PMID:24788034

  8. CD4+ T cell recovery beyond the first year of complete suppression of viral replication during highly active antiretroviral therapy is not influenced by CD8+ T cell activation.

    PubMed

    Benito, Jose M; Lopez, Mariola; Lozano, Sara; Ballesteros, Celia; Capa, Laura; Martinez, Pilar; Gonzalez-Lahoz, Juan; Soriano, Vincent

    2005-12-15

    CD38 expression on CD8(+) T cells was longitudinally assessed in 31 human immunodeficiency virus (HIV)-infected persons with undetectable plasma viremia who had undergone highly active antiretroviral therapy (HAART) for 12 months and were followed for a mean of 30 months thereafter. Overall, CD4(+)T cell counts increased during follow-up, whereas CD38 expression remained stable. However, a subset of patients showed declines in CD38 expression, and, conversely, another subset showed increases in CD38 expression. No association could be found between long-term gains in CD4(+) T cells and evolution of CD38 expression. Thus, activation of CD8(+) T cells does not seem to be associated with the extent of CD4(+) T cell recovery beyond the first year of successful HAART.

  9. 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

  10. 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

  11. 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.

  12. 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

  13. A clinical isolate of Leishmania donovani with ITS1 sequence polymorphism as a cause of para-kala-azar dermal leishmaniasis in an Ethiopian human immunodeficiency virus-positive patient on highly active antiretroviral therapy.

    PubMed

    Gelanew, T; Amogne, W; Abebe, T; Kuhls, K; Hailu, A; Schönian, G

    2010-10-01

    The diagnosis of para-kala-azar dermal leishmaniasis (PKDL/VL), either as an immune reconstitution inflammatory syndrome (IRIS)-associated syndrome or as a complication of visceral leishmaniasis (VL) during human immunodeficiency virus (HIV) co-infection in patients with or without highly active antiretroviral therapy, represents a challenge for prompt treatment. The aim of this study was to identify the causative Leishmania species and to clarify whether the post-kala-azar dermal leishmaniasis (PKDL)-like lesions appeared as a result of IRIS or not. A 31-year-old Ethiopian male patient, with stage IV HIV/acquired immune deficiency syndrome (AIDS), was clinically diagnosed with PKDL/VL. He had developed a generalized maculopapular rash on his face after initiation of highly active antiretroviral therapy. The Leishmania isolate obtained from the skin lesions was analysed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and sequencing of the ribosomal DNA internal transcribed spacer 1 (ITS1) and partial coding sequences of the heat shock protein 70 gene (hsp70). Restriction analysis of the ITS1 PCR product gave a unique RFLP pattern not seen before for any Leishmania isolate. Sequencing of both the ITS1 and hsp70 PCR products identified the causative species as Leishmania donovani, and further revealed the existence of five different sequence variants of the ITS1 among the 10 clones sequenced. The results indicate that PKDL/VL resulted from an infection by L. donovani. The sequence variants of ITS1 might be due to the presence of multiple strains/clones or the existence of intragenomic variations in the multicopy ITS1, or a combination of both.

  14. A randomized trial of the discontinuation of primary and secondary prophylaxis against Pneumocystis carinii pneumonia after highly active antiretroviral therapy in patients with HIV infection. Grupo de Estudio del SIDA 04/98.

    PubMed

    Lopez Bernaldo de Quiros, J C; Miro, J M; Peña, J M; Podzamczer, D; Alberdi, J C; Martínez, E; Cosin, J; Claramonte, X; Gonzalez, J; Domingo, P; Casado, J L; Ribera, E

    2001-01-18

    Prophylaxis against Pneumocystis carinii pneumonia is indicated in patients with human immunodeficiency virus (HIV) infection who have less than 200 CD4 cells per cubic millimeter and in those with a history of P. carinii pneumonia. However, it is not clear whether prophylaxis can be safely discontinued after CD4 cell counts increase in response to highly active antiretroviral therapy. We conducted a randomized trial of the discontinuation of primary or secondary prophylaxis against P. carinii pneumonia in HIV-infected patients with a sustained response to antiviral therapy, defined by a CD4 cell count of 200 or more per cubic millimeter and plasma HIV type 1 (HIV-1) RNA level of less than 5000 copies per milliliter for at least three months. Prophylactic treatment was restarted if the CD4 cell count declined to less than 200 per cubic millimeter. The 474 patients receiving primary prophylaxis had a median CD4 cell count at entry of 342 per cubic millimeter, and 38 percent had detectable HIV-1 RNA. After a median follow-up period of 20 months (758 person-years), there had been no episodes of P. carinii pneumonia in the 240 patients who discontinued prophylaxis (95 percent confidence interval, 0 to 0.85 episode per 100 person-years). For the 113 patients receiving secondary prophylaxis, the median CD4 cell count at entry was 355 per cubic millimeter, and 24 percent had detectable HIV-1 RNA. After a median follow-up period of 12 months (123 person-years), there had been no episodes of P. carinii pneumonia in the 60 patients who discontinued prophylaxis (95 percent confidence interval, 0 to 4.5 episodes per 100 person-years). In HIV-infected patients receiving highly active antiretroviral therapy, primary and secondary prophylaxis against P. carinii pneumonia can be safely discontinued after the CD4 cell count has increased to 200 or more per cubic millimeter for more than three months.

  15. Modeling CD4+ cell count increase over a six-year period in HIV-1-infected patients on highly active antiretroviral therapy in Senegal.

    PubMed

    De Beaudrap, Pierre; Etard, Jean-François; Diouf, Assane; Ndiaye, Ibrahima; Guèye, Ndèye Fatou; Guèye, Pape Mandoumbé; Sow, Papa Salif; Mboup, Souleymane; Ndoye, Ibra; Ecochard, René; Eric, Delaporte

    2009-06-01

    To assess the extents and determinants of long-term CD4 cell increases after initiation of antiretroviral therapy (ART), changes in CD4 cell counts were analyzed in a cohort of HIV-1-infected Senegalese using a mixed-effects model. After a median follow-up of 54 months, an average of 483 CD4 cells/mm3 (95% confidence interval [CI] = 331; 680) was reached. The average asymptote level was approximately 421 cells/mm3 (95% CI = 390; 454) in patients with < 200 cells/mm3 at baseline and approximately 500 cells/mm3 in patients with > 200 cells/mm3. The independent predictors of long-term CD4 cell reconstitution were the baseline CD4 cell count and the monthly average viral load over the entire follow-up. This good long-term immune reconstitution, optimal in subjects with low average viral loads and > 200 CD4 cells/mm3 at baseline, argues in favor of the earliest possible access to ART and underlines the importance of strict compliance with the treatment.

  16. Development and assessment of an innovative culturally sensitive educational videotape to improve adherence to highly active antiretroviral therapy in Soweto, South Africa.

    PubMed

    Wong, Ilene Y; Lawrence, Nicholas V; Struthers, Helen; McIntyre, James; Friedland, Gerald H

    2006-12-01

    The increasing availability of antiretroviral medication (ARV) therapy in the face of limited chronic medication-taking experience among resource-poor South Africans has raised concerns about adequate adherence to these medications. We hypothesized that a culturally sensitive audiovisual patient education program would be of substantial and measurable benefit in increasing patient understanding of the concepts of ARV resistance risk and medication-taking skills. To identify potential barriers to adherence and successful strategies to promote adherence, 6 focus groups with health care providers and HIV-positive adherence counselors were held, resulting in the production of a 17-minute culturally sensitive educational videotape. Basic drug-taking concepts and practical advice on how to improve adherence were presented in the videotape. Thirty-four HIV-positive patients (including 11 ARV-naive patients and 23 ARV-experienced patients) were shown the educational videotape, and their knowledge about medication taking was evaluated by a 24-point pre- and postvideotape questionnaire. On average, the 34 patients gained 2.2 knowledge points (P = 0.021). ARV-naive patients had an average improvement of 3.0 points (P = 0.0028), with most significant gains in the areas of understanding medication-taking strategies and side effects. These preliminary findings indicate that a culturally sensitive educational videotape can improve medication-taking knowledge in South Africa and that further study of the potential efficacy of using media technology to improve individuals' adherence to ARV therapy is warranted.

  17. 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

  18. Trends in reported AIDS defining illnesses (ADIs) among participants in a universal antiretroviral therapy program: an observational study.

    PubMed

    Jafari, Siavash; Chan, Keith; Aboulhosn, Kewan; Yip, Benita; Lima, Viviane D; Hogg, Robert S; Montaner, Julio; Moore, David M

    2011-09-05

    We examined trends in AIDS-defining illnesses (ADIs) among individuals receiving highly active antiretroviral therapy (HAART) in British Columbia (BC), Canada to determine whether declines in ADIs could be contributing to previously observed improvements in life-expectancy among HAART patients in BC since 1996. HAART-naïve individuals aged ≥ 18 years who initiated treatment in BC each of the following time-periods 1996 - 1998; 1999 - 2001; 2002 - 2004; 2005 - 2007 were included. The proportion of participants with reported ADIs were examined for each time period and trends were analyzed using the Cochran-Armitage Trend Test. Cox proportional hazards models were used to examine factors associated with ADIs. A total of 3721 individuals (81% male) initiated HAART during the study period. A total of 251 reports of ADIs were received from 214 unique patients. These occurred in a median of 4 months (IQR = 1-19 months) from HAART initiation. The proportion of individuals with a reported ADI did not change significantly from 4.6% in the earliest time period to 5.8% in the latest period (p = 0.181 for test of trend). There were no significant declines in any specific ADI over the study period. Multivariable Cox models found that individuals initiating HAART during 2002-04 were at an increased risk of ADIs (AHR = 1.55; 95% CI 1.04-2.32) in comparison to 1996 - 98, but there were no significant differences in other time periods. Trends in reported ADIs among individuals receiving HAART since 1996 in BC do not appear to parallel improvements in life-expectancy over the same period.

  19. Trends in reported AIDS defining illnesses (ADIs) among participants in a universal antiretroviral therapy program: an observational study

    PubMed Central

    2011-01-01

    Background We examined trends in AIDS-defining illnesses (ADIs) among individuals receiving highly active antiretroviral therapy (HAART) in British Columbia (BC), Canada to determine whether declines in ADIs could be contributing to previously observed improvements in life-expectancy among HAART patients in BC since 1996. Methods HAART-naïve individuals aged ≥ 18 years who initiated treatment in BC each of the following time-periods 1996 - 1998; 1999 - 2001; 2002 - 2004; 2005 - 2007 were included. The proportion of participants with reported ADIs were examined for each time period and trends were analyzed using the Cochran-Armitage Trend Test. Cox proportional hazards models were used to examine factors associated with ADIs. Results A total of 3721 individuals (81% male) initiated HAART during the study period. A total of 251 reports of ADIs were received from 214 unique patients. These occurred in a median of 4 months (IQR = 1-19 months) from HAART initiation. The proportion of individuals with a reported ADI did not change significantly from 4.6% in the earliest time period to 5.8% in the latest period (p = 0.181 for test of trend). There were no significant declines in any specific ADI over the study period. Multivariable Cox models found that individuals initiating HAART during 2002-04 were at an increased risk of ADIs (AHR = 1.55; 95% CI 1.04-2.32) in comparison to 1996 - 98, but there were no significant differences in other time periods. Conclusions Trends in reported ADIs among individuals receiving HAART since 1996 in BC do not appear to parallel improvements in life-expectancy over the same period. PMID:21892955

  20. Incidence and risk factors for liver enzyme elevation during highly active antiretroviral therapy in HIV-HCV co-infected patients: results from the Italian EPOKA-MASTER Cohort

    PubMed Central

    Torti, Carlo; Lapadula, Giuseppe; Casari, Salvatore; Puoti, Massimo; Nelson, Mark; Quiros-Roldan, Eugenia; Bella, Daniele; Pastore, Giuseppe; Ladisa, Nicoletta; Minoli, Lorenzo; Sotgiu, Giovanni; Mazzotta, Francesco; Caputo, Sergio Lo; Di Perri, Giovanni; Filice, Gaetano; Tinelli, Carmine; Carosi, Giampiero

    2005-01-01

    Background The risk of hepatotoxicity associated with different highly active antiretroviral therapy (HAART) regimens (containing multiple-protease inhibitors, single-protease inhibitors or non nucleoside reverse transcriptase inhibitors) in HIV-HCV co-infected patients has not been fully assessed. Methods Retrospective analysis of a prospective cohort of 1,038 HIV-HCV co-infected patients who commenced a new HAART in the Italian MASTER database. Patients were stratified into naïve and experienced to antiretroviral therapy before starting the study regimens. Time to grade ≥III hepatotoxicity (as by ACTG classification) was the primary outcome. Secondary outcome was time to grade IV hepatotoxicity. Results Incidence of grade ≥III hepatotoxicity was 17.71 per 100 patient-years (p-yr) of follow up in naïve patient group and 8.22 per 100 p-yrs in experienced group (grade IV: 4.13 per 100 p-yrs and 1.08 per 100 p-yrs, respectively). In the latter group, the only independent factors associated with shorter time to the event at proportional hazards regression model were: previous liver transaminase elevations to grade ≥III, higher baseline alanine amino-transferase values, and use of a non nucleoside reverse transcriptase inhibitor based regimen. In the naive group, baseline aspartate transaminase level was associated with the primary outcome. Conclusion Use of a single or multiple protease inhibitor based regimen was not associated with risk of hepatotoxicity in either naïve or experienced patient groups to a statistically significant extent. A cautious approach with strict monitoring should be applied in HIV-HCV co-infected experienced patients with previous liver transaminase elevations, higher baseline alanine amino-transferase values and who receive regimens containing non nucleoside reverse transcriptase inhibitors. PMID:16018804

  1. Prevalence and pattern of neuropsychological impairment in human immunodeficiency virus-infected/acquired immunodeficiency syndrome (HIV/AIDS) patients across pre- and post-highly active antiretroviral therapy eras: a combined study of two cohorts.

    PubMed

    Cysique, Lucette A; Maruff, Paul; Brew, Bruce J

    2004-12-01

    The objective of this study was to assess the prevalence and pattern of neuropsychological impairment in cohorts of human immunodeficiency virus (HIV)-infected individuals across pre- and post-HAART (highly active antiretroviral therapy) eras. Two cohorts of HIV-infected individuals attending tertiary referral hospital outpatient clinics were studied. The cohorts represented two eras of antiretroviral medication: monotherapy (n = 51) and HAART (n = 90). Each was compared in nine neuropsychological domains in regard to the prevalence as well as pattern of neuropsychological impairment. Because the authors intended to characterize the prevalence and pattern of neuropsychological deficits in nondemented advanced HIV-infected individuals, patients with a current diagnosis of acquired immunodeficiency syndrome (AIDS) dementia complex were not included. The prevalence of impairment was not significantly different across pre-HAART and HAART eras using a standard criterion to define impairment: -2 SD in two neuropsychological measures (41.1%/38.8%). Prevalence of deficits was not significantly reduced in patients with undetectable plasma viral load. The pattern of neuropsychological impairment was different across pre-HAART and HAART eras, with an improvement in attention, verbal fluency, visuoconstruction deficits, but a deterioration in learning efficiency and complex attention. This change remained even in patients with an undetectable plasma viral load, although the severity was partially diminished. Neuropsychological deficits remain common in the HAART era, essentially uninfluenced by HAART. The finding that some neuropsychological functions are improving while other are deteriorating indicates that these deficits do not reflect "burnt out" damage but rather that there is an active intracerebral process occurring, the nature of which is still to be determined.

  2. Ophthalmic manifestations and risk factors for mortality of HIV patients in the post-highly active anti-retroviral therapy era.

    PubMed

    Lai, Timothy Y Y; Wong, Raymond L M; Luk, Fiona O J; Chow, Vanissa W S; Chan, Carmen K M; Lam, Dennis S C

    2011-03-01

    To evaluate the ophthalmic manifestations and risk factors for mortality in HIV patients in the post-highly active anti-retrovirus therapy (HAART) era. Retrospective study. 151 patients with HIV infection. Review of all HIV patients who have attended the Hong Kong Eye Hospital between 2000 and 2007. Ocular findings especially opportunistic infections and medical information including mortality during follow up. At presentation, 139 (92.1%) patients were already diagnosed with HIV and 58 (41.7%) had an AIDS indicator condition. Fifty-one (33.8%) patients had HIV-related eye disease on presentation and the leading manifestations were cytomegalovirus (CMV) retinitis and HIV microangiopathy. Low baseline CD4 cell count <100 cells/L was significantly related with HIV-related ophthalmic manifestations and CMV retinitis at presentation (P < 0.013). 105 patients were followed for 6 months or more and the mean follow-up was 4.8 years. There was no significant change in visual acuity compared with baseline (P = 0.13). 20 (19.0%) patients had one eye with final visual acuity of 20/200 or worse and the leading cause for poor vision was CMV retinitis. 11 (10.5%) patients died during the follow-up due to complications of HIV/AIDS. The presence of HIV retinal microangiopathy was significantly associated with mortality (P = 0.005). CMV retinitis remains the main HIV-related ocular disease in the post-HAART era. HIV retinal microangiopathy might be an important prognostic factor for mortality. Appropriate ophthalmic monitoring is justified to detect for ophthalmic complications in HIV patients regardless of HAART use in order for prompt initiation of treatment. © 2010 The Authors. Clinical and Experimental Ophthalmology © 2010 Royal Australian and New Zealand College of Ophthalmologists.

  3. Oral manifestations of human immunodeficiency virus/acquired immunodeficiency syndrome and their correlation to cluster of differentiation lymphocyte count in population of North-East India in highly active antiretroviral therapy era.

    PubMed

    Nayak, Sarat Kumar; Das, Bijay Kumar; Das, Surya Narayan; Mohapatra, Namita; Nayak, Suryakanti; Bhuyan, Lipsa

    2016-01-01

    The human immunodeficiency virus (HIV) infection which manifests as acquired immunodeficiency syndrome (AIDS) is a disease involving the defects of the T-lymphocyte arm of the immune system. Certain laboratory parameters such as the cluster of differentiation (CD4) count and clinical parameters have long been used as markers of disease progression. In industrialized countries, many studies show a highly correlation between the incidence of oral lesions and immunosuppression and hence, can be used as a marker of immunosuppression. This might not be applicable to a developing country like India. In this study, efforts have been made to supplement the present knowledge on various aspects of oral manifestations in HIV patients in the Indian subcontinent. To correlate the oral manifestations in HIV/AIDS patients to the level of circulating CD4+ T-lymphocyte count and their effect in anti-retroviral therapy (ART). A total of 104 HIV positive patients were examined for oral lesions. The CD4 count estimated on the same day by fluorescent activated cell sort count machine was then correlated with various oral lesions. Oral manifestations appeared when CD4 count decreased below 500 cells/mm(3). Moreover, oral lesions found at different stages showed very strong correlation to their respective CD4 count. Furthermore, there was considerable decline in the incidence of oral manifestations in patients undergoing highly active ART. Oral manifestations are highly predictive markers of severe immune deterioration and disease progression in HIV patients.

  4. 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

  5. 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.

  6. Oral manifestations of human immunodeficiency virus/acquired immunodeficiency syndrome and their correlation to cluster of differentiation lymphocyte count in population of North-East India in highly active antiretroviral therapy era

    PubMed Central

    Nayak, Sarat Kumar; Das, Bijay Kumar; Das, Surya Narayan; Mohapatra, Namita; Nayak, Suryakanti; Bhuyan, Lipsa

    2016-01-01

    Background: The human immunodeficiency virus (HIV) infection which manifests as acquired immunodeficiency syndrome (AIDS) is a disease involving the defects of the T-lymphocyte arm of the immune system. Certain laboratory parameters such as the cluster of differentiation (CD4) count and clinical parameters have long been used as markers of disease progression. In industrialized countries, many studies show a highly correlation between the incidence of oral lesions and immunosuppression and hence, can be used as a marker of immunosuppression. This might not be applicable to a developing country like India. In this study, efforts have been made to supplement the present knowledge on various aspects of oral manifestations in HIV patients in the Indian subcontinent. Aims: To correlate the oral manifestations in HIV/AIDS patients to the level of circulating CD4+ T-lymphocyte count and their effect in anti-retroviral therapy (ART). Subjects and Methods: A total of 104 HIV positive patients were examined for oral lesions. The CD4 count estimated on the same day by fluorescent activated cell sort count machine was then correlated with various oral lesions. Results: Oral manifestations appeared when CD4 count decreased below 500 cells/mm3. Moreover, oral lesions found at different stages showed very strong correlation to their respective CD4 count. Furthermore, there was considerable decline in the incidence of oral manifestations in patients undergoing highly active ART. Conclusions: Oral manifestations are highly predictive markers of severe immune deterioration and disease progression in HIV patients. PMID:27994425

  7. WD 1145+017 photometric observations during eight months of high activity

    NASA Astrophysics Data System (ADS)

    Gary, B. L.; Rappaport, S.; Kaye, T. G.; Alonso, R.; Hambschs, F.-J.

    2017-03-01

    WD 1145+017 was observed from 2015 November to 2016 July, for the purpose of characterizing transit behaviour of the white dwarf by dust clouds thought to be produced by fragments of an asteroid in close orbit with the star. Fortuitously, most of these observations were carried out during a time when the overall 'dip' activity was dramatically enhanced over that during its discovery with Kepler K2. By the end of our reported observations, the dip activity had declined to a level close to its K2 discovery state. Three notable events were observed. In 2016 January, a large number of dust clouds appeared that had an orbital period of 4.4912 h, and this event also marked the end of a three-month interval dominated by the K2 'A' period. The second event was a 2016 April 21 appearance of four dip features with drift lines in a waterfall (date versus phase) diagram that diverged from their origin date, at a location away from the 'A' asteroid, and which lasted for two weeks. The third event was the sudden appearance of a dip feature with a period of 4.6064 h, which is essentially the same as the K2 'B' period. The evolution of dip shape, depth, and total fade amount provide constraints on dust production and loss mechanisms. Collisions can account for the sudden appearance of dust clouds, and the sudden increase in dust amount, but another mechanism for continual dust production is also required.

  8. Observations of cold magnetospheric ions at geosynchronous orbit during times of high activity

    SciTech Connect

    Elphic, R.C.; Weiss, L.A.; Thomsen, M.F.; McComas, D.J.; Bame, S.J.

    1994-10-01

    Flowing, cold magnetospheric ions have been observed in conjunction with geosynchronous orbit magnetopause crossings since the earliest ATS and OGO missions. The authors have reported on the occurrence and convection of low-energy (10-100 eV) ions seen by multiple satellites in association with geosynchronous orbit magnetopause and low-latitude boundary layer (LLBL) encounters. More generally, Los Alamos 3-D plasma instruments observe these ions following storm sudden commencements (SSCs), when activity levels are high. The ions appear to be convecting radially outward and usually westward at speeds of a few to several tens of kilometers per second. Often the energy spectra reveal peaks at energies appropriate for cold convecting H{sup +}, He{sup +} and O{sup +}. The occurrence frequency distribution of these dense cold ions is peaked near 1400 LT, with an overall range from 1000 to beyond 1800 LT. This local time distribution is greatly skewed from the overall plasmaspheric distribution, which peaks closer to 1800 LT. Multisatellite observations show that the ions are seen first at late afternoon local times and then at progressively earlier and earlier local times (though usually no earlier than 1000 LT). This apparent evolution in local time suggests that the late-afternoon plasmaspheric plasma moves out and dawnward during times of increased magnetospheric activity. The three-satellite observations also allow the authors to track cold plasma convection at multiple points in the magnetosphere, and potentially provide a glimpse of the large-scale convection pattern.

  9. Longitudinal Use of a Line Probe Assay for Human Immunodeficiency Virus Type 1 Protease Predicts Phenotypic Resistance and Clinical Progression in Patients Failing Highly Active Antiretroviral Therapy

    PubMed Central

    Servais, Jean; Lambert, Christine; Plesséria, Jean-Marc; Fontaine, Elodie; Robert, Isabelle; Arendt, Vic; Staub, Thérèse; Hemmer, Robert; Schneider, François; Schmit, Jean-Claude

    2002-01-01

    An observational study assessed the longitudinal use of a new line probe assay for the detection of protease mutations. Probe assays for detection of reverse transcriptase (Inno-LiPA HIV-1 RT; Innogenetics) and protease (prototype kit Inno-LiPA HIV Protease; Innogenetics) mutations gave results for 177 of 199 sequential samples collected over 2 years from 26 patients failing two nucleoside reverse transcriptase inhibitors and one protease inhibitor (first line: indinavir, n = 6; ritonavir, n = 10; and saquinavir, n = 10). Results were compared to recombinant virus protease inhibitor susceptibility data (n = 87) and to clinical and virological data. Combinations of protease mutations (M46I, G48V, I54V, V82A or -F, I84V, and L90M) predicted phenotypic resistance to the protease inhibitor and to nelfinavir. The sum of protease mutations was associated with virological and clinical outcomes from 6 and 3 months on, respectively. Moreover, a poorer clinical outcome was linked to the sum of reverse transcriptase mutations. In conclusion, despite the limited number of patients studied and the restricted number of codons investigated, probe assay-based genotyping correlates with phenotypic drug resistance and predicts new Centers for Disease Control and Prevention stage B and C clinical events and virological outcome. Line probe assays provide additional prognostic information and should be prospectively investigated for their potential for treatment monitoring. PMID:12019110

  10. High Prevalence of Multiple Human Herpesviruses in Saliva from Human Immunodeficiency Virus-Infected Persons in the Era of Highly Active Antiretroviral Therapy

    PubMed Central

    Miller, Craig S.; Berger, Joseph R.; Mootoor, Yunanan; Avdiushko, Sergei A.; Zhu, Hua; Kryscio, Richard J.

    2006-01-01

    Human immunodeficiency virus (HIV) infection is associated with an increased risk for human herpesviruses (HHVs) and their related diseases. Methods for limiting the transmission of HHVs require a better understanding of the prevalence and infectiousness of oral HHVs in HIV-infected patients. We performed quantitative PCR to investigate the prevalence, quantity, risk, and correlates of salivary HHVs from 58 HIV-seropositive individuals in a case control study. HHVs were significantly more prevalent in the salivas of HIV-seropositive persons than in those of the controls (odds ratios [ORs], 4.2 to 26.2; P ≤ 0.008). In HIV-infected patients, Epstein-Barr virus (EBV), human herpesvirus 8 (HHV-8), cytomegalovirus (CMV), and herpes simplex virus type 1 (HSV-1) were detected in 90%, 57%, 31% and 16% of samples, respectively, compared with 48%, 24%, 2%, and 2%, respectively, of samples from controls. Multiple HHVs were observed in 71% of HIV-seropositive persons and only 16% of controls (OR, 13.0; 95% confidence interval, 5.29 to 32.56). HIV-positive patients had significantly higher EBV loads than HIV-negative persons (P < 0.0001). HIV-infected patients with CD4 counts above 200 cells/μl had increased probability for having HHV-8 in saliva (P = 0.009) compared with patients whose counts were less than 200. In contrast, HSV-1, EBV, and CMV were detected more often when CD4 counts were low. High salivary HHV loads were detected for those (n = 7) with oral lesions. These findings suggest that saliva is a potential risk factor for the acquisition of multiple HHVs, and several host factors may function to accelerate HHV reactivation or replication in patients with HIV infection. PMID:16825357

  11. Clinical manifestations of treatment-naive patients with acquired immunodeficiency syndrome and responses to highly active antiretroviral therapy in the Taipei Veterans General Hospital: a 5-year prospective study.

    PubMed

    Hsu, Shih-Fen; Yang, Su-Pen; Chan, Yu-Jiun; Wang, Yung-Wei

    2011-06-01

    Taipei Veterans General Hospital, one of the medical centers in Taiwan, has provided highly active antiretroviral therapy (HAART) to human immunodeficiency virus/AIDS patients for more than 10 years. Five years ago, we began a prospective follow-up of our patients' clinical manifestations and responses to HAART by collecting their clinical data. In this study, we analyzed the morbidity, mortality, and responses to HAART of treatment-naive AIDS patients. The purpose was to provide local data that may be valuable in Taiwan. Study cases were enrolled from January 1, 2004, to February 28, 2009, with inclusion criteria of newly diagnosed AIDS during hospitalization and being naive to HAART. Antiretroviral therapy was initiated. To evaluate the clinical responses to HAART, we excluded patients who were pregnant, died within 1 month after confirmation of an AIDS diagnosis, failed to initiate HAART, or were lost to follow-up for more than 6 months. Plasma viral loads and CD4(+) counts were quantified by reverse-transcriptase polymerase chain reaction and flow cytometry, respectively. Statistical analysis was performed using SPSS statistical software. A total of 49 patients were enrolled and 45 patients fulfilled the inclusion criteria for evaluating the efficacy of HAART. At 3 months, 12 months, and 30 months after the initiation of HAART, 64.4% (29 of 45), 88.2% (30 of 34), and 93.8% (15 of 16) had undetectable plasma viral loads, respectively, and 37.8% (17 of 45), 73.5% (25 of 34), and 81.2% (13 of 16) had CD4(+) counts of more than 200 cells/μL, respectively. Median CD4(+) counts increased from baseline at Month 3 by 171 cells/μL and at Month 30 by 375 cells/μL. The overall mortality was 22.4% (11 of 49). The virologic and immunologic responses after initiating HAART in this study demonstrated our achievements in providing care and treatment for AIDS patients during this 5-year period, which provides a strong evidence of the efficacy of HAART. Copyright © 2011

  12. Oral manifestations of HIV infection in children and adults receiving highly active anti-retroviral therapy [HAART] in Dar es Salaam, Tanzania

    PubMed Central

    Hamza, Omar JM; Matee, Mecky IN; Simon, Elison NM; Kikwilu, Emil; Moshi, Mainen J; Mugusi, Ferdinand; Mikx, Frans HM; Verweij, Paul E; van der Ven, André JAM

    2006-01-01

    Background The aim of the study was to compare the prevalence and types of HIV-related oral lesions between children and adult Tanzanian patients on HAART with those not on HAART and to relate the occurrence of the lesions with anti-HIV drug regimen, clinical stage of HIV disease and CD4+ cell count. Methods Participants were 532 HIV infected patients, 51 children and 481 adults, 165 males and 367 females. Children were aged 2–17 years and adults 18 and 67 years. Participants were recruited consecutively at the Muhimbili National Hospital (MNH) HIV clinic from October 2004 to September 2005. Investigations included; interviews, physical examinations, HIV testing and enumeration of CD4+ T cells. Results A total of 237 HIV-associated oral lesions were observed in 210 (39.5%) patients. Oral candidiasis was the commonest (23.5%), followed by mucosal hyperpigmentation (4.7%). There was a significant difference in the occurrence of oral candidiasis (χ2 = 4.31; df = 1; p = 0.03) and parotid enlargement (χ2 = 36.5; df = 1; p = 0.04) between children and adults. Adult patients who were on HAART had a significantly lower risk of; oral lesions (OR = 0.32; 95% CI = 0.22 – 0.47; p = 0.005), oral candidiasis (OR = 0.28; 95% CI = 0.18 – 0.44; p = 0.003) and oral hairy leukoplakia (OR = 0.18; 95% CI = 0.04 – 0.85; p = 0.03). There was no significant reduction in occurrence of oral lesions in children on HAART (OR = 0.35; 95% CI = 0.11–1.14; p = 0.15). There was also a significant association between the presence of oral lesions and CD4+ cell count < 200 cell/mm3 (χ2 = 52.4; df = 2; p = 0.006) and with WHO clinical stage (χ2 = 121; df = 3; p = 0.008). Oral lesions were also associated with tobacco smoking (χ2 = 8.17; df = 2; p = 0.04). Conclusion Adult patients receiving HAART had a significantly lower prevalence of oral lesions, particularly oral candidiasis and oral hairy leukoplakia. There was no significant change in occurrence of oral lesions in children

  13. Factors associated with the immune response to hepatitis A vaccination in HIV-infected patients in the era of highly active antiretroviral therapy.

    PubMed

    Mena, Guillermo; García-Basteiro, Alberto L; Llupià, Anna; Díez, Consolación; Costa, Josep; Gatell, Josep-María; García, Felipe; Bayas, José-María

    2013-08-12

    HIV seropositivity is considered a risk factor for complications in hepatitis A virus (HAV) infection. HAV vaccination schedules are widely implemented in HIV-infected patients, but the immune response remains impaired. We analysed the response to vaccination (antiHAV titres ≥20IU/l) in 282 HIV-infected patients included in a standard (1440 Elisa Units (EU) at 0, 6 months) or rapidly accelerated schedule (720 EU at 0, 7, 21 days and 6 months) between 1997 and 2009. Factors associated with the response to vaccination were analysed using logistic regression. The overall response rate was 73.4%. Male sex (OR: 0.16, 95% CI 0.05-0.51) and hepatitis C virus co-infection (OR: 0.30, 95% CI 0.14-0.74) were associated with a lower probability of response. Protective antibody response was associated with a higher CD4/CD8 ratio (OR: 3.69, 95% CI 1.3-10.5) and having received two doses of standard schedule (compared with patients receiving only one dose of the same schedule) (OR: 2.51, 95% CI 1.22-5.15). Three doses of the rapidly accelerated schedule were not more effective than a single dose of 1440 EU (OR: 1.32, 95% CI 0.48-3.63). The low responses observed in patients receiving a single dose suggest the need to emphasize adhesion to vaccination protocols to avoid failure. The CD4/CD8 ratio may be considered as an immune status marker which could help to better choose the moment of vaccination. Our findings underscore the importance of identifying strategies that optimize the timing and effectiveness of hepatitis A vaccination in HIV-infected patients and of the need for further studies on individual factors such as sex and hepatitis C co-infection that may affect the response to vaccination. Likewise, the sub-optimal effectiveness of three doses of 720 EU in the rapidly accelerated schedule, if confirmed in future studies, might lead to a revision of the current schedule recommended for HIV-infected travellers. Copyright © 2013 Elsevier Ltd. All rights reserved.

  14. Evaluation of HIV and highly active antiretroviral therapy on the natural history of human papillomavirus infection and cervical cytopathologic findings in HIV-positive and high-risk HIV-negative women.

    PubMed

    Blitz, Sandra; Baxter, Joanna; Raboud, Janet; Walmsley, Sharon; Rachlis, Anita; Smaill, Fiona; Ferenczy, Alex; Coutlée, François; Hankins, Catherine; Money, Deborah

    2013-08-01

    The Canadian Women's HIV Study (CWHS) enrolled human immunodeficiency virus (HIV)-positive and high-risk HIV-negative women in a longitudinal cohort. This analysis considered the effects of HIV and highly active antiretroviral therapy (HAART) on HPV persistence and cervical squamous intraepithelial lesions (SILs). Longitudinal cytopathologic and HPV DNA results were analyzed using multistate models. States of cervical SIL were defined as absent, present, and treatment; HPV states were defined as negative or positive. Demographic variables and markers of sexual activity were considered predictors. Results were calculated on the basis of transition probabilities and reported as hazard ratios (HRs). The CWHS followed 750 HIV-positive and 323 HIV-negative women during 1993-2002. A total of 467 and 456 women were included in the longitudinal cervical cytopathologic and HPV DNA analyses, respectively. HIV-positive women had increased prevalence (46.6% vs 28.7%; P < .0001), increased acquisition (HR, 2.3; P = .03), and decreased clearance (HR, 0.4; P < .001) of oncogenic HPV as compared to HIV-negative women. Oncogenic HPV infection predicted progression of cervical dysplasia from normal to abnormal SIL (HR, 2.8; P = .002). Among HIV-positive participants, HAART increased the likelihood of regression (from present to absent) of cervical SIL (HR, 3.3; P = .02) and increased the clearance of oncogenic HPV types other than HPV-16 or HPV-18 (HR, 2.2; P = .01). This analysis demonstrated beneficial effects of HAART on cervical SIL in HIV-positive women.

  15. Prevalence and risk factors of poor immune recovery among adult HIV patients attending care and treatment centre in northwestern Tanzania following the use of highly active antiretroviral therapy: a retrospective study.

    PubMed

    Gunda, Daniel W; Kilonzo, Semvua B; Kamugisha, Erasmus; Rauya, Engelbert Z; Mpondo, Bonaventura C

    2017-06-08

    Highly Active Antiretroviral therapy (HAART) reverses the effect of Human Immunodeficiency Virus/Acquired Immune Deficiency Syndrome (HIV/AIDS) by durably suppressing viral replication. This allows CD4 gain to levels that are adequate enough to restore the body's capability to fight against opportunistic infections (OIs). Patients with poor immune recovery have been shown to have higher risk of developing both AIDS and non AIDS related clinical events. This study aimed at assessing the proportions and risk factors of poor immune recovery in adult HIV-infected patients on 48 months of HAART attending care and treatment center (CTC) in northwestern Tanzania. A retrospective analysis of adult HIV patients' data attending CTC at Sekou Toure hospital and who initiated HAART between February 2004 and January 2008 was done. Poor immune recovery was defined as a CD4 count less than 350 cells/µl on follow up as used in other studies. A total of 734 patients were included in the study. In this study 50.25% of patients attending CTC at Sekou Toure hospital were found to have poor immune recovery. The risk of developing inadequate immune recovery was independently associated with male gender, age older than 50 years, low baseline CD4 counts, and advanced World Health Organization (WHO) clinical stage. Poor immune recovery is prevalent among adult HIV patients attending CTC at Sekou Toure hospital in Northwestern part of Tanzania and opportunistic infections are common in this sub group of patients. Clinicians in resource limited countries need to identify these patients timely and plan them for targeted viral assessment and close clinical follow up to improve their long term clinical outcome.

  16. Causes of death in the era of highly active antiretroviral therapy: a retrospective analysis of a hybrid hematology-oncology and HIV practice and the Seattle/King county adult/adolescent spectrum of HIV-related diseases project.

    PubMed

    Uhlenkott, Matthew C; Buskin, Susan E; Kahle, Erin M; Barash, Elizabeth; Aboulafia, David M

    2008-09-01

    HIV-infected patients continue to die in the era of highly active antiretroviral therapy (HAART). To describe the cause of mortality in the HAART era between 2 cohorts by conducting a comparative retrospective analysis. The Virginia Mason Medical Center (VMMC) cohort was composed of 60 died HIV-infected patients from 600 patients. The second cohort was comprised of 351 died patients from the Seattle portion of the Adult and Adolescent Spectrum of Diseases Project (Seattle-ASD) of 4721 patients. Among the abstracted data were the conditions present at death, defined as any major cause of morbidity present at death for both cohorts. Non-AIDS defining illnesses (non-ADI) were a major source of mortality in 60% and 45% for the VMMC and Seattle-ASD cohorts, respectively. The most common fatal non-ADI in both cohorts were cancer (7% and 19%), bacterial infections (15%), and liver failure (9% and 14%). Cancer (10%) and wasting (7%) were prominent fatal ADI in both cohorts. In each cohort, patients died despite a nondetectable HIV viral load and a CD4 lymphocyte count >200 cells/microL. This included 11 of 60 (18%) VMMC patients (all of whom died of non-ADI) and 35 of 351 (10%) Seattle-ASD patients (81% died with non-ADI). In 2 well-characterized urban HIV cohorts, non-ADI were a major cause of mortality in the HAART era. A substantial number of these patients died despite nondetectable HIV viral loads and reasonably well-preserved immune function measured by CD4 cell counts.

  17. Responsiveness of T Cells to Interleukin-7 Is Associated with Higher CD4+ T Cell Counts in HIV1-Positive Individuals with Highly Active Antiretroviral Therapy-Induced Viral Load Suppression

    PubMed Central

    Camargo, Jose F.; Kulkarni, Hemant; Agan, Brian K.; Gaitan, Alvaro A.; Beachy, Lisa A.; Srinivas, Sowmya; He, Weijing; Anderson, Stephanie; Marconi, Vincent C.; Dolan, Matthew J.; Ahuja, Sunil K.

    2013-01-01

    Background Despite suppression of the human immunodeficiency virus type 1(HIV-1) load by highly active antiretroviral therapy (HAART), recovery of CD4+ T cell counts can be impaired. We investigated whether this impairment may be associated with hyporesponsiveness of T cells to γ-chain (γc) cytokines known to influence T cell homeostasis. Methods The responsiveness of T cells to interleukin (IL)-2, IL-7, and IL-15 was determined by assessing cytokine-induced phosphorylation of the signal transducer and activator of transcription 5 (STAT5) in peripheral T cells obtained from 118 HIV-positive subjects and 13 HIV-negative subjects. Results The responsiveness of T cells to interleukin (IL)-7 but not to IL-2 or IL-15 was lower among HIV-positive subjects than among HIV-negative subjects. Among subjects with viral load suppression, the degree of IL-7 responsiveness (1) correlated with naive CD4+ T cell counts and was a better immune correlate of the prevailing CD4+ T cell count than were levels of human leukocyte antigen-DR1 or programmed death-1, which are predictors of T cell homeostasis during HIV infection; and (2) was greater in subjects with complete (i.e., attainment of ≥500 CD4+ T cells/mm3 ≥5 years after initiation of HAART) versus incomplete immunologic responses. The correlation between plasma levels of IL-7 and CD4+ T cell counts during HAART was maximal in subjects with increased IL-7 responsiveness. Conclusions Responsiveness of T cells to IL-7 is associated with higher CD4+ T cell counts during HAART and thus may be a determinant of the extent of immune reconstitution. PMID:19432535

  18. A multicenter observational study of the potential benefits of initiating combination antiretroviral therapy during acute HIV infection.

    PubMed

    Hecht, Frederick M; Wang, Lei; Collier, Ann; Little, Susan; Markowitz, Martin; Margolick, Joseph; Kilby, J Michael; Daar, Eric; Conway, Brian; Holte, Sarah

    2006-09-15

    Uncontrolled studies have suggested a benefit, after treatment discontinuation, of initiating highly active antiretroviral therapy (HAART) during primary human immunodeficiency virus (HIV) infection. We assessed whether initiation of HAART within 2 weeks of (acute treatment) or between 2 weeks and 6 months after (early treatment) HIV seroconversion was associated with improvements in the viral load and the CD4+ T cell count after discontinuation of treatment in an observational cohort. Subjects from the multicenter Acute Infection and Early Disease Research Program cohort were enrolled in the present study within 6 months of HIV seroconversion and self-selected whether to initiate HAART. Subjects who received acute (n=13) or early (n=45) treatment received HAART for at least 12 weeks and then subsequently stopped treatment, whereas untreated subjects (n=337) declined treatment. HIV RNA levels and CD4+ T cell counts at 24, 48, and 72 weeks after treatment cessation in the 2 treatment groups were compared with those noted in the untreated group during the same periods of observation after enrollment. The acute treatment group had lower mean HIV RNA levels at 24 weeks without therapy (-0.48 log(10) copies/mL [95% confidence interval {CI}, -0.82 to -0.13 log(10) copies/mL]) and higher mean CD4+ T cell counts (112 cells/ mu L [95% CI, 20-205 cells/ microL]), compared with the untreated group at 24 weeks. The differences in the laboratory values for the acute treatment group versus the untreated group at 72 weeks without therapy were as follows: for the HIV RNA level, -0.35 log(10) copies/mL (95% CI, -0.91 to 0.21 log(10) copies/mL) and, for the CD4 T+ cell count, 112 cells/ microL (95% CI, -15 to 213 cells/ microL). The early treatment group had lower HIV RNA levels at 24 weeks than did the untreated group, but differences were no longer apparent by week 48; CD4+ T cell counts were higher in the early treatment group at week 24 (116 cells/ microL [95% CI, 75-157 cells

  19. Using observational data to emulate a randomized trial of dynamic treatment-switching strategies: an application to antiretroviral therapy.

    PubMed

    Cain, Lauren E; Saag, Michael S; Petersen, Maya; May, Margaret T; Ingle, Suzanne M; Logan, Roger; Robins, James M; Abgrall, Sophie; Shepherd, Bryan E; Deeks, Steven G; John Gill, M; Touloumi, Giota; Vourli, Georgia; Dabis, François; Vandenhende, Marie-Anne; Reiss, Peter; van Sighem, Ard; Samji, Hasina; Hogg, Robert S; Rybniker, Jan; Sabin, Caroline A; Jose, Sophie; Del Amo, Julia; Moreno, Santiago; Rodríguez, Benigno; Cozzi-Lepri, Alessandro; Boswell, Stephen L; Stephan, Christoph; Pérez-Hoyos, Santiago; Jarrin, Inma; Guest, Jodie L; D'Arminio Monforte, Antonella; Antinori, Andrea; Moore, Richard; Campbell, Colin Nj; Casabona, Jordi; Meyer, Laurence; Seng, Rémonie; Phillips, Andrew N; Bucher, Heiner C; Egger, Matthias; Mugavero, Michael J; Haubrich, Richard; Geng, Elvin H; Olson, Ashley; Eron, Joseph J; Napravnik, Sonia; Kitahata, Mari M; Van Rompaey, Stephen E; Teira, Ramón; Justice, Amy C; Tate, Janet P; Costagliola, Dominique; Sterne, Jonathan Ac; Hernán, Miguel A

    2016-12-01

    When a clinical treatment fails or shows suboptimal results, the question of when to switch to another treatment arises. Treatment switching strategies are often dynamic because the time of switching depends on the evolution of an individual's time-varying covariates. Dynamic strategies can be directly compared in randomized trials. For example, HIV-infected individuals receiving antiretroviral therapy could be randomized to switching therapy within 90 days of HIV-1 RNA crossing above a threshold of either 400 copies/ml (tight-control strategy) or 1000 copies/ml (loose-control strategy). We review an approach to emulate a randomized trial of dynamic switching strategies using observational data from the Antiretroviral Therapy Cohort Collaboration, the Centers for AIDS Research Network of Integrated Clinical Systems and the HIV-CAUSAL Collaboration. We estimated the comparative effect of tight-control vs. loose-control strategies on death and AIDS or death via inverse-probability weighting. Of 43 803 individuals who initiated an eligible antiretroviral therapy regimen in 2002 or later, 2001 met the baseline inclusion criteria for the mortality analysis and 1641 for the AIDS or death analysis. There were 21 deaths and 33 AIDS or death events in the tight-control group, and 28 deaths and 41 AIDS or death events in the loose-control group. Compared with tight control, the adjusted hazard ratios (95% confidence interval) for loose control were 1.10 (0.73, 1.66) for death, and 1.04 (0.86, 1.27) for AIDS or death. Although our effective sample sizes were small and our estimates imprecise, the described methodological approach can serve as an example for future analyses.

  20. Immune recovery of middle-aged HIV patients following antiretroviral therapy: An observational cohort study.

    PubMed

    Wong, Ngai Sze; Chan, Kenny Chi Wai; Cheung, Edward Ka Hin; Wong, Ka Hing; Lee, Shui Shan

    2017-07-01

    In HIV-infected persons, age is negatively associated with optimal CD4 recovery following antiretroviral therapy. Our understanding of the situation in older adults, especially the middle-aged is, however, limited. We undertook to examine the latter's pattern of CD4/CD8 recovery following antiretroviral therapy.Retrospective clinical cohort data of HIV patients diagnosed between 1985 and 2014 in Hong Kong were collected. They were categorized by age at treatment initiation, viz., young adults (age 18-49), middle-aged (age 50-64), and elderly (≥65 years' old). Predictors of immune recovery (CD4 count, CD8 count, CD4/CD8 ratio) over time were examined using multivariable linear generalized estimating equations.A total of 2754 patients (aged ≥18) have been on antiretroviral therapy, with baseline characteristics similar between middle-aged and the elderly. Late diagnosis, defined as progression to AIDS within 3 months of HIV diagnosis, was less common in middle-aged (odds ratio = 0.58, 95% confidence interval = 0.37-0.91). Among Chinese patients who have been on treatment for ≥4 years (n = 913), 80.6%, 14.6%, and 4.8% were young adults, middle-aged, and elderly respectively. Late treatment initiation, defined as AIDS diagnosis or CD4 count ≤100 cells/μL before treatment, was common in middle-aged and elderly, the former however had faster CD4 recovery (3.95 vs. 3.36 cells/μL/month), but slower CD8 decline (-1.76 vs. -4.34 cells/μL/month) and CD4/CD8 normalization (0.009 vs. 0.0101/month).As a transitional age group, the immune recovery of middle-aged patients lagged behind young adults largely because of late treatment initiation. Following adoption of early and non-CD4-guided treatment initiation, their long-term clinical outcome is expected to improve.

  1. 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

    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

    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. 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. 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. 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. HAART for 180 days or more was associated with 79% decrease in all-cause in-hospital mortality and lower

  2. Increased pericardial fat accumulation is associated with increased intramyocardial lipid content and duration of highly active antiretroviral therapy exposure in patients infected with human immunodeficiency virus: a 3T cardiovascular magnetic resonance feasibility study.

    PubMed

    Diaz-Zamudio, Mariana; Dey, Damini; LaBounty, Troy; Nelson, Michael; Fan, Zhaoyang; Szczepaniak, Lidia S; Hsieh, Bill Pei-Chin; Rajani, Ronak; Berman, Daniel; Li, Debiao; Dharmakumar, Rohan; Hardy, W David; Conte, Antonio Hernandez

    2015-10-31

    The aim of the current study was to examine whether the use of highly active antiretroviral therapy (HAART) in patients with HIV is associated with changes in pericardial fat and myocardial lipid content measured by cardiovascular magnetic resonance (CMR). In this prospective case-control study, we compared 27 HIV seropositive (+) male subjects receiving HAART to 22 control male subjects without HIV matched for age, ethnicity and body mass index. All participants underwent CMR imaging for determination of pericardial fat [as volume at the level of the origin of the left main coronary artery (LM) and at the right ventricular free wall] and magnetic resonance spectroscopy (MRS) for evaluation of intramyocardial lipid content (% of fat to water in a single voxel at the interventricular septum). All measurements were made by two experienced readers blinded to the clinical history of the study participants. Two-sample t-test, Spearman's correlation coefficient or Pearson's correlation coefficient and multivariable logistic regression were used for statistical analysis. Pericardial fat volume at the level of LM origin was higher in HIV (+) subjects (33.4 cm(3) vs. 27.4 cm(3), p = 0.03). On multivariable analysis adjusted for age, Framingham risk score (FRS) and waist/hip ratio, pericardial fat remained significantly associated to HIV-status (OR 1.09, p = 0.047). For both HIV (+) and HIV (-) subjects, pericardial fat volume showed strong correlation with intramyocardial lipid content (r = 0.58, p < 0.0001) and FRS (r = 0.53, p = 0.0002). Among HIV (+) subjects, pericardial fat was significantly higher in patients with lipo-accumulation (37 cm(3) vs. 27.1 cm(3), p = 0.03) and showed significant correlation with duration of both HIV infection (r = 0.5, p = 0.01) and HAART (r = 0.46, p = 0.02). Pericardial fat content is increased in HIV (+) subjects on chronic HAART (>5 years), who demonstrate HAART-related lipo

  3. 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

  4. Three different patterns of CD4 recovery in a cohort of Chinese HIV patients following antiretroviral therapy - a five-year observational study.

    PubMed

    Naftalin, Claire M; Wong, Ngai Sze; Chan, Denise P C; Wong, Ka Hing; Reidpath, Daniel D; Lee, Shui Shan

    2015-10-01

    To explore the heterogeneity of CD4 responses following highly active antiretroviral therapy, the patterns of CD4 recovery of HIV-1-infected Chinese patients who have been on their first antiretroviral regimen for ≥5 years were analysed. The CD4 trajectories were traced, smoothed and differentiated into three defined profiles. Half (56.3%) were 'satisfactory responders', with CD4 gain of >100 cells/μL and a peak of >350 cells/μL, plateauing before the end of Year 5. Thirty-three (24.4%) were 'continuing responders' whose CD4 rise persisted at Year 4-5. The remaining 26 (19.3%) were 'poor responders'. Presentation with AIDS before therapy was common not just among 'poor' but also paradoxically the 'continuing' responders. While a majority had responded well to antiretroviral therapy, older patients and those with AIDS diagnosis before initiation of therapy may never achieve a satisfactory level even with effective treatment. Categorization of HIV patients by their CD4 trajectory may support the prediction of immunological outcome over time, and ultimately inform treatment choices.

  5. Forgiveness of non-adherence to HIV-1 antiretroviral therapy.

    PubMed

    Shuter, Jonathan

    2008-04-01

    Superior adherence to HIV-1 antiretroviral therapy is a mainstay of successful HIV management. Studies performed in the early era of highly active antiretroviral therapy demonstrated the need for > or =95% adherence in order to achieve and sustain viral suppression. High rates of viral suppression have been observed at more moderate levels of adherence with newer antiretroviral regimens. The term 'forgiveness' is being used to describe the ability of a regimen to achieve and sustain viral suppression, despite suboptimal adherence. A variety of pharmacological, viral and host properties determine the level of forgiveness of any specific regimen. As the choice of treatment options continues to expand, forgiveness of non-adherence is likely to emerge as an increasingly important factor in therapeutic decision-making.

  6. 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

  7. Trends in first-line antiretroviral therapy in Asia: results from the TREAT Asia HIV observational database.

    PubMed

    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

    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. 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. 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 <30 years), 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). The observed trends in first-line ART use in Asia reflect changes in drug availability, global treatment recommendations and prescriber preferences over the past decade. These changes have contributed to a declining rate of

  8. Retention in Care of Adult HIV Patients Initiating Antiretroviral Therapy in Tigray, Ethiopia: A Prospective Observational Cohort Study

    PubMed Central

    Bucciardini, Raffaella; Fragola, Vincenzo; Abegaz, Teshome; Lucattini, Stefano; Halifom, Atakilt; Tadesse, Eskedar; Berhe, Micheal; Pugliese, Katherina; Binelli, Andrea; De Castro, Paola; Terlizzi, Roberta; Fucili, Luca; Di Gregorio, Massimiliano; Mirra, Marco; Olivieri, Erika; Teklu, Tsigemariam; Zegeye, Teame; Haile, Amanuel; Vella, Stefano; Abraham, Loko; Godefay, Hagos

    2015-01-01

    Introduction Although Ethiopia has been scaling up the antiretroviral therapy (ART) services, low retention in care of patients remains one of the main obstacles to treatment success. We report data on retention in care and its associated determinants in Tigray, Ethiopia. Methods We used data from the CASA project, a prospective observational and multi-site study of a cohort of HIV-infected patients who initiated ART for the first time in Tigray. Four participating health facilities (HFs) located in the South of Tigray were considered for this study. Patients were followed for one year after ART initiation. The main outcome measure was represented by the current retention in care, defined as the proportion of patients who were alive and receiving ART at the same HF one year after ART initiation. Patients who started ART between January 1, 2013 and December 31, 2013 were included in this analysis. Patients were followed for one year after ART initiation. The determinants of retention were analysed using univariate and multivariate Cox Proportional Hazards model with robust sandwich estimates to account for within HF correlation. Results The four participating HFs in Tigray were able to retain overall 85.1% of their patients after one year from starting ART. Loss to follow-up (5.5%) and transfers to other HF (6.6) were the main determinant of attrition. A multivariate analysis shows that the factors significantly associated with retention were the type of HF, gender and active TB. Alamata health center was the HF with the highest attrition rate (HR 2.99, 95% CI: 2.77–3.23). Active TB (HR 1.72, 95% CI: 1.23–2.41) and gender (HR 1.64, 95% CI: 1.10–2.56) were also significantly associated with attrition. Conclusions Although Ethiopia has significantly improved access to the ART program, achieving and maintaining a satisfactory long-term retention rate is a future goal. This is difficult because of different retention rates among HFs. Moreover specific

  9. Cardiovascular risks of antiretroviral therapies.

    PubMed

    Mondy, Kristin; Tebas, Pablo

    2007-01-01

    The use of highly active antiretroviral therapy (HAART) has resulted in sustained reductions in mortality from HIV infection. In recent years, HAART has also been associated with metabolic complications that may increase patients' cardiovascular disease risk. Recent studies have begun to support a more complex interaction between HAART, HIV infection itself, and other traditional social and immunologic factors that may predispose patients to premature cardiovascular disease. Substantial progress has been made in the development of newer antiretroviral therapies that have a better metabolic profile with respect to dyslipidemia, hyperglycemia, and lipodystrophy. Optimal selection of metabolically neutral antiretroviral therapies, together with aggressive management of other modifiable coronary risk factors, may improve cardiovascular disease risk in the long term.

  10. Body fat distribution in perinatally HIV-infected and HIV-exposed but uninfected children in the era of highly active antiretroviral therapy: outcomes from the Pediatric HIV/AIDS Cohort Study1234

    PubMed Central

    Jacobson, Denise L; Patel, Kunjal; Siberry, George K; Van Dyke, Russell B; DiMeglio, Linda A; Geffner, Mitchell E; Chen, Janet S; McFarland, Elizabeth J; Borkowsky, William; Silio, Margarita; Fielding, Roger A; Siminski, Suzanne; Miller, Tracie L

    2011-01-01

    Background: Associations between abnormal body fat distribution and clinical variables are poorly understood in pediatric HIV disease. Objective: Our objective was to compare total body fat and its distribution in perinatally HIV-infected and HIV-exposed but uninfected (HEU) children and to evaluate associations with clinical variables. Design: In a cross-sectional analysis, children aged 7–16 y in the Pediatric HIV/AIDS Cohort Study underwent regionalized measurements of body fat via anthropometric methods and dual-energy X-ray absorptiometry. Multiple linear regression was used to evaluate body fat by HIV, with adjustment for age, Tanner stage, race, sex, and correlates of body fat in HIV-infected children. Percentage total body fat was compared with NHANES data. Results: Males accounted for 47% of the 369 HIV-infected and 51% of the 176 HEU children. Compared with HEU children, HIV-infected children were older, were more frequently non-Hispanic black, more frequently had Tanner stage ≥3, and had lower mean height (−0.32 compared with 0.29), weight (0.13 compared with 0.70), and BMI (0.33 compared with 0.63) z scores. On average, HIV-infected children had a 5% lower percentage total body fat (TotF), a 2.8% lower percentage extremity fat (EF), a 1.4% higher percentage trunk fat (TF), and a 10% higher trunk-to-extremity fat ratio (TEFR) than did the HEU children and a lower TotF compared with NHANES data. Stavudine use was associated with lower EF and higher TF and TEFR. Non-nucleotide reverse transcriptase inhibitor use was associated with higher TotF and EF and lower TEFR. Conclusion: Although BMI and total body fat were significantly lower in the HIV-infected children than in the HEU children, body fat distribution in the HIV-infected children followed a pattern associated with cardiovascular disease risk and possibly related to specific antiretroviral drugs. PMID:22049166

  11. Housing Stability and Medication Adherence among HIV-Positive Individuals in Antiretroviral Therapy: A Meta-Analysis of Observational Studies in the United States

    PubMed Central

    Xue, Xiaonan; Selwyn, Peter A.

    2017-01-01

    Background: Previous research has produced inconsistent evidence of an association between housing stability and medication adherence among HIV-positive individuals in antiretroviral therapy. Objective: We conducted a meta-analysis of the housing–adherence relationship based on a comprehensive search of observational studies in the PubMed, Embase, and Cochrane databases (January 2000–January 2016). Ten qualifying studies were identified representing 10,556 individuals. Methods: A random-effects model was used to estimate the overall effect size and 95% confidence interval (CI). Robustness of the estimate was determined by sensitivity analysis. Heterogeneity was assessed by meta-regression analysis, subgroup analysis, and quality effects estimation. Publication bias was evaluated with a funnel plot and the Egger and Begg tests. Results: The summary effect for the association between housing stability and medication adherence was positive and significant (standardized mean difference = 0.15, 95% CI: 0.02 to 0.29). The association was slightly larger in the quality effects analysis (standardized mean difference = 0.20, 95% CI: 0.01 to 0.39). Sensitivity analysis disclosed that the association was robust at the P = 0.09 level. Results of the subgroup and meta-regression analyses were nonsignificant. Publication bias was not detected. Conclusion: Antiretroviral medication adherence is an increasing function of housing stability, but the magnitude of the effect is small. The finding challenges the view that unstable housing is incompatible with adherence and questions the potential benefit of deferring antiretroviral therapy initiation until the patient's housing circumstances are improved. PMID:27787347

  12. Tenofovir-based Antiretroviral Therapy in Hepatitis B Virus/HIV Co-infection: Results from the TREAT Asia HIV Observational Database

    PubMed Central

    Boettiger, David C; Kerr, Stephen; Ditangco, Rossana; Chaiwarith, Romanee; Li, Patrick CK; Merati, Tuti Parwati; Pham, Thuy Thi Thanh; Kiertiburanakul, Sasisopin; Kumarasamy, Nagalingeswaran; Vonthanak, Saphonn; Lee, Christopher KC; 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; Durier, Nicolas; Law, Matthew

    2016-01-01

    Background The World Health Organisation recommends Hepatitis B virus (HBV)/HIV co-infected individuals start antiretroviral therapy containing tenofovir. Here we describe first-line tenofovir use and treatment outcomes in co-infected patients in Asia. Methods HBV surface antigen positive patients enrolled in the TREAT Asia HIV Observational Database who started first-line antiretroviral therapy were included. Logistic regression adjusted for period of treatment initiation was used to determine factors associated with tenofovir use. Generalised estimating equations were used to evaluate factors associated with alanine transaminase levels and CD4 cell count on treatment. Results There were 548 eligible patients, of whom 149 (27.2%) started tenofovir. Patients treated in high/high-middle income countries (odds ratio 4.4 vs. low/low-middle, 95%CI 2.6-7.4, p<0.001) and those with elevated baseline alanine transaminase (odds ratio 4.2 vs. normal, 95%CI 2.4-7.2, p<0.001) were more likely to receive tenofovir. Hepatitis C antibody positive patients (odds ratio 0.4 vs. negative, 95%CI 0.2-0.8, p=0.008) were less likely. In those starting antiretroviral therapy with elevated alanine transaminase, mean reduction after tenofovir initiation was 11.2 IU/L (95%CI 0.9-21.6, p=0.034) lower compared with those using a non-tenofovir-based regimen although this did not significantly increase the chance of alanine transaminase normalization. Tenofovir use was not associated with a superior CD4 response. Conclusions HBV/HIV co-infected patients in Asia are most likely to receive tenofovir if they are treated in a high/high-middle income country, have elevated alanine transaminase levels, and are hepatitis C antibody negative. Compared to other antiretroviral therapy, tenofovir-based regimens more effectively reduce liver inflammation in HBV/HIV co-infection but do not result in superior CD4 recovery. PMID:26069150

  13. Decreased CD95 expression on naive T cells from HIV-infected persons undergoing highly active anti-retroviral therapy (HAART) and the influence of IL-2 low dose administration

    PubMed Central

    Amendola, A; Poccia, F; Martini, F; Gioia, C; Galati, V; Pierdominici, M; Marziali, M; Pandolfi, F; Colizzi, V; Piacentini, M; Girardi, E; D'Offizi, G

    2000-01-01

    The functional recovery of the immune system in HIV-infected persons receiving HAART and the role of adjuvant immune therapy are still matters of intensive investigation. We analysed the effects of HAART combined with cytokines in 22 naive asymptomatic individuals, randomized to receive HAART (n = 6), HAART plus a low dose (1000 000 U/daily) of rIL-2 (n = 8), and HAART plus rIL-2 after previous administration of granulocyte colony-stimulating factor (n = 8). After 3 months of therapy, increased CD4+ T cell counts and diminished viral loads were observed in all patients, independently of cytokine addition. A decreased expression of CD95 (Apo 1/Fas) was evident in all groups when compared with values before therapy. The percentages of peripheral blood mononuclear cells (PBMC) expressing CD95 after therapy decreased by 15%, 22% and 18% in the three treatment groups, respectively (P < 0·05). Analysis of PBMC subsets demonstrated that CD95 expression was significantly reduced on CD45RA+CD62L+ naive T cells (25·3%, 22·4%, and 18·6%, respectively; P < 0·05) in each group, after therapy. Accordingly, all patients showed a reduced rate of in vitro spontaneous apoptosis (P < 0·05). Another effect induced by HAART was a significant increase in IL-2Rα expression on total PBMC (P < 0·05), independently of cytokine addition. Altogether, our results suggest that very low dose administration of rIL-2 (1000 000 U/daily) may be not enough to induce a significant improvement in the immune system as regards HAART alone. The employment of higher doses of recombinant cytokines and/or different administration protocols in clinical trials might however contribute to ameliorate the immune reconstitution in patients undergoing HAART. PMID:10792383

  14. Joint longitudinal data analysis in detecting determinants of CD4 cell count change and adherence to highly active antiretroviral therapy at Felege Hiwot Teaching and Specialized Hospital, North-west Ethiopia (Amhara Region).

    PubMed

    Seyoum, Awoke; Ndlovu, Principal; Temesgen, Zewotir

    2017-03-16

    parsimonious as compared to separate analysis, as it reduces type I error and subject-specific analysis improved its model fit. The joint model operates multivariate analysis simultaneously; and it has great power in parameter estimation. Developing joint model helps validate the observed correlation between the outcomes that have emerged from the association of intercepts. There should be a special attention and intervention for HIV positive adults, especially for those who had poor adherence and with low CD4 cell count change. The intervention may be important for pre-treatment counseling and awareness creation. The study also identified a group of patients who were with maximum risk of CD4 cell count change. It is suggested that this group of patients needs high intervention for counseling.

  15. 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.

  16. Effect of point-of-care CD4 cell count tests on retention of patients and rates of antiretroviral therapy initiation in primary health clinics: an observational cohort study.

    PubMed

    Jani, Ilesh V; Sitoe, Nádia E; Alfai, Eunice R; Chongo, Patrina L; Quevedo, Jorge I; Rocha, Beatriz M; Lehe, Jonathan D; Peter, Trevor F

    2011-10-29

    Loss to follow-up of HIV-positive patients before initiation of antiretroviral therapy can exceed 50% in low-income settings and is a challenge to the scale-up of treatment. We implemented point-of-care counting of CD4 cells in Mozambique and assessed the effect on loss to follow-up before immunological staging and treatment initiation. In this observational cohort study, data for enrolment into HIV management and initiation of antiretroviral therapy were extracted retrospectively from patients' records at four primary health clinics providing HIV treatment and point-of-care CD4 services. Loss to follow-up and the duration of each preparatory step before treatment initiation were measured and compared with baseline data from before the introduction of point-of-care CD4 testing. After the introduction of point-of-care CD4 the proportion of patients lost to follow-up before completion of CD4 staging dropped from 57% (278 of 492) to 21% (92 of 437) (adjusted odds ratio [OR] 0·2, 95% CI 0·15-0·27). Total loss to follow-up before initiation of antiretroviral treatment fell from 64% (314 of 492) to 33% (142 of 437) (OR 0·27, 95% CI 0·21-0·36) and the proportion of enrolled patients initiating antiretroviral therapy increased from 12% (57 of 492) to 22% (94 of 437) (OR 2·05, 95% CI 1·42-2·96). The median time from enrolment to antiretroviral therapy initiation reduced from 48 days to 20 days (p<0·0001), primarily because of a reduction in the median time taken to complete CD4 staging, which decreased from 32 days to 3 days (p<0·0001). Loss to follow-up between staging and antiretroviral therapy initiation did not change significantly (OR 0·84, 95% CI 0·49-1·45). Point-of-care CD4 testing enabled clinics to stage patients rapidly on-site after enrolment, which reduced opportunities for pretreatment loss to follow-up. As a result, more patients were identified as eligible for and initiated antiretroviral treatment. Point-of-care testing might therefore be an

  17. Antiretroviral Tissue Kinetics: In Vivo Imaging Using Positron Emission Tomography▿

    PubMed Central

    Di Mascio, Michele; Srinivasula, Sharat; Bhattacharjee, Abesh; Cheng, Lily; Martiniova, Lucia; Herscovitch, Peter; Lertora, Juan; Kiesewetter, Dale

    2009-01-01

    Our current knowledge on the antiviral efficacy, dosing, and toxicity of available highly active antiretroviral therapy regimens is mostly derived from plasma or blood kinetics of anti-human immunodeficiency virus (anti-HIV) drugs. However, the blood comprises only 2% of the total target cells in the body. Tissue drug levels may differ substantially from corresponding plasma levels, and drug distribution processes may be characterized by high intertissue variability, leading to suboptimal target site concentrations and the potential risk for therapeutic failures. Positron emission tomography has greatly expanded the scope of the pharmacokinetic measurements that can be performed noninvasively in animal models or humans. We have prepared [18F]FPMPA, a fluorine-18-radiolabeled analogue of tenofovir, to study antiretroviral tissue kinetics in vivo noninvasively and tested the imaging probe in rats. The biodistribution of the fluorine-18 analogue closely follows that of nonfluorinated tenofovir. Compared to that in the blood, the levels of penetration of the antiretroviral drug were found to be significantly reduced in the spleen and submandibular lymph nodes (∼2-fold), in the mesenteric lymph nodes and the testes (∼4-fold), and in the brain compartment (∼25-fold). Intersubject variability of the trough drug concentration (measured at 120 min) in certain tissues, like the colon (coefficient of variation, >100%), is not reflected by the intersubject variability in the blood compartment (coefficient of variation, 24%). Positron emission tomography imaging of the fluorine-18 analogue revealed the accumulation of the antiretroviral drug in the cortex of the kidneys, a potential correlate of tenofovir-induced nephrotoxicity observed in HIV-1-infected treated patients. Thus, [18F]FPMPA is a promising radiotracer for evaluation of tenofovir biodistribution under carefully controlled drug administration protocols. PMID:19667288

  18. Validation of an Algorithm to Identify Antiretroviral-Naïve Status at Time of Entry into a Large, Observational Cohort of HIV-infected Patients

    PubMed Central

    Gandhi, Neel R.; Tate, Janet P.; Rodriguez-Barradas, Maria C.; Rimland, David; Goetz, Matthew Bidwell; Gibert, Cynthia; Brown, Sheldon T.; Mattocks, Kristin; Justice, Amy C.

    2013-01-01

    Purpose Large, observational HIV cohorts play an important role in answering questions which are difficult to study in randomized trials; however, they often lack detailed information regarding previous antiretroviral treatment (ART). Knowledge of ART treatment history is important when ascertaining the long-term impact of medications, co-morbidities, or adverse reactions on HIV outcomes. Methods We performed a retrospective study to validate a prediction algorithm for identifying ART-naïve patients using the Veterans Aging Cohort Study’s Virtual Cohort—an observational cohort of 40,594 HIV-infected veterans nationwide. Medical records for 3070 HIV-infected patients were reviewed to determine history of combination ART treatment. An algorithm using Virtual Cohort laboratory data was used to predict ART treatment status and compared to medical record review. Results Among 3070 patients’ medical records reviewed, 1223 were eligible for analysis. Of these, 990 (81%) were ART naïve at cohort entry based on medical record review. The prediction algorithm’s sensitivity was 86%, specificity 47%, positive predictive value (PPV) 87% and negative predictive value 45%, using a viral load threshold of <400 copies/ml. Sensitivity analysis revealed that PPV would be maximized by increasing the viral load threshold, whereas sensitivity would be maximized by lowering the viral load threshold. Conclusions A prediction algorithm using available laboratory data can be used to accurately identify ART-naïve patients in large, observational HIV cohorts. Use of this algorithm will allow investigators to accurately limit analyses to ART-naïve patients when studying the contribution of ART to outcomes and adverse events. PMID:23836591

  19. A randomized controlled trial examining the efficacy of motivational counseling with observed therapy for antiretroviral therapy adherence.

    PubMed

    Goggin, Kathy; Gerkovich, Mary M; Williams, Karen B; Banderas, Julie W; Catley, Delwyn; Berkley-Patton, Jannette; Wagner, Glenn J; Stanford, James; Neville, Sally; Kumar, Vinutha K; Bamberger, David M; Clough, Lisa A

    2013-07-01

    This study determined whether motivational interviewing-based cognitive behavioral therapy (MI-CBT) adherence counseling combined with modified directly observed therapy (MI-CBT/mDOT) is more effective than MI-CBT counseling alone or standard care (SC) in increasing adherence over time. A three-armed randomized controlled 48-week trial with continuous electronic drug monitored adherence was conducted by randomly assigning 204 HIV-positive participants to either 10 sessions of MI-CBT counseling with mDOT for 24 weeks, 10 sessions of MI-CBT counseling alone, or SC. Poisson mixed effects regression models revealed significant interaction effects of intervention over time on non-adherence defined as percent of doses not-taken (IRR = 1.011, CI = 1.000-1.018) and percent of doses not-taken on time (IRR = 1.006, CI = 1.001-1.011) in the 30 days preceding each assessment. There were no significant differences between groups, but trends were observed for the MI-CBT/mDOT group to have greater 12 week on-time and worse 48 week adherence than the SC group. Findings of modest to null impact on adherence despite intensive interventions highlights the need for more effective interventions to maintain high adherence over time.

  20. Switching to boosted protease inhibitor plus a second antiretroviral drug (dual therapy) for treatment simplification: a multicenter observational study.

    PubMed

    Latini, Alessandra; Fabbiani, Massimiliano; Borghi, Vanni; Sterrantino, Gaetana; Giannetti, Alberto; Lorenzini, Patrizia; Loiacono, Laura; Ammassari, Adriana; Bellagamba, Rita; Colafigli, Manuela; D'Ettorre, Gabriella; Di Giambenedetto, Simona; Antinori, Andrea; Zaccarelli, Mauro

    2016-08-11

    Aim of the study was to assess predictors of discontinuation/toxicity of boosted PI-based (PI/r) dual therapy (DT). Observational, retrospective switch study in patients successfully treated with triple drugs regimen. Patients switched to PI/r based DT [darunavir (DRV/r), lopinavir (LPV/r) or atazanavir (ATV/r)] plus a second drug: [raltegravir (RAL), maraviroc (MVC) etravirine (ETR), lamivudine (3TC) or tenofovir (TDF)] between 2009 and 2014 were included. The effect of each drug as well as other clinical and virological cofactors over treatment discontinuation (TD) was assessed using survival analysis. Overall, 376 patients were included with mean follow-up of 73 weeks. The most commonly used drugs in DT were DRV/r (63.0 %) and RAL (53.7 %). TD was observed in 77 (20,4 %) patients: 38 (10,1 %) virological failure, 35 (9,3 %) toxicity/intolerance (4 deaths) and 4 (1 %) interruptions for patients decision. At Cox Model, adjusted by demographic and laboratory variables, DRV/r and ATV/r significantly reduced the likelihood of TD and longer treatment was associated with lower risk, while low CD4 count at baseline and number of previous regimens with a higher risk. Moreover, RAL and 3TC use were significantly associated with lower TD by toxicity. In our clinical practice experience, switching virologically suppressed patients to PI/r based DT showed adequate safety and efficacy, so that it may be used in selected patients with specific medical needs.

  1. Efficacy of second-line antiretroviral therapy among people living with HIV/AIDS in Asia: results from the TREAT Asia HIV observational database.

    PubMed

    Boettiger, David C; Nguyen, Van K; Durier, Nicolas; Bui, Huy V; Heng Sim, Benedict L; Azwa, Iskandar; Law, Matthew; Ruxrungtham, Kiat

    2015-02-01

    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. 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. 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 per cubic millimeter, and median HIV viral load was 16,224 copies per milliliter. 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 therapy was 2.3 years. The rates of treatment failure and mortality per 100 patient/years were 8.8 (95% confidence interval: 7.1 to 10.9) and 1.1 (95% confidence interval: 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. 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.

  2. Trends in CD4 counts in HIV-infected patients with HIV viral load monitoring while on combination antiretroviral treatment: results from The TREAT Asia HIV Observational Database

    PubMed Central

    2010-01-01

    Background The aim of this study was to examine the relationship between trends in CD4 counts (slope) and HIV viral load (VL) after initiation of combination antiretroviral treatment (cART) in Asian patients in The TREAT Asia HIV Observational Database (TAHOD). Methods Treatment-naive HIV-infected patients who started cART with three or more and had three or more CD4 count and HIV VL tests were included. CD4 count slopes were expressed as changes of cells per microliter per year. Predictors of CD4 count slopes from 6 months after initiation were assessed by random-effects linear regression models. Results A total of 1676 patients (74% male) were included. The median time on cART was 4.2 years (IQR 2.5-5.8 years). In the final model, CD4 count slope was associated with age, concurrent HIV VL and CD4 count, disease stage, hepatitis B or C co-infection, and time since cART initiation. CD4 count continues to increase with HIV VL up to 20 000 copies/mL during 6-12 months after cART initiation. However, the HIV VL has to be controlled below 5 000, 4 000 and 500 copies/mL for the CD4 count slope to remain above 20 cells/microliter per year during 12-18, 18-24, and beyond 24 months after cART initiation. Conclusions After cART initiation, CD4 counts continued to increase even when the concurrent HIV VL was detectable. However, HIV VL needed to be controlled at a lower level to maintain a positive CD4 count slope when cART continues. The effect on long-term outcomes through the possible development of HIV drug resistance remains uncertain. PMID:21182796

  3. 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

  4. Clinical Predictors of Immune Reconstitution following Combination Antiretroviral Therapy in Patients from the Australian HIV Observational Database

    PubMed Central

    Rajasuriar, Reena; Gouillou, Maelenn; Spelman, Tim; Read, Tim; Hoy, Jennifer; Law, Matthew; Cameron, Paul U.; Petoumenos, Kathy; Lewin, Sharon R.

    2011-01-01

    Background A small but significant number of patients do not achieve CD4 T-cell counts >500cells/µl despite years of suppressive cART. These patients remain at risk of AIDS and non-AIDS defining illnesses. The aim of this study was to identify clinical factors associated with CD4 T-cell recovery following long-term cART. Methods Patients with the following inclusion criteria were selected from the Australian HIV Observational Database (AHOD): cART as their first regimen initiated at CD4 T-cell count <500cells/µl, HIV RNA<500copies/ml after 6 months of cART and sustained for at least 12 months. The Cox proportional hazards model was used to identify determinants associated with time to achieve CD4 T-cell counts >500cells/µl and >200cells/µl. Results 501 patients were eligible for inclusion from AHOD (n = 2853). The median (IQR) age and baseline CD4 T-cell counts were 39 (32–47) years and 236 (130–350) cells/µl, respectively. A major strength of this study is the long follow-up duration, median (IQR) = 6.5(3–10) years. Most patients (80%) achieved CD4 T-cell counts >500cells/µl, but in 8%, this took >5 years. Among the patients who failed to reach a CD4 T-cell count >500cells/µl, 16% received cART for >10 years. In a multivariate analysis, faster time to achieve a CD4 T-cell count >500cells/µl was associated with higher baseline CD4 T-cell counts (p<0.001), younger age (p = 0.019) and treatment initiation with a protease inhibitor (PI)-based regimen (vs. non-nucleoside reverse transcriptase inhibitor, NNRTI; p = 0.043). Factors associated with achieving CD4 T-cell counts >200cells/µl included higher baseline CD4 T-cell count (p<0.001), not having a prior AIDS-defining illness (p = 0.018) and higher baseline HIV RNA (p<0.001). Conclusion The time taken to achieve a CD4 T-cell count >500cells/µl despite long-term cART is prolonged in a subset of patients in AHOD. Starting cART early with a PI-based regimen (vs. NNRTI-based regimen

  5. Oxidative Imbalance in HIV-1 Infected Patients Treated with Antiretroviral Therapy

    PubMed Central

    Mandas, Antonella; Iorio, Eugenio Luigi; Congiu, Maria Gabriella; Balestrieri, Cinzia; Mereu, Antonello; Cau, Daniela; Dessì, Sandra; Curreli, Nicoletta

    2009-01-01

    It is generally accepted that oxidative stress is involved in HIV infection. However, the role in oxidative balance of Highly Active Antiretroviral Therapy (HAART) is still debated. In our study we assessed serum oxidant and antioxidant levels in an HIV-1-infected population treated with HAART, and compared them with those of untreated HIV-1 patients and HIV-1-negative subjects. The study included 116 HIV-1-infected patients (86 HAART-treated and 30 untreated), and 46 HIV-negative controls. Serum oxidant levels were significantly higher in the HIV-1 treated group as compared to untreated and control groups. In addition, a decrease of serum total antioxidant status was observed in the HIV-1 treated group. To be noted is that patients who rigorously follow antiretroviral therapy (optimal HAART adherence) have significantly higher oxidative status than those who do not closely follow the therapy (poor HAART adherence). Analysis of variance revealed no significant further increase in oxidative status in HIV-1-infected patients taking antiretroviral and other drugs with the exception of psychiatric drugs (e.g. anxiolytics or antidepressants). Taken together, our results indicate that HAART may affect oxidative stress in HIV-1-infected patients and suggest that antiretroviral therapy plays an important role in the synergy of HIV infection and oxidative stress. PMID:19884983

  6. Incidence of virological failure and major regimen change of initial combination antiretroviral therapy in the Latin America and the Caribbean: an observational cohort study.

    PubMed

    Cesar, Carina; Jenkins, Cathy A; Shepherd, Bryan E; Padgett, Denis; Mejía, Fernando; Ribeiro, Sayonara Rocha; Cortes, Claudia P; Pape, Jean W; Madero, Juan Sierra; Fink, Valeria; Sued, Omar; McGowan, Catherine; Cahn, Pedro

    2015-11-01

    Access to combination antiretroviral therapy (ART) is expanding in Latin America (Mexico, Central America, and South America) and the Caribbean. We assessed the incidence of and factors associated with regimen failure and regimen change of initial ART in this region. This observational cohort study included antiretroviral-naive adults starting ART from 2000 to 2014 at sites in seven countries throughout Latin America and the Caribbean. Primary outcomes were time from ART initiation until virological failure, major regimen modification, and a composite endpoint of the first of virological failure or major regimen modification. Cumulative incidence of the primary outcomes was estimated with death considered a competing event. 14,027 patients starting ART were followed up for a median of 3.9 years (2.0-6.5): 8374 (60%) men, median age 37 years (IQR 30-44), median CD4 count 156 cells per μL (61-253), median plasma HIV RNA 5.0 log10 copies per mL (4.4-5.4), and 3567 (28%) had clinical AIDS. 1719 (12%) patients had virological failure and 1955 (14%) had a major regimen change. Excluding the site in Haiti, which did not regularly measure HIV RNA, cumulative incidence of virological failure was 7.8% (95% CI 7.2-8.5) 1 year after ART initiation, 19.2% (18.2-20.2) at 3 years, and 25.8% (24.6-27.0) at 5 years; cumulative incidence of major regimen change was 5.9% (5.3-6.4) at 1 year, 12.7% (11.9-13.5) at 3 years, and 18.2% (17.2-19.2) at 5 years. Incidence of major regimen change at the site in Haiti was 10.7% (95% CI 9.7-11.6) at 5 years. Virological failure was associated with younger age (adjusted hazard ratio [HR] 2.03, 95% CI 1.68-2.44, for 20 years vs 40 years), infection through injection drug use (vs infection through heterosexual sex; 1.60, 1.02-2.52), and initiation in earlier calendar years (1.28, 1.13-1.46, for 2002 vs 2006), but was not significantly associated with boosted protease inhibitor-based regimens (vs non-nucleoside reverse transcriptase inhibitor; 1

  7. Antiretroviral Therapy in Relation to Birth Outcomes among HIV-infected Women: A Cohort Study.

    PubMed

    Li, Nan; Sando, Mary Mwanyika; Spiegelman, Donna; Hertzmark, Ellen; Liu, Enju; Sando, David; Machumi, Lameck; Chalamilla, Guerino; Fawzi, Wafaie

    2016-04-01

    Although the beneficial effects of antiretroviral (ARV) therapy for preventing mother-to-child transmission are indisputable, studies in developed and developing countries have reported conflicting findings on the association between ARV exposure and adverse birth outcomes. We conducted a prospective observational study at 10 human immunodeficiency virus (HIV) care and treatment centers in Dar es Salaam, Tanzania. Multivariate log-binomial regression was used to investigate the associations between ARV use and adverse birth outcomes among HIV-negative HIV-exposed infants. Our findings demonstrate an increased risk of adverse birth outcomes associated with the use of highly active antiretroviral therapy during pregnancy. Further studies are needed to investigate the underlying mechanisms and identify the safest ARV regimens for use during pregnancy.

  8. Trends in the burden of HIV mortality after roll-out of antiretroviral therapy in KwaZulu-Natal, South Africa: an observational community cohort study.

    PubMed

    Reniers, Georges; Blom, Sylvia; Calvert, Clara; Martin-Onraet, Alexandra; Herbst, Abraham J; Eaton, Jeffrey W; Bor, Jacob; Slaymaker, Emma; Li, Zehang R; Clark, Samuel J; Bärnighausen, Till; Zaba, Basia; Hosegood, Victoria

    2017-03-01

    Antiretroviral therapy (ART) substantially decreases morbidity and mortality in people living with HIV. In this study, we describe population-level trends in the adult life expectancy and trends in the residual burden of HIV mortality after the roll-out of a public sector ART programme in KwaZulu-Natal, South Africa, one of the populations with the most severe HIV epidemics in the world. Data come from the Africa Centre Demographic Information System (ACDIS), an observational community cohort study in the uMkhanyakude district in northern KwaZulu-Natal, South Africa. We used non-parametric survival analysis methods to estimate gains in the population-wide life expectancy at age 15 years since the introduction of ART, and the shortfall of the population-wide adult life expectancy compared with that of the HIV-negative population (ie, the life expectancy deficit). Life expectancy gains and deficits were further disaggregated by age and cause of death with demographic decomposition methods. Covering the calendar years 2001 through to 2014, we obtained information on 93 903 adults who jointly contribute 535 42 8 person-years of observation to the analyses and 9992 deaths. Since the roll-out of ART in 2004, adult life expectancy increased by 15·2 years for men (95% CI 12·4-17·8) and 17·2 years for women (14·5-20·2). Reductions in pulmonary tuberculosis and HIV-related mortality account for 79·7% of the total life expectancy gains in men (8·4 adult life-years), and 90·7% in women (12·8 adult life-years). For men, 9·5% is the result of a decline in external injuries. By 2014, the life expectancy deficit had decreased to 1·2 years for men (-2·9 to 5·8) and to 5·3 years for women (2·6-7·8). In 2011-14, pulmonary tuberculosis and HIV were responsible for 84·9% of the life expectancy deficit in men and 80·8% in women. The burden of HIV on adult mortality in this population is rapidly shrinking, but remains large for women, despite their better

  9. The emergence of drug resistant HIV variants and novel anti-retroviral therapy

    PubMed Central

    Paydary, Koosha; Khaghani, Parisa; Emamzadeh-Fard, Sahra; Alinaghi, Seyed Ahmad Seyed; Baesi, Kazem

    2013-01-01

    After its identification in 1980s, HIV has infected more than 30 million people worldwide. In the era of highly active anti-retroviral therapy, anti-retroviral drug resistance results from insufficient anti-retroviral pressure, which may lead to treatment failure. Preliminary studies support the idea that anti-retroviral drug resistance has evolved largely as a result of low-adherence of patients to therapy and extensive use of anti-retroviral drugs in the developed world; however, a highly heterogeneous horde of viral quasi-species are currently circulating in developing nations. Thus, the prioritizing of strategies adopted in such two worlds should be quite different considering the varying anti-retroviral drug resistance prevalence. In this article, we explore differences in anti-retroviral drug resistance patterns between developed and developing countries, as they represent two distinct ecological niches of HIV from an evolutionary standpoint. PMID:23835806

  10. 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

  11. When to initiate combined antiretroviral therapy to reduce mortality and AIDS-defining illness in HIV-infected persons in developed countries: an observational study.

    PubMed

    Cain, Lauren E; Logan, Roger; Robins, James M; Sterne, Jonathan A C; Sabin, Caroline; Bansi, Loveleen; Justice, Amy; Goulet, Joseph; van Sighem, Ard; de Wolf, Frank; Bucher, Heiner C; von Wyl, Viktor; Esteve, Anna; Casabona, Jordi; del Amo, Julia; Moreno, Santiago; Seng, Remonie; Meyer, Laurence; Perez-Hoyos, Santiago; Muga, Roberto; Lodi, Sara; Lanoy, Emilie; Costagliola, Dominique; Hernan, Miguel A

    2011-04-19

    Most clinical guidelines recommend that AIDS-free, HIV-infected persons with CD4 cell counts below 0.350 × 10(9) cells/L initiate combined antiretroviral therapy (cART), but the optimal CD4 cell count at which cART should be initiated remains a matter of debate. To identify the optimal CD4 cell count at which cART should be initiated. Prospective observational data from the HIV-CAUSAL Collaboration and dynamic marginal structural models were used to compare cART initiation strategies for CD4 thresholds between 0.200 and 0.500 × 10(9) cells/L. HIV clinics in Europe and the Veterans Health Administration system in the United States. 20, 971 HIV-infected, therapy-naive persons with baseline CD4 cell counts at or above 0.500 × 10(9) cells/L and no previous AIDS-defining illnesses, of whom 8392 had a CD4 cell count that decreased into the range of 0.200 to 0.499 × 10(9) cells/L and were included in the analysis. Hazard ratios and survival proportions for all-cause mortality and a combined end point of AIDS-defining illness or death. Compared with initiating cART at the CD4 cell count threshold of 0.500 × 10(9) cells/L, the mortality hazard ratio was 1.01 (95% CI, 0.84 to 1.22) for the 0.350 threshold and 1.20 (CI, 0.97 to 1.48) for the 0.200 threshold. The corresponding hazard ratios were 1.38 (CI, 1.23 to 1.56) and 1.90 (CI, 1.67 to 2.15), respectively, for the combined end point of AIDS-defining illness or death. CD4 cell count at cART initiation was not randomized. Residual confounding may exist. Initiation of cART at a threshold CD4 count of 0.500 × 10(9) cells/L increases AIDS-free survival. However, mortality did not vary substantially with the use of CD4 thresholds between 0.300 and 0.500 × 10(9) cells/L.

  12. Impact of drug classes and treatment availability on the rate of antiretroviral treatment change in the TREAT Asia HIV Observational Database (TAHOD)

    PubMed Central

    Srasuebkul, Preeyaporn; Calmy, Alexandra; Zhou, Jialun; Kumarasamy, Nagalingeswaran; Law, Matthew; Lim, Poh Lian

    2007-01-01

    Background It is critical to understand the pattern of antiretroviral treatment (ART) prescription in different regions of the world as ART procurement needs to be anticipated. We aimed at exploring rates and predictors of ART combination changes in clinical practice in Treat Asia HIV Observational Database (TAHOD). Methods Rates of ART changes were examined in patients who started first line triple or more ART combination in TAHOD, and had at least one follow-up visit. Rates of ART changes were summarised per follow-up year, and factors associated with changes assessed using random-effect Poisson regression. The Kaplan-Meier method was used to determine durations of patients in their first, second and third regimen. Results A total of 1846 patients initiated an ART combination with at least three drugs. Median follow up time for the first treatment was 3.2 years. The overall rate of ART change was 29 per 100-person-year. In univariate analyses, rate of treatment change was significantly associated with exposure category, the country income category, the drug class combination, calendar year and the number of combinations. In multivariate analysis, compared to d4T/3TC/NVP, starting ART with another NNRTI-containing regimen, with PI only or with a triple NRTI regimen was associated with a higher risk of combination change (relative risk (RR) 1.6 (95% CI 1.64 – 1.96), p < 0.001, RR 3.39 (2.76 – 4.16) p < 0.001, RR 6.37 (4.51 – 9.00), p < 0.001). Being on a second or a third combination regimen was also associated with a decreased rate of ART change, compared with first ART combination (RR 0.82 (0.68 – 0.99), p = 0.035, RR 0.77 (0.61 – 0.97), p = 0.024). Sites with fewer than 12 drugs used had an increased rate of treatment changes (1.31 (1.13 – 1.51), p < 0.001). Injecting drug users, and other/unknown exposure was found to increase rate of treatment change (1.24 (1.00 – 1.54), p = 0.055). Percentages of patients who stopped treatment due to adverse

  13. HIV-1 mother-to-child transmission, post-test counselling, and antiretroviral prophylaxis in Northern Viet Nam: a prospective observational study.

    PubMed

    Ha, Tran T T; Anh, Nguyen M; Bao, Nguyen H; Tuan, Pham L; Caridha, Rozina; Gaseitsiwe, Simani; Hien, Nguyen T; Cam, Phung D; Ehrnst, Anneka

    2012-11-01

    Pregnant women fear being identified as HIV-1-infected and this has hampered prevention programmes and the calculation of transmission rates in Viet Nam. We introduced post-test counselling, antiretroviral prophylaxis, and formula feeding, and determined the vertical transmission rate in parts of Northern Viet Nam. HIV infection was identified in 234 pregnant women; 182 (77.8%) accepted follow-up of their children. Counselling was given on 3-7 occasions for altogether approximately 6 h on antiretroviral prophylaxis and formula feeding to avoid transmission, and on the importance of surveillance of the child. All children were formula-fed. A polymerase chain reaction (PCR) was used for the diagnosis of HIV-1 in the children. One hundred and thirty-five of the 182 mothers allowed ≥ 3 blood samples to be taken from birth to ≥ 1 y of age, 32/182 provided a birth sample only, and 15/182 provided a sample later only. Nevirapine was given at delivery to 93/135 (69%) women, and to 128/135 (95%) children. Additionally, combination therapy was given to 15/135 (11%) who entered the study before delivery, and azidothymidine to their children for 1 week. Nine of 135 (6.7%) children became infected and 2/15 of the others, giving altogether 11/150 infected (7.3%). Intrauterine transmission was identified in 7/167 (4.2%) children by a positive PCR test at birth. PCR was negative at birth but positive at 1 month in 2/135 (1.5%), pointing to delivery-associated transmission. Thus, intrauterine transmission accounted for 78% (7/9). None of the uninfected children died, but 3/11 (p =0.004) of the HIV-1-infected died (in AIDS). Post-test confidential counselling, formula feeding, and antiretroviral prophylaxis resulted in low rates of delivery-associated and late HIV-1 transmissions.

  14. Comparative impact of antiretroviral drugs on markers of inflammation and immune activation during the first two years of effective therapy for HIV-1 infection: an observational study

    PubMed Central

    2014-01-01

    Background Few studies have compared the impact of different antiretroviral regimens on residual immune activation and inflammation with discordant results. Aim of the study was to investigate the impact of various antiretroviral regimens on markers of immune activation and inflammation during the first two years of effective therapy. Methods We studied HIV-infected antiretroviral-naïve patients who began cART with either abacavir/lamivudine or tenofovir/emtricitabine, combined with ritonavir-boosted lopinavir (LPV/r), atazanavir (ATV/r) or efavirenz (EFV). All the patients had a virological response within 6 months, which was maintained for 2 years with no change in their ART regimen. C-reactive protein (hs-CRP), interleukin-6 (IL-6), soluble CD14 (sCD14), monokine induced by interferon-γ (MIG) and interferon-γ-inducible protein-10 (IP-10) were measured in stored plasma obtained at cART initiation and 24 months later. Mean changes from baseline were analyzed on loge-transformed values and multivariable linear regression models were used to study the effect of the treatment components, after adjusting for factors that might have influenced the choice of ART regimen or biomarker levels. Differences were expressed as the mean fold change percentage difference (Δ). Results Seventy-eight patients (91% males) with a median age of 43 years met the inclusion criteria. Their median baseline CD4 cell count was 315/mm3 and HIV-1 RNA level 4.6 log10 copies/ml. During the 2-years study period, IL-6, IP-10 and MIG levels fell significantly, while hs-CRP and sCD14 levels remained stable. IP-10 and MIG levels declined significantly less strongly with ATV/r than with EFV (IP-10Δ -57%, p = 0.011; MIGΔ -136%, p = 0.007), while no difference was noted between LPV/r and EFV. The decline in IL-6 did not differ significantly across the different treatment components. Conclusions After the first 2 years of successful cART, IL-6, IP-10 and MIG fell markedly while hs

  15. Durability of viral suppression with first-line antiretroviral therapy in patients with HIV in the UK: an observational cohort study.

    PubMed

    O'Connor, Jemma; Smith, Colette; Lampe, Fiona C; Johnson, Margaret A; Chadwick, David R; Nelson, Mark; Dunn, David; Winston, Alan; Post, Frank A; Sabin, Caroline; Phillips, Andrew N

    2017-07-01

    The length of time that people with HIV on antiretroviral therapy (ART) with viral load suppression will be able to continue before developing viral rebound is unknown. We aimed to investigate the rate of first viral rebound in people that have achieved initial suppression with ART, to determine factors associated with viral rebound, and to use these estimates to predict long-term durability of viral suppression. The UK Collaborative HIV Cohort (UK CHIC) Study is an ongoing multicentre cohort study that brings together in a standardised format data on people with HIV attending clinics around the UK. We included participants who started ART with three or more drugs and who had achieved viral suppression (≤50 copies per mL) by 9 months after the start of ART (baseline). Viral rebound was defined as the first single viral load of more than 200 copies per mL or treatment interruption (for ≥1 month). We investigated factors associated with viral rebound with Poisson regression. These results were used to calculate the rate of viral rebound according to several key factors, including age, calendar year at start of ART, and time since baseline. Of the 16 101 people included, 4519 had a first viral rebound over 58 038 person-years (7·8 per 100 person-years, 95% CI 7·6-8·0). Of the 4519 viral rebounds, 3105 (69%) were defined by measurement of a single viral load of more than 200 copies per mL, and 1414 (31%) by a documented treatment interruption. The rate of first viral rebound declined substantially over time until 7 years from baseline. The other factors associated with viral rebound were current age at follow-up and calendar year at ART initiation (p<0·0001) and HIV risk group (p<0·0001); higher pre-ART CD4 count (p=0·0008) and pre-ART viral load (p=0·0003) were associated with viral rebound in the multivariate analysis only. For 1322 (29%) of the 3105 people with observed viral rebound, the next viral load value after rebound was 50 copies per mL or

  16. 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

  17. The highly active Anhur-Bes regions in the 67P/Churyumov-Gerasimenko comet: results from OSIRIS/ROSETTA observations

    NASA Astrophysics Data System (ADS)

    Fornasier, S.; Feller, C.; Lee, J.-C.; Ferrari, S.; Massironi, M.; Hasselmann, P. H.; Deshapriya, J. D. P.; Barucci, M. A.; El-Maarry, M. R.; Giacomini, L.; Mottola, S.; Keller, H. U.; Ip, W.-H.; Lin, Z.-Y.; Sierks, H.; Barbieri, C.; Lamy, P. L.; Rodrigo, R.; Koschny, D.; Rickman, H.; Agarwal, J.; A'Hearn, M.; Bertaux, J.-L.; Bertini, I.; Cremonese, G.; Da Deppo, V.; Davidsson, B.; Debei, S.; De Cecco, M.; Deller, J.; Fulle, M.; Groussin, O.; Gutierrez, P. J.; Güttler, C.; Hofmann, M.; Hviid, S. F.; Jorda, L.; Knollenberg, J.; Kovacs, G.; Kramm, R.; Kührt, E.; Küppers, M.; Lara, M. L.; Lazzarin, M.; Lopez Moreno, J. J.; Marzari, F.; Naletto, G.; Oklay, N.; Pajola, M.; Shi, X.; Thomas, N.; Toth, I.; Tubiana, C.; Vincent, J.-B.

    2017-07-01

    The Southern hemisphere of the 67P/Churyumov-Gerasimenko comet has become visible from Rosetta only since 2015 March. It was illuminated during the perihelion passage and therefore it contains the regions that experienced the strongest heating and erosion rates, thus exposing the sub-surface most pristine material. In this work we investigate, thanks to the OSIRIS images, the geomorphology, the spectrophotometry and some transient events of two Southern hemisphere regions: Anhur and part of Bes. Bes is dominated by outcropping consolidated terrain covered with fine particle deposits, while Anhur appears strongly eroded with elongated canyon-like structures, scarp retreats, different kinds of deposits and degraded sequences of strata indicating a pervasive layering. We discovered a new 140 m long and 10 m high scarp formed in the Anhur-Bes boundary during/after the perihelion passage, close to the area where exposed CO2 and H2O ices were previously detected. Several jets have been observed originating from these regions, including the strong perihelion outburst, an active pit and a faint optically thick dust plume. We identify several areas with a relatively bluer slope (i.e. a lower spectral slope value) than their surroundings, indicating a surface composition enriched with some water ice. These spectrally bluer areas are observed especially in talus and gravitational accumulation deposits where freshly exposed material had fallen from nearby scarps and cliffs. The investigated regions become spectrally redder beyond 2 au outbound when the dust mantle became thicker, masking the underlying ice-rich layers.

  18. 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

  19. [The antiretroviral agent Fullevir].

    PubMed

    Nosik, D N; Lialina, I K; Kalnina, L B; Lobach, O A; Chataeva, M S; Rasnetsov, L D

    2009-01-01

    The antiretroviral properties of Fullevir (sodium salt of fullerenepolyhydropolyaminocaproic acid) manufactured by IntelFarm Co.) were studied in the human cell culture infected with human immunodeficiency virus (HIV). The agent was ascertained to be able to protect the cell from the cytopathic action of HIV. The 90% effective concentration (EF90) was 5 microg/ml. The 50% average toxic concentration was 400 microg/ml. Testing of different (preventive and therapeutic) Fullevir dosage regimens has shown that the drug is effective when used both an hour before and an hour after infection and when administered simultaneously with cell infection. The longer contact time for the agent with the cells increased the degree of antiviral defense. Co-administration of Fullevir and the HIV reverse transcriptase inhibitor Retrovir (azidothymidine) showed a synergistic antiretroviral effect. Thus, Fullevir may be regarded as a new promising antiretroviral drug for the treatment of HIV infection.

  20. Outcomes of antiretroviral treatment in HIV-infected adults: a dynamic and observational cohort study in Shenzhen, China, 2003-2014.

    PubMed

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

    2015-05-22

    To report 10-year outcomes of virological and immunological treatment failure rates and risk factors. Prospective cohort study. Shenzhen, China. 2172 HIV-positive adults in the national treatment database of Shenzhen from December 2003 to January 2014. Antiretroviral therapy according to the Chinese national treatment guidelines. Virological and immunological treatment failure rates. Of the 3099 patients surveyed, 2172 (70.1%) were included in the study. The median age was 33 years; 78.2% were male and 51.8% were infected through heterosexual contact. The median follow-up time was 31 months (IQR, 26-38). A total of 81 (3.7%) patients died, whereas 292 (13.4%) and 400 (18.4%) patients experienced virological and immunological failures, respectively. Adjusted Cox regression analysis indicated that baseline viral load (HR=2.19, 95% CI 1.52 to 4.48 for patients with a baseline viral load greater than or equal to 1,000,000 copies/mL compared to those with less than 10,000 copies/mL) and WHO stage (HR=4.16, 95% CI 2.01 to 10.57 for patients in WHO stage IV compared with those in stage I) were significantly associated with virological failure. The strongest risk factors for immunological treatment failure were a low CD4 cell count (HR=0.46, 95% CI 0.32 to 0.66 for patients with CD4 cell counts of 50-99 cells/mm(3) compared to those with less than 50 cells/mm(3)) and higher baseline WHO stage at treatment initiation (HR=2.15, 95% CI 1.38 to 3.34 for patients in WHO stage IV compared to those in stage I). Sustained virological and immunological outcomes show that patients have responded positively to long-term antiretroviral treatment with low mortality. This 10-year data study provides important information for clinicians and policymakers in the region as they begin to evaluate and plan for the future needs of their own rapidly expanding programmes. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please

  1. Antiretroviral treatment outcomes from a nurse-driven, community-supported HIV/AIDS treatment programme in rural Lesotho: observational cohort assessment at two years

    PubMed Central

    2009-01-01

    Introduction Lesotho has the third highest HIV prevalence in the world (an adult prevalence of 23.2%). Despite a lack of resources for health, the country has implemented state-of-the-art antiretroviral treatment guidelines, including early initiation of treatment (<350 cells/mm3), tenofovir in first line, and nurse-initiated and managed HIV care, including antiretroviral therapy (ART), at primary health care level. Programme approach We describe two-year outcomes of a decentralized HIV/AIDS care programme run by Doctors Without Borders/Médecins Sans Frontières, the Ministry of Health and Social Welfare, and the Christian Health Association of Lesotho in Scott catchment area, a rural health zone covering 14 clinics and one district hospital. Outcome data are described through a retrospective cohort analysis of adults and children initiated on ART between 2006 and 2008. Discussion and Evaluation Overall, 13,243 people have been enrolled in HIV care (5% children), and 5376 initiated on ART (6.5% children), 80% at primary care level. Between 2006 and 2008, annual enrolment more than doubled for adults and children, with no major external increase in human resources. The proportion of adults arriving sick (CD4 <50 cells/mm3) decreased from 22.2% in 2006 to 11.9% in 2008. Twelve-month outcomes are satisfactory in terms of mortality (11% for adults; 9% for children) and loss to follow up (8.8%). At 12 months, 80% of adults and 89% of children were alive and in care, meaning they were still taking their treatment; at 24 months, 77% of adults remained in care. Conclusion Despite major resource constraints, Lesotho is comparing favourably with its better resourced neighbour, using the latest international ART recommendations. The successful two-year outcomes are further evidence that HIV/AIDS care and treatment can be provided effectively at the primary care level. The programme highlights how improving HIV care strengthened the primary health care system, and validates

  2. Incidence of virological failure and major regimen change of initial combination antiretroviral therapy in the Latin America and the Caribbean: an observational cohort study

    PubMed Central

    Cesar, Carina; Jenkins, Cathy A.; Shepherd, Bryan E.; Padgett, Denis; Mejía, Fernando; Ribeiro, Sayonara Rocha; Cortes, Claudia P.; Pape, Jean W.; Madero, Juan Sierra; Fink, Valeria; Sued, Omar; McGowan, Catherine; Cahn, Pedro

    2015-01-01

    Background Access to combination antiretroviral therapy (cART) is expanding in Latin America and the Caribbean (LAC). There is little information in this region regarding incidence of and factors associated with regimen failure and regimen change. Methods Antiretroviral-naïve adults starting cART from 2000-2014 at sites in seven countries throughout LAC were included. Cumulative incidence of virologic failure and major regimen change were estimated with death considered a competing event. Findings 14,027 cART initiators (60% male, median age 37 years, median CD4 156 cells/mm3, median HIV-RNA 5·0 log10 copies/mL, and 28% with clinical AIDS) were followed for a median of 3·9 years. 1,719 patients presented virologic failure and 1,955 had a major regimen change. Excluding GHESKIO-Haiti (which did not regularly measure HIV-RNA), cumulative incidence of virologic failure was 7·8%, 19·2%, and 25·8% at one, three, and five years after cART initiation, respectively; cumulative incidence of major regimen change was 5·9%, 12·7%, and 18·2%. Incidence of major regimen change at GHESKIO-Haiti at five years was 10·7%. Virologic failure was associated with younger age (adjusted hazard ratio[aHR]=2·03 for 20 vs. 40 years; 95% confidence interval[CI] 1·68-2·44), infection through injection-drug use (IDU) (aHR=1·60; 95%CI 1·02-2·52), initiation in earlier calendar years (aHR=1·28 for 2002 vs. 2006; 95%CI 1·13-1·46), and starting with a boosted protease inhibitor (aHR=1·17 vs. non-nucleoside reverse transcriptase inhibitor; 95%CI 1·00-1·64). Interpretation Incidence of virologic failure was generally lower than in North America/Europe. Our results suggest the need to design strategies to reduce failure and major regimen change among younger patients and those with a history of IDU. Funding US National Institutes of Health: U01 AI069923. PMID:26520929

  3. Effect of deworming on disease progression markers in HIV-1-infected pregnant women on antiretroviral therapy: a longitudinal observational study from Rwanda.

    PubMed

    Ivan, Emil; Crowther, Nigel J; Mutimura, Eugene; Rucogoza, Aniceth; Janssen, Saskia; Njunwa, Kato K; Grobusch, Martin P

    2015-01-01

    Deworming human immunodeficiency virus (HIV)-infected individuals on antiretroviral therapy (ART) may be beneficial, particularly during pregnancy. We determined the efficacy of targeted and nontargeted antihelminth therapy and its effects on Plasmodium falciparum infection status, hemoglobin levels, CD4 counts, and viral load in pregnant, HIV-positive women receiving ART. Nine hundred eighty HIV-infected pregnant women receiving ART were examined at 2 visits during pregnancy and 2 postpartum visits within 12 weeks. Women were given antimalarials when malaria-positive whereas albendazole was given in a targeted (n = 467; treatment when helminth stool screening was positive) or nontargeted (n = 513; treatment at all time points, with stool screening) fashion. No significant differences were noted between targeted and nontargeted albendazole treatments for the variables measured at each study visit except for CD4 counts, which were lower (P < .05) in the latter group at the final visit. Albendazole therapy was associated with favorable changes in subjects' hemoglobin levels, CD4 counts, and viral loads, particularly with helminth infections. Antihelminthic therapy reduces detectable viral load, and increases CD4 counts and hemoglobin levels in pregnant HIV-infected women with helminth coinfections receiving ART. © The Author 2014. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  4. 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

  5. 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

    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

    2016-03-15

    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. 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. 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. 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. NCT01789879. © The Author 2015. Published by Oxford University Press for the Infectious Diseases Society of America.

  6. Antiretrovirals: reality or illusion?

    PubMed

    Mazin, R; Zacarias, F

    1998-10-01

    The use of antiretroviral drugs and combination therapy to treat HIV disease has been widely favored, despite obstacles such as cost, difficult dosing schedules, management of side effects, and inexperience of health practitioners in customizing treatment and counseling patients on use and adherence. Several benefits of drug therapy are discussed. One benefit is that the cost of therapy is lower than the overall cost of a patient not on therapy who will need more services and hospitalizations and will have higher incidences of opportunistic infections. Drug therapy also enables individuals to continue contributing to society by slowing the development of HIV and improving the quality of life. The Pan American Health Organization and UNAIDS are investigating ways to improve access to drugs in Latin America, the Caribbean, and other countries by working with pharmaceutical companies to coordinate drug purchases or negotiate price reductions. In addition, in order for antiretroviral therapy to be most effective, treatment should also include counseling, testing, and education.

  7. Pharmacogenetics of antiretroviral therapy.

    PubMed

    Barreiro, Pablo; Fernández-Montero, José Vicente; de Mendoza, Carmen; Labarga, Pablo; Soriano, Vincent

    2014-08-01

    Human genetic testing is rapidly entering into most medical disciplines, mainly as a way to predict hereditary conditions including predisposition to cancers or degenerative diseases. Another area of interest for human genomics is to ascertain the therapeutic effect and prevent potential toxicities and/or drug-drug interactions of medication. Several human genotypes have been associated with differences in the metabolism and transport of antiretroviral agents that ultimately affect drug exposure. The accelerated discovery of new gene mutations and polymorphisms that influence the effects of antiretroviral drugs provides a unique opportunity for a personalized medicine approach in the management of lifelong HIV therapy. Integration of human genomic screening into HIV clinical management will be cost-effective, maximizing the benefit of drugs with the lowest risk of side effects for a given patient.

  8. Immune reconstitution syndromes in human immuno-deficiency virus infection following effective antiretroviral therapy.

    PubMed

    Behrens, G M; Meyer, D; Stoll, M; Schmidt, R E

    2000-08-01

    Effective antiretroviral therapy leads to rapid decrease in plasma HIV-1 RNA, frequently followed by an increase in CD4 T-helper cell counts. The improvement of immune function during highly active antiretroviral therapy has important impact on natural history of AIDS-related opportunistic disorders. Here we describe cases of unusual clinical inflammatory syndromes in CMV retinitis, hepatitis C, and atypical mycobacteriosis in HIV-1 infected patients associated with the initiation of antiretroviral therapy. Pathogenetic implications and therapeutic management of these new immunopathologic syndromes are discussed.

  9. Comparative effectiveness of immediate antiretroviral therapy versus CD4-based initiation in HIV-positive individuals in high-income countries: observational cohort study.

    PubMed

    Lodi, Sara; Phillips, Andrew; Logan, Roger; Olson, Ashley; Costagliola, Dominique; Abgrall, Sophie; van Sighem, Ard; Reiss, Peter; Miró, José M; Ferrer, Elena; Justice, Amy; Gandhi, Neel; Bucher, Heiner C; Furrer, Hansjakob; Moreno, Santiago; Monge, Susana; Touloumi, Giota; Pantazis, Nikos; Sterne, Jonathan; Young, Jessica G; Meyer, Laurence; Seng, Rémonie; Dabis, Francois; Vandehende, Marie-Anne; Pérez-Hoyos, Santiago; Jarrín, Inma; Jose, Sophie; Sabin, Caroline; Hernán, Miguel A

    2015-08-01

    Recommendations have differed nationally and internationally with respect to the best time to start antiretroviral therapy (ART). We compared effectiveness of three strategies for initiation of ART in high-income countries for HIV-positive individuals who do not have AIDS: immediate initiation, initiation at a CD4 count less than 500 cells per μL, and initiation at a CD4 count less than 350 cells per μL. We used data from the HIV-CAUSAL Collaboration of cohort studies in Europe and the USA. We included 55,826 individuals aged 18 years or older who were diagnosed with HIV-1 infection between January, 2000, and September, 2013, had not started ART, did not have AIDS, and had CD4 count and HIV-RNA viral load measurements within 6 months of HIV diagnosis. We estimated relative risks of death and of death or AIDS-defining illness, mean survival time, the proportion of individuals in need of ART, and the proportion of individuals with HIV-RNA viral load less than 50 copies per mL, as would have been recorded under each ART initiation strategy after 7 years of HIV diagnosis. We used the parametric g-formula to adjust for baseline and time-varying confounders. Median CD4 count at diagnosis of HIV infection was 376 cells per μL (IQR 222-551). Compared with immediate initiation, the estimated relative risk of death was 1·02 (95% CI 1·01-1·02) when ART was started at a CD4 count less than 500 cells per μL, and 1·06 (1·04-1·08) with initiation at a CD4 count less than 350 cells per μL. Corresponding estimates for death or AIDS-defining illness were 1·06 (1·06-1·07) and 1·20 (1·17-1·23), respectively. Compared with immediate initiation, the mean survival time at 7 years with a strategy of initiation at a CD4 count less than 500 cells per μL was 2 days shorter (95% CI 1-2) and at a CD4 count less than 350 cells per μL was 5 days shorter (4-6). 7 years after diagnosis of HIV, 100%, 98·7% (95% CI 98·6-98·7), and 92·6% (92·2-92·9) of individuals would have

  10. Do patents for antiretroviral drugs constrain access to AIDS treatment in Africa?

    PubMed

    Attaran, A; Gillespie-White, L

    2001-10-17

    Public attention and debate recently have focused on access to treatment of acquired immunodeficiency syndrome (AIDS) in poor, severely affected countries, such as those in Africa. Whether patents on antiretroviral drugs in Africa are impeding access to lifesaving treatment for the 25 million Africans with human immunodeficiency virus infection is unknown. We studied the patent statuses of 15 antiretroviral drugs in 53 African countries. Using a survey method, we found that these antiretroviral drugs are patented in few African countries (median, 3; mode, 0) and that in countries where antiretroviral drug patents exist, generally only a small subset of antiretroviral drugs are patented (median and mode, 4). The observed scarcity of patents cannot be simply explained by a lack of patent laws because most African countries have offered patent protection for pharmaceuticals for many years. Furthermore, in this particular case, geographic patent coverage does not appear to correlate with antiretroviral treatment access in Africa, suggesting that patents and patent law are not a major barrier to treatment access in and of themselves. We conclude that a variety of de facto barriers are more responsible for impeding access to antiretroviral treatment, including but not limited to the poverty of African countries, the high cost of antiretroviral treatment, national regulatory requirements for medicines, tariffs and sales taxes, and, above all, a lack of sufficient international financial aid to fund antiretroviral treatment. We consider these findings in light of policies for enhancing antiretroviral treatment access in poor countries.

  11. Anti-retroviral drugs do not facilitate hepatitis C virus (HCV) infection in vitro.

    PubMed

    Sandmann, Lisa; Wilson, Matthew; Back, David; Wedemeyer, Heiner; Manns, Michael P; Steinmann, Eike; Pietschmann, Thomas; von Hahn, Thomas; Ciesek, Sandra

    2012-10-01

    An estimated 4 to 5 million people are co-infected with HIV/HCV worldwide. Recently observed outbreaks of acute HCV infection among HIV-positive men who have sex with men (MSM) have been linked to behavioral factors such as high risk sexual practices and recreational drug use. However, at the molecular level, many drugs such as glucocorticoids or cyclosporine A have been found to modulate viral replication. Thus, it is conceivable that drugs used in highly active antiretroviral therapy (HAART) may heighten susceptibility to HCV infection and contribute to the recent outbreaks. We therefore performed a comprehensive screen of antiretroviral drugs covering all available drug classes both individually and in typical combinations used during HAART to probe for direct effects on HCV cell entry, replication, new particle assembly and release. Importantly, no significant enhancement or inhibition of HCV cell entry, replication or new particle production was detected. While raltegravir and ritonavir boosted atazanavir reduce HCV replication, a tenfold reduction of HCVcc entry by the CCR5 antagonist maraviroc was observed. In conclusion, commonly used HAART agents do not specifically enhance HCV replication. Thus recent epidemic outbreaks of acute HCV in HIV-infected MSM are unlikely to be related to enhancing effects of HAART drugs.

  12. Antiretroviral drugs: Critical issues and recent advances

    PubMed Central

    Desai, Mira; Iyer, Geetha; Dikshit, R. K.

    2012-01-01

    Human immunodeficiency virus (HIV) infection is now recognized as a chronic illness. Although the success of highly active antiretroviral therapy is beyond question, several issues still persist. Since the drugs cannot eradicate the virus, cure is not yet possible, and patients have to maintain a lifelong adherence with the risk of toxic effects, drug-drug interactions and drug resistance. A clear understanding of the viral replication and its interaction with host cell factors has led to the development of a large number of effective antiretroviral drugs (ARVs). New drugs in the existing class such as apricitabine, elvucitabine and etravirine have shown promising results against HIV isolates resistant to first line drugs. These drugs have offered a new choice for patients with drug resistant disease. However, the impact of their long term use on safety is yet to be assessed. Novel drugs with unique mechanism of action such as CD4 receptor attachment inhibitors, maturation inhibitors, pharmacokinetic enhancers, capsid assembly inhibitors and lens epithelium derived growth factor inhibitors are still under development. Currently, ARVs, especially tenofovir and emtricitabine, are also being evaluated for prevention of sexual transmission of HIV-1. The initial results of an HIV prevention trial network are encouraging and have recommended the use of ARVs for pre-exposure prophylaxis. Thus, ARVs form the key component of HIV prevention and treatment strategy. This article discusses the challenges associated with HIV-1 treatment and updates several major advances in the development of ARVs. PMID:22701234

  13. [Peripheral neuropathies and antiretroviral drugs. Preliminary results].

    PubMed

    Thiam, A; Diagne, M; Ndiaye, Ng; Ngom Gueye, N F; Diakhate, N D; Sow, P S; Ndiaye, I P

    2005-01-01

    In order to appreciate the antiretroviral drugs impact in the HIV positive patients with peripheral neuropathy, a clinical, electrophysiological and neurpathological study of nerve biopsies was performed. A group of 8 HIV seropositive patients with peripheral neuropathy was compared with an other group of 10 HIV seropositive patients treated with multiple antiretroviral drugs. Electrophysiological examination with motor nerve conduction velocity (MNCV) mesure of the median and the sciatic popliteal nerve was followed by nerve biopsy. Nerve fragments carried out the neuropathological technics for morphological examination. Eighteen seropositive HIV patients (16 HIV-1 and 2 HIV-2) were included in this study. Six patients among them had motor and sensitive neuropathy of the four limbs and 2 patients had sensitive neuropathy associated with pyramidal signs. In fine, 1 patient had sensitive neuropathy with distal amyotrophy of the four limbs. Slow MNCV was observed in all the patients and more severe in the lower limbs. Nerve were unexciting in the lower limbs in 2 patients. Nerve biopsy showed severe axonal loss in all the patients treated but one. They associated axonal lesion in 5 cases and myelinated lesions in 2 cases. Two patients non treated had normal nerve biopsy. Axonal loss was mild in 2 cases and very severe in one case associated with non inflammatory demyelinated lesions. we observed more severe and more frequent nerve lesions in treated patients than in no treated patients, as at the clinical, electrophysiological and neuropathological examination. Antiretroviral drugs cause more frequently pain motor and sensitive neuropathies at usual posologies. The occurence of recrudescence of pain peripheral neuropathy under antiretroviral treatment allows to reconsider drugs posologies.

  14. Prognostic significance of the interval between the initiation of antiretroviral therapy and the initiation of anti-tuberculosis treatment in HIV/tuberculosis-coinfected patients: results from the TREAT Asia HIV Observational Database.

    PubMed

    Han, S H; Zhou, J; Lee, M P; Zhao, H; Chen, Y-M A; Kumarasamy, N; Pujari, S; Lee, C; Omar, S F S; Ditangco, R; Phanuphak, N; Kiertiburanakul, S; Chaiwarith, R; Merati, T P; Yunihastuti, E; Tanuma, J; Saphonn, V; Sohn, A H; Choi, J Y

    2014-02-01

    We evaluated the effect of the time interval between the initiation of antiretroviral therapy (ART) and the initiation of tuberculosis (TB) treatment on clinical outcomes in HIV/TB-coinfected patients in an Asian regional cohort. Adult HIV/TB-coinfected patients in an observational HIV-infected cohort database who had a known date of ART initiation and a history of TB treatment were eligible for study inclusion. The time interval between the initiation of ART and the initiation of TB treatment was categorized as follows: TB diagnosed while on ART, ART initiated ≤ 90 days after initiation of TB treatment ('early ART'), ART initiated > 90 days after initiation of TB treatment ('delayed ART'), and ART not started. Outcomes were assessed using survival analyses. A total of 768 HIV/TB-coinfected patients were included in this study. The median CD4 T-cell count at TB diagnosis was 100 [interquartile range (IQR) 40-208] cells/μL. Treatment outcomes were not significantly different between the groups with early ART and delayed ART initiation. 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 for early ART, 1.46 for delayed ART, and 2.94 for ART not started). In a multivariate model, the interval between ART initiation and TB therapy initiation did not significantly impact all-cause mortality. A negative impact of delayed ART in patients coinfected with TB was not observed in this observational cohort of moderately to severely immunosuppressed patients. The broader impact of earlier ART initiation in actual clinical practice should be monitored more closely. © 2013 British HIV Association.

  15. Structured antiretroviral treatment interruptions in chronically HIV-1-infected subjects

    PubMed Central

    Ortiz, Gabriel M.; Wellons, Melissa; Brancato, Jason; Vo, Ha T. T.; Zinn, Rebekah L.; Clarkson, Daniel E.; Van Loon, Katherine; Bonhoeffer, Sebastian; Miralles, G. Diego; Montefiori, David; Bartlett, John A.; Nixon, Douglas F.

    2001-01-01

    The risks and benefits of structured treatment interruption (STI) in HIV-1-infected subjects are not fully understood. A pilot study was performed to compare STI with continuous highly active antiretroviral therapy (HAART) in chronic HIV-1-infected subjects with HIV-1 plasma RNA levels (VL) <400 copies per ml and CD4+ T cells >400 per μl. CD4+ T cells, VL, HIV-1-specific neutralizing antibodies, and IFN-γ-producing HIV-1-specific CD8+ and CD4+ T cells were measured in all subjects. STIs of 1-month duration separated by 1 month of HAART, before a final 3-month STI, resulted in augmented CD8+ T cell responses in all eight STI subjects (P = 0.003), maintained while on HAART up to 22 weeks after STI, and augmented neutralization titers to autologous HIV-1 isolate in one of eight subjects. However, significant decline of CD4+ T cell count from pre-STI level, and VL rebound to pre-HAART baseline, occurred during STI (P = 0.001 and 0.34, respectively). CD4+ T cell counts were regained on return to HAART. Control subjects (n = 4) maintained VL <400 copies per ml and stable CD4+ T cell counts, and showed no enhancement of antiviral CD8+ T cell responses. Despite increases in antiviral immunity, no control of VL was observed. Future studies of STI should proceed with caution. PMID:11687611

  16. An update and review of antiretroviral therapy.

    PubMed

    Piacenti, Frank J

    2006-08-01

    The human immunodeficiency virus (HIV) was discovered in 1982, but treatment strategies were not introduced until 5 years later. Early regimens consisted of one or two drugs and often led to treatment failure. Since the advent in 1995 of highly active antiretroviral therapy (HAART), which consists of at least three agents, a dramatic improvement has been seen in the number of patients attaining undetectable viral loads, improved CD4 counts, and improved survival. However, early HAART often consisted of drugs with complex dosing schedules, strict food requirements, treatment-limiting adverse effects, and the need to take 16-20 pills/day. These treatment barriers often led to patient nonadherence, with subsequent treatment failure and development of resistant strains. The CD4 count and viral load are the most important surrogate markers used to determine if treatment is indicated. Current guidelines suggest starting treatment in patients who are symptomatic with an acquired immunodeficiency syndrome-defining illness regardless of CD4 count or viral load, as well as in asymptomatic patients with a CD4 count of 350 cells/mm(3) or below. In patients with CD4 counts above 350 cells/mm(3) and viral loads above 100,000 copies/ml, some clinicians prefer to defer treatment, whereas others will consider starting therapy; treatment is deferred in patients with CD4 counts above 350 cells/mm(3) and viral load s below 100,000 copies/ml. If therapy is started, the selection of appropriate agents is based on comorbidities (liver disease, depression, cardiovascular disease), pregnancy status, adherence potential (dosage regimen, pill burden, dosing frequency), food restrictions (dosing with regard to meals), adverse drug effects, and potential drug-drug interactions. Within the last 8 years, newer antiretroviral agents have focused on ways to improve adherence, such as convenient dosing (fewer pills), pharmacokinetic and formulation changes to reduce dosing frequency or pill burden

  17. Pharmacogenetics as a tool to tailor antiretroviral therapy: A review.

    PubMed

    Aceti, Antonio; Gianserra, Laura; Lambiase, Lara; Pennica, Alfredo; Teti, Elisabetta

    2015-08-12

    Highly active antiretroviral therapy (HAART) has substantially changed human immunodeficiency virus (HIV) infection from an inexorably fatal condition into a chronic disease with a longer life expectancy. This means that HIV patients should receive antiretroviral drugs lifelong, and the problems concerning with a chronic treatment (tolerability, side effects, adherence to treatment) have now become dominant. In this context, strategies for the treatment personalization have taken a central role in optimizing the therapeutic response and prevention of adverse drug reactions. In this setting, the study of pharmacogenetics features could be a very useful tool in clinical practice; moreover, nowadays the study of genetic profiles allows optimizations in the therapeutic management of People Living With HIV (PLWH) through the use of test introduced into clinical practice and approved by international guidelines for the adverse effects prevention such as the genetic test HLA-B*5701 to detect hypersensitivity to Abacavir. For other tests further studies are needed: CYP2B6 516 G > T testing may be able to identify patients at higher risk of Central Nervous System side effects following standard dosing of Efavirenz, UGT1A1*28 testing before initiation of antiretroviral therapy containing Atazanavir may aid in identifying individuals at risk of hyperbilirubinaemia. Pharmacogenetics represents a ​​research area with great growth potential which may be useful to guide the rational use of antiretrovirals.

  18. Pharmacogenetics as a tool to tailor antiretroviral therapy: A review

    PubMed Central

    Aceti, Antonio; Gianserra, Laura; Lambiase, Lara; Pennica, Alfredo; Teti, Elisabetta

    2015-01-01

    Highly active antiretroviral therapy (HAART) has substantially changed human immunodeficiency virus (HIV) infection from an inexorably fatal condition into a chronic disease with a longer life expectancy. This means that HIV patients should receive antiretroviral drugs lifelong, and the problems concerning with a chronic treatment (tolerability, side effects, adherence to treatment) have now become dominant. In this context, strategies for the treatment personalization have taken a central role in optimizing the therapeutic response and prevention of adverse drug reactions. In this setting, the study of pharmacogenetics features could be a very useful tool in clinical practice; moreover, nowadays the study of genetic profiles allows optimizations in the therapeutic management of People Living With HIV (PLWH) through the use of test introduced into clinical practice and approved by international guidelines for the adverse effects prevention such as the genetic test HLA-B*5701 to detect hypersensitivity to Abacavir. For other tests further studies are needed: CYP2B6 516 G > T testing may be able to identify patients at higher risk of Central Nervous System side effects following standard dosing of Efavirenz, UGT1A1*28 testing before initiation of antiretroviral therapy containing Atazanavir may aid in identifying individuals at risk of hyperbilirubinaemia. Pharmacogenetics represents a ​​research area with great growth potential which may be useful to guide the rational use of antiretrovirals. PMID:26279982

  19. [Pneumocystis jiroveci pneumonia characteristics in adults with AIDS with or without antiretroviral therapy].

    PubMed

    Bahamondes M, Laura; Villar Z, M José; Orellana C, Carolina; González R, Jimena; Montenegro U, Cristian

    2006-09-01

    Highly active antiretroviral therapy (HAART) has changed the epidemiology of Pneumocystis jiroveci pneumonia (PCP) in AIDS patients. Global incidence of PCP has decreased and now it is prevalent in AIDS patients who do not receive HAART or are unsuccessfully treated with persistent immune depression. Moreover, the immunologic response to HAART has caused a PCP form which is included in the immune restoration inflammatory syndrome (IRIS). As of late 2004, 75.5% of patients cared for at Dr. Lucio Córdova Infectious Diseases Hospital were receiving HAART. This study compares PCP clinical characteristics in patients under the effect of HAART (n: 6) with those without antiretroviral therapy (n: 12). Among those with HAART, 83.3% (5/6) were without immunologic responses and 16.7% with virologic response. The median CD4 counts were low in both groups: 20 cells/mm(3) without HAART and 51 cells/mm(3) with HAART. There were no differences in most of PCP characteristics, and no IRIS cases were observed. HAART-receiving group had less severe disease and lower frequency of both, complications and steroidal therapy prescription (P 0.023).

  20. Monitoring of HAART regime antiretrovirals in serum of acquired immunodeficiency syndrome patients by micellar liquid chromatography.

    PubMed

    Casas-Breva, I; Peris-Vicente, J; Rambla-Alegre, M; Carda-Broch, S; Esteve-Romero, J

    2012-09-21

    A methodology based on micellar liquid chromatography to monitor five antiretroviral drugs (lamivudine, stavudine, tenofovir, zidovudine and efavirenz) was proposed. Antiretrovirals were studied in sets of three, corresponding to each highly active antiretroviral therapy (HAART) regime, prescribed to acquired immunodeficiency syndrome (AIDS)-infected patients. Four aqueous micellar mobile phases buffered at pH 7 were optimized to separate these compounds, using sodium dodecyl sulfate as the tensioactive, and 1-propanol or 1-pentanol as the organic modifier. The composition of each mobile phase was optimized for each antiretroviral. The common separation conditions were: C18 apolar column (125 × 4.6 mm, 5 μm particle size), UV detection set at 214 nm, and mobile phase running at 1 mL min(-1) without controlling the temperature. The finally suggested method was validated for five analysed antiretroviral drugs following the US Food and Drug Administration guidelines in terms of: linearity between 0.5 and 50 ppm (r(2) > 0.9995), sensitivity (LOD lower than 0.25 ppm), intra- and inter-day precision (<7.1 and <5.2%, respectively) and accuracy (recovery 88.5-105.3% and 93.5-101.3%, respectively), as well as robustness (<6.5%). The proposed method was used to monitor the level of antiretrovirals in the serum of AIDS patients. The suggested methodology was found to be useful in the routine analysis of antiretrovirals in serum samples.

  1. Bridging the gap between antiretroviral access and adherence in Mexico.

    PubMed

    Campero, Lourdes; Herrera, Cristina; Kendall, Tamil; Caballero, Marta

    2007-05-01

    The goal in this article is to examine social problems associated with highly active antiretroviral therapy (HAART) adherence in Mexico and the related challenges for Mexican persons living with HIV/AIDS (PLWHAs). The study was conducted from the perspective of infected and affected individuals. The authors completed 64 in-depth interviews with heterosexual male and female PLWHAs, as well as with some key individuals from their social network. Following the principles of grounded theory, they carried out inductive analysis to create codes and organize central themes. The authors identified problems related to accessing HAART and found that conditions for implementing recommendations made in the international literature to improve adherence are poor. The findings highlight the importance of social factors, such as health care system irregularities, ineffective physician-patient communication, and availability of family and other sources of social support such as self-help groups for PLWHAs' access and adherence to antiretroviral therapy in Mexico.

  2. Antiretroviral therapy: Shifting sands

    PubMed Central

    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

  3. 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

  4. Therapy of highly active pediatric multiple sclerosis.

    PubMed

    Huppke, Peter; Huppke, Brenda; Ellenberger, David; Rostasy, Kevin; Hummel, Hannah; Stark, Wiebke; Brück, Wolfgang; Gärtner, Jutta

    2017-09-01

    Study aims were to determine the frequency of highly active disease in pediatric multiple sclerosis (MS), the response to natalizumab (NTZ) and fingolimod (FTY) treatment, and the impact of current treatment modalities on the clinical course. Retrospective single-center study in the German Center for MS in Childhood and Adolescence. Of 144 patients with first MS manifestation between 2011 and 2015, 41.6% fulfilled the criteria for highly active MS. In total, 55 patients treated with NTZ and 23 with FTY demonstrated a significant reduction in relapse rate (NTZ: 95.2%, FTY: 75%), new T2 lesions (NTZ: 97%, FTY: 81%), and contrast-enhancing lesions (NTZ: 97%, FTY: 93%). However, seven patients switched from NTZ to FTY experienced an increase in disease activity. Comparing pediatric MS patients treated in 2005 with those treated in 2015 showed a 46% reduction in relapse rate and a 44% reduction in mean Expanded Disability Status Scale (EDSS). The rate of highly active disease among pediatric MS patients is high; more than 40% in our cohort. Response to NTZ and FTY treatment is similar if not better than observed in adults. Current treatment modalities including earlier treatment initiation and the introduction of NTZ and FTY have significantly improved the clinical course of pediatric MS.

  5. 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

  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. 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…

  8. Effectiveness of Highly Active Antiretroviral Therapy (HAART) Among HIV-Infected Patients in Mexico

    PubMed Central

    Villasís-Keever, Angelina; Galindo-Fraga, Arturo; del Río, Carlos; Sierra-Madero, Juan

    2010-01-01

    Abstract The National Government HAART Program (NGP) for the provision of HAART to uninsured HIV-infected persons in Mexico began in 2001. The objective was to describe the virologic outcome of patients enrolled in the NGP in a large HIV treatment center in Mexico City. HIV-infected persons, naive or ≤6 months on HAART, who entered the NGP from 2001 to 2005 were included. Patients with virological suppression were compared to those with virologic failure (VF) during follow-up. Of 377 patients enrolled, 191 where eligible for analysis. The median age was 35.9 (18–75 years) and 85% were male. The median baseline CD4+ T cell count was 183 cells/mm3; 63.9% had <200 cells/mm3 and/or an AIDS-defining event. During follow-up (median: 17.77 months), 55 patients (28.7%) changed their first regimen: 8.3% because of VF and the remaining due to toxicity. The probability of VF at 48 months was 20%. VF was associated with age <30 years (p = 0.003, RR 4.7, IC 95% 1.5–14.4). The use of NNRTI was associated with lower risk of VF (p = 0.042, RR 0.3, IC 95% 0.12–0.99). Nadir CD4+ and AIDS-defining at baseline were not associated with VF. Implementation of NGP for HAART access in a specialized care setting in Mexico resulted in an excellent virologic response. Younger age was a significant risk factor for VF. PMID:20377418

  9. [Pharmacological strategies to improve the adherence to highly active antiretroviral therapy].

    PubMed

    Clapé-Laffita, Oneyda

    2013-01-01

    Introducción: la adherencia a la terapia antirretroviral es un factor importante para suprimir el virus de la inmunodeficiencia humana. El propósito de la investigación que se presenta fue aplicar estrategias farmacológicas basadas en medidas farmacocinéticas para facilitar la adherencia a la terapia antirretroviral. Métodos: se realizó un estudio descriptivo durante ocho meses, con 75 pacientes positivos al virus de inmunodeficiencia humana, con criterios clínicos y sociales para una terapia antirretroviral altamente activa, en Opuwo, Namibia. Se analizaron aspectos farmacológicos como la no existencia de efectos adversos graves ni interacciones medicamentosas riesgosas. El análisis de resultado fue realizado con estadística descriptiva. Resultados: fueron detectados tres efectos adversos leves (dos para efavirenz y uno para nevirapina) y uno grave para estavudina/lamivudina. Se evitaron las interacciones medicamentosas riesgosas aplicando medidas farmacocinéticas con efavirenz, estavudina/ lamivudina y zidovudina; así como entre nevirapina y fluconazol (o ketoconazol). Conclusiones: la adherencia a la terapia antirretroviral altamente activa se facilitó al aplicar las estrategias farmacológicas propuestas y se evitaron efectos adversos e interacciones medicamentosas riesgosas.

  10. [Improving adhesion to antiretroviral treatment].

    PubMed

    2008-01-01

    To facilitate unified criteria for health professionals to improve adhesion to antiretroviral therapy. The recommendations were drawn up and agreed upon by an expert panel from the SPNS, GESIDA and SEFH, after an exhaustive review of the latest relevant epidemiological and clinical studies that have been published in the medical literature and/or presented at congresses and scientific forums. The factors related to adhesion with antiretroviral therapy came from individuals, health care professionals and treatment variables. Current available methods for measuring adhesion are diverse and classified as direct and indirect. The ideal method is shown to be one which is highly sensitive and specific, enables quantitative and continuous measurement and is reliable, reproducible, economical and quick. The doctor, nurse and pharmacist play a key role in the strategies for adhesion improvement. Specific programmes based on exhaustive knowledge of individualized variables from patients and their antiretroviral therapy should be developed. The use of combined methods which are adapted to healthcare facility characteristics for adhesion improvement is recommended. The structured support to interpersonal adhesion developed by trained healthcare professionals and individualized strategies has been demonstrated as being the most effective intervention strategy to improve adhesion with antiretroviral treatment.

  11. High-Activity Dealloyed Catalysts

    SciTech Connect

    Kongkanand, Anusorn

    2014-09-30

    Reduction of costly Pt usage in proton exchange membrane fuel cell electrodes is one of the major challenges towards development and commercialization of fuel cell vehicles. Although few have met the initial-kinetic activity requirements in a realistic fuel cell device, no catalyst material has ever met the demanding fuel cell durability targets set by DOE. In this project, a team of 4 universities and 2 companies came together to investigate a concept that appeared promising in preliminary non-fuel cell tests then to further develop the catalyst to a mature level ready for vehicle implementation. The team consists of academia with technical leadership in their respective areas, a catalyst supplier, and a fuel cell system integrator.The tightly collaborative project enabled development of a highly active and durable catalyst with performance that significantly exceeds that of previous catalysts and meets the DOE targets for the first time (Figure 1A). The catalyst was then further evaluated in full-active-area stack in a realistic vehicle operating condition (Figure 1B). This is the first public demonstration that one can realize the performance benefit and Pt cost reduction over a conventional pure Pt catalyst in a long-term realistic PEMFC system. Furthermore, systematic analyses of a range of catalysts with different performance after fuel cell testing allowed for correlation between catalyst microstructure and its electrocatalytic activity and durability. This will in turn aid future catalyst development.

  12. Investigational protease inhibitors as antiretroviral therapies

    PubMed Central

    Midde, Narasimha M.; Patters, Benjamin J.; Rao, PSS; Cory, Theodore J.; Kumar, Santosh

    2017-01-01

    Introduction Highly Active Antiretroviral Therapy (HAART) has tremendously improved the life expectancy of the HIV-infected population over the past three decades. Protease inhibitors have been one of the major classes of drugs in HAART regimens that are effective in treating HIV. However, the emergence of resistance and cross-resistance against protease inhibitors encourages researchers to develop new PIs with broad-spectrum activity, as well as novel means of enhancing the efficacy of existing PIs. Areas covered In this article we discuss recent advances in HIV protease inhibitor (PI) development, focusing on both investigational and experimental agents. We also include a section on pharmacokinetic booster drugs for improved bioavailability of protease inhibitors. Further, we discuss novel drug delivery systems using a variety of nanocarriers for the delivery of PIs across the blood-brain barrier to treat the HIV in the brain. Expert opinion We discuss our opinion on the promises and challenges on the development of novel investigational and experimental PIs that are less toxic and more effective in combating drug-resistance. Further, we discuss the future of novel nanocarriers that have been developed to deliver PIs to the brain cells. Although these are promising findings, many challenges need to be overcome prior to making them a viable option. PMID:27415449

  13. Comparison of dynamic monitoring strategies based on CD4 cell counts in virally suppressed, HIV-positive individuals on combination antiretroviral therapy in high-income countries: a prospective, observational study.

    PubMed

    Caniglia, Ellen C; Cain, Lauren E; Sabin, Caroline A; Robins, James M; Logan, Roger; Abgrall, Sophie; Mugavero, Michael J; Hernández-Díaz, Sonia; Meyer, Laurence; Seng, Remonie; Drozd, Daniel R; Seage, George R; Bonnet, Fabrice; Dabis, Francois; Moore, Richard D; 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; Justice, Amy C; Tate, Janet P; Gill, John; Pacheco, Antonio; Veloso, Valdilea G; Bucher, Heiner C; Egger, Matthias; Furrer, Hansjakob; Porter, Kholoud; Touloumi, Giota; Crane, Heidi; Miro, Jose M; Sterne, Jonathan A; Costagliola, Dominique; Saag, Michael; Hernán, Miguel A

    2017-06-01

    Clinical guidelines vary with respect to the optimal monitoring frequency of HIV-positive individuals. We compared dynamic monitoring strategies based on time-varying CD4 cell counts in virologically suppressed HIV-positive individuals. In this observational study, we used data from prospective studies of HIV-positive individuals in Europe (France, Greece, the Netherlands, Spain, Switzerland, and the UK) and North and South America (Brazil, Canada, and the USA) in The HIV-CAUSAL Collaboration and The Centers for AIDS Research Network of Integrated Clinical Systems. We compared three monitoring strategies that differ in the threshold used to measure CD4 cell count and HIV RNA viral load every 3-6 months (when below the threshold) or every 9-12 months (when above the threshold). The strategies were defined by the threshold CD4 counts of 200 cells per μL, 350 cells per μL, and 500 cells per μL. Using inverse probability weighting to adjust for baseline and time-varying confounders, we estimated hazard ratios (HRs) of death and of AIDS-defining illness or death, risk ratios of virological failure, and mean differences in CD4 cell count. 47 635 individuals initiated an antiretroviral therapy regimen between Jan 1, 2000, and Jan 9, 2015, and met the eligibility criteria for inclusion in our study. During follow-up, CD4 cell count was measured on average every 4·0 months and viral load every 3·8 months. 464 individuals died (107 in threshold 200 strategy, 157 in threshold 350, and 200 in threshold 500) and 1091 had AIDS-defining illnesses or died (267 in threshold 200 strategy, 365 in threshold 350, and 459 in threshold 500). Compared with threshold 500, the mortality HR was 1·05 (95% CI 0·86-1·29) for threshold 200 and 1·02 (0·91·1·14) for threshold 350. Corresponding estimates for death or AIDS-defining illness were 1·08 (0·95-1·22) for threshold 200 and 1·03 (0·96-1·12) for threshold 350. Compared with threshold 500, the 24 month risk ratios of

  14. 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

  15. Antiretroviral treatment reduces increased CSF neurofilament protein (NFL) in HIV-1 infection.

    PubMed

    Mellgren, A; Price, R W; Hagberg, L; Rosengren, L; Brew, B J; Gisslén, M

    2007-10-09

    Increased levels of the light-chain neurofilament protein (NFL) in CSF provide a marker of CNS injury in several neurodegenerative disorders and have been reported in the AIDS dementia complex (ADC). We examined the effects of highly active antiretroviral treatment (HAART) on CSF NFL in HIV-1-infected subjects with and without ADC who underwent repeated lumbar punctures (LPs). NFL was measured by ELISA (normal reference value < 250 ng/L) in archived CSF samples from 53 patients who had undergone LPs before and after initiation of HAART. Twenty-one of the subjects had increased CSF NFL at baseline, with a median level of 780 ng/L and an intraquartile range (IQR) of 480 to 7300. After 3 months of treatment, NFL concentrations had fallen to normal in 48% (10/21), and the median decreased to 340 ng/L (IQR < 250 to 4070) (p < 0.001), whereas at 1 year, only 4 of 16 of the 21 subjects observed for this length still had elevated NFL levels. Thirty-two subjects had normal NFL at baseline, and all but one remained normal at follow-up. These effects on CSF NFL were seen in association with clinical improvement in ADC patients, decreases in plasma and CSF HIV-1 RNA and CSF neopterin, and increases in blood CD4 T cell counts. HAART seems to halt the neurodegenerative process(es) caused by HIV-1, as shown by the significant decrease in CSF NFL after treatment initiation. CSF NFL may serve as a useful marker in monitoring CNS injury in HIV-1 infection and in evaluating CNS efficacy of antiretroviral therapy.

  16. Reduced human herpesvirus-8 oropharyngeal shedding associated with protease inhibitor-based antiretroviral therapy.

    PubMed

    Gantt, Soren; Cattamanchi, Ashok; Krantz, Elizabeth; Magaret, Amalia; Selke, Stacy; Kuntz, Steven R; Huang, Meei-Li; Corey, Lawrence; Wald, Anna; Casper, Corey

    2014-06-01

    Human herpesvirus 8 (HHV-8) replication increases the risk of Kaposi sarcoma (KS). Highly-active antiretroviral therapy (HAART) reduces the incidence of KS, and regimens that contain protease inhibitors (PIs) may be particularly effective. To determine whether PI-based HAART regimens may more effectively inhibit HHV-8 shedding compared to regimens without PIs. Prospective, observational study of 142 HIV-1 and HHV-8 co-infected men conducted in Seattle, Washington. Quantitative HHV-8 PCR testing was performed on daily swabs of the oropharynx, the primary site of HHV-8 replication. Associations between antiretroviral regimen and detection of HHV-8 DNA in swabs were evaluated using generalized estimating equations. HHV-8 DNA was detected in 3016 (26%) of 11,608 specimens collected. PI-based HAART was associated with a statistically significantly lower frequency of detection (RR 0.2; 95% CI 0.1-0.5) compared to ART-naïve persons, whereas HAART without a PI was not (RR 0.7; 95% CI 0.4-1.3). Compared to ART-naïve persons, there was also a trend toward lower quantities of HHV-8 detected during treatment with HAART regimens that contained a PI. These associations between PIs and measures of HHV-8 shedding could not be attributed to use of nelfinavir, which inhibits HHV-8 replication in vitro, and were independent of CD4 count and HIV plasma viral load (VL). HAART regimens that contain PIs appear to decrease HHV-8 shedding compared to NNRTIs. Further study of PI-based HAART is warranted to determine the optimal regimens for prevention and treatment of KS. Copyright © 2014 Elsevier B.V. All rights reserved.

  17. Reduced Human Herpesvirus-8 Oropharyngeal Shedding Associated with Protease Inhibitor-Based Antiretroviral Therapy

    PubMed Central

    Gantt, Soren; Cattamanchi, Ashok; Krantz, Elizabeth; Magaret, Amalia; Selke, Stacy; Kuntz, Steven R.; Huang, Meei-Li; Corey, Lawrence; Wald, Anna; Casper, Corey

    2014-01-01

    Background Human herpesvirus 8 (HHV-8) replication increases the risk of Kaposi sarcoma (KS). Highly-active antiretroviral therapy (HAART) reduces the incidence of KS, and regimens that contain protease inhibitors (PIs) may be particularly effective. Objective To determine whether PI-based HAART regimens may more effectively inhibit HHV-8 shedding compared to regimens without PIs. Study design Prospective, observational study of 142 HIV-1 and HHV-8 co-infected men conducted in Seattle, Washington. Quantitative HHV-8 PCR testing was performed on daily swabs of the oropharynx, the primary site of HHV-8 replication. Associations between antiretroviral regimen and detection of HHV-8 DNA in swabs were evaluated using generalized estimating equations. Results HHV-8 DNA was detected in 3,016 (26%) of 11,608 specimens collected. PI-based HAART was associated with a statistically significantly lower frequency of detection (RR 0.2; 95% CI 0.1 to 0.5) compared to ART-naïve persons, whereas HAART without a PI was not (RR 0.7; 95% CI 0.4 to 1.3). Compared to ART-naïve persons, there was also a trend toward lower quantities of HHV-8 detected during treatment with HAART regimens that contained a PI. These associations between PIs and measures of HHV-8 shedding could not be attributed to use of nelfinavir, which inhibits HHV-8 replication in vitro, and were independent of CD4 count and HIV plasma viral load (VL). Conclusions HAART regimens that contain PIs appear to decrease HHV-8 shedding compared to NNRTIs. Further study of PI-based HAART is warranted to determine the optimal regimens for prevention and treatment of KS. PMID:24698158

  18. AIDS in Brazilian children: history, surveillance, antiretroviral therapy, and epidemiologic transition, 1984-2008.

    PubMed

    Ramos, Alberto Novaes; Matida, Luiza Harunari; Hearst, Norman; Heukelbach, Jorg

    2011-04-01

    We present a systematic review of historical, political, and epidemiologic aspects of AIDS in Brazilian children. Over 25 years, Brazil has developed different strategies to control AIDS in children. Three revisions of criteria for defining AIDS cases in children and nine national guidelines on antiretroviral therapy administration for management of HIV infection were published. These guidelines represent important progress, including aspects of HIV/AIDS surveillance, antiretroviral treatment, opportunistic conditions, prophylaxis, and laboratory testing. Brazil has significantly expanded access to free therapy with different classes of antiretroviral drugs. Initially focusing on treatment for HIV and opportunistic conditions, the scope of treatment guidelines gradually expanded to comprehensive health care for children and adolescents. From 1996 to 2008, the number of AIDS cases and deaths in children has been reduced by 67% and 65%, respectively, as a result of different strategies to prevent mother-to-child transmission of HIV and highly active antiretroviral therapy administration to infected children. Improved morbidity, mortality, and survival of Brazilian children with AIDS demonstrate clear benefits of adopting a policy of free and universal access to antiretroviral drugs associated with comprehensive care. However, important issues remain to be resolved, mainly concerning social, operational, and regional inequalities in coverage and quality of care, and epidemiological surveillance in different regions of the country. This broad review shows that the overall situation of pediatric AIDS in Brazil represents an incomplete process of epidemiologic and demographic transition, with the coexistence of old and new clinical and epidemiologic challenges.

  19. [Infections with human immunodeficiency viruses. Part II: Antiretroviral drugs, therapeutic options, and diagnostics].

    PubMed

    Stock, Ingo

    2011-07-01

    Infections with the human immunodeficiency virus 1 (HIV- 1) lead to the acquired immunodeficiency syndrome (AIDS), resulting in the establishment of a wide range of severe opportunistic infections. Since the introduction of the highly active antiretroviral therapy (HAART) into the treatment of HIV infections, in many cases a delayed appearance of AIDS-defining diseases is achievable. Life expectancy of antiretrovirally treated HIV-infected people applying HAART could be considerably extended and now resembles that of several other chronic diseases. For the initial treatment of HIV-1 infection, an adjunction with three antiretroviral agents is generally used. In most cases, the application of two nucleoside or nucleotide reverse transcriptase inhibitors (NRTI) together with a non-nucleoside reverse transcriptase inhibitor (NNRTI), a protease inhibitor (PI) or an integrase inhibitor (II) is recommended. Before and during antiretroviral treatment, antiretroviral drug resistances, individual tolerance profiles and the needs of the individual patient, as well as several interactions with other drugs have to be considered. Diagnostics of HIV infection is based upon the proof of specific antibodies.

  20. Once-daily antiretroviral therapy in a cohort of HIV-infected children and adolescents.

    PubMed

    Jiménez-Montero, Beatriz; Beceiro, José; de José-Gómez, M Isabel; González-Tomé, M Isabel; Gurbindo-Gutierrez, Dolores; Martínez-Pérez, Jorge; Mellado-Peña, M José; Navarro-Gómez, M Luisa; Roa-Francia, Miguel A; Rojo-Conejo, Pablo; Saavedra-Lozano, Jesús; Jiménez de Ory, Santiago; Ramos-Amador, José T

    2014-10-01

    We evaluated the evolution over time of once-daily antiretroviral therapy in HIV-infected children and its relationship with adherence. An increase on the prevalence of once-daily antiretroviral therapy was observed over time (from 0.9% in 2002 to 44.2% in 2011). There was no difference in adherence regarding once-daily or BID regimens in 2011. Adherence was related to age and pill burden.

  1. Kinetics of the viral cycle influence pharmacodynamics of antiretroviral therapy.

    PubMed

    Sedaghat, Ahmad R; Wilke, Claus O

    2011-09-12

    More and more antiretroviral therapies are being developed for treatment of HIV infection. The in-vivo efficacy of these drugs is commonly predicted based on in-vitro measures of antiviral effect. One primary in-vitro measure is the IC50, the amount of drug required for 50% inhibition of viral replication. We have previously shown that HIV life-cycle kinetics impact clinically observed HIV viral dynamics. Here we present a mathematical model of how they affect the pharmacodynamics of antiretroviral drugs. We find that experimentally measured antiretroviral IC50s are determined by three factors: (i) intrinsic drug properties (e.g. drug-target binding), (ii) kinetics of the HIV life cycle, and (iii) kinetics of drug-inhibited infected cells. Our model predicts that the IC50 is a declining function of the duration of the drug-susceptible stage in the host cell. We combine our model with known viral life-cycle kinetics to derive a measure of intrinsic properties, reflecting drug action, for known antiretroviral drugs from previously measured IC50s. We show that this measure of intrinsic drug property correlates very well with in vitro-measured antiviral activity, whereas experimentally measured IC50 does not. Our results have implications for understanding pharmacodynamics of and improving activity of antiretroviral drugs. Our findings predict that drug activity can be improved through co-administration of synergistic drugs that delay the viral life cycle but are not inhibitory by themselves. Moreover, our results may easily extend to treatment of other pathogens.

  2. Antiretroviral therapy reduces neurodegeneration in human immunodeficiency virus infection

    PubMed Central

    Bryant, Alex K.; Ellis, Ronald J.; Umlauf, Anya; Gouaux, Ben; Soontornniyomkij, Virawudh; Letendre, Scott L.; Achim, Cristian L.; Masliah, Eliezer; Grant, Igor; Moore, David J.

    2015-01-01

    Objective To determine the effect of virally-suppressive antiretroviral therapy on cortical neurodegeneration and associated neurocognitive impairment. Design Retrospective, postmortem observational study. Methods Clinical neuropsychological and postmortem neuropathology data were analyzed in 90 human immunodeficiency virus-infected volunteers from the general community who had never undergone antiretroviral therapy (n=7, “naïve”) or who had undergone antiretroviral therapy and whose plasma viral load was detectable (n = 64 “unsuppressed”) or undetectable (n = 19, “suppressed”) at the last clinical visit prior to death. Subjects were predominately male (74/90, 82%) with a mean age of 44.7 years (SD 9.8). Cortical neurodegeneration was quantified by measuring microtubule-associated protein (MAP2) and synaptophysin (SYP) density in midfrontal cortex tissue sections. Results The suppressed group had higher SYP density than the naïve group (p = 0.007) and higher MAP2 density than the unsuppressed group (p = 0.04). The suppressed group had lower odds of human immunodeficiency virus-associated neurocognitive disorders than naïve (OR 0.07, p = 0.03). Higher SYP was associated with lower likelihood of human immunodeficiency virus-associated neurocognitive disorders in univariable (OR 0.8, p=0.03) and multivariable models after controlling for antiretroviral treatment and brain human immunodeficiency virus p24 protein levels (OR 0.72, p=0.01). Conclusions We conclude that virally suppressive antiretroviral treatment protects against cortical neurodegeneration. Further, we find evidence supporting the causal chain from treatment-mediated peripheral and central nervous system viral load suppression to reduced neurodegeneration and improved neurocognitive outcomes. PMID:25686681

  3. 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

    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

    2016-06-01

    To illustrate an approach to compare CD4 cell count and HIV-RNA monitoring strategies in HIV-positive individuals on antiretroviral therapy (ART). 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. 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. 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. 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.

  4. 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

  5. High prevalence of HIV-1 drug resistance among patients on first-line antiretroviral treatment in Lomé, Togo

    PubMed Central

    2011-01-01

    Background With widespread use of antiretroviral (ARV) drugs in Africa, one of the major potential challenges is the risk of emergence of ARV drug-resistant HIV strains. Our objective is to evaluate the virological failure and genotypic drug-resistance mutations in patients receiving first-line highly active antiretroviral therapy (HAART) in routine clinics that use the World Health Organization public health approach to monitor antiretroviral treatment (ART) in Togo. Methods Patients on HAART for one year (10-14 months) were enrolled between April and October 2008 at three sites in Lomé, the capital city of Togo. Plasma viral load was measured with the NucliSENS EasyQ HIV-1 assay (Biomérieux, Lyon, France) and/or a Generic viral load assay (Biocentric, Bandol, France). Genotypic drug-resistance testing was performed with an inhouse assay on plasma samples from patients with viral loads of more than 1000 copies/ml. CD4 cell counts and demographic data were also obtained from medical records. Results A total of 188 patients receiving first-line antiretroviral treatment were enrolled, and 58 (30.8%) of them experienced virologic failure. Drug-resistance mutations were present in 46 patients, corresponding to 24.5% of all patients enrolled in the study. All 46 patients were resistant to non-nucleoside reverse-transcriptase inhibitors (NNRTIs): of these, 12 were resistant only to NNRTIs, 25 to NNRTIs and lamivudine/emtricitabine, and eight to all three drugs of their ARV regimes. Importantly, eight patients were already predicted to be resistant to etravirine, the new NNRTI, and three patients harboured the K65R mutation, inducing major resistance to tenofovir. Conclusions In Togo, efforts to provide access to ARV therapy for infected persons have increased since 2003, and scaling up of ART started in 2007. The high number of resistant strains observed in Togo shows clearly that the emergence of HIV drug resistance is of increasing concern in countries where ART is

  6. Antiretroviral prophylaxis of perinatal HIV-1 transmission and the potential impact of antiretroviral resistance.

    PubMed

    Nolan, Monica; Fowler, Mary Glenn; Mofenson, Lynne M

    2002-06-01

    Since 1994, trials of zidovudine, zidovudine and lamivudine, and nevirapine have demonstrated that these antiretroviral drugs can substantially reduce the risk of perinatal HIV-1 transmission. With reductions in drug price, identification of simple, effective antiretroviral regimens to prevent perinatal HIV-1 transmission, and an increasing international commitment to support health care infrastructure, antiretrovirals for both perinatal HIV-1 prevention and HIV-1 treatment will likely become more widely available to HIV-1-infected persons in resource-limited countries. In the United States, widespread antiretroviral usage has been associated with increased antiretroviral drug resistance. This raises concern that drug resistance may reduce the effectiveness of perinatal antiretroviral prophylaxis as well as therapeutic intervention strategies. The purpose of this article is to review what is known about resistance and risk of perinatal HIV transmission, assess the interaction between antiretroviral resistance and the prevention of perinatal HIV-1 transmission, and discuss implications for current global prevention and treatment strategies.

  7. Systematic Review of Antiretroviral-Associated Lipodystrophy: Lipoatrophy, but Not Central Fat Gain, Is an Antiretroviral Adverse Drug Reaction

    PubMed Central

    de Waal, Reneé; Cohen, Karen; Maartens, Gary

    2013-01-01

    Background Lipoatrophy and/or central fat gain are observed frequently in patients on antiretroviral therapy (ART). Both are assumed to be antiretroviral adverse drug reactions. Methods We conducted a systematic review to determine whether fat loss or gain was more common in HIV-infected patients on ART than in uninfected controls; was associated with specific antiretrovirals; and would reverse after switching antiretrovirals. Results Twenty-seven studies met our inclusion criteria. One cohort study reported more lipoatrophy, less subcutaneous fat gain, but no difference in central fat gain in HIV-infected patients on ART than in controls. Randomised controlled trials (RCTs) showed more limb fat loss (or less fat gain) with the following regimens: stavudine (versus other nucleoside reverse transcriptase inhibitors (NRTIs)); efavirenz (versus protease inhibitors (PIs)); and NRTI-containing (versus NRTI-sparing). RCTs showed increased subcutaneous fat after switching to NRTI-sparing regimens or from stavudine/zidovudine to abacavir/tenofovir. There were no significant between-group differences in trunk and/or visceral fat gain in RCTs of various regimens, but results from efavirenz versus PI regimens were inconsistent. There was no significant between-group differences in central fat gain in RCTs switched to NRTI-sparing regimens, or from PI-containing regimens. Conclusions There is clear evidence of a causal relationship between NRTIs (especially thymidine analogues) and lipoatrophy, with concomitant PIs possibly having an ameliorating effect or efavirenz causing additive toxicity. By contrast, central fat gain appears to be a consequence of treating HIV infection, because it is not different from controls, is not linked to any antiretroviral class, and doesn't improve on switching. PMID:23723990

  8. Immune restoration disease after antiretroviral therapy.

    PubMed

    French, Martyn A; Price, Patricia; Stone, Shelley F

    2004-08-20

    Suppression of HIV replication by highly active antiretroviral therapy (HAART) often restores protective pathogen-specific immune responses, but in some patients the restored immune response is immunopathological and causes disease [immune restoration disease (IRD)]. Infections by mycobacteria, cryptococci, herpesviruses, hepatitis B and C virus, and JC virus are the most common pathogens associated with infectious IRD. Sarcoid IRD and autoimmune IRD occur less commonly. Infectious IRD presenting during the first 3 months of therapy appears to reflect an immune response against an active (often quiescent) infection by opportunistic pathogens whereas late IRD may result from an immune response against the antigens of non-viable pathogens. Data on the immunopathogenesis of IRD is limited but it suggests that immunopathogenic mechanisms are determined by the pathogen. For example, mycobacterial IRD is associated with delayed-type hypersensitivity responses to mycobacterial antigens whereas there is evidence of a CD8 T-cell response in herpesvirus IRD. Furthermore, the association of different cytokine gene polymorphisms with mycobacterial or herpesvirus IRD provides evidence of different pathogenic mechanisms as well as indicating a genetic susceptibility to IRD. Differentiation of IRD from an opportunistic infection is important because IRD indicates a successful, albeit undesirable, effect of HAART. It is also important to differentiate IRD from drug toxicity to avoid unnecessary cessation of HAART. The management of IRD often requires the use of anti-microbial and/or anti-inflammatory therapy. Investigation of strategies to prevent IRD is a priority, particularly in developing countries, and requires the development of risk assessment methods and diagnostic criteria.

  9. 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

  10. Mutations in the Reverse Transcriptase and Protease Genes of Human Immunodeficiency Virus-1 from Antiretroviral Naïve and Treated Pediatric Patients

    PubMed Central

    Bure, Dinesh; Makhdoomi, Muzamil A.; Lodha, Rakesh; Prakash, Somi Sankaran; Kumar, Rajesh; Parray, Hilal A.; Singh, Ravinder; Kabra, Sushil K.; Luthra, Kalpana

    2015-01-01

    The success of highly active antiretroviral therapy (HAART) is challenged by the emergence of resistance-associated mutations in human immunodeficiency virus-1 (HIV-1). In this study, resistance associated mutations in the reverse transcriptase (RT) and protease (PR) genes in antiretroviral therapy (ART) naïve and treated HIV-1 infected pediatric patients from North India were evaluated. Genotyping was successfully performed in 46 patients (30 ART naive and 16 treated) for the RT gene and in 53 patients (27 ART naive and 26 treated) for PR gene and mutations were identified using Stanford HIV Drug Resistance Database. A major drug resistant mutation in RT gene, L74I (NRTI), and two such mutations, K101E and G190A (NNRTI), were observed in two ART naïve patients, while M184V was detected in two ART treated patients. Overall, major resistance associated mutations in RT gene were observed in nine (30%) and seven (36%) of ART naïve and treated children respectively. Minor mutations were identified in PR gene in five children. Few non-clade C viral strains (≈30%) were detected, although subtype C was most predominant. The screening of ART naïve children for mutations in HIV-1 RT and protease genes, before and after initiation of ART is desirable for drug efficacy and good prognosis. PMID:25674767

  11. Mutations in the reverse transcriptase and protease genes of human immunodeficiency virus-1 from antiretroviral naïve and treated pediatric patients.

    PubMed

    Bure, Dinesh; Makhdoomi, Muzamil A; Lodha, Rakesh; Prakash, Somi Sankaran; Kumar, Rajesh; Parray, Hilal A; Singh, Ravinder; Kabra, Sushil K; Luthra, Kalpana

    2015-02-10

    The success of highly active antiretroviral therapy (HAART) is challenged by the emergence of resistance-associated mutations in human immunodeficiency virus-1 (HIV-1). In this study, resistance associated mutations in the reverse transcriptase (RT) and protease (PR) genes in antiretroviral therapy (ART) naïve and treated HIV-1 infected pediatric patients from North India were evaluated. Genotyping was successfully performed in 46 patients (30 ART naive and 16 treated) for the RT gene and in 53 patients (27 ART naive and 26 treated) for PR gene and mutations were identified using Stanford HIV Drug Resistance Database. A major drug resistant mutation in RT gene, L74I (NRTI), and two such mutations, K101E and G190A (NNRTI), were observed in two ART naïve patients, while M184V was detected in two ART treated patients. Overall, major resistance associated mutations in RT gene were observed in nine (30%) and seven (36%) of ART naïve and treated children respectively. Minor mutations were identified in PR gene in five children. Few non-clade C viral strains (≈30%) were detected, although subtype C was most predominant. The screening of ART naïve children for mutations in HIV-1 RT and protease genes, before and after initiation of ART is desirable for drug efficacy and good prognosis.

  12. Audiological and electrophysiological alterations in HIV-infected individuals subjected or not to antiretroviral therapy.

    PubMed

    Matas, Carla Gentile; Samelli, Alessandra Giannella; Magliaro, Fernanda Cristina Leite; Segurado, Aluisio

    2017-08-02

    The Human Immunodeficiency Virus (HIV) and infections related to it can affect multiple sites in the hearing system. The use of High-Activity Anti-Retroviral Therapy (HAART) can cause side effects such as ototoxicity. Thus, no consistent patterns of hearing impairment in adults with Human Immunodeficiency Virus / Acquired Immune Deficiency Syndrome have been established, and the problems that affect the hearing system of this population warrant further research. This study aimed to compare the audiological and electrophysiological data of Human Immunodeficiency Virus-positive patients with and without Acquired Immune Deficiency Syndrome, who were receiving High-Activity Anti-Retroviral Therapy, to healthy individuals. It was a cross-sectional study conducted with 71 subjects (30-48 years old), divided into groups: Research Group I: 16 Human Immunodeficiency Virus-positive individuals without Acquired Immunodeficiency Syndrome (not receiving antiretroviral treatment); Research Group II: 25 Human Immunodeficiency Virus-positive individuals with Acquired Immunodeficiency Syndrome (receiving antiretroviral treatment); Control Group: 30 healthy subjects. All individuals were tested by pure-tone air conduction thresholds at 0.25-8kHz, extended high frequencies at 9-20kHz, electrophysiological tests (Auditory Brainstem Response - ABR, Middle Latency Responses - MLR, Cognitive Potential - P300). Research Group I and Research Group II had higher hearing thresholds in both conventional and high frequency audiometry when compared to the control group, prolonged latency of waves I, III, V and interpeak I-V in Auditory Brainstem Response and prolonged latency of P300 Cognitive Potential. Regarding Middle Latency Responses, there was a decrease in the amplitude of the Pa wave of Research Group II compared to the Research Group I. Both groups with Human Immunodeficiency Virus had higher hearing thresholds when compared to healthy individuals (group exposed to antiretroviral

  13. Examining the production costs of antiretroviral drugs.

    PubMed

    Pinheiro, Eloan; Vasan, Ashwin; Kim, Jim Yong; Lee, Evan; Guimier, Jean Marc; Perriens, Joseph

    2006-08-22

    To present direct manufacturing costs and price calculations of individual antiretroviral drugs, enabling those responsible for their procurement to have a better understanding of the cost structure of their production, and to indicate the prices at which these antiretroviral drugs could be offered in developing country markets. Direct manufacturing costs and factory prices for selected first and second-line antiretroviral drugs were calculated based on cost structure data from a state-owned company in Brazil. Prices for the active pharmaceutical ingredients (API) were taken from a recent survey by the World Health Organization (WHO). The calculated prices for antiretroviral drugs are compared with quoted prices offered by privately-owned, for-profit manufacturers. The API represents the largest component of direct manufacturing costs (55-99%), while other inputs, such as salaries, equipment costs, and scale of production, have a minimal impact. The calculated prices for most of the antiretroviral drugs studied fall within the lower quartile of the range of quoted prices in developing country markets. The exceptions are those drugs, primarily for second-line therapy, for which the API is either under patent, in short supply, or in limited use in developing countries (e.g. abacavir, lopinavir/ritonavir, nelfinavir, saquinavir). The availability of data on the cost of antiretroviral drug production and calculation of factory prices under a sustainable business model provide benchmarks that bulk purchasers of antiretroviral drugs could use to negotiate lower prices. While truly significant price decreases for antiretroviral drugs will depend largely on the future evolution of API prices, the present study demonstrates that for several antiretroviral drugs price reduction is currently possible. Whether or not these reductions materialize will depend on the magnitude of indirect cost and profit added by each supplier over the direct production costs. The ability to

  14. Antiretroviral medication adherence and the development of class-specific antiretroviral resistance

    PubMed Central

    Gardner, Edward M.; Burman, William J.; Steiner, John F.; Anderson, Peter L.; Bangsberg, David R.

    2009-01-01

    Objective: To assess the association between antiretroviral adherence and the development of class-specific antiretroviral medication resistance. Design and methods: Literature and conference abstract review of studies assessing the association between adherence to antiretroviral therapy and the development of antiretroviral medication resistance. Results: Factors that determine class-specific adherence–resistance relationships include antiretroviral regimen potency, viral fitness or more specifically the interplay between the fold-change in resistance and fold-change in fitness caused by drug resistance mutations, and the genetic barrier to antiretroviral resistance. During multidrug therapy, differential drug exposure increases the likelihood of developing resistance. In addition, antiretroviral medications with higher potency and higher genetic barriers to resistance decrease the incidence of resistance for companion antiretroviral medications at all adherence levels. Conclusion: Knowledge of class-specific adherence–resistance relationships may help clinicians and patients tailor therapy to match individual patterns of adherence in order to minimize the development of resistance at failure. In addition, this information may guide the selection of optimal drug combinations and regimen sequences to improve the durability of antiretroviral therapy. PMID:19381075

  15. Initiation of antiretroviral therapy and viral suppression after home HIV testing and counselling in KwaZulu-Natal, South Africa, and Mbarara district, Uganda: a prospective, observational intervention study

    PubMed Central

    Barnabas, Ruanne V.; van Rooyen, Heidi; Tumwesigye, Elioda; Murnane, Pamela M.; Baeten, Jared M.; Humphries, Hilton; Turyamureeba, Bosco; Joseph, Philip; Krows, Meighan; Hughes, James P; Celum, Connie

    2014-01-01

    Objective Antiretroviral therapy (ART) significantly decreases HIV-associated morbidity, mortality, and HIV transmission through HIV viral load suppression. In high HIV prevalence settings, outreach strategies are needed to find asymptomatic HIV positive persons, link them to HIV care and ART, and achieve viral suppression. Methods We conducted a prospective intervention study in two rural communities in KwaZulu-Natal, South Africa, and Mbabara district, Uganda. The intervention included home HIV testing and counseling (HTC), point-of-care CD4 count testing for HIV positive persons, referral to care, and one month then quarterly lay counselor follow-up visits. The outcomes at 12 months were linkage to care, and ART initiation and viral suppression among HIV positive persons eligible for ART (CD4≤350 cells/μL). Findings 3,393 adults were tested for HIV (96% coverage), of whom 635 (19%) were HIV positive. At baseline, 36% of HIV positive persons were newly identified (64% were previously known to be HIV positive) and 40% were taking ART. By month 12, 619 (97%) of HIV positive persons visited an HIV clinic, and of 123 ART eligible participants, 94 (76%) initiated ART by 12 months. Of the 77 participants on ART by month 9, 59 (77%) achieved viral suppression by month 12. Among all HIV positive persons, the proportion with viral suppression (<1,000 copies/mL) increased from 50% to 65% (p=<0.001) at 12 months. Interpretation Community-based HTC in rural South Africa and Uganda achieved high testing coverage and linkage to care. Among those eligible for ART, a high proportion initiated ART and achieved viral suppression, indicating high adherence. Implementation of this HTC approach by existing community health workers in Africa should be evaluated to determine effectiveness and costs. PMID:25601912

  16. Structural normalization of the lymphoid tissue in asymptomatic HIV-infected patients after 48 weeks of potent antiretroviral therapy.

    PubMed

    Macías, J; Japón, M A; Leal, M; Sáez, C; Pineda, J A; Segura, D I; Ortega, J; Lissen, E

    2001-12-07

    The hallmark of HIV infection is the involution and destruction of lymphoid tissue. However, very little information exists on the effect of highly active antiretroviral therapy (HAART) on lymphoid tissue structure. To evaluate the effect of a HAART regimen after 48 weeks on the architecture and cell regeneration of tonsil lymphoid tissue in HIV-infected patients with CD4 T cell counts > or = 500/microl. From June 1997 to February 1998 all asymptomatic HIV-infected patients with CD4 T cell counts > or = 500/microl seen at our unit were offered quadruple antiretroviral therapy. Tonsil biopsies were obtained at baseline and at 48 weeks. Tonsil tissue sections were examined to evaluate structural and immunohistochemical changes by two blinded and independent pathologists. Cell numbers were counted for selected markers in T-dependent zones. Eleven patients were evaluable, six were excluded because of insufficient or inadequate sampling in at least one of the biopsies. Cellular depletion, plasma cell accumulation and prominent vessels were observed in all cases; three excluded patients with evaluable baseline biopsies showed similar tissue lesions. Follow-up biopsies demonstrated some degree of improvement in all patients. Germinal centres appeared in seven cases that were not seen at baseline. CD4 cell counts increased and CD8 cell counts decreased significantly in lymphoid tissue. An increase in CD45RA+ cells was observed; however, the proportion of CD45+Ki67+ cells did not differ between baseline and 48 weeks. This study shows an unexpected range of moderate to severe lymphoid tissue lesions in mildly immunosuppressed HIV-infected patients, which was partly restored after 48 weeks of HAART.

  17. Access to antiretroviral treatment, incidence of sustained therapy interruptions, and risk of clinical events according to sex: evidence from the I.Co.N.A. Study.

    PubMed

    Murri, Rita; Lepri, Alessandro Cozzi; Phillips, Andrew N; Girardi, Enrico; Nasti, Guglielmo; Ferrara, Sergio; Mura, Maria Stella; Mussini, Cristina; Petrelli, Enzo; Arlotti, Massimo; De Stefano, Carlo; Vigano, Paola; Novati, Roberto; Cargnel, Antonietta; Monforte, Antonella D'Arminio

    2003-10-01

    Objectives of the study were to assess the differences between sexes in the likelihood of starting antiretroviral therapy (ART), in rates of sustained discontinuation from highly active antiretroviral therapy (HAART), and in clinical progression. In a multicenter cohort study (I.Co.N.A. Study), 2323 men and 1335 women previously naive to antiretrovirals were enrolled. As of September 2002, 807 women and 1480 men started ART. The median time to starting ART was 28 weeks for women and 17 weeks for men (P = 0.0003 by log-rank test). This difference was no longer significant after adjusting for either HIV RNA (P = 0.21) or CD4 count (P = 0.28) at enrollment. Women tend to start HAART less frequently than mono/dual ART after adjusting for potential confounders (odds ratio = 0.78, 95% confidence interval [CI]: 0.60-1.01; P = 0.06). Women who started HAART were 1.4 times more likely than men (95% CI: 1.00-1.99; P = 0.05) to interrupt at least 1 drug because of toxicity. Twenty-one percent of women and 19% of men interrupted HAART altogether for more than 3 months (P = 0.3). Clinical progression was observed in 53 women (22.6%) and 137 men (23.4%; P = 0.56). Risk of developing a clinical event was found to be no different between women and men (relative hazard = 0.84, 95% CI: 0.56-1.26; P = 0.40).

  18. Managing issues related to antiretroviral therapy.

    PubMed

    Lesho, Emil P; Gey, Daniela C

    2003-08-15

    Antiretroviral regimens are complicated and difficult for patients to follow, and they can have serious side effects, such as osteonecrosis and bone demineralization. Protease inhibitor therapy has been associated with hyperlipidemia, hyperglycemia, gastrointestinal symptoms, and body-fat distribution abnormalities. Nonnucleoside reverse transcriptase inhibitors can cause rashes and hepatotoxicity, and nucleoside reverse transcriptase inhibitors can cause lactic acidosis, hypersensitivity reactions, neuropathies, pancreatitis, anemia, and neutropenia. Malabsorption can occur if antiretroviral agents are taken improperly with regard to meals or if they are taken with certain other drugs or herbal remedies. Some commonly prescribed drugs can cause dangerous drug toxicities if they are taken by patients who are also taking certain antiretroviral medications. Suboptimal exposure to antiretrovirals because of noncompliance or malabsorption can result in viral resistance and loss of future treatment options.

  19. CROI 2014: Advances in antiretroviral therapy.

    PubMed

    Taylor, Barbara S; Shalev, Noga; Wilkin, Timothy J

    2014-05-01

    The 2014 Conference on Retroviruses and Opportunistic Infections (CROI) highlighted important advances in antiretroviral therapy, with an emphasis on HIV eradication strategies. Follow-up information about the Mississippi baby who remains free of HIV infection off antiretroviral therapy was presented, and a second baby and 1 adult may also have been cured with very early initiation of antiretroviral therapy. The HIV care cascade was again a major focus of the conference. Investigators from around the world presented data on the implementation, and limitations, of the care cascade paradigm. Scale-up of antiretroviral therapy continues and a number of presentations featured optimal ways to measure the impact of these efforts by applying lessons from implementation science and health care economics. Encouraging results from expanded prevention of mother-to-child transmission programs, especially Option B+, were highlighted. Extensive data on transmitted (primary) drug resistance in the United States and Europe were presented.

  20. [Antiretroviral therapy in HIV-infected children and adolescents: lessons learned in 30 years of the epidemic].

    PubMed

    Bazin, Gabriela Ricordi; Gaspar, Mariza Curto Saavedra; Silva, Nicole Carvalho Xavier Micheloni da; Mendes, Carolina da Costa; Oliveira, Cora Pichler de; Bastos, Leonardo Soares; Cardoso, Claudete Aparecida Araújo

    2014-04-01

    This study aims to evaluate antiretroviral therapy in children and adolescents with AIDS. We selected 247 abstracts published from 1983 to 2013, collected from the PubMed and LILACS databases. Sixty-nine articles were selected. Attention to research in the pediatric age bracket in 30 years of the epidemic is explained by the age group's immunological characteristics, since AIDS progresses faster in children than in adults. Recent studies focus on the initiation of highly active antiretroviral therapy before the onset of symptoms. Early introduction of combination antiretroviral therapy has been implemented effectively and safely in populations with limited resources, leading to significantly improved survival. The current challenge is to manage a chronic disease with acute complications. New studies should focus on population specificities and identify the individual needs of pediatric patients.

  1. New Antiretroviral Therapies for Pediatric HIV Infection

    PubMed Central

    Morris, Jennifer L.; Kraus, Donna M.

    2005-01-01

    Human immunodeficiency virus (HIV) infection and acquired immunodeficiency syndrome affect millions of children worldwide. The development of antiretroviral therapy has significantly improved the morbidity and mortality of pediatric patients infected with HIV. Currently, 4 classes of antiretroviral agents exist: nucleoside / nucleotide reverse transcriptase inhibitors, non-nucleoside reverse transcriptase inhibitors, protease inhibitors, and entry inhibitors. A total of 21 single-entity antiretroviral agents and 4 co-formulated antiretroviral products hold Food and Drug Administration (FDA) approval for treatment of HIV-1 infection. However, not all of these agents are indicated for use in patients less than 18 years of age. Since the year 2000, 7 new antiretroviral agents (atazanavir, emtricitabine, enfuvirtide, fosamprenavir, lopinavir/ritonavir, tenofovir, and tipranavir) have been approved by the FDA for use in adult patients as part of combination therapy for the treatment of HIV-1 infection. Although only 3 of these newer agents (emtricitabine, enfuvirtide, and lopinavir/ritonavir) are currently FDA approved for use in pediatric patients, pediatric clinical studies of the other 4 new agents are currently underway. The purpose of this article is to review these 7 new antiretroviral agents and describe their roles in the treatment of pediatric HIV infection. For each drug, the following information will be addressed: FDA-approved indication and age groups, clinical efficacy, pharmacokinetics, adverse drug reactions, clinically relevant drug interactions, pediatric and adult dosing, dosage forms, administration, and place in the treatment of pediatric HIV infection. PMID:23118639

  2. Antiretroviral Treatment 2010: Progress and Controversies

    PubMed Central

    Gulick, Roy M.

    2011-01-01

    Effective antiretroviral therapy (ART) changes the clinical course of HIV infection. There are 25 antiretroviral drugs approved for the treatment of HIV infection, and current antiretroviral drug regimens are highly effective, convenient, and relatively nontoxic. ART regimens should be chosen in consideration of a patient’s particular clinical situation. Successful treatment is associated with durable suppression of HIV viremia over years, and consequently, ART reduces the risk of clinical progression. In fact, current models estimate that an HIV-infected individual appropriately treated with antiretroviral drugs has a life expectancy that approaches that of the general HIV-uninfected population, although some patient groups such as injection drug users do less well. Despite these advances, continued questions about ART persist: What is the optimal time to start ART? What is the best regimen to start? When is the optimal time to change ART? What is the best regimen to change to? In addition, newer antiretroviral agents are in development, both in existing classes and in new classes such as the CD4 receptor attachment inhibitors and the maturation inhibitors. Further research will help optimize current antiretroviral treatments and strategies. PMID:21045599

  3. Drug interactions between hormonal contraceptives and antiretrovirals.

    PubMed

    Nanda, Kavita; Stuart, Gretchen S; Robinson, Jennifer; Gray, Andrew L; Tepper, Naomi K; Gaffield, Mary E

    2017-04-24

    To summarize published evidence on drug interactions between hormonal contraceptives and antiretrovirals. Systematic review of the published literature. We searched PubMed, POPLINE, and EMBASE for peer-reviewed publications of studies (in any language) from inception to 21 September 2015. We included studies of women using hormonal contraceptives and antiretrovirals concurrently. Outcomes of interest were effectiveness of either therapy, toxicity, or pharmacokinetics. We used standard abstraction forms to summarize and assess strengths and weaknesses. Fifty reports from 46 studies were included. Most antiretrovirals whether used for therapy or prevention, have limited interactions with hormonal contraceptive methods, with the exception of efavirenz. Although depot medroxyprogesterone acetate is not affected, limited data on implants and combined oral contraceptive pills suggest that efavirenz-containing combination antiretroviral therapy may compromise contraceptive effectiveness of these methods. However, implants remain very effective despite such drug interactions. Antiretroviral plasma concentrations and effectiveness are generally not affected by hormonal contraceptives. Women taking antiretrovirals, for treatment or prevention, should not be denied access to the full range of hormonal contraceptive options, but should be counseled on the expected rates of unplanned pregnancy associated with all contraceptive methods, in order to make their own informed choices.

  4. Drug interactions between hormonal contraceptives and antiretrovirals

    PubMed Central

    Nanda, Kavita; Stuart, Gretchen S.; Robinson, Jennifer; Gray, Andrew L.; Tepper, Naomi K.; Gaffield, Mary E.

    2017-01-01

    Objective: To summarize published evidence on drug interactions between hormonal contraceptives and antiretrovirals. Design: Systematic review of the published literature. Methods: We searched PubMed, POPLINE, and EMBASE for peer-reviewed publications of studies (in any language) from inception to 21 September 2015. We included studies of women using hormonal contraceptives and antiretrovirals concurrently. Outcomes of interest were effectiveness of either therapy, toxicity, or pharmacokinetics. We used standard abstraction forms to summarize and assess strengths and weaknesses. Results: Fifty reports from 46 studies were included. Most antiretrovirals whether used for therapy or prevention, have limited interactions with hormonal contraceptive methods, with the exception of efavirenz. Although depot medroxyprogesterone acetate is not affected, limited data on implants and combined oral contraceptive pills suggest that efavirenz-containing combination antiretroviral therapy may compromise contraceptive effectiveness of these methods. However, implants remain very effective despite such drug interactions. Antiretroviral plasma concentrations and effectiveness are generally not affected by hormonal contraceptives. Conclusion: Women taking antiretrovirals, for treatment or prevention, should not be denied access to the full range of hormonal contraceptive options, but should be counseled on the expected rates of unplanned pregnancy associated with all contraceptive methods, in order to make their own informed choices. PMID:28060009

  5. Health and Federal Budgetary Effects of Increasing Access to Antiretroviral Medications for HIV by Expanding Medicaid

    PubMed Central

    Kahn, James G.; Haile, Brain; Kates, Jennifer; Chang, Sophia

    2001-01-01

    Objectives. This study modeled the health and federal fiscal effects of expanding Medicaid for HIV-infected people to improve access to highly active antiretroviral therapy. Methods. A disease state model of the US HIV epidemic, with and without Medicaid expansion, was used. Eligibility required a CD4 cell count less than 500/mm3 or viral load greater than 10 000, absent or inadequate medication insurance, and annual income less than $10 000. Two benefits were modeled, “full” and “limited” (medications, outpatient care). Federal spending for Medicaid, Medicare, AIDS Drug Assistance Program, Supplemental Security Income, and Social Security Disability Insurance were assessed. Results. An estimated 38 000 individuals would enroll in a Medicaid HIV expansion. Over 5 years, expansion would prevent an estimated 13 000 AIDS diagnoses and 2600 deaths and add 5816 years of life. Net federal costs for all pro