Fatigue among HIV-infected patients in the era of highly active antiretroviral therapy.

PubMed

Henderson, M; Safa, F; Easterbrook, P; Hotopf, M

2005-09-01

To describe the prevalence of operationally defined fatigue in an ethnically diverse HIV-infected population in south London, and to examine the association of fatigue with demographic characteristics, stage of disease, antiretroviral therapy and psychological factors. A descriptive comparative cross-sectional study of HIV-infected patients attending a London HIV clinic over a 5-month period in 2002 was performed. Demographic and clinical data were obtained from the local database. Participants completed four self-administered questionnaires-the Chalder Fatigue Scale (CFS), a measure of physical and mental fatigue; the General Health Questionnaire (GHQ-12) to detect anxiety and depression; the Medical Outcomes Study 36-Item Short-Form Health Survey (SF-36) to measure functional status, and the Illness Perception Questionnaire (IPQ). Fatigue 'cases' were defined as those scoring at least 4 on the CFS. Multivariate logistic regression was used to identify factors associated with the presence of fatigue. Two hundred and five patients were approached and 148 (72%) agreed to participate. Overall, 65% of patients were defined as fatigued. Significant psychological distress on the GHQ-12, functional impairment on the SF-36 and a higher CD4 count were all independently associated with the presence of fatigue. There was no association with use of antiretroviral therapy or demographic characteristics. The presence of fatigue in HIV-infected patients is most strongly associated with psychological factors and not with more advanced HIV disease or the use of highly active antiretroviral therapy. This highlights the importance of investigation and management of underlying depression and anxiety in patients presenting with fatigue.

Adherence to Highly Active Antiretroviral Treatment in HIV-Infected Rwandan Women

PubMed Central

Musiime, Stephenson; Muhairwe, Fred; Rutagengwa, Alfred; Mutimura, Eugene; Anastos, Kathryn; Hoover, Donald R.; Qiuhu, Shi; Munyazesa, Elizaphane; Emile, Ivan; Uwineza, Annette; Cowan, Ethan

2011-01-01

Background Scale-up of highly active antiretroviral treatment therapy (HAART) programs in Rwanda has been highly successful but data on adherence is limited. We examined HAART adherence in a large cohort of HIV+ Rwandan women. Methods The Rwanda Women's Interassociation Study Assessment (RWISA) was a prospective cohort study that assessed effectiveness and toxicity of ART. We analyzed patient data 12±3 months after HAART initiation to determine adherence rates in HIV+ women who had initiated HAART. Results Of the 710 HIV+ women at baseline, 490 (87.2%) initiated HAART. Of these, 6 (1.2%) died within 12 months, 15 others (3.0%) discontinued the study and 80 others (19.0%) remained in RWISA but did not have a post-HAART initiation visit that fell within the 12±3 month time points leaving 389 subjects for analysis. Of these 389, 15 women stopped their medications without being advised to do so by their doctors. Of the remaining 374 persons who reported current HAART use 354 completed the adherence assessment. All women, 354/354, reported 100% adherence to HAART at the post-HAART visit. The high self-reported level of adherence is supported by changes in laboratory measures that are influenced by HAART. The median (interquartile range) CD4 cell count measured within 6 months prior to HAART initiation was 185 (128, 253) compared to 264 (182, 380) cells/mm3 at the post-HAART visit. Similarly, the median (interquartile range) MCV within 6 months prior to HAART initiation was 88 (83, 93) fL compared to 104 (98, 110) fL at the 12±3 month visit. Conclusion Self-reported adherence to antiretroviral treatment 12±3 months after initiating therapy was 100% in this cohort of HIV-infected Rwandan women. Future studies should explore country-specific factors that may be contributing to high levels of adherence to HAART in this population. PMID:22114706

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.

[Efficacy of highly active antiretroviral therapy for childhood acquired immunodeficiency syndrome].

PubMed

Hao, Jin-Li; Wang, Bao-Jin; Baptiste, Jean

2010-11-01

To investigate the efficacy of highly active antiretroviral therapy (HAART) for acquired immunodeficiency syndrome (AIDS) in children. The clinical data of 38 children (2-15 years old) with AIDS from a region of Rwanda and who had received HAART were retrospectively reviewed. All of 13 children with anemia showed improved anemia symptoms after HAART. The hemoglobin contents returned to normal levels in 12 children with mild or moderate anemia. CD4 T lymphocytes increased by 24%-1 181% in 5 out of 6 cases with severe immunodeficiency after HAART. During the HAART, the weight gain averaged 2.3 kg yearly. The growth and development in 5 out of 8 children with delayed growth restored the levels of normal children of the same age after HAART. HAART can improve the health status in children with AIDS and is effective for childhood AIDS.

HIV, human papillomavirus, and cervical neoplasia and cancer in the era of highly active antiretroviral therapy.

PubMed

De Vuyst, Hugo; Lillo, Flavia; Broutet, Nathalie; Smith, Jennifer S

2008-11-01

The objective of this study was to review the literature on the epidemiological association between human papillomavirus (HPV), HIV, and cervical neoplasia, and the impact of highly active antiretroviral therapy (HAART) on this association. MEDLINE was searched using the terms 'human papillomavirus', 'HPV', 'HIV', 'cervix', 'neoplasm', and 'antiretroviral' to identify articles published before December 2006. HIV-infection was strongly associated with a higher prevalence, incidence, and persistence of HPV infection and correlated with prevalence, incidence, persistence, and progression of squamous intraepithelial lesions. The association between HIV and invasive cervical carcinoma has been more difficult to establish, but is now fully recognized. HAART seems to have little, if any, beneficial effect on the natural history of intraepithelial lesions in HIV-positive women. Despite this fact, HAART, does increase the life expectancy of HIV-positive women. Therefore, it remains important to closely monitor HPV-related disease in women with HIV who are receiving HAART, particularly in regions of the world where cervical screening is not available routinely.

Subacute Sclerosing Panencephalitis in a Child Suffering from Human Immunodeficiency Virus on "Highly Active Antiretroviral Therapy" - Can This be Another Instance of Immune Reconstitution Inflammatory Syndrome?

PubMed

Gupta, Ashutosh; Kushwaha, Suman; Manzoor, Mushbiq; Tarfarosh, Shah Faisal Ahmad

2017-06-13

We report a 12-year-old boy with human immunodeficiency virus (HIV) who presented with rapidly progressive difficulty in ambulation. The symptoms started to worsen when he was put on antiretroviral therapy (ART). Our findings show that the dynamics of HIV-related immune suppression and highly active antiretroviral therapy (HAART) have an impact on the clinical course of Subacute sclerosing panencephalitis (SSPE). Slow progression is expected in children on HAART but in our case, we observe a complex interaction of the virus with the immune system and modification of disease course of SSPE with ART. The child we discuss in this case report developed rapidly progressive SSPE on HAART regime; so the possibility of SSPE to be labeled as immune reconstitution inflammatory syndrome (IRIS) should be considered.

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

Initiation of highly active antiretroviral therapy among pregnant women in Cape Town, South Africa.

PubMed

Stinson, Kathryn; Boulle, Andrew; Coetzee, David; Abrams, Elaine J; Myer, Landon

2010-07-01

To investigate highly active antiretroviral therapy (HAART) initiation among pregnant women and the optimum model of service delivery for integrating HAART services into antenatal care. We analysed clinic records to reconstruct a cohort of all HIV-infected pregnant women eligible for HAART at four antenatal clinics representing three service delivery models in Cape Town, South Africa. To assess HAART coverage, records of women determined to be eligible for HAART in pregnancy were reviewed at corresponding HIV treatment services. Of 13,208 pregnant women tested for HIV, 26% were HIV-infected and 15% were HAART-eligible based on a CD4 cell count of antiretroviral intervention before delivery. The proportions of women initiating HAART between the different service delivery models were comparable. The median gestational age at first presentation was 26 weeks, and early gestational age at first presentation was the strongest predictor of being on HAART by delivery. Of the women who did not initiate HAART in pregnancy, 24% started treatment within 2 years postpartum. In this setting with clear PMTCT and HAART protocols, services failed to prioritize and initiate a high proportion of eligible pregnant women on HAART. The initiation of HAART in pregnancy requires strengthened antenatal and HIV services that target women with advanced stage disease.

Relationship of postprandial nonesterified fatty acids, adipokines, and insulin across gender in human immunodeficiency virus-positive patients undergoing highly active antiretroviral therapy.

PubMed

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

2009-06-01

Metabolic derangements are common in human immunodeficiency virus (HIV)-positive subjects undergoing antiretroviral therapy, but little is known about postprandial conditions. 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). 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 (r(2) = 0.25, P = 0.016), and the postbreakfast decrease in NEFA levels correlated significantly with the postbreakfast increase in insulin levels (r(2) = 0.17, P = 0.038). No significant association between postprandial adipokines and insulin was observed. 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.

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.

Blockade of the spinal BDNF-activated JNK pathway prevents the development of antiretroviral-induced neuropathic pain.

PubMed

Sanna, Maria Domenica; Ghelardini, Carla; Galeotti, Nicoletta

2016-06-01

Although antiretroviral agents have been used successfully in suppressing viral production, they have also been associated with a number of side effects. The antiretroviral toxic neuropathy induces debilitating and extremely difficult to treat pain syndromes that often lead to discontinuation of antiretroviral therapy. Due to the critical need for the identification of novel therapeutic targets to improve antiretroviral neuropathic pain management, we investigated the role of the JNK signalling pathway in the mechanism of antiretroviral painful neuropathy. Mice were exposed to zalcitabine (2',3'-dideoxycytidine, ddC) and stavudine (2',3'-didehydro-3'-deoxythymidine, d4T) that induced a persistent mechanical allodynia and a transient cold allodynia. Treatment with the JNK blocker SP600125 before antiretroviral administration abolished mechanical hypersensitivity with no effect on thermal response. A robust spinal JNK overphosphorylation was observed on post-injection day 1 and 3, along with a JNK-dependent increase in p-c-Jun and ATF3 protein levels. Co-immunoprecipitation experiments showed the presence of a heterodimeric complex between ATF3 and c-Jun indicating that these transcription factors can act together to regulate transcription through heterodimerization. A rise in BDNF and caspase-3 protein levels was detected on day 1 and BDNF sequestration prevented both caspase-3 and p-JNK increase. These data suggest that BDNF plays a role in the early stages of ddC-induced allodynia by promoting apoptotic events and the activation of a hypernociceptive JNK-mediated pathway. We illustrated the activation of a BDNF-mediated JNK pathway involved in the early events responsible for the promotion of neuropathic pain, leading to a better knowledge of the mechanisms involved in the antiretroviral neuropathy. JNK blockade prevents antiretroviral-induced pain hypersensitivity. This may represent a potential prophylactic treatment of neuropathic pain to improve antiretroviral

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

PubMed

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

2012-01-01

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. A cohort study of HIV-infected individuals aged 15 years or older who were on ARV medicines was conducted at four sentinel sites. 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). 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 introduce less toxic first-line ARV regimens

Prevalence of Adverse Drug Reactions to Highly Active Antiretroviral Therapy (HAART) among HIV Positive Patients in Imam Khomeini Hospital of Tehran, Iran.

PubMed

Koochak, Hamid E; Babaii, Azita; Pourdast, Alia; Golrokhy, Raheleh; Rasoolinejad, Mehrnaz; Khodaei, Sepideh; Moghadam, Saeed R J; Taheri, Reza R; Seyed Alinaghi, Seyed Ahmad

2017-01-01

The present study assessed the prevalence of adverse drug reactions (ADRs) among HIV positive patients taking antiretroviral therapy referred to Imam Khomeini Hospital in Tehran, Iran. This is a cross sectional study regarding side effects of Highly Active Antiretroviral Therapy (HAART) in HIV positive patients referred to Voluntary Counseling and Testing (VCT) center in Imam Khomeini Hospital of Tehran, Iran during a period of the year 2009 to 2010. Two hundred patients under antiretroviral treatment evaluated for the side effects of drug based on available records, face to face interviews and written lab data. Data was collected from a sample of 200 HIV positive patients (72% male). Injection drug use was the most common route of HIV transmission. Co-Infections with Hepatitis C virus (HCV) found in the majority of patients (60.5%). Tuberculosis was the most prevalent opportunistic infection. One hundred eighty eight (94%) patients experienced at least one adverse drug reaction. The most frequent clinical and paraclinical findings were skin rash (28%) and abnormal liver function tests (36%). Given the high prevalence of adverse drug reactions among HIV positive patients taking antiretroviral therapy (ART) in this study, clinicians should be aware of ADRs at the initiation of ART as complications can affect patients' adherence to the therapy. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Otitis media in Brazilian human immunodeficiency virus infected children undergoing antiretroviral therapy.

PubMed

Miziara, I D; Weber, R; Araújo Filho, B Cunha; Pinheiro Neto, C Diógenes

2007-11-01

To assess changes in the prevalence of otitis media, associated with the use of highly active antiretroviral therapy, in Brazilian human immunodeficiency virus (HIV) infected children. Division of otorhinolaryngology, Hospital das Clínicas, Sao Paulo University Medical School, Brazil. A cohort of 459 HIV-infected children aged below 13 years. The prevalence of otitis media and the serum cluster of differentiation four glycoprotein T lymphocyte count were compared for children receiving highly active antiretroviral therapy (with protease inhibitors) and those receiving standard antiretroviral therapy (without protease inhibitors). Otitis media was present in 33.1 per cent of the children. Children aged from zero years to five years 11 months receiving highly active antiretroviral therapy had a higher prevalence of acute otitis media (p=0.02) and a lower prevalence of chronic otitis media (p=0.02). Children who were receiving highly active antiretroviral therapy had a mean serum cluster of differentiation four glycoprotein T lymphocyte count greater than that of those who were receiving standard antiretroviral therapy (p<0.001). The use of highly active antiretroviral therapy in Brazilian HIV-infected children was associated with a lower prevalence of chronic otitis media.

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

Predictors of psychological well-being in a diverse sample of HIV-positive patients receiving highly active antiretroviral therapy.

PubMed

Safren, Steven A; Radomsky, Adam S; Otto, Michael W; Salomon, Elizabeth

2002-01-01

The purpose of the present study was to identify variables relevant to psychological well-being in HIV patients receiving highly active antiretroviral therapy (HAART). Multiple stressors accompany living with HIV while managing a HAART regimen. However, a variety of cognitive and behavioral variables can protect against or augment the deleterious effects of stress in this population. The authors hypothesized that satisfaction with social support, coping styles, and maladaptive attributions about HIV would explain more variance in psychological well-being than stressful life events per se. Participants were individuals with HIV receiving antiretroviral therapy-either starting a new HAART regimen or having difficulties adhering to their current regimen. Satisfaction with social support, coping styles, and punishment beliefs about HIV were uniquely associated with depression, quality of life, and self-esteem over and above the effects of stressful life events. These results provide support for continued psychosocial interventions that target these variables among patients with HIV.

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…

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.

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.

[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.

Incidence of Cytomegalovirus Retinitis in the Era of Highly Active Antiretroviral Therapy

PubMed Central

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

2011-01-01

Purpose 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. Design Prospective cohort study Methods 1600 participants with acquired immune deficiency syndrome (AIDS) but without CMV retinitis at enrollment who completed at least one 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. Results The incidence rate of CMV retinitis in individuals with AIDS was 0.36/100 person years (PY) based upon 29 incident cases during 8,134 person-years 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 < 0.01), whereas only one individual with a CD4+ T cell count of 50–99 cells/μL and two 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 < 0.0001) for developing retinitis. Conclusions 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. PMID:22310076

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.

Impact of hepatitis C virus co-infection on HIV patients before and after highly active antiretroviral therapy: an immunological and clinical chemistry observation, Addis Ababa, Ethiopia.

PubMed

Taye, Solomon; Lakew, Mekuria

2013-05-17

Hepatitis C virus (HCV) is an RNA virus which has been known to cause acute and chronic necro-inflammatory disease of the liver. It is the leading cause of end-stage liver disease and hepatocellular carcinoma. HIV is known to have a negative impact on the natural disease outcome and immune response of HCV infection, whereas the reverse remains unclear. We evaluated the impact of HCV co-infection on recovery of CD4+ and CD8+ T-cells and liver enzyme levels before and after initiation of highly active antiretroviral therapy (HAART) in HIV/HCV co-infected patients. A hospital-based, observational, prospective cohort study design was used for this study. Pre-antiretroviral treatment (Pre-ART) and under HAART HIV mono-infected and HCV/HIV co-infected individuals who are under regular follow-up were recruited for this study. 387 blood samples were collected from volunteer, known HIV positive Ethiopian patients and screened for HCV. Twenty five HCV/HIV co-infected patients were prospectively followed for four years. CD4+ and CD8+ T-cells and liver enzyme levels were determined annually for each of the participant. The prevalence of HCV/HIV co-infection in this study was 6.5%. Both HCV/HIV co-infected and HIV mono-infected under HAART groups showed CD4+ recovery (343 Vs 426; P < 0.004, OR = 4.97, 95% CI = 2.41 to 10.27) respectively; but, the recovery rate was higher in mono-infected (80 Vs 426) than co-infected group (148 Vs 343). The recovery and/or decline pattern of CD8+ T-cells was the same with that of CD4+. In 75% of co-infected groups, the mean alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels were above the upper limit of normal reference range. Analyses restricted to individuals who initiated HAART and pre-ART showed similar results. We found that CD4+ T-cell recovery was negatively affected by the presence of ongoing HCV replication in under HAART co-infected individuals and fast decline of CD4+ T-cells in pre-ART patients

Adherence to highly active antiretroviral therapy in a tertiary care hospital in West Bengal, India.

PubMed

Saha, Rajib; Saha, Indranil; Sarkar, Aditya Prasad; Das, Dilip Kumar; Misra, Raghunath; Bhattacharya, Krishnadas; Roy, Rabindra Nath; Bhattacharya, Abantika

2014-02-01

The introduction of highly active antiretroviral therapy (HAART) for the treatment of human immunodeficiency virus (HIV) infection and acquired immunodeficiency syndrome (AIDS) has led to the reduction of mortality and the improvement of the quality of life of people living with HIV/AIDS (PLWHA). The present study was conducted to determine the pattern of adherence to HAART among PLWHA, and to assess the factor(s) affecting nonadherence, if any. This study was a hospital-based analytical, cross-sectional epidemiological study conducted between July and October 2011. A total of 370 adult HIV-positive patients registered in the Antiretroviral Therapy Centre of Burdwan Medical College and Hospital, West Bengal, India, were included. Nonadherence was defined as missing at least a single dose of medicine within the last four days. Data was analysed using the Statistical Package for the Social Sciences version 19.0 (IBM Corp, Armonk, NY, USA). A total of 87.6% of patients were found to be adherent to HAART. Principal causes of nonadherence were forgetting to take medicine (70.2%), being away from home (65.2%), and busyness with other things (64.7%). Multivariate logistic regression analysis revealed that nonadherence was significantly associated with a positive family history of HIV/AIDS (odds ratio [OR] 16; 95% confidence interval [CI] 2.2-114.3; p = 0.01), occurrence of side effects with HAART (OR 9.81; 95% CI 1.9-51.7; p = 0.01) and employment (OR 5.93; 95% CI 1.5-23.2; p = 0.01). Although overall adherence was high, the factors that affect nonadherence can be addressed with proper counselling and motivation of patients and their family members. Adherence to HAART could delay the progression of this lethal disease and minimise the risk of developing drug resistance.

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.

High Prevalence of Echocardiographic Abnormalities among HIV-infected Persons in the Era of Highly Active Antiretroviral Therapy.

PubMed

Mondy, Kristin E; Gottdiener, John; Overton, E Turner; Henry, Keith; Bush, Tim; Conley, Lois; Hammer, John; Carpenter, Charles C; Kojic, Erna; Patel, Pragna; Brooks, John T

2011-02-01

in the era of highly active antiretroviral therapy (HAART), human immunodeficiency virus (HIV)-infected persons have higher cardiovascular disease risk. Little is known about asymptomatic abnormalities in cardiac structure and function in this population. the Study to Understand the Natural History of HIV/AIDS in the Era of Effective Therapy (SUN Study) is a prospective, observational, multi-site cohort of 656 HIV-infected participants who underwent baseline echocardiography during 2004-2006. We examined prevalence of and factors associated with left ventricular systolic dysfunction (LVSD), diastolic dysfunction (DD), pulmonary hypertension (PHTN), left ventricular hypertrophy (LVH), and left atrial enlargement (LAE). participant characteristics were as follows: median age, 41 years; 24% women; 29% non-Hispanic black; 73% receiving HAART; and median CD4+ cell count, 462 cells/μL. Among evaluable participants, 18% had LVSD, 26% had DD, 57% had PHTN (right ventricular pressure >30 mm Hg), 6.5% had LVH, and 40% had LAE. In multivariate analyses, significant factors (P < .05) associated with LVSD were history of MI, elevated highly sensitive C-reactive protein (hsCRP) level, and current tobacco smoking; for DD, elevated hsCRP level and hypertension; for PHTN, current use of ritonavir; for LVH, hypertension, diabetes, non-white race, female sex with elevated body mass index, calculated as the weight in kilograms divided by the square of height in meters, of ≥ 25, elevated hsCRP level, and current use of abacavir; for LAE, hypertension and recent marijuana use. in this large contemporary HIV cohort, the prevalence of subclinical functional and structural cardiac abnormalities was greater than expected for age. Abnormalities were mostly associated with expected and often modifiable risks. Lifestyle modification should become a greater priority in the management of chronic HIV disease.

Polymeric nanoparticles affect the intracellular delivery, antiretroviral activity and cytotoxicity of the microbicide drug candidate dapivirine.

PubMed

das Neves, José; Michiels, Johan; Ariën, Kevin K; Vanham, Guido; Amiji, Mansoor; Bahia, Maria Fernanda; Sarmento, Bruno

2012-06-01

To assess the intracellular delivery, antiretroviral activity and cytotoxicity of poly(ε-caprolactone) (PCL) nanoparticles containing the antiretroviral drug dapivirine. Dapivirine-loaded nanoparticles with different surface properties were produced using three surface modifiers: poloxamer 338 NF (PEO), sodium lauryl sulfate (SLS) and cetyl trimethylammonium bromide (CTAB). The ability of nanoparticles to promote intracellular drug delivery was assessed in different cell types relevant for vaginal HIV transmission/microbicide development. Also, antiretroviral activity of nanoparticles was determined in different cell models, as well as their cytotoxicity. Dapivirine-loaded nanoparticles were readily taken up by different cells, with particular kinetics depending on the cell type and nanoparticles, resulting in enhanced intracellular drug delivery in phagocytic cells. Different nanoparticles showed similar or improved antiviral activity compared to free drug. There was a correlation between increased antiviral activity and increased intracellular drug delivery, particularly when cell models were submitted to a single initial short-course treatment. PEO-PCL and SLS-PCL nanoparticles consistently showed higher selectivity index values than free drug, contrasting with high cytotoxicity of CTAB-PCL. These results provide evidence on the potential of PCL nanoparticles to affect in vitro toxicity and activity of dapivirine, depending on surface engineering. Thus, this formulation approach may be a promising strategy for the development of next generation microbicides.

Structured intermittent interruption of chronic HIV infection treatment with highly active antiretroviral therapy: effects on leptin and TNF-alpha.

PubMed

Arjona, M Montes de Oca; Pérez-Cano, R; Garcia-Juárez, R; Martín-Aspas, A; del Alamo, C Fernández Gutiérrez; Girón-González, J A

2006-04-01

The changes in nutritional parameters and adipocytokines after structured intermittent interruption of highly active antiretroviral treatment of patients with chronic HIV infection are analyzed. Twenty-seven patients with chronic HIV infection (median CD4+ T cell count/microl: nadir, 394; at the beginning of structured interruptions, 1041; HIV viral load: nadir, 41,521 copies/ml; at the beginning of structured interruptions <50 copies/ml; median time of previous treatment: 60 months) were evaluated during three cycles of intermittent interruptions of therapy (8 weeks on/4 weeks off). CD4+ T cell count, HIV viral load, anthropometric measures, and serum concentrations of triglycerides, cholesterol, leptin, and tumor necrosis factor and its soluble receptors I and II were determined. After the three cycles of intermittent interruptions of therapy, no significant differences in CD4+ T cell count/microl, viral load, or serum concentrations of cholesterol or triglycerides with reference to baseline values were found. A near-significant higher fatty mass (skinfold thicknesses, at the end, 121 mm, at the beginning, 100 mm, p = 0.100), combined with a significant increase of concentration of leptin (1.5 vs. 4.7 ng/ml, p = 0,044), as well as a decrease in serum concentrations of soluble receptors of tumor necrosis factor (TNFRI, 104 vs. 73 pg/ml, p = 0.022; TNFRII 253 vs. 195 pg/ml, p = 0.098) were detected. Structured intermittent interruption of highly active antiretroviral treatment of patients with chronic HIV infection induces a valuable positive modification in markers of lipid turnover and adipose tissue mass.

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

DOE Office of Scientific and Technical Information (OSTI.GOV)

Fraunholz, Ingeborg, E-mail: inge.fraunholz@kgu.d; Weiss, Christian; Eberlein, Klaus

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,more » 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.« less

The antiretroviral efficacy of highly active antiretroviral therapy and plasma nevirapine concentrations in HIV-TB co-infected Indian patients receiving rifampicin based antituberculosis treatment

PubMed Central

2011-01-01

Background Rifampicin reduces the plasma concentrations of nevirapine in human immunodeficiency virus (HIV) and tuberculosis (TB) co-infected patients, who are administered these drugs concomitantly. We conducted a prospective interventional study to assess the efficacy of nevirapine-containing highly active antiretroviral treatment (HAART) when co-administered with rifampicin-containing antituberculosis treatment (ATT) and also measured plasma nevirapine concentrations in patients receiving such a nevirapine-containing HAART regimen. Methods 63 cases included antiretroviral treatment naïve HIV-TB co-infected patients with CD4 counts less than 200 cells/mm3 started on rifampicin-containing ATT followed by nevirapine-containing HAART. In control group we included 51 HIV patients without tuberculosis and on nevirapine-containing HAART. They were assessed for clinical and immunological response at the end of 24 and 48 weeks. Plasma nevirapine concentrations were measured at days 14, 28, 42 and 180 of starting HAART. Results 97 out of 114 (85.1%) patients were alive at the end of 48 weeks. The CD4 cell count showed a mean increase of 108 vs.113 cells/mm3 (p=0.83) at 24 weeks of HAART in cases and controls respectively. Overall, 58.73% patients in cases had viral loads of less than 400 copies/ml at the end of 48 weeks. The mean (± SD) Nevirapine concentrations of cases and control at 14, 28, 42 and 180 days were 2.19 ± 1.49 vs. 3.27 ± 4.95 (p = 0.10), 2.78 ± 1.60 vs. 3.67 ± 3.59 (p = 0.08), 3.06 ± 3.32 vs. 4.04 ± 2.55 (p = 0.10) respectively and 3.04 μg/ml (in cases). Conclusions Good immunological and clinical response can be obtained in HIV-TB co-infected patients receiving rifampicin and nevirapine concomitantly despite somewhat lower nevirapine trough concentrations. This suggests that rifampicin-containing ATT may be co administered in resource limited setting with nevirapine-containing HAART regimen without substantial reduction in antiretroviral

When to initiate highly active antiretroviral therapy in low-resource settings: the Moroccan experience.

PubMed

Loubiere, Sandrine; el Filal, Kamal Marhoum; Sodqi, Mustapha; Loundou, Anderson; Luchini, Stéphane; Cleary, Susan; Moatti, Jean-Paul; Himmich, Hakima

2008-01-01

The aim of this study was to assess the cost-effectiveness of HIV treatment alternatives - with and without highly active antiretroviral therapy (HAART) - within alternative strata based on the CD4+ T-cell count at the initiation of treatment in a low-resource setting. A retrospective observational study was conducted following 286 HIV-positive individuals admitted to the principal teaching hospital in Casablanca, Morocco, between 1995 and 2002. Patients were stratified by CD4+ T-cell count and regression models were fitted to determine risk of opportunistic infection. Data on healthcare resource use were derived from patient records and were evaluated from the hospital perspective. HAART led to a significant reduction in the number of HIV-related opportunistic infections (P<0.0001), extended survival (61.3 versus 55.2 months; P<0.0001) and reduced hospital stays (P<0.0001) in comparison with care in the absence of HAART. When medical care and drug costs were considered together, HAART was more costly than providing treatment for opportunistic infections. The incremental cost-effectiveness ratio was lower than gross domestic product (GDP) per capita for patients starting HAART with a CD4+ T-cell count <200 cells/mm3, but this increased to nearly three times GDP per capita when HAART was initiated at CD4+ T-cell counts above this threshold. HAART is more cost-effective than treating HIV-related opportunistic infections and, contrary to conclusions drawn in developed countries, HAART is more cost-effective when the CD4+ T-cell count drops to <200 cells/mm3.

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

[Factors predicting lack of adherence to highly active antiretroviral treatment].

PubMed

Martín-Sánchez, Vicente; Ortega-Valín, Luis; Pérez-Simón, María del Rosario; Mostaza-Fernández, José Luis; Ortiz de Urbina-González, Juan José; Rodríguez-María, Miriam; Carro-Fernández, José Antonio; Cuevas-González, María José; Alcoba-Leza, Manuel

2002-12-01

Knowledge of adherence to highly active antiretroviral treatment (HAART) and the variables associated with poor compliance is useful for the follow-up of HIV infected patients. Patients were consecutively recruited from the HIV outpatient clinics of the Hospitals of Leon and El Bierzo from January to June 2000. Patients were considered non-adherent to treatment if they failed to take 10% or more of their prescribed total dose of at least one drug during the 4 days before the interview, or if they had accumulated a delay of more than 9 days over the previous 3 months in picking up their prescribed drugs from the hospital pharmacy. Logistic regression analysis was performed with variables found to be associated with adherence in the univariate analysis. The methods used to determine adherence had a Kappa index of 12.6%. Among the 206 patients interviewed, 108 were considered non-adherent (52.4%; CI 95% 5 45.6-59.2). Multivariate analysis showed that the following factors were associated with poor treatment adherence: cocaine consumption in the previous six months (adjusted OR 5 5.1); patients unsure about the proper way to take prescribed treatment; (adjusted OR 5 2.5); and patients not prescribed the zidovudine-lamivudine combination (adjusted OR 5 1.9). Over one-third of patients with no variable associated with treatment adherence were considered non-compliant. Measurement of medication adherence and its predictive factors involved methodological difficulties. With the criteria used in the present study more than half the patients were considered non-compliant. The variables found to be related to poor adherence can be modified by social, psychological or health care interventions.

High level of APOBEC3F/3G editing in HIV-2 DNA vif and pol sequences from antiretroviral-naive patients.

PubMed

Bertine, Mélanie; Charpentier, Charlotte; Visseaux, Benoit; Storto, Alexandre; Collin, Gilles; Larrouy, Lucile; Damond, Florence; Matheron, Sophie; Brun-Vézinet, Françoise; Descamps, Diane

2015-04-24

In HIV-1, hypermutation introduced by APOBEC3F/3G cytidine deaminase activity leads to defective viruses. In-vivo impact of APOBEC3F/3G editing on HIV-2 sequences remains unknown. The objective of this study was to assess the level of APOBEC3F/3G editing in HIV-2-infected antiretroviral-naive patients. Direct sequencing of vif and pol regions was performed on HIV-2 proviral DNA from antiretroviral-naive patients included in the French Agence Nationale de Recherches sur le SIDA et les hépatites virales CO5 HIV-2 cohort. Hypermutated sequences were identified using Hypermut2.0 program. HIV-1 proviral sequences from Genbank were also assessed. Among 82 antiretroviral-naive HIV-2-infected patients assessed, 15 (28.8%) and five (16.7%) displayed Vif proviral defective sequences in HIV-2 groups A and B, respectively. A lower proportion of defective sequences was observed in protease-reverse transcriptase region. A higher median number of G-to-A mutations was observed in HIV-2 group B than in group A, both in Vif and protease-reverse transcriptase regions (P = 0.02 and P = 0.006, respectively). Compared with HIV-1 Vif sequences, a higher number of Vif defective sequences was observed in HIV-2 group A (P = 0.00001) and group B sequences (P = 0.013). We showed for the first time a high level of APOBEC3F/3G editing in HIV-2 sequences from antiretroviral-naive patients. Our study reported a group effect with a significantly higher level of APOBEC3F/3G editing in HIV-2 group B than in group A sequences.

Abacavir use and risk of acute myocardial infarction and cerebrovascular events in the highly active antiretroviral therapy era.

PubMed

Bedimo, Roger J; Westfall, Andrew O; Drechsler, Henning; Vidiella, Gabriela; Tebas, Pablo

2011-07-01

Some studies have suggested that exposure to antiretroviral therapy (ART) with abacavir is associated with an increased risk of acute myocardial infarction (AMI). Using the Veterans Health Administration's Clinical Case Registry we calculated the risk of AMI and cerebrovascular events (CVA) associated with the cumulative use of abacavir and other nucleoside combinations. We also evaluated the impact of pre-existing chronic kidney disease on the selection of abacavir versus tenofovir in the last recorded ART regimen, and on highly active antiretroviral therapy-associated AMI and CVA risks. A total of 19,424 human immunodeficiency virus-infected patients contributed 76,376 patient-years of follow. After adjusting for age, hypercholesterolemia, hypertension, type 2 diabetes, and smoking, the hazard ratio (HR) for each year of abacavir use was 1.18 (95% confidence interval [CI], .92-1.50; P=.191) for AMI and 1.16 (95% CI, .98-1.37; P=.096) for CVA. Abacavir use was more common among patients with prior chronic kidney disease than was tenofovir use (12.46% versus 7.15%; P=.0001), and chronic kidney disease was associated with a significantly higher risk of AMI (HR, 2.41; 95% CI, 1.73-3.36), and CVA (HR, 1.80; 95% CI, 1.44-2.24). Compared with patients who received neither tenofovir nor abacavir, patients who received tenofovir had lower risk of AMI (HR, 0.16; 95% CI, .08-.33; P=.0001) and CVA (HR, 0.22; 95% CI, .15-.32; P=.001). Use of abacavir was associated with lower risk of CVA (HR, 0.60; 95% CI, .45-.79). We observed no association between cumulative or current abacavir use and AMI or CVA. Abacavir use was more common than was tenofovir use among patients with prior chronic kidney disease, and chronic kidney disease independently predicted higher rates of AMI and CVA. © The Author 2011. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved.

High prevalence of antiretroviral drug resistance among HIV-1-untreated patients in Guinea-Conakry and in Niger.

PubMed

Charpentier, Charlotte; Bellecave, Pantxika; Cisse, Mohamed; Mamadou, Saidou; Diakite, Mandiou; Peytavin, Gilles; Tchiombiano, Stéphanie; Teisseire, Pierre; Pizarro, Louis; Storto, Alexandre; Brun-Vézinet, Françoise; Katlama, Christine; Calvez, Vincent; Marcelin, Anne-Geneviève; Masquelier, Bernard; Descamps, Diane

2011-01-01

The aim of the study was to assess the prevalence of antiretroviral drug resistance mutations in HIV-1 from recently diagnosed and untreated patients living in Conakry, Guinea-Conakry and in Niamey, Niger. The study was performed in two countries of Western Africa - Guinea-Conakry and Niger - using the same survey method in both sites. All newly HIV-1 diagnosed patients, naive of antiretroviral drugs, were consecutively included during September 2009 in each of the two sites. Protease and reverse transcriptase sequencing was performed using the ANRS procedures. Drug resistance mutations were identified according to the 2009 update surveillance drug resistance mutations. In Conakry, 99 patients were included, most of whom (89%) were infected with CRF02_AG recombinant virus. Resistance analysis among the 93 samples showed that ≥1 drug resistance mutation was observed in 8 samples, leading to a prevalence of primary resistance of 8.6% (95% CI 2.91-14.29%). In Niamey, 96 patients were included; a high diversity in HIV-1 subtypes was observed with 47 (51%) patients infected with CRF02_AG. Resistance analysis performed among the 92 samples with successful genotypic resistance test showed that ≥1 drug resistance mutation was observed in 6 samples, leading to a prevalence of primary resistance of 6.5% (95% CI 1.50-11.50%). We reported the first antiretroviral drug resistance survey studies in antiretroviral-naive patients living in Guinea-Conakry and in Niger. The prevalence of resistance was between 6% and 9% in both sites, which is higher than most of the other countries from Western Africa region.

Medical resource utilization and cost of HIV-related care in the highly active antiretroviral therapy era at a University Clinic in Sweden.

PubMed

Ghatnekar, Ola; Hjortsberg, Catharina; Gisslén, Magnus; Lindbäck, Stefan; Löthgren, Mickael

2010-01-01

Little is known regarding healthcare costs for HIV/AIDS patients in the era of highly active antiretroviral therapy (HAART) and subgroups of patients according to the severity and progression of HIV infection in Sweden. The objective of this study is therefore to describe the direct medical resource use and cost of healthcare for HIV patients at a university clinic in Sweden. A patient registry database for HIV treatment at the Department of Infectious Diseases, Sahlgrenska University Hospital, between 2000 and 2005 provided information on patient characteristics, antiretroviral drugs and dosages, tests and diagnostic procedures, outpatient visits and inpatient stays. The review used publicly available unit costs with a county council perspective, expressed in 2006 Euros. Two hundred and eighty-five patients with a mean age of 38 years in 2000 (64% men) were followed for 1368 patient-years. They had a mean (median) of 6.3 (0) inpatient days, 4.1 (3.7) physician visits, 4.2 (3.8) nurse visits, 2.6 (0.7) counsellor visits and 11.5 (7.7) tests and diagnostic procedures per patient-year. Only 12 deaths were recorded during the study period, and the proportion of treated patients with successful treatment (HIV-RNA < 50 copies/mL) increased from 74% to 92% during the period. The mean cost per patient-month amounted to €1069. The main cost driver was HIV drugs (51%), followed by inpatient stays (including hospitalizations for opportunistic infections; 22%), outpatient physician, nurse or therapist visits (19%) and diagnostics and tests (7%). All non-drug costs increased with a decreasing CD4 cell count. Overall, approximately half of the direct costs of HIV treatment were not related to antiretroviral treatment. The non-antiretroviral costs were inversely correlated with HIV-induced immune deficiency.

HIV and antiretroviral therapy: lipid abnormalities and associated cardiovascular risk in HIV-infected patients.

PubMed

Kotler, Donald P

2008-09-01

It has been demonstrated that patients on highly active antiretroviral therapy are at increased risk for developing metabolic abnormalities that include elevated levels of serum triglycerides and low-density lipoprotein cholesterol and reduced levels of high-density lipoprotein cholesterol. This dyslipidemia is similar to that seen in the metabolic syndrome, raising the concern that highly active antiretroviral therapy also potentially increases the risk for cardiovascular complications. This paper reviews the contribution of both HIV infection and the different components of highly active antiretroviral therapy to dyslipidemia and the role of these abnormalities toward increasing the risk of cardiovascular disease in HIV-infected patients; therapeutic strategies to manage these risks are also considered.

Cumulative HIV viremia during highly active antiretroviral therapy is a strong predictor of AIDS-related lymphoma.

PubMed

Zoufaly, Alexander; Stellbrink, Hans-Jürgen; Heiden, Matthias An der; Kollan, Christian; Hoffmann, Christian; van Lunzen, Jan; Hamouda, Osamah

2009-07-01

AIDS-related lymphoma contributes to significant morbidity and mortality among human immunodeficiency virus (HIV)-infected patients receiving highly active antiretroviral therapy (HAART). We assessed the predictive role of cumulative HIV viremia and other risk factors in the development of AIDS-related non-Hodgkin lymphoma. Data from the Clinical Surveillance of HIV Disease (ClinSurv) study, an ongoing, observational, open cohort study of HIV-infected patients from different urban areas in Germany, were analyzed using a Cox proportional hazards model. In the Cox model, which comprised 6022 patients and 27,812 patient-years of follow-up while patients were receiving HAART from 1999 through 2006, cumulative HIV viremia was found to be independently associated with the risk of lymphoma (hazard ratio, [HR], 1.67 [95% confidence interval {CI}, 1.27-2.20]) (P < .001]). This association differed markedly between lymphoma subtypes. Although the association was more pronounced for Burkitt-type lymphoma (HR, 3.45 [95% CI, 1.52-7.85]) (P = .003), there was no association between cumulative HIV viremia and the incidence of primary central nervous system lymphoma (HR, 1.00 [95% CI, 0.39-2.57]) (P = .997). Other risk factors associated with an increased risk in a multivariable analysis included the latest CD4 T cell count as well as age per 10-year increment. Cumulative HIV viremia is an independent and strong predictor of AIDS-related lymphoma among patients receiving HAART. The influence of cumulative HIV viremia may differ between lymphoma subtypes.

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

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.

The incidence of cytomegalovirus (CMV) antigenemia and CMV disease is reduced by highly active antiretroviral therapy.

PubMed

Varani, S; Spezzacatena, P; Manfredi, R; Chiodo, F; Mastroianni, A; Ballarini, P; Boschini, A; Lazzarotto, T; Landini, M P

2000-05-01

Cytomegalovirus (CMV) infection was one of the most common opportunistic infections in AIDS patients, leading to blindness or life-threatening disease in about 40% of patients in the later stages of AIDS before highly active antiretroviral therapy (HAART). In a retrospective multicenter study we investigated the incidence of CMV retinitis and organ involvement in Northern Italy before (1995 and 1996) and after the introduction of HAART (1997 and 1998) as well as the data regarding CMV antigenemia. We found a sharp drop in the incidence of CMV disease in AIDS patients as well as a decline in the incidence of relapses of CMV-disease after the widespread introduction of HAART. Moreover, there was a decrease in the incidence of antigenemia-positive cases in AIDS patients in the era of HAART and the median CMV viral load was significantly higher in patients who didn't receive HAART than in patients who received HAART (p = 0.001, t test).

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

High prevalence of HIV-1 drug resistance among patients on first-line antiretroviral treatment in Lomé, Togo.

PubMed

Dagnra, Anoumou Y; Vidal, Nicole; Mensah, Akovi; Patassi, Akouda; Aho, Komi; Salou, Mounerou; Monleau, Marjorie; Prince-David, Mireille; Singo, Assétina; Pitche, Palokinam; Delaporte, Eric; Peeters, Martine

2011-06-10

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. 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. 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. 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 now widely used, and can compromise the

Antiretroviral therapy in children: recent advances.

PubMed

Lodha, Rakesh; Manglani, Mamta

2012-12-01

Availability and successful use of various antiretroviral drugs has transformed HIV/AIDS from an incurable to a treatable chronic condition. The antiretroviral therapy can successfully suppress viral replication and preserve the immune system for many years. The implementation of antiretroviral therapy program in resource limited settings using the 'public health approach' of the World Health Organization has had a dramatic impact on the lives of millions of HIV infected individuals. Antiretroviral therapy (ART) in children has many challenges: use of appropriate formulations, regular need for modification of doses as the child grows, adherence issues, etc. To reduce the high morbidity and mortality in HIV infected children, it is currently recommended that all HIV infected children less than 24 mo should receive ART; in older children the indications are based on clinical and/or immunological criteria. Highly active antiretroviral therapy regimens include at least 3 antiretroviral drugs. The first line therapy recommended for children is a combination of two nucleoside reverse transcriptase inhibitors and a non-nucleoside reverse transcriptase inhibitor. Infants who have had exposure to nevirapine should receive a combination of two nucleoside reverse transcriptase inhibitors and a protease inhibitor; the protease inhibitor of choice is ritonavir boosted lopinavir. The success of therapy is dependent on >95 % adherence. The second line regimen, used when the first line therapy fails, is based on a protease inhibitor. The ongoing research focuses on simplification of regimen, discovery of more potent drugs, availability of more pediatric formulations, treatment of drug resistant strains etc. The optimal indications for initiation of therapy in children, are also being studied.

Thymidine analogue-sparing highly active antiretroviral therapy (HAART).

PubMed

Nolan, David; Mallal, Simon

2003-02-01

The use of alternative nucleoside reverse transcriptase inhibitors (NRTIs) to the thymidine analogues stavudine (d4T) and zidovudine(ZDV) has been advocated as a means of limiting long-term NRTI-associated toxicity, particularly the development of lipoatrophy or fat wasting. This approach reflects an increasing knowledge of the distinct toxicity profiles of NRTI drugs. However, recent clinical trials have demonstrated that the use of thymidine analogue NRTIs and newer alternative backbone NRTIs, such as tenofovir (TNF) and abacavir (ABC), is associated with comparable short-term efficacy and tolerability. Given the importance of toxicity profile differences in determining clinical management, it is important to recognise that d4T and ZDV cary significantly different risks for long-term NRTI toxicity. Recognising that all NRTIs, including thymidine analogues, have individual toxicity profiles provides a more appropriate basis for selecting optimal antiretroviral therapy. The safety and efficacy of TNF and ABC are also reviewed here, although the available data provide only limited knowledge of the long-term effects of these drugs in terms of toxicity and antiviral durability.

Antiretroviral-based HIV-1 Prevention: Antiretroviral Treatment and Pre-Exposure Prophylaxis

PubMed Central

Celum, Connie; Baeten, Jared

2012-01-01

Antiretroviral-based HIV-1 prevention strategies – including antiretroviral treatment (ART) to reduce the infectiousness of HIV-1 infected persons and oral and topical pre-exposure prophylaxis (PrEP) for uninfected persons to prevent HIV-1 acquisition – are the most promising new approaches for decreasing HIV-1 spread. Observational studies among HIV-1 serodiscordant couples have associated ART initiation with a reduction in HIV-1 transmission risk of 80–92%, and a recent randomized trial demonstrated that earlier initiation of ART (i.e., at CD4 counts between 350 and 550 cells/mm3), in the context of virologic monitoring and adherence support, resulted in a 96% reduction in HIV-1 transmission. A number of ongoing and recently-completed clinical trials have assessed the efficacy of PrEP for HIV-1 prevention as peri-coitally administered or daily-administered 1% tenofovir gel and daily oral tenofovir and combination emtricitabine/tenofovir. Completed studies have demonstrated HIV-1 protection efficacies ranging from 39% to 75%. However, two trials in African women have shown no HIV-1 protection with PrEP; the reasons for lack of efficacy in those trials are being investigated. Adherence is likely key to efficacy of antiretrovirals for HIV-1 prevention, both as ART and PrEP. Critical unanswered questions for successful delivery of antiretroviral-based HIV-1 prevention include how to target ART and PrEP to realize maximum population benefits, whether HIV-1 infected persons at earlier stages of infection would accept ART to reduce their risk for transmitting HIV-1 and highest-risk HIV-1 negative persons would use PrEP, and whether high adherence could be sustained to achieve high effectiveness. PMID:23221365

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

PKC-mediated HuD-GAP43 pathway activation in a mouse model of antiretroviral painful neuropathy.

PubMed

Sanna, M D; Quattrone, A; Ghelardini, C; Galeotti, N

2014-03-01

Patients treated with nucleoside reverse transcriptase inhibitors (NRTIs) develop painful neuropathies that lead to discontinuation of antiretroviral therapy thus limiting viral suppression strategies. The mechanisms by which NRTIs contribute to the development of neuropathy are not known. In order to elucidate the mechanisms underlying this drug-induced neuropathy, we have characterized cellular events in the central nervous system following antiretroviral treatment. Systemic administration of the antiretroviral agent, 2',3'-dideoxycytidine (ddC) considerably increased the expression and phosphorylation of protein kinase C (PKC) γ and ɛ, enzymes highly involved in pain processes, within periaqueductal grey matter (PAG), and, to a lesser extent, within thalamus and prefrontal cortex. These events appeared in coincidence with thermal and mechanical allodynia, but PKC blockade did not prevent the antiretroviral-induced pain hypersensitivity, ruling out a major involvement of PKC in the ddC-induced nociceptive behaviour. An increased expression of GAP43, a marker of neuroregeneration, and decreased levels of ATF3, a marker of neuroregeneration, were detected in all brain areas. ddC treatment also increased the expression of HuD, a RNA-binding protein target of PKC known to stabilize GAP43 mRNA. Pharmacological blockade of PKC prevented HuD and GAP43 overexpression. Silencing of both PKCγ and HuD reduced GAP43 levels in control mice and prevented the ddC-induced GAP43 enhanced expression. Present findings illustrate the presence of a supraspinal PKC-mediated HuD-GAP43 pathway activated by ddC. Based on our results, we speculate that antiretroviral drugs may recruit the HuD-GAP43 pathway, potentially contributing to a response to the antiretroviral neuronal toxicity. Copyright © 2014 Elsevier Ltd. All rights reserved.

An investigation of the possible interaction between the use of Vitamin C and highly active antiretroviral therapy (HAART) adherence and effectiveness in treated HIV+ women.

PubMed

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

2012-08-01

Our goal in this study was to examine how Vitamin C interacts with antiretroviral therapy in individuals with HIV. We specifically evaluated how Vitamin C impacts highly active antiretroviral therapy (HAART) adherence and HAART effectiveness as adjudicated by HIV viral loads and CD4 cell counts. Women served as their own controls, comparing periods of Vitamin C usage with periods of non-usage. An intra-individual, cross-sectional comparative study 'nested' in the WIHS observational cohort study. Women in the Women's Interagency HIV Study (WIHS). Adherence, CD4 count and viral load. Our study population was drawn from 2813 HIV+ participants who contributed 44,588 visits in WIHS from October, 1994 to April, 2009. Among them, there were 1122 Vitamin C users with 4954 total visits where use was reported. In the multivariate model adjusting for age, education, race, income, drug use, Vitamin C use order and depression score, there was a 44% increase in the odds of ≥ 95% HAART adherence among participants during their period of Vitamin C use compared to when they were not using Vitamin C (OR=1.44; 95% CI=1.1-1.9; P-value=0.0179). There was an association with Vitamin C usage and CD4 counts on viral loads. Vitamin C usage appears to be associated with improved adherence. Future Vitamin C studies should target specific HAART drugs, and prospective clinical outcomes. Copyright © 2012 Elsevier Ltd. All rights reserved.

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

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.

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

PubMed

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

2002-04-15

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

High Cellular Monocyte Activation in People Living With Human Immunodeficiency Virus on Combination Antiretroviral Therapy and Lifestyle-Matched Controls Is Associated With Greater Inflammation in Cerebrospinal Fluid

PubMed Central

Booiman, Thijs; Wit, Ferdinand W.; Maurer, Irma; De Francesco, Davide; Sabin, Caroline A.; Harskamp, Agnes M.; Prins, Maria; Garagnani, Paolo; Pirazzini, Chiara; Franceschi, Claudio; Fuchs, Dietmar; Gisslén, Magnus; Winston, Alan; Reiss, Peter; Reiss, P.; Wit, F. W. N. M.; Schouten, J.; Kooij, K. W.; van Zoest, R. A.; Elsenga, B. C.; Janssen, F. R.; Heidenrijk, M.; Zikkenheiner, W.; van der Valk, M.; Kootstra, N. A.; Booiman, T.; Harskamp-Holwerda, A. M.; Boeser-Nunnink, B.; Maurer, I.; Mangas Ruiz, M. M.; Girigorie, A. F.; Villaudy, J.; Frankin, E.; Pasternak, A.; Berkhout, B.; van der Kuyl, T.; Portegies, P.; Schmand, B. A.; Geurtsen, G. J.; ter Stege, J. A.; Klein Twennaar, M.; Majoie, C. B. L. M.; Caan, M. W. A.; Su, T.; Weijer, K.; Bisschop, P. H. L. T.; Kalsbeek, A.; Wezel, M.; Visser, I.; Ruhé, H. G.; Franceschi, C.; Garagnani, P.; Pirazzini, C.; Capri, M.; Dall’Olio, F.; Chiricolo, M.; Salvioli, S.; Hoeijmakers, J.; Pothof, J.; Prins, M.; Martens, M.; Moll, S.; Berkel, J.; Totté, M.; Kovalev, S.; Gisslén, M.; Fuchs, D.; Zetterberg, H.; Winston, A.; Underwood, J.; McDonald, L.; Stott, M.; Legg, K.; Lovell, A.; Erlwein, O.; Doyle, N.; Kingsley, C.; Sharp, D. J.; Leech, R.; Cole, J. H.; Zaheri, S.; Hillebregt, M. M. J.; Ruijs, Y. M. C.; Benschop, D. P.; Burger, D.; de Graaff-Teulen, M.; Guaraldi, G.; Bürkle, A.; Sindlinger, T.; Moreno-Villanueva, M.; Keller, A.; Sabin, C.; de Francesco, D.; Libert, C.; Dewaele, S.

2017-01-01

Abstract Background. Increased monocyte activation and intestinal damage have been shown to be predictive for the increased morbidity and mortality observed in treated people living with human immunodeficiency virus (PLHIV). Methods. A cross-sectional analysis of cellular and soluble markers of monocyte activation, coagulation, intestinal damage, and inflammation in plasma and cerebrospinal fluid (CSF) of PLHIV with suppressed plasma viremia on combination antiretroviral therapy and age and demographically comparable HIV-negative individuals participating in the Comorbidity in Relation to AIDS (COBRA) cohort and, where appropriate, age-matched blood bank donors (BBD). Results. People living with HIV, HIV-negative individuals, and BBD had comparable percentages of classical, intermediate, and nonclassical monocytes. Expression of CD163, CD32, CD64, HLA-DR, CD38, CD40, CD86, CD91, CD11c, and CX3CR1 on monocytes did not differ between PLHIV and HIV-negative individuals, but it differed significantly from BBD. Principal component analysis revealed that 57.5% of PLHIV and 62.5% of HIV-negative individuals had a high monocyte activation profile compared with 2.9% of BBD. Cellular monocyte activation in the COBRA cohort was strongly associated with soluble markers of monocyte activation and inflammation in the CSF. Conclusions. People living with HIV and HIV-negative COBRA participants had high levels of cellular monocyte activation compared with age-matched BBD. High monocyte activation was predictive for inflammation in the CSF. PMID:28680905

High Cellular Monocyte Activation in People Living With Human Immunodeficiency Virus on Combination Antiretroviral Therapy and Lifestyle-Matched Controls Is Associated With Greater Inflammation in Cerebrospinal Fluid.

PubMed

Booiman, Thijs; Wit, Ferdinand W; Maurer, Irma; De Francesco, Davide; Sabin, Caroline A; Harskamp, Agnes M; Prins, Maria; Garagnani, Paolo; Pirazzini, Chiara; Franceschi, Claudio; Fuchs, Dietmar; Gisslén, Magnus; Winston, Alan; Reiss, Peter; Kootstra, Neeltje A

2017-01-01

Increased monocyte activation and intestinal damage have been shown to be predictive for the increased morbidity and mortality observed in treated people living with human immunodeficiency virus (PLHIV). A cross-sectional analysis of cellular and soluble markers of monocyte activation, coagulation, intestinal damage, and inflammation in plasma and cerebrospinal fluid (CSF) of PLHIV with suppressed plasma viremia on combination antiretroviral therapy and age and demographically comparable HIV-negative individuals participating in the Comorbidity in Relation to AIDS (COBRA) cohort and, where appropriate, age-matched blood bank donors (BBD). People living with HIV, HIV-negative individuals, and BBD had comparable percentages of classical, intermediate, and nonclassical monocytes. Expression of CD163, CD32, CD64, HLA-DR, CD38, CD40, CD86, CD91, CD11c, and CX3CR1 on monocytes did not differ between PLHIV and HIV-negative individuals, but it differed significantly from BBD. Principal component analysis revealed that 57.5% of PLHIV and 62.5% of HIV-negative individuals had a high monocyte activation profile compared with 2.9% of BBD. Cellular monocyte activation in the COBRA cohort was strongly associated with soluble markers of monocyte activation and inflammation in the CSF. People living with HIV and HIV-negative COBRA participants had high levels of cellular monocyte activation compared with age-matched BBD. High monocyte activation was predictive for inflammation in the CSF. © The Author 2017. Published by Oxford University Press on behalf of Infectious Diseases Society of America.

Kaposi's sarcoma: Good outcome with doxorubicin, bleomycin and vincristine sulphate (ABV) chemotherapy and highly active antiretroviral therapy.

PubMed

Hesseling, P B; Katayi, E; Wharin, P; Bardin, R; Kouya, F; Palmer, D; Glenn, M; Kruger, M

2017-10-31

There is little published information on effective treatment of Kaposi's sarcoma (KS) in children in low-income countries. We prospectively treated 12 patients with an institutional review board-approved protocol consisting of four monthly courses of doxorubicin (Adriamycin), bleomycin and vincristine sulphate (ABV), with highly active antiretroviral therapy (HAART) plus co-trimoxazole prophylaxis for those who were HIV-positive, with additional vincristine if remission was not achieved after 4 months. Maintenance HAART plus co-trimoxazole was given to all HIV-positive patients. A fine-needle aspirate and CD4+ count were done if possible, and staging was performed according to Mitsuyasu. Eight of ten HIV-positive patients with stage III - IVB disease, and both HIV-negative patients with stage I disease, were in remission after 473 - 1 490 (mean 939) days. One patient died after absconding during treatment, and one died from neutropenia-related pulmonary infection. ABV with or without HAART is an effective treatment option for children with KS.

[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.

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

The effect of individual antiretroviral drugs on body composition in HIV-infected persons initiating highly active antiretroviral therapy.

PubMed

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

2009-07-01

To examine the long-term effects of individual antiretroviral drugs on body composition among 416 persons initiating antiretroviral therapy (ART). In a substudy of a clinical trial of persons initiating ART, changes in body composition attributable to individual ART were examined. ARTs assessed were as follows: indinavir, ritonavir, nelfinavir, efavirenz, nevirapine, stavudine (d4T), zidovudine (ZDV), lamivudine (3TC), didanosine, and abacavir. Skinfolds and circumferences were measured at baseline and every 4 months. Mid arm, mid thigh, and waist subcutaneous tissue areas and nonsubcutaneous tissue areas were calculated. Rates of change per year of exposure to each individual ART drug were determined using multivariate longitudinal regression. d4T and ZDV use was associated with losses in subcutaneous tissue area and skinfold thickness. 3TC use was associated with gains in all subcutaneous tissue areas and skinfold thickness, whereas abacavir use was associated with an increase in waist subcutaneous tissue area. Indinavir was associated with gains in waist subcutaneous tissue area, whereas indinavir, efavirenz, and nevirapine were associated with increases in upper back skinfolds. d4T use was also associated with increases in all nonsubcutaneous tissue areas; 3TC use was associated with the greatest increase in waist nonsubcutaneous tissue area. In this prospective nonrandomized evaluation, the nucleoside reverse transcriptase inhibitors d4T and ZDV were associated with decreases in subcutaneous tissue areas, whereas 3TC use was associated with increased subcutaneous tissue areas and waist nonsubcutaneous tissue area.

Adherence to and effectiveness of highly active antiretroviral treatment for HIV infection: assessing the bidirectional relationship.

PubMed

Lamiraud, Karine; Moatti, Jean-Paul; Raffi, François; Carrieri, Maria-Patrizia; Protopopescu, Camelia; Michelet, Christian; Schneider, Luminita; Collin, Fideline; Leport, Catherine; Spire, Bruno

2012-05-01

It is well established that high adherence to HIV-infected patients on highly active antiretroviral treatment (HAART) is a major determinant of virological and immunologic success. Furthermore, psychosocial research has identified a wide range of adherence factors including patients' subjective beliefs about the effectiveness of HAART. Current statistical approaches, mainly based on the separate identification either of factors associated with treatment effectiveness or of those associated with adherence, fail to properly explore the true relationship between adherence and treatment effectiveness. Adherence behavior may be influenced not only by perceived benefits-which are usually the focus of related studies-but also by objective treatment benefits reflected in biological outcomes. Our objective was to assess the bidirectional relationship between adherence and response to treatment among patients enrolled in the ANRS CO8 APROCO-COPILOTE study. We compared a conventional statistical approach based on the separate estimations of an adherence and an effectiveness equation to an econometric approach using a 2-equation simultaneous system based on the same 2 equations. Our results highlight a reciprocal relationship between adherence and treatment effectiveness. After controlling for endogeneity, adherence was positively associated with treatment effectiveness. Furthermore, CD4 count gain after baseline was found to have a positive significant effect on adherence at each observation period. This immunologic parameter was not significant when the adherence equation was estimated separately. In the 2-equation model, the covariances between disturbances of both equations were found to be significant, thus confirming the statistical appropriacy of studying adherence and treatment effectiveness jointly. Our results, which suggest that positive biological results arising as a result of high adherence levels, in turn reinforce continued adherence and strengthen the argument

Association of complementary and alternative medicine use with highly active antiretroviral therapy initiation.

PubMed

Merenstein, Daniel; Yang, Yang; Schneider, Michael F; Goparaju, Lakshmi; Weber, Kathleen; Sharma, Anjali; Levine, Alexandra M; Sharp, Gerald B; Gandhi, Monica; Liu, Chenglong

2008-01-01

To assess whether complementary and alternative medicine (CAM) use is associated with the timing of highly active antiretroviral therapy (HAART) initiation among human immunodeficiency virus (HIV)-infected participants of the Women's Interagency HIV Study. Prospective cohort study between January 1996 and March 2002. Differences in the cumulative incidence of HAART initiation were compared between CAM users and non-CAM users using a logrank test. Cox regression model was used to assess associations of CAM exposures with time to HAART initiation. MAIN OUTCOME AND EXPOSURES: Study outcome was time from January 1996 to initiation of HAART. Primary exposure was use of any CAM modality before January 1996, and secondary exposures included the number and type of CAM modalities used (ingestible CAM medication, body practice, or spiritual healing) during the same period. One thousand thirty-four HIV-infected women contributed a total of 4987 person-visits during follow-up. At any time point, the cumulative incidence of HAART initiation among CAM users was higher than that among non-CAM users. After adjustment for potential confounders, those reporting CAM use were 1.34 times (95% confidence interval: 1.09, 1.64) more likely to initiate HAART than non-CAM users. Female CAM users initiated HAART regimens earlier than non-CAM users. Initiation of HAART is an important clinical marker, but more research is needed to elucidate the role specific CAM modalities play in HIV disease progression.

ASSOCIATION OF COMPLEMENTARY AND ALTERNATIVE MEDICINE USE WITH HIGHLY ACTIVE ANTIRETROVIRAL THERAPY INITIATION

PubMed Central

Merenstein, Daniel; Yang, Yang; Schneider, Michael F.; Goparaju, Lakshmi; Weber, Kathleen; Sharma, Anjali; Levine, Alexandra M.; Sharp, Gerald B.; Gandhi, Monica; Liu, Chenglong

2009-01-01

Objective To assess whether complementary and alternative medicine (CAM) use is associated with the timing of highly active antiretroviral therapy (HAART) initiation among human immunodeficiency virus (HIV)–infected participants of the Women’s Interagency HIV Study. Study Methods Prospective cohort study between January 1996 and March 2002. Differences in the cumulative incidence of HAART initiation were compared between CAM users and non–CAM users using a logrank test. Cox regression model was used to assess associations of CAM exposures with time to HAART initiation. Main Outcome and Exposures Study outcome was time from January 1996 to initiation of HAART. Primary exposure was use of any CAM modality before January 1996, and secondary exposures included the number and type of CAM modalities used (ingestible CAM medication, body practice, or spiritual healing) during the same period. Results One thousand thirty-four HIV-infected women contributed a total of 4987 person-visits during follow-up. At any time point, the cumulative incidence of HAART initiation among CAM users was higher than that among non–CAM users. After adjustment for potential confounders, those reporting CAM use were 1.34 times (95% confidence interval: 1.09, 1.64) more likely to initiate HAART than non–CAM users. Conclusion Female CAM users initiated HAART regimens earlier than non–CAM users. Initiation of HAART is an important clinical marker, but more research is needed to elucidate the role specific CAM modalities play in HIV disease progression. PMID:18780580

Iatrogenic osteoporosis, bilateral HIP osteonecrosis, and secondary adrenal suppression in an HIV-infected man receiving inhaled corticosteroids and ritonavir-boosted highly active antiretroviral therapy.

PubMed

Kaviani, Nargess; Bukberg, Phillip; Manessis, Anastasios; Yen, Vincent; Young, Iven

2011-01-01

To report the first case of severe osteoporosis associated with a vertebral pathologic fracture and osteonecrosis of femoral heads in an HIV-infected man receiving inhaled corticosteroids and ritonavir-boosted antiretroviral therapy. We describe an HIV-infected man with severe osteoporosis, bilateral hip osteonecrosis, and secondary adrenal suppression, including detailed clinical, laboratory, and radiographic data, and review the related literature. A 60-year-old man with a 15-year history of HIV infection and a medical history of long-standing bronchiectasis treated with inhaled corticosteroids and hypogonadism treated with testosterone was referred to the endocrinology clinic after experiencing an osteoporotic vertebral fracture. He was taking ritonavir-boosted antiretroviral therapy. Osteonecrosis of both hips was also diagnosed, which required total hip replacement therapy. Laboratory evaluation revealed adrenal insufficiency due to increased effect of exogenous inhaled steroids and no other secondary causes of osteoporosis. A bone densitometry study showed osteoporosis of both hips and the lumbar spine. He was treated with intravenous pamidronate. During treatment, he developed bilateral femoral fractures after minor trauma. Given the potential for increased serum levels of inhaled corticosteroids in patients taking ritonavir-boosted highly active antiretroviral therapy, attention must be paid to the risk of bone loss in HIV-infected patients taking inhaled corticosteroids. Prescribing calcium and vitamin D supplementation and considering early osteoporosis screening are reasonable measures for this patient population. Interaction between inhaled corticosteroids and ritonavir may increase risk of hypothalamus-pituitary-adrenal axis suppression.

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

Pharmacokinetics of Antiretrovirals in Mucosal Tissue

PubMed Central

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

2015-01-01

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

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

Dual Candida albicans and Cryptococcus neoformans fungaemia in an AIDS presenter: a unique disease association in the highly active antiretroviral therapy (HAART) era.

PubMed

Manfredi, Roberto; Calza, Leonardo; Chiodo, Francesco

2002-12-01

A case report of a patient who discovered his HIV infection concurrently with an advanced immunodeficiency and a dual Candida albicans and Cryptococcus neoformans fungaemia is discussed with reference to the changing epidemiology and clinical features of HIV infection and AIDS in the highly active antiretroviral therapy (HAART) era. The tendency to develop multiple concomitant AIDS-defining illnesses at the time of first hospitalisation seems to be an increasing feature in patients who remain unaware of or neglect their HIV disease and who are still at risk of opportunist infections even with the availability of HAART.

Increasingly successful highly active antiretroviral therapy delays the emergence of new HLA class I-associated escape mutations in HIV-1.

PubMed

Knapp, David J H F; Brumme, Zabrina L; Huang, Sheng Yuan; Wynhoven, Brian; Dong, Winnie W Y; Mo, Theresa; Harrigan, P Richard; Brumme, Chanson J

2012-06-01

HLA class I-restricted cytotoxic T lymphocytes and highly active antiretroviral therapy (HAART) exert strong selective pressures on human immunodeficiency virus type 1 (HIV-1), leading to escape mutations compromising virologic control. Immune responses continue to shape HIV-1 evolution after HAART initiation, but the extent and rate at which this occurs remain incompletely quantified. Here, we characterize the incidence and clinical correlates of HLA-associated evolution in HIV-1 Pol after HAART initiation in a large, population-based observational cohort. British Columbia HAART Observational, Medical Evaluation and Research cohort participants with available HLA class I types and longitudinal posttherapy protease/reverse transcriptase sequences were studied (n = 619; median, 5 samples per patient and 5.2 years of follow-up). HLA-associated polymorphisms were defined according to published reference lists. Rates and correlates of immune-mediated HIV-1 evolution were investigated using multivariate Cox proportional hazard models incorporating baseline and time-dependent plasma viral load and CD4 response data. New HLA-associated escape events were observed in 269 (43%) patients during HAART and occurred at 49 of 63 (78%) investigated immune-associated sites in Pol. In time-dependent analyses adjusting for baseline factors, poorer virologic, but not immunologic, response to HAART was associated with increased risk of immune escape of 1.9-fold per log(10) viral load increment (P < .0001). Reversion of escape mutations following HAART initiation was extremely rare. HLA-associated HIV-1 evolution continues during HAART to an extent that is inversely related to the virologic success of therapy. Minimizing the degree of immune escape could represent a secondary benefit of effective HAART.

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.

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

Antiretroviral therapy in HIV-1-infected individuals with CD4 count below 100 cells/mm3 results in differential recovery of monocyte activation

PubMed Central

Patro, Sean C.; Azzoni, Livio; Joseph, Jocelin; Fair, Matthew G.; Sierra-Madero, Juan G.; Rassool, Mohammed S.; Sanne, Ian; Montaner, Luis J.

2016-01-01

Reversal of monocyte and macrophage activation and the relationship to viral suppression and T cell activation are unknown in patients with advanced HIV-1 infection, initiating antiretroviral therapy. This study aimed to determine whether reduction in biomarkers of monocyte and macrophage activation would be reduced in conjunction with viral suppression and resolution of T cell activation. Furthermore, we hypothesized that the addition of CCR5 antagonism (by maraviroc) would mediate greater reduction of monocyte/macrophage activation markers than suppressive antiretroviral therapy alone. In the CCR5 antagonism to decrease the incidence of immune reconstitution inflammatory syndrome study, antiretroviral therapy-naïve patients received maraviroc or placebo in addition to standard antiretroviral therapy. PBMCs and plasma from 65 patients were assessed during 24 wk of antiretroviral therapy for biomarkers of monocyte and macrophage activation. Markers of monocyte and macrophage activation were reduced significantly by 24 wk, including CD14++CD16+ intermediate monocytes (P < 0.0001), surface CD163 (P = 0.0004), CD169 (P < 0.0001), tetherin (P = 0.0153), and soluble CD163 (P < 0.0001). A change in CD38+, HLA-DR+ CD8 T cells was associated with changes in CD169 and tetherin expression. Maraviroc did not affect biomarkers of monocyte/macrophage activation but resulted in greater percentages of CCR5-positive monocytes in PBMC. HIV-1 suppression after 24 wk of antiretroviral therapy, with or without maraviroc, demonstrates robust recovery in monocyte subset activation markers, whereas soluble markers of activation demonstrate minimal decrease, qualitatively differentiating markers of monocyte/macrophage activation in advanced disease. PMID:26609048

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.

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

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.

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).

"Damaging what wasn't damaged already": psychological tension and antiretroviral adherence among HIV-infected methadone-maintained drug users.

PubMed

Batchelder, A W; Brisbane, M; Litwin, A H; Nahvi, S; Berg, K M; Arnsten, J H

2013-01-01

Active drug use among HIV-infected persons is associated with poor adherence to highly active antiretroviral therapy (HAART) and suboptimal treatment outcomes. To understand adherence experiences among HIV-infected drug users, we conducted semistructured interviews with 15 participants in a randomized controlled trial evaluating the efficacy of directly observed HAART delivered in methadone maintenance clinics. Interviews were recorded, transcribed, and thematically analyzed. We identified negative and positive psychological themes associated with both drug use and adherence. Participants described tension between negative feelings (denial, shame, and perceived isolation) and positive feelings (acceptance, motivation, empowerment, and perceived connectedness), and they associated this tension with their own drug using and adherence behaviors. Sustained antiretroviral therapy adherence may require increased emphasis on understanding the psychological experience of HIV-infected drug users.

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.

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.

AIDS incidence and mortality in a hospital-based cohort of HIV-1-seropositive patients receiving highly active antiretroviral therapy in São Paulo, Brazil.

PubMed

Casseb, Jorge; Fonseca, Luiz Augusto Marcondes; Veiga, Ana Paula Rocha; de Almeida, Alexandre; Bueno, Analice; Ferez, Antonio Carlos; Gonsalez, Claudio R; Brigido, Luis F M; Mendonça, Marcelo; Rodrigues, Rosangela; Santos, Niraldo; Malacarne, Eunice; Ronchini, Karla O M; Zihlmann, Karina F; Duarte, Alberto J S

2003-09-01

Brazilian AIDS and HIV-1-seropositive patients have had free access to highly active antiretroviral therapy (HAART) since November 1996. Although secondary data based on official mortality statistics indicate a sharp decrease in AIDS mortality, few if any studies tried to estimate the prognosis for patients with HIV who have been followed from the beginning of the HAART era. An observational study, with retrospective and prospective components, was done in 233 adult HIV-1-infected subjects who were recruited in the last 10 years at the outpatient sector of the Secondary Immunodeficiencies Clinic of the Department of Dermatology, Hospital das Clinicas da FMUSP, Sao Paulo, Brazil. The definition of AIDS followed the guidelines issued by the Centers for Disease Control (CDC) in 1987. One hundred sixty patients were asymptomatic, 46 had AIDS, 24 had AIDS-related complex, and 3 presented with acute infection at study entry. Twenty-nine (18%) of the asymptomatic subjects developed AIDS during follow-up, with 5 (3%) deaths. Among the 46 AIDS cases at entry, 7 (17%) died during follow-up. Thus, a total of 12 people (5.2%) died of AIDS in this cohort over a mean follow-up of 5.2 years and 24 people were lost to follow-up (10.3%). Ninety percent of the survivors were on combined therapy (82% with 3 or more drugs, and 8% with 2 drugs), while 10% were not taking antiretrovirals. People with AIDS at entry were 5 times more likely to die during this period compared to patients who were asymptomatic at entry (p = 0.006). Women showed better outcomes than men, reflecting differences in CD4+ T-cell counts at study entry. All but 1 patient progressed to AIDS during the pre-HAART era (before 1996). In spite of its recent decline, mortality from AIDS-related conditions remains an important public health issue.

Incidence of anaemia among HIV-infected patients treated with highly active antiretroviral therapy.

PubMed

Curkendall, S M; Richardson, J T; Emons, M F; Fisher, A E; Everhard, F

2007-11-01

The aim of the study was to compare the incidence of anaemia in patients treated with zidovudine (ZDV) with that in patients treated with highly active antiretroviral therapy (HAART) not including ZDV. Using HIV Insight, a database of abstracted US HIV care centre medical charts, ZDV-naïve patients starting ZDV-containing HAART were compared with those starting non-ZDV, nucleoside reverse transcriptase inhibitor-containing HAART. Cohorts were divided as follows: group 1: without baseline anaemia [haemoglobin (Hb) >or=11 g/dL]; group 2: with baseline anaemia (Hb <11 g/dL). The incidence of anaemia (anaemia diagnosis, Hb <11 g/dL, erythropoietic therapy or blood transfusion) was computed for group 1. The anaemia hazard ratio (HR) was adjusted using Cox regression. The rate of worsening anaemia (Hb decrease >or=1.0 g/dL) was computed for group 2. In group 1, the incidence of anaemia was 24.3 and 8.1 per 100 person-years in the ZDV and non-ZDV cohorts, respectively, after 6 months of follow-up, and 12.5 and 5.3 per 100 person-years after 24 months. Significant predictors of anaemia were ZDV, low initial Hb, injecting drug use, CD4 count <200 cells/microL and AIDS. The adjusted HR for ZDV was 1.6 (P=0.005). In group 2, the ZDV/non-ZDV risk ratio for worsening anaemia was 2.2 (95% confidence interval 1.1-4.3). Patients initiating ZDV-containing HAART are at greater risk of developing new anaemia or worsening anaemia than patients initiating non-ZDV-containing HAART.

Effect of antiretroviral therapy use and adherence on the risk of hyperlipidemia among HIV-infected patients, in the highly active antiretroviral therapy era

PubMed Central

Tsai, Fuu-Jen; Cheng, Chi-Fung; Lai, Chih-Ho; Wu, Yang-Chang; Ho, Mao-Wang; Wang, Jen-Hsien; Tien, Ni; Liu, Xiang; Tsang, Hsinyi; Lin, Ting-Hsu; Liao, Chiu-Chu; Huang, Shao-Mei; Li, Ju-Pi; Lin, Jung-Chun; Lin, Chih-Chien; Chen, Jin-Hua; Liang, Wen-Miin; Lin, Ying-Ju

2017-01-01

HIV-infected patients exposed to antiretroviral therapy (ART) have an increased risk for hyperlipidemia and cardiovascular disease. We performed a longitudinal, comprehensive, and population-based study to investigate the cumulative effect of different types of ART regimens on hyperlipidemia risk in the Taiwanese HIV/ART cohort. A total of 13,370 HIV-infected patients (2,674 hyperlipidemia and 10,696 non-hyperlipidemia patients) were recruited after matching for age, gender, and the first diagnosis date of HIV infection by using the National Health Insurance Research Database in Taiwan. Hyperlipidemia risk associated with cumulative ART use, ART adherence, and their combination was assessed. The matched hyperlipidemia group had a larger number of patients using ART and a higher incidence of comorbidities, specifically, respiratory disease and diabetes. Patients with high ART dosage and dose-dependent manner adherence, respectively, demonstrated an increased risk of hyperlipidemia. For single ART regimens, patients receiving nucleoside reverse-transcriptase inhibitors (NRTI/NRTI)- containing regimen had the highest hyperlipidemia risk, followed by protease inhibitor (PI)- containing and non-NRTI- containing regimens. For combination ART regimens, patients receiving a NRTI/NRTI + PI regimen had the highest hyperlipidemia risk. An increased cumulative drug dose was observed in patients who received the PI, NRTI/NRTI, NRTI, and NNRTI regimens in the hyperlipidemia group, when compared to the non-hyperlipidemia group. In conclusion, ART cumulative use, adherence, and regimen may affect hyperlipidemia risk among HIV-infected patients in a dose-dependent manner. PMID:29290955

[Impact of highly active antiretroviral therapy in the clinical, immunological and virological response from AIDS patients].

PubMed

Reyes Corcho, Andrés; Mosquera Fernández, Miguel A; Bouza Jiménez, Yanelka; Pérez Avila, Jorge; Hernández, Vivian; Jam Morales, Blas; Alvarez Amador, Gustavo; Bouza Jiménez, Yadira

2007-01-01

A longitudinal prospective study was made to evaluate the clinical, immunological and virological response of a cohort of 34 AIDS patients in Cienfuegos provinces, who had been treated with highly active antiretroviral therapy (HAART). Males comprised 67.6% of the total number and average age was 32 years. Sexual infection path was identified in 91.2% of cases. The CD4+ T counting under 200 cells defined AIDS in 79.4% of individuals. Twenty six patients suffered minor opportunistic infections (76.5%) whereas 32.4% got sick due to some major opportunistic disease prior to the therapy. After this therapy, these frequencies lowered to 20.6% and 11.8% respectively. Average CD4+ counting at the starting of HAART was 196 cell/mm3 and exceeded 400 cells in the rest of further countings. From a PVC average of 15 251 copies/mL one year after therapy, this figure reduced to 8 048 copies at 2 years. Only 10 cases required hospitalization after a HAART (29.4%). Treatment adherence reached over 80% and was correlated to immunological restoration. Survival after one year was 100% and only 2 patients died in the following 4 years. The positive impact of HAART on the frequency of opportunistic infections, immunological restoration and survival was proved.

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

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.

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

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

Association of Helicobacter pylori infection with the metabolic syndrome among HIV-infected black Africans receiving highly active antiretroviral therapy

PubMed Central

Longo-Mbenza, Benjamin; Apalata, Teke; Longokolo, Murielle; Mbula Mambimbi, Marcel; Etienne, Mokondjimobe; Buassa-bu-Tsumbu, Baudouin; Gombet, Thierry; Ellenga, Bertrain; Milongo Dipa, Guy; Lukoki Luila, Evelyne; Nge Okwe, Augustin

2015-01-01

Summary Introduction The metabolic syndrome (MetS) is common in human immune deficiency virus (HIV)-infected individuals receiving highly active antiretroviral therapy (HAART). Immune deficiencies caused by HIV give rise to numerous opportunistic gastrointestinal pathogens such as Helicobacter pylori, the commonest cause of chronic gastritis. The study sought to determine the relationship between H pylori infection and the MetS among HIV-infected clinic attendees. Methods This cross-sectional study was carried out in a specialised heart clinic in Kinshasa, DR Congo. Between January 2004 and December 2008, 116 HIV-infected patients (61 with MetS and 55 without MetS) who underwent upper gastrointestinal endoscopy for dyspeptic symptoms were included in the study following an informed consent. Univariate associations were determined by odds ratios (OR), while multivariate logistic regression analysis was used to identify factors associated with the MetS. Results H pylori infection (OR = 13.5, 95% CI: 10.3–17.6; p < 0.0001) and peripheral obesity (median hip circumference ≥ 97 cm) (OR = 4.7, 95% CI: 1.2–18.8; p = 0.029) were identified as MetS-related factors in HIV-infected patients. Higher rates of the MetS were associated with increased incidence of HIV-related immunocompromise using World Health Organisation (WHO) staging criteria. There was a univariate significant difference in the prevalence of the MetS between antiretroviral therapy (ART)-naïve patients and patients treated by means of a first-line HAART regimen of stavudine (d4T), lamivudine (3TC) and nevirapine (NVP). However, this difference was not significant in multivariate logistic analysis. Conclusion H pylori infection was significantly associated with the MetS in HIV-infected patients. PMID:25940117

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.

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

PubMed

Nattrass, Nicoli J

2008-12-01

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

[Stopping secondary prevention in AIDS patients with inactive CMV retinitis treated with HAART (highly active antiretroviral therapy)].

PubMed

Best, J; Althaus, C; Kersten, A; Theisen, A; Gantke, B

2000-08-01

Immune recovery of AIDS patients with cytomegalovirus (CMV) retinitis treated and healed by highly active antiretroviral therapy (HAART) is reflected by increased CD4 cell count and decreased virus load. Due to partial reconstitution of the immune status the risk of opportunistic infections decreases, as well as the risk of reactivating inactive CMV retinitis. It may therefore be possible to stop anti-CMV maintenance therapy may after HAART-induced immune recovery. We present six patients (nine eyes) with a follow-up of 9.5 months (range 7-12 months) after cessation of the CMV-specific maintenance therapy (five orally, one intravenously). There was no reactivation of retinal CMV infection during the follow-up period. The virus load (< 50 Eq/ml; a single value of one patient was 2047 Eq/ml) and CD4 cell counts (range 207-454/microliter; mean: 313/microliter) remained stable during the follow-up period, reflecting immune recovery. Our findings confirm the expected low risk of retinal CMV reactivation after immune recovery in AIDS patients receiving HAART without secondary prophylaxis with an anti-CMV maintenance therapy. Regular ophthalmic and medical follow-up is mandatory in these patients. Cessation of maintenance therapy represents a major improvement in quality of live in AIDS patients.

Increased soluble vascular cell adhesion molecule-1 plasma levels and soluble intercellular adhesion molecule-1 during antiretroviral therapy interruption and retention of elevated soluble vascular cellular adhesion molecule-1 levels following resumption of antiretroviral therapy.

PubMed

Papasavvas, Emmanouil; Azzoni, Livio; Pistilli, Maxwell; Hancock, Aidan; Reynolds, Griffin; Gallo, Cecile; Ondercin, Joe; Kostman, Jay R; Mounzer, Karam; Shull, Jane; Montaner, Luis J

2008-06-19

We investigated the effect of short viremic episodes on soluble markers associated with endothelial stress and cardiovascular disease risk in chronically HIV-1-infected patients followed during continuous antiretroviral therapy, antiretroviral therapy interruption and antiretroviral therapy resumption. We assessed changes in plasma levels of von Willebrand factor, soluble vascular cell adhesion molecule-1 and intercellular adhesion molecule-1 by enzyme-linked immunosorbent assay, as well as T-cell activation (CD8+/CD38+, CD8+/HLA-DR+ and CD3+/CD95+) by flow cytometry, in 36 chronically HIV-1-infected patients participating in a randomized study. Patients were divided into the following three groups: a, on continuous antiretroviral therapy; b, on a 6-week antiretroviral therapy interruption; or c, on antiretroviral therapy interruption extended to the achievement of viral set point. Although all measurements remained stable over a 40-week follow-up on antiretroviral therapy, plasma levels of soluble vascular cell adhesion molecule-1 (P < 0.0001) and soluble intercellular adhesion molecule-1 (P = 0.003) increased during treatment interruption in correlation with viral rebound and T-cell activation. No significant changes in von Willebrand factor were observed in any of the groups. After resuming antiretroviral therapy, soluble vascular cell adhesion molecule-1 levels remained elevated even after achievement of viral suppression to less than 50 copies/ml. The prompt rise in plasma soluble vascular cell adhesion molecule-1 and soluble intercellular adhesion molecule-1 upon viral rebound suggests an acute increase in endothelial stress upon treatment interruption, which may persists after viral resuppression of virus. Thus, viral replication during short-term treatment interruption may increase the overall cardiovascular risk during and beyond treatment interruption.

Prices paid for adult and paediatric antiretroviral treatment by low- and middle-income countries in 2012: high, low or just right?

PubMed

Perriëns, Joseph H; Habiyambere, Vincent; Dongmo-Nguimfack, Boniface; Hirnschall, Gottfried

2014-01-01

A viable market for antiretroviral drugs in low- and middle-income countries is key to the continued scale-up of antiretroviral treatment. We describe the price paid by low- and middle-income countries for 10 first- and 7 second-line adult and paediatric treatment regimens from 2003 to 2012, and compare the price of their finished formulations with the price of their active pharmaceutical ingredients in 2005, 2007, 2010 and 2012. Between 2003 and 2012 the median price of adult first-line treatment regimens per treatment-year decreased from USD499 to USD122, and that of second-line regimens from USD2,934 to USD497. In 2005 adult formulations were sold for a price 170% higher than the cost of their active pharmaceutical ingredients. This margin had decreased to 28% in 2012. Between 2004 and 2013, the price of paediatric treatment per treatment-year decreased from USD585 to USD147 for first-line and from USD763 to USD288 for second-line treatment. In 2005, paediatric treatment regimens were sold at a price 231% higher than the cost of their active pharmaceutical ingredients. This margin remained high and was 195% in 2012. The prices paid for antiretroviral drugs by low- and middle-income countries decreased between 2003 and 2012. Although the margins on their sale decreased, there is likely still space for price reduction, especially for the more recent World Health Organization recommended adult first-line regimens and for paediatric treatment.

Trends in causes of death among persons with acquired immunodeficiency syndrome in the era of highly active antiretroviral therapy, San Francisco, 1994-1998.

PubMed

Louie, Janice K; Hsu, Ling Chin; Osmond, Dennis H; Katz, Mitchell H; Schwarcz, Sandra K

2002-10-01

To understand recent temporal trends in acquired immunodeficiency syndrome (AIDS) mortality in the era of highly active antiretroviral therapy (HAART), trends in causes of death among persons with AIDS in San Francisco who died between 1994 and 1998 were analyzed. Among 5234 deaths, the mortality rate for human immunodeficiency virus (HIV)-related or AIDS-related deaths declined after 1995 (P<.01), whereas the mortality rate for non-HIV- or non-AIDS-related deaths remained stable. The proportion of deaths of persons with AIDS associated with septicemia, non-AIDS-defining malignancy, chronic liver disease, viral hepatitis, overdose, obstructive lung disease, coronary artery disease, and pancreatitis increased (P<.05). The standardized mortality ratio was high for these causes in both pre- and post-HAART periods, except for pancreatitis, a possible complication of HAART, which demonstrated an increasing standardized mortality ratio trend after 1996. With increasing AIDS survival, prevention of chronic diseases, assessment of long-term toxicity from HAART, and surveillance for additional causes of mortality will become increasingly important.

An evaluation of serum soluble CD30 levels and serum CD26 (DPPIV) enzyme activity as markers of type 2 and type 1 cytokines in HIV patients receiving highly active antiretroviral therapy

PubMed Central

Keane, N M; Price, P; Lee, S; Stone, S F; French, M A

2001-01-01

This study evaluates serum CD26 (dipeptidyl peptidase IV, DPPIV) enzyme activity and serum levels of soluble CD30 as markers of T1 and T2 cytokine environments in HIV patients who achieved immune reconstitution after highly active antiretroviral therapy (HAART). Patients who had experienced inflammatory disease associated with pre-existent opportunistic infections after HAART (immune restoration diseases, IRD) were considered separately. Serum sCD30 levels and CD26 (DPPIV) enzyme activity were compared with IFN-γ production by PBMC cultured with cytomegalovirus (CMV) antigen in controls and patient groups. High sCD30 levels were associated with low IFN-γ production after antigenic stimulation in control subjects and, to a lesser extent, in immune reconstituted HIV patients. There was no association between serum CD26 (DPPIV) enzyme activity and IFN-γ production or sCD30 levels. Serum sCD30 levels and CD26 (DPPIV) enzyme activity were significantly increased in immune reconstituted patients with high HIV viral loads. Patients who had experienced CMV retinitis as an IRD had significantly higher sCD30 levels than all other patient groups. Hence, high sCD30 levels may be a marker of a T2 cytokine environment in HIV patients with immune reconstitution and are associated with higher HIV viral loads and a history of CMV associated IRD. PMID:11678906

Diet quality of persons living with HIV/AIDS on highly active antiretroviral therapy.

PubMed

Duran, A C F L; Almeida, L B; Segurado, A A C; Jaime, P C

2008-08-01

This study sought to assess the diet quality of individuals living with HIV/AIDS who were receiving antiretroviral therapy in São Paulo, Brazil. This cross-sectional study involved 56 HIV-infected adults. Demographic and anthropometric data were collected, and diet quality was measured using the Healthy Eating Index (HEI), modified for Brazilians, which included ten components: adequacy of intake of six different food groups, total fat, cholesterol, dietary fibre and dietary variety. Among the individuals assessed, 64.3% of the participants had a diet needing improvement, while 8.7% had a poor diet. The overall HEI score was 68.3 points (SD = 14.9). Mean scores were low for fruits, vegetables, dairy products and dietary fibre; and high for meats and eggs, total fat and cholesterol. The overall HEI score was higher among individuals who were not overweight (P = 0.003), who were also more likely to achieve dietary goals for dairy products (P = 0.039) and grains (P = 0.005). Most of these adults living with HIV/AIDS had diets that required improvement, and being overweight was associated with poorer diet quality. Nutritional interventions aimed at maintaining healthy body weight and diet should be taken into account in caring for HIV-infected people.

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

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.

Highly active antiretroviral therapy in Brazil: the challenge of universal access in a context of social inequality.

PubMed

Hacker, Mariana A; Petersen, Maya L; Enriquez, Melissa; Bastos, Francisco I

2004-08-01

To investigate trends in AIDS mortality and incidence in Brazil over the period of 1984 to 2000 and to assess the impact of the introduction of universal access to highly active antiretroviral therapy (HAART) in the country in 1996. Data from the Brazilian disease notification system and the national mortality information system were used to calculate annual region-specific and sex-specific AIDS incidence and mortality rates. We also calculated sex- and region-specific ratios of the number of AIDS deaths in one year to the number of AIDS cases notified two years earlier. AIDS mortality rates for both men and women and in all five of the geographic regions of Brazil declined following introduction of HAART, despite continued growth in AIDS incidence. The ratio of the number of AIDS deaths in one year to the number of AIDS cases notified two years earlier for men equalized rapidly with the ratio for women following introduction of HAART. More recently, AIDS incidence declined for both sexes and in most of the regions of Brazil. Despite Brazil's resource limitations and disparities in wealth between men and women and among the country's regions, the introduction of universal access to HAART in Brazil has helped achieve impressive declines in AIDS mortality, and it may also be contributing to declines in AIDS incidence.

In-vitro photo-translocation of antiretroviral drug delivery into TZMbl cells

NASA Astrophysics Data System (ADS)

Malabi, Rudzani; Manoto, Sello; Ombinda-Lemboumba, Saturnin; Maaza, Malik; Mthunzi-Kufa, Patience

2017-02-01

The current human immunodeficiency virus (HIV) treatment regime possesses the ability to diminish the viral capacity to unnoticeable levels; however complete eradication of the virus cannot be achieved while latent HIV-1 reservoirs go unchallenged. Therapeutic targeting of HIV therefore requires further investigation and current therapies need modification in order to address HIV eradication. This deflects research towards investigating potential novel antiretroviral drug delivery systems. The use of femtosecond (fs) laser pulses in promoting targeted optical drug delivery of antiretroviral drugs (ARVs) into TZMbl cells revolves around using ultrafast laser pulses that have high peak powers, which precisely disrupt the cell plasma membrane in order to allow immediate transportation and expression of exogenous material into the live mammalian cells. A photo-translocation optical setup was built and validated by characterisation of the accurate parameters such as wavelength (800 nm) and pulse duration (115 fs). Optimisation of drug translocation parameters were done by performing trypan blue translocation studies. Cellular responses were determined via cell viability (Adenosine Triphosphate activity) and cell cytotoxicity (Lactate Dehydrogenase) assays which were done to study the influence of the drugs and laser exposure on the cells. After laser irradiation, high cell viability was observed and low toxicity levels were observed after exposure of the cells to both the ARVs and the laser. Our results confirmed that, with minimal damage and high therapeutic levels of ARVs, the fs laser assisted drug delivery system is efficient with benefits of non-invasive and non-toxic treatment to the cells.

Human immunodeficiency virus/acquired immunodeficiency syndrome and infertility: emerging problems in the era of highly active antiretrovirals.

PubMed

Kushnir, Vitaly A; Lewis, William

2011-09-01

To review the effects of human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS) in terms of its associated comorbid conditions and the side effects of antiretroviral treatment on fertility. PubMed computer search to identify relevant articles. Research institution. None. None. None. Biological alterations in reproductive physiology may account for subfertility in patients infected with HIV. Psychosocial factors in patients with HIV infection may affect their 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 couples with HIV-discordant infection status, although the potential risk of viral transmission cannot be completely eliminated. Because their potential reproductive desires are increasingly becoming a concern in the health care of young HIV-infected patients, additional data are needed to address the effect of HIV and its treatments on their fertility and reproductive outcomes. Copyright © 2011 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

Cellular Profile and Expression of Immunologic Markers in Chronic Apical Periodontitis from HIV-infected Patients Undergoing Highly Active Antiretroviral Therapy.

PubMed

Gama, Túlio Gustavo Veiga; Pires, Fabio Ramoa; Armada, Luciana; Gonçalves, Lucio Souza

2016-06-01

This study tested the hypothesis that the inflammatory cell profile (CD3-, CD4-, CD8-, CD20-, and CD68-positive cells) and the expression of immunologic markers (tumor necrosis factor α, interferon-γ, interleukin-6, and interleukin-18) in chronic apical periodontitis are the same between non-HIV-infected patients and HIV-infected patients undergoing highly active antiretroviral therapy (HAART). Thirty-four surgically excised chronic apical periodontitis lesions were sampled from 34 patients (17 HIV-infected and 17 non-HIV-infected). The lesions were extracted from teeth with no previous endodontic treatment. All HIV-infected patients were undergoing HAART. The specimens were submitted to histopathologic and immunohistochemical analyses by using an optical microscope. Immunoexpression was graded into 2 levels, focal to weak and moderate to strong. The χ(2), Fisher exact, and Mann-Whitney tests were used to analyze all significant differences between groups. Periapical cysts represented 70.6% and 52.9% of the lesions in the HIV-infected and non-HIV-infected groups, respectively; however, no statistically significant difference was observed (P = .481). There were no statistically significant differences between groups for the inflammatory cell profile and for any of the immunologic markers (P > .05). There are no statistically significant differences of the cellular profile and expression of immunologic markers in chronic apical periodontitis between non-HIV-infected patients and HIV-infected patients undergoing HAART. Copyright © 2016 American Association of Endodontists. Published by Elsevier Inc. All rights reserved.

Antiretroviral pre-exposure prophylaxis (PrEP) for preventing HIV in high-risk individuals.

PubMed

Okwundu, Charles I; Uthman, Olalekan A; Okoromah, Christy An

2012-07-11

More than 30 years into the global HIV/AIDS epidemic, infection rates remain alarmingly high, with over 2.7 million people becoming infected every year. There is a need for HIV prevention strategies that are more effective. Oral antiretroviral pre-exposure prophylaxis (PrEP) in high-risk individuals may be a reliable tool in preventing the transmission of HIV. To evaluate the effects of oral antiretroviral chemoprophylaxis in preventing HIV infection in HIV-uninfected high-risk individuals. We revised the search strategy from the previous version of the review and conducted an updated search of MEDLINE, the Cochrane Central Register of Controlled Trials and EMBASE in April 2012. We also searched the WHO International Clinical Trials Registry Platform and ClinicalTrials.gov for ongoing trials. Randomised controlled trials that evaluated the effects of any antiretroviral agent or combination of antiretroviral agents in preventing HIV infection in high-risk individuals Data concerning outcomes, details of the interventions, and other study characteristics were extracted by two independent authors using a standardized data extraction form. Relative risk with a 95% confidence interval (CI) was used as the measure of effect. We identified 12 randomised controlled trials that meet the criteria for the review. Six were ongoing trials, four had been completed and two had been terminated early. Six studies with a total of 9849 participants provided data for this review. The trials evaluated the following: daily oral tenofovir disoproxil fumarate (TDF) plus emtricitabine (FTC) versus placebo; TDF versus placebo and daily TDF-FTC versus intermittent TDF-FTC. One of the trials had three study arms: TDF, TDF-FTC and placebo arm. The studies were carried out amongst different risk groups, including HIV-uninfected men who have sex with men, serodiscordant couples and other high risk men and women.Overall results from the four trials that compared TDF-FTC versus placebo showed a

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.

Characteristics of untreated AIDS-related cytomegalovirus retinitis. II. Findings in the era of highly active antiretroviral therapy (1997 to 2000).

PubMed

Holland, Gary N; Vaudaux, Jean D; Shiramizu, Kevin M; Yu, Fei; Goldenberg, David T; Gupta, Anurag; Carlson, Margrit; Read, Russell W; Novack, Roger D; Kuppermann, Baruch D

2008-01-01

To describe host characteristics (use of highly active antiretroviral therapy [HAART]; CD4+ T-lymphocyte count; HIV ribonucleic acid [RNA] blood level) of people who were diagnosed with AIDS-related cytomegalovirus (CMV) retinitis after HAART became available and to investigate effects of HAART on ophthalmic findings. Retrospective, observational case series. We collected demographic, medical, laboratory, and ophthalmic data for all patients with AIDS and newly diagnosed, untreated CMV retinitis from January 1997 through December 2000 at 10 sites in Los Angeles and Orange Counties, California. The proportions of Hispanic and African-American patients were equivalent to or greater than their prevalences in the AIDS and general populations of Los Angeles County. Most patients (n = 80; 63.5%) were known to be receiving HAART at the time of CMV retinitis diagnosis; only 22 patients (17.5%) were HAART-naïve. Median CD4+ T-lymphocyte count was 15 cells/microl and median HIV RNA blood level was 103,000 copies/ml for all patients, but in 10 patients, CMV retinitis developed despite good immunologic and virologic responses to HAART. When compared with HAART-naïve patients, HAART-failure patients with CMV retinitis had more asymptomatic disease (P = .073), better visual acuity in the better eye (P = .003), more bilateral disease (P = .007), less zone 1 involvement (P = .042), and lower lesion border opacity scores (P = .054). Most patients with AIDS and newly diagnosed CMV retinitis in an urban setting are HAART-experienced. HAART may influence characteristics of new CMV retinitis lesions at presentation, despite laboratory evidence of treatment failure, possibly because of residual CMV-specific immunity.

Low-level viremia and proviral DNA impede immune reconstitution in HIV-1-infected patients receiving highly active antiretroviral therapy.

PubMed

Ostrowski, Sisse R; Katzenstein, Terese L; Thim, Per T; Pedersen, Bente K; Gerstoft, Jan; Ullum, Henrik

2005-02-01

Immunological and virological consequences of low-level viremia in human immunodeficiency virus (HIV) type 1-infected patients receiving highly active antiretroviral therapy (HAART) remain to be determined. For 24 months, 101 HAART-treated, HIV-1-infected patients with HIV RNA levels 20 copies/mL at >/=1 visit (dVL patients) (median increase, 81 copies/mL [interquartile range, 37-480 copies/mL]). dVL patients had higher concentrations of CD8 cells, activated and memory T cells, and proviral DNA, compared with uVL patients (P<.05). A higher HIV RNA level was independently associated with reduced CD4 gain (P<.001). A higher HIV RNA level also was associated with increases in activated CD8(+)CD38(+) and CD8(+)HLA-DR(+) cells (P<.05), and a higher level of activated CD8(+)CD38(+) cells was independently associated with reduced CD4 gain (P<.05). A higher proviral DNA level was associated with increases in CD4(+)CD45RA(-)CD28(-) effector cells and reductions in naive CD4(+)CD45RA(+)CD62L(+) and CD8(+)CD45RA(+)CD62L(+) cells (P<.05). Higher levels of activated CD4(+)HLA-DR(+) and early differentiated CD4(+)CD45RA(-)CD28(+) cells predicted increased risk of subsequent detectable viremia in patients with undetectable HIV RNA (P<.05). These findings indicate that low-level viremia and proviral DNA are intimately associated with the immunological and virological equilibrium in patients receiving HAART.

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

Cost-effectiveness of population-level expansion of highly active antiretroviral treatment for HIV in British Columbia, Canada: a modelling study.

PubMed

Nosyk, Bohdan; Min, Jeong E; Lima, Viviane D; Hogg, Robert S; Montaner, Julio S G

2015-09-01

Widespread HIV screening and access to highly active antiretroviral treatment (ART) were cost effective in mathematical models, but population-level implementation has led to questions about cost, value, and feasibility. In 1996, British Columbia, Canada, introduced universal coverage of drug and other health-care costs for people with HIV/AIDS and and began extensive scale-up in access to ART. We aimed to assess the cost-effectiveness of ART scale-up in British Columbia compared with hypothetical scenarios of constrained treatment access. Using comprehensive linked population-level data, we populated a dynamic, compartmental transmission model to simulate the HIV/AIDS epidemic in British Columbia from 1997 to 2010. We estimated HIV incidence, prevalence, mortality, costs (in 2010 CAN$), and quality-adjusted life-years (QALYs) for the study period, which was 1997-2010. We calculated incremental cost-effectiveness ratios from societal and third-party-payer perspectives to compare actual practice (true numbers of individuals accessing ART) to scenarios of constrained expansion (75% and 50% probability of accessing ART). We also investigated structural and parameter uncertainty. Actual practice resulted in 263 averted incident cases compared with 75% of observed access and 676 averted cases compared with 50% of observed access to ART. From a third-party-payer perspective, actual practice resulted in incremental cost-effectiveness ratios of $23 679 per QALY versus 75% access and $24 250 per QALY versus 50% access. From a societal perspective, actual practice was cost saving within the study period. When the model was extended to 2035, current observed access resulted in cumulative savings of $25·1 million compared with the 75% access scenario and $65·5 million compared with the 50% access scenario. ART scale-up in British Columbia has decreased HIV-related morbidity, mortality, and transmission. Resulting incremental cost-effectiveness ratios for actual practice

HIV-infected patients receiving lopinavir/ritonavir-based antiretroviral therapy achieve high rates of virologic suppression despite adherence rates less than 95%.

PubMed

Shuter, Jonathan; Sarlo, Julie A; Kanmaz, Tina J; Rode, Richard A; Zingman, Barry S

2007-05-01

The observation that extremely high levels of medication adherence are required to achieve complete virologic suppression is based largely on studies of treatment-experienced patients receiving HIV protease inhibitor (PI)-based therapy without ritonavir boosting. This study aims to define the level of adherence needed to achieve virologic suppression in patients receiving boosted PI-based highly active antiretroviral therapy (HAART) with lopinavir/ritonavir. HIV-infected adults receiving a regimen containing lopinavir/ritonavir were recruited into a prospective, observational study of the relation between adherence to lopinavir/ritonavir and virologic outcomes. Adherence was measured using the Medication Event Monitoring System (MEMS; Aardex, Union City, CA). HIV-1 viral load (VL) was measured at week 24. The final study population contained 64 subjects. Eighty percent had AIDS, 97% received lopinavir/ritonavir before enrollment, and most had more than 7 years of HAART experience. Mean adherence overall was 73%. Eighty percent and 59% achieved a VL <400 copies/mL and a VL <75 copies/mL, respectively. Mean adherence was 75% in those achieving a VL <75 copies/mL. High rates of virologic suppression were observed in all adherence quartiles, including the lowest quartile (range of adherence: 23.5%-53.3%). Moderate levels of adherence can lead to virologic suppression in most patients taking lopinavir/ritonavir-based HAART.

Incidence of opportunistic illness before and after initiation of highly active antiretroviral therapy in children.

PubMed

Nesheim, Steven R; Hardnett, Felicia; Wheeling, John T; Siberry, George K; Paul, Mary E; Emmanuel, Patricia; Bohannon, Beverly; Dominguez, Kenneth

2013-10-01

Little is known about immune reconstitution inflammatory syndrome in children in the United States. LEGACY is a longitudinal cohort study of HIV-infected participants 0-24 years at enrollment during 2005 to 2007 from 22 US clinics. For this analysis, we included participants with complete medical record abstraction from birth or time of HIV diagnosis through 2006. Opportunistic illness (OI) included AIDS-defining conditions and selected HIV-related diagnoses. We calculated the incidence (#/100 patient-years) of OI diagnosed in the months pre- and postinitiation of the first highly active antiretroviral therapy (HAART) regimen which was followed by ≥1 log reduction in HIV viral load. We defined OI as immune reconstitution inflammatory syndrome if an OI incidence increased after HAART initiation. "Responders" were defined as experiencing ≥1 log decline in viral load within 6 months after HAART initiation. Among 575 patients with complete chart abstraction, 524 received HAART. Of these 524 patients, 343 were responders, 181 were nonresponders and 86 experienced OI. Responders accounted for 98 of 124 (79%) of OI. Pre-HAART and post-HAART OI incidences were 43.7 and 24.4 (P = 0.003), respectively, among responders and 15.9 and 9.1 (P = 0.2), respectively, among nonresponders. Overall, OI incidences among responders and nonresponders were 33.8 and 12.3, respectively (P = 0.002). Responders were more likely than nonresponders to experience herpes simplex and herpes zoster before HAART initiation (all, P < 0.002). The lack of immune reconstitution inflammatory syndrome in participants initiating HAART may be due to low overall OI rates. The unexpectedly higher OI prevalence comprised mainly of herpes simplex and zoster, before HAART initiation among responders, may have motivated them to better adhere to HAART.

Breast cancer and HIV in the era of highly active antiretroviral therapy: two case reports and review of the literature.

PubMed

Latif, Naeem; Rana, Fauzia; Guthrie, Troy

2011-01-01

The incidence of human immunodeficiency virus (HIV) infection is rising in US women; however its impact on breast cancer incidence, stage at presentation, response and treatment toxicity remains unknown. To address the impact of HIV infection and use of highly active antiretroviral therapy (HAART) on the natural history of breast cancer we present two cases of breast cancer in HIV-infected women and also review the literature. A literature search was done on Medline using the key words HIV/AIDS, breast cancer, and HAART therapy, restricted to English language. There were mostly case reports and one large series of 20 cases reported by Hurley et al. Data concerning the impact of HIV infection and HAART therapy regarding pathogenesis, stage at presentation, tumor type, response, and toxicity associated with treatment were reviewed. The literature review shows that the breast cancer incidence is either same or less in HIV-infected patients compared to the general population. However, the patients with HIV infection present with more advanced stage and aggressive disease, and they also have poor chemotherapy tolerance. The impact of HAART on breast cancer incidence in HIV-infected patients is still unclear. © 2010 Wiley Periodicals, Inc.

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

Anal intraepithelial neoplasia in the highly active antiretroviral therapy era among HIV-positive men who have sex with men.

PubMed

Palefsky, Joel M; Holly, Elizabeth A; Efirdc, Jimmy T; Da Costa, Maria; Jay, Naomi; Berry, J Michael; Darragh, Teresa M

2005-09-02

The incidence of anal cancer among men who have sex with men (MSM) has continued to increase since the introduction of highly active antiretroviral therapy (HAART). The prevalence of the putative anal cancer precursor, anal intraepithelial neoplasia (AIN) was high among HIV-positive MSM prior to the availability of HAART but little is known about AIN since HAART was introduced. We characterized the prevalence of AIN among HIV-positive MSM and examined the association between AIN and various factors including use of HAART. A baseline point-prevalence analyses in a prospective cohort study of AIN was performed at a university-based research clinic. A total of 357 HIV-positive MSM with no history of anal cancer completed a questionnaire detailing behaviors and medical history, anal cytology and human papillomavirus (HPV) testing, and high-resolution anoscopy with biopsy for detection of AIN. Eighty-one percent of participants with available CD4+ cell counts at baseline had AIN of any grade; 52% had AIN 2 or 3; and 95% had anal HPV infection. In multivariate analysis, detection of > or = 6 HPV types [odds ratio (OR), 36; 95% confidence interval (CI), 7.4-171) and use of HAART (OR, 10; 95% CI, 2.6-38) were associated with AIN after adjustment for length of time participants were HIV-positive, CD4+ cell count and HIV viral load. The prevalence of AIN has remained high among HIV-positive MSM after the introduction of HAART. Our data indicate that HAART is not associated with a reduced prevalence of AIN and support measures to prevent anal cancer among HIV-positive MSM whether or not they are using HAART.

Antiretroviral therapy: current drugs.

PubMed

Pau, Alice K; George, Jomy M

2014-09-01

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

Antiretroviral Resistance in HIV/AIDS Patients

NASA Astrophysics Data System (ADS)

Manosuthi, W.; MD

2018-03-01

The higher prevalence of HIV drug resistance was observed in areas with greater ART coverage. The HIV resistance-associated mutations occur when people have inadequate levels of antiretroviral drugs as well as inadequate potency, inadequate adherence, and preexisting resistance. The degree to drug cross-resistance is observed depends on the specific mutations and number of mutation accumulation. In the Southeast Asia region, the challenging of people with treatment failure is the availability and accessibility to subsequent new antiretroviral drugs to construct he second and salvage regimen. Genotypic resistance testing is a useful tool because it can identify the existing drug resistance-associated mutations under the selective drug pressure. Thus, understanding the basic interpretation of HIV drug resistance- associated mutation is useful in guiding clinical decisions for treatment-experienced people living with HIV.

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.

HIV-associated fatigue in the era of highly active antiretroviral therapy: novel biological mechanisms?

PubMed

Payne, B A I; Hateley, C L; Ong, E L C; Premchand, N; Schmid, M L; Schwab, U; Newton, J L; Price, D A

2013-04-01

The aim of the study was to determine the prevalence and risk factors for HIV-associated fatigue in the era of highly active antiretroviral therapy (HAART). A cross-sectional survey of 100 stable HIV-infected out-patients was carried out. Severity of fatigue was measured using the Fatigue Impact Scale (FIS). Symptoms of orthostatic intolerance (dysautonomia) were evaluated using the Orthostatic Grading Scale (OGS). Data for HIV-infected patients were compared with those for 166 uninfected controls and 74 patients with chronic fatigue syndrome (CFS)/myalgic encephalomyelitis (encephalopathy) (ME). Ninety-one per cent of HIV-infected patients were on HAART and 78% had suppressed plasma HIV viral load (≤ 40 HIV-1 RNA copies/mL). Fifty-one per cent of HIV-infected patients reported excessive symptomatic fatigue (FIS ≥ 40), and 28% reported severe fatigue symptoms (FIS ≥ 80). The mean FIS score among HIV-infected patients was 50.8 [standard deviation (SD) 41.9] compared with 13.0 (SD 17.6) in uninfected control subjects, and 92.9 (SD 29.0) in CFS patients (P < 0.001 for comparison of HIV-infected patients and uninfected controls). Among HIV-infected patients, fatigue severity was not significantly associated with current or nadir CD4 lymphocyte count, HIV plasma viral load, or whether on HAART. Prior dideoxynucleoside analogue (d-drug) exposure (P = 0.016) and the presence of clinical lipodystrophy syndrome (P = 0.011) were associated with fatigue. Additionally, fatigue severity correlated strongly with symptomatic orthostatic intolerance (r = 0.65; P < 0.001). Fatigue is very common and often severe in HIV-infected out-patients, despite viral suppression and good immune function. In a subgroup of patients, prior d-drug exposure may contribute to fatigue, suggesting a metabolic basis. Dysautonomia may also drive fatigue associated with HIV infection, as in other chronic diseases, and CFS/ME, and should be further evaluated with the potential for a shared

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

Impact of antiretroviral therapy (ART) timing on chronic immune activation/inflammation and end-organ damage.

PubMed

Rajasuriar, Reena; Wright, Edwina; Lewin, Sharon R

2015-01-01

The purpose of this review was to summarize recent studies on the effect of early antiretroviral therapy (ART) in HIV-infected patients on markers of immune activation/inflammation, viral persistence and serious non-AIDS events. Early ART, initiated within days to months of HIV infection, was associated with marked reduction in T-cell activation often reaching levels observed in HIV-uninfected individuals. However, the impact of early ART on markers of innate immune activation, microbial translocation and inflammation/coagulation was less clear. Early ART has also been associated with a significant reduction in the frequency of latently infected cells, which was greater if ART was initiated within days to weeks rather than months following infection. However, few studies have evaluated the relationship between immune activation and viral reservoirs, specifically following early ART. Early ART may potentially reduce serious non-AIDS events and associated mortality, but most of these studies have extrapolated from changes in surrogate markers, such as CD4 : CD8 ratio. Early ART was associated with beneficial effects on multiple markers of immune activation, inflammation and viral persistence. Longer term prospective studies are still needed to determine whether early ART translates to a significant reduction in serious non-AIDS events and mortality.

Barriers to adherence to highly active antiretroviral therapy as expressed by people living with HIV/AIDS.

PubMed

Proctor, V E; Tesfa, A; Tompkins, D C

1999-09-01

The primary objective of this study was to gain a clearer understanding of the barriers to adherence to highly active antiretroviral therapy (HAART) faced by people living with HIV/AIDS (PLWHIV/AIDS) on Long Island, New York. Focus group, a qualitative research method, was used to study these barriers. The study was conducted in 1998 on Long Island, NY, at five institutions that provide services to 1700 PLWHIV/AIDS. Five focus groups were conducted with 6 to 13 PLWHIV/AIDS in each group, a total of 39 subjects. PLWHIV/AIDS identified eight common barriers to adherence to HAART. In descending order, the barriers include: (1) frequency and severity of side effects, (2) conflicts with daily routines, (3) dietary requirements, (4) frequency of taking medications, (5) number and dosage of medications, (6) psychosocial factors (i.e., stress, feeling good, and bad news), (7) pharmacy refills, and (8) physiological needs (i.e., sleep, hunger, or thirst). Many factors play a role in the success or failure of HAART, including preexisting drug resistance, drug-drug interactions, and the ability of PLWHIV/AIDS to adhere to a rigid and frequently changing medication regimen. The information gleaned from focus groups is limited in that it may not be generalized to a larger population with any known reliability. However, clinicians sensitive to barriers to adherence to HAART, including those identified by PLWHIV/AIDS in this study, may play a more proactive role in supporting adherence to the medication regimen, increasing the durability of effective viral suppression, decreasing morbidity and mortality, and decreasing the selection and transmission of resistant strains of HIV.

Predictors of early mortality in a cohort of HIV-infected children receiving high active antiretroviral treatment in public hospitals in Ethiopia.

PubMed

Ebissa, Getachew; Deyessa, Negusse; Biadgilign, Sibhatu

2015-01-01

Highly active antiretroviral therapy (HAART) is the breakthrough in care and treatment of people living with HIV, leading to a reduction in mortality and an improvement in the quality of life. Without antiretroviral treatment, most HIV-infected children die before their fifth birthday. So the objective of this study is to determine the mortality and associated factors in a cohort of HIV-infected children receiving ART in Ethiopia. A multicentre facility-based retrospective cohort study was done in selected pediatric ART units in hospitals found in Addis Ababa, Ethiopia. The probability of survival was estimated using the Kaplan-Meier method, and multivariate analysis by Cox proportional hazards regression models was conducted to determine the independent predictor of survival. A total of 556 children were included in this study. Of the total children, 10.4% were died in the overall cohort. More deaths (70%) occurred in the first 6 months of ART initiation, and the remaining others were still on follow-up at different hospitals. Underweight (moderate and severe; HR: 10.10; 95% CI: 2.08, 28.00; P = 0.004; and HR: 46.69; 95% CI: 9.26, 200.45; P < 0.01, respectively), advanced disease stage (WHO clinical stages III and IV; HR: 10.13: 95% CI: 2.25, 45.58; P = 0.003), poor ART adherence (HR: 11.72; 95% CI: 1.60, 48.44; P = 0.015), and hemoglobin level less than 7 g/dl (HR: 4.08: 95% CI: 1.33, 12.56; P = 0.014) were confirmed as significant independent predictors of death after controlling for other factors. Underweight, advanced disease stage, poor adherence to ART, and anemia appear to be independent predictor of survival in HIV-infected children receiving HAART at the pediatric units of public hospitals in Ethiopia. Nutritional supplementations, early initiation of HAART, close supervision, and monitoring of patients during the first 6 months, the follow up period is recommended.

Course of Cytomegalovirus Retinitis in the Era of Highly Active Antiretroviral Therapy: Five-year Outcomes

PubMed Central

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

2010-01-01

Purpose To describe the five-year outcomes of patients with cytomegalovirus (CMV) retinitis and AIDS in the era of highly active antiretroviral therapy (HAART). Design Prospective, multicenter, observational study Participants 503 patients with AIDS and CMV retinitis Methods 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 prior to enrollment). Main outcome measures 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 (to worse than 20/40 and to 20/200 or worse), Results 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 worse than 20/40 and to 20/200 or worse 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

Antiretroviral Use Among Active Injection-Drug Users: The Role of Patient–Provider Engagement and Structural Factors

PubMed Central

Arnsten, Julia H.; Eldred, Lois J.; Wilkinson, James D.; Shade, Starley B.; Bohnert, Amy S.; Yang, Cui; Wissow, Lawrence S.; Purcell, David W.

2010-01-01

Abstract HIV-seropositive, active injection-drug users (IDUs), compared with other HIV populations, continue to have low rates of highly active antiretroviral therapy (HAART) use, contributing to disparities in their HIV health outcomes. We sought to identify individual-level, interpersonal, and structural factors associated with HAART use among active IDUs to inform comprehensive, contextually tailored intervention to improve the HAART use of IDUs. Prospective data from three semiannual assessments were combined, and logistic general estimating equations were used to identify variables associated with taking HAART 6 months later. Participants were a community sample of HIV-seropositive, active IDUs enrolled in the INSPIRE study, a U.S. multisite (Baltimore, Miami, New York, San Francisco) prevention intervention. The analytic sample included 1,225 observations, and comprised 62% males, 75% active drug users, 75% non-Hispanic blacks, and 55% with a CD4 count <350; 48% reported HAART use. Adjusted analyses indicated that the later HAART use of IDUs was independently predicted by patient–provider engagement, stable housing, medical coverage, and more HIV primary care visits. Significant individual factors included not currently using drugs and a positive attitude about HAART benefits even if using illicit drugs. Those who reported patient-centered interactions with their HIV primary care provider had a 45% greater odds of later HAART use, and those with stable housing had twofold greater odds. These findings suggest that interventions to improve the HIV treatment of IDUs and to reduce their HIV health disparities should be comprehensive, promoting better patient–provider engagement, stable housing, HAART education with regard to illicit drug use, and integration of drug-abuse treatment with HIV primary care. PMID:20578910

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

Heavy Cannabis Use Associated With Reduction in Activated and Inflammatory Immune Cell Frequencies in Antiretroviral Therapy-Treated Human Immunodeficiency Virus-Infected Individuals.

PubMed

Manuzak, Jennifer A; Gott, Toni M; Kirkwood, Jay S; Coronado, Ernesto; Hensley-McBain, Tiffany; Miller, Charlene; Cheu, Ryan K; Collier, Ann C; Funderburg, Nicholas T; Martin, Jeffery N; Wu, Michael C; Isoherranen, Nina; Hunt, Peter W; Klatt, Nichole R

2018-06-01

Cannabis is a widely used drug in the United States, and the frequency of cannabis use in the human immunodeficiency virus (HIV)-infected population is disproportionately high. Previous human and macaque studies suggest that cannabis may have an impact on plasma viral load; however, the relationship between cannabis use and HIV-associated systemic inflammation and immune activation has not been well defined. The impact of cannabis use on peripheral immune cell frequency, activation, and function was assessed in 198 HIV-infected, antiretroviral-treated individuals by flow cytometry. Individuals were categorized into heavy, medium, or occasional cannabis users or noncannabis users based on the amount of the cannabis metabolite 11-nor-carboxy-tetrahydrocannabinol (THC-COOH) detected in plasma by mass spectrometry. Heavy cannabis users had decreased frequencies of human leukocyte antigen (HLA)-DR+CD38+CD4+ and CD8+ T-cell frequencies, compared to frequencies of these cells in non-cannabis-using individuals. Heavy cannabis users had decreased frequencies of intermediate and nonclassical monocyte subsets, as well as decreased frequencies of interleukin 23- and tumor necrosis factor-α-producing antigen-presenting cells. While the clinical implications are unclear, our findings suggest that cannabis use is associated with a potentially beneficial reduction in systemic inflammation and immune activation in the context of antiretroviral-treated HIV infection.

Highly active antiretroviral therapy started during pregnancy or postpartum suppresses HIV-1 RNA, but not DNA, in breast milk.

PubMed

Shapiro, Roger L; Ndung'u, Thumbi; Lockman, Shahin; Smeaton, Laura M; Thior, Ibou; Wester, Carolyn; Stevens, Lisa; Sebetso, Gaseene; Gaseitsiwe, Simani; Peter, Trevor; Essex, Max

2005-09-01

The ability of highly active antiretroviral therapy (HAART) to reduce human immunodeficiency virus type 1 (HIV-1) RNA and DNA in breast milk has not been described. We compared breast-milk HIV-1 RNA and DNA loads of women in Botswana who received HAART (nevirapine, lamivudine, and zidovudine) and women who did not receive HAART. Women in the HAART group received treatment for a median of 98 days (range, 67-222 days) at the time of breast-milk sampling; 23 (88%) of 26 had whole breast-milk HIV-1 RNA loads <50 copies/mL, compared with 9 (36%) of 25 women who did not receive HAART (P=.0001). This finding remained significant in a multivariate logistic-regression model (P = .0006). The whole-milk HIV-1 DNA load was unaffected by HAART. Of women who received HAART, 13 (50%) of 26 had HIV-1 DNA loads <10 copies/10(6) cells, compared with 15 (65%) of 23 who did not receive HAART (P = .39). HAART suppressed cell-free HIV-1 RNA in breast milk and may therefore reduce mother-to-child transmission (MTCT) of HIV-1 via breast-feeding. However, HAART initiated during pregnancy or early after delivery had no apparent effect on cell-associated HIV-1 DNA loads in breast milk. Clinical trials to determine MTCT among breast-feeding women receiving HAART are needed.

Highly active antiretroviral therapy including protease inhibitors does not confer a unique CD4 cell benefit. The AVANTI and INCAS Study Groups.

PubMed

2000-07-07

To determine if triple combination therapy, particularly including HIV protease inhibitors (PI), confers an unique immunological benefit that is independent of reductions of plasma viral load (pVL). The correlation between changes from baseline in CD4 cell count and pVL was examined at all time points up to 52 weeks in three randomized clinical trials (AVANTI-2, AVANTI-3 and INCAS) that compared dual nucleoside therapy with triple combination therapy. Individual pVL and CD4 cell counts changes from baseline were entered into multivariate linear regression models for patients receiving double therapy and for those receiving triple therapy including a PI and/or a non-nucleoside reverse transcriptase inhibitor (NNRTI), and the null hypothesis was tested. After 52 weeks of therapy, the relationship between changes from baseline CD4 cell count and pVL was independent of whether patients were assigned double or triple therapy (P = 0.23 and 0.69 for intercept and slope, respectively), or whether patients were assigned triple therapy including a PI or triple therapy including an NNRTI (P = 0.92 and 0.95, respectively). Less than 5% of patients ever had 'discordant' increases in both CD4 cell count and pVL compared with baseline, and this proportion was unrelated to the class of therapy used. 'Discordant' decreases from baseline in both parameters were observed in up to 35% of individuals. The correlation between pVL and CD4 cell count changes from baseline improved over time on therapy, regardless of the therapeutic regimen involved. The data provide no evidence for a CD4 cell count benefit of highly active antiretroviral therapy (HAART) unique to triple therapy or PI-containing regimens.

Evaluation of hypophosphataemia in tenofovir disoproxil fumarate (TDF)-exposed and TDF-unexposed HIV-infected out-patients receiving highly active antiretroviral therapy.

PubMed

Buchacz, K; Brooks, J T; Tong, T; Moorman, A C; Baker, R K; Holmberg, S D; Greenberg, A

2006-10-01

Cases of hypophosphataemia (often coincident with renal dysfunction) have been reported in HIV-infected patients taking tenofovir disoproxil fumarate (TDF), but randomized placebo-controlled trials of HIV-infected persons with normal baseline renal function have found a comparable incidence of hypophosphataemia in the TDF and placebo groups. We assessed the incidence of grade 2 and higher hypophosphataemia in the HIV Outpatient Study (HOPS). We analysed a prospective cohort of patients who initiated either a TDF-containing highly active antiretroviral therapy (HAART) regimen [TDF-exposed (TDF+) group; n = 165] or a TDF-sparing HAART regimen [TDF-unexposed (TDF-) group; n = 90], and who had normal baseline phosphate and creatinine values. The TDF+ and TDF- groups had comparable median follow-up times (10.9 vs 8.8 months, respectively; P = 0.18) and number of phosphate measurements (median = 3 for both) and were similar on most clinical and demographic factors. During follow up, 12.7% of TDF+vs 6.7% of TDF-patients developed grade 2 hypophosphataemia (2.0-2.4 mg/dL), and 2.4% of TDF+ patients vs 0% of TDF-patients developed grade 3 hypophosphataemia (1.0-1.9 mg/dL); none developed grade 4 hypophosphataemia (<1.0 mg/dL). The incidence of grade 2 or higher hypophosphataemia was 16.7 per 100 person-years among TDF+ patients vs 8.0 per 100 person-years among TDF-patients (P = 0.11). The incidence of hypophosphataemia was somewhat elevated in HOPS patients who took TDF-containing HAART compared with those who took TDF-sparing HAART during the first 1 to 2 years of observation, but the difference was not statistically significant. Longer follow-up of a larger population is needed to determine if this trend towards an association achieves statistical significance and to evaluate the clinical consequences of hypophosphataemia.

Neurotoxicity in the Post-HAART Era: Caution for the Antiretroviral Therapeutics

PubMed Central

Shah, Ankit; Gangwani, Mohitkumar R.; Chaudhari, Nitish S.; Glazyrin, Alexy; Bhat, Hari K.; Kumar, Anil

2016-01-01

Despite the advent of highly active antiretroviral therapy (HAART), HIV-associated neurological disorders (HAND) remain a major challenge in human immunodeficiency virus (HIV) treatment. The early implementation of HAART in the infected individuals helps suppress the viral replication in the plasma and other compartments. Several studies also report the beneficial effect of drugs that successfully penetrate central nervous system (CNS). However, recent data in both clinical setup and in in vitro studies indicate CNS toxicity of the antiretrovirals (ARVs). Although the evidence is limited, correlation between prolonged use of ARVs and neurotoxicity strongly suggests that it is essential to study the underlying mechanisms responsible for such toxicity. Furthermore, closer attention toward clinical outcomes is required to screen various ARV regimens for their association with HAND and other comorbidities. A growing body of literature also indicates a possible role of accelerated aging in the antiretroviral therapy-associated neurotoxicity. Lastly, owing to high pill burden, multiple drugs in the HIV treatment also invite a possible role of drug–drug interaction via various cytochrome P450 enzymes. The particular emphasis of this review is to highlight the need to identify alternative approaches in reducing the CNS toxicity of the ARV drugs in HIV-infected individuals. PMID:27364698

Association between discordant immunological response to highly active anti-retroviral therapy, regulatory T cell percentage, immune cell activation and very low-level viraemia in HIV-infected patients

PubMed Central

Saison, J; Ferry, T; Demaret, J; Maucort Boulch, D; Venet, F; Perpoint, T; Ader, F; Icard, V; Chidiac, C; Monneret, G

2014-01-01

The mechanisms sustaining the absence of complete immune recovery in HIV-infected patients upon long-term effective highly active anti-retroviral therapy (HAART) remain elusive. Immune activation, regulatory T cells (Tregs) or very low-level viraemia (VLLV) have been alternatively suspected, but rarely investigated simultaneously. We performed a cross-sectional study in HIV-infected aviraemic subjects (mean duration of HAART: 12 years) to concomitantly assess parameters associated independently with inadequate immunological response. Patients were classified as complete immunological responders (cIR, n = 48) and inadequate immunological responders (iIR, n = 39), depending on the CD4+ T cell count (> or < 500/mm3). Clinical and virological data (including very low-level viraemia) were collected. In parallel, immunophenotyping of CD4+ lymphocytes, including Treg subsets, and CD8+ T cells was performed. Percentages of activated CD4+ T cells, Tregs, effector Tregs and terminal effector Tregs were found to be significantly elevated in iIR. Neither the percentage of activated CD8+ T cells nor VLLV were found to be associated with iIR. In the multivariate analysis, nadir of CD4+ T cell count and percentage of Tregs were the only two parameters associated independently with iIR [odds ratio (OR) = 2·339, P = 0·001, and OR = 0·803, P = 0·041]. We present here the largest study investigating simultaneously the immune response to long-term HAART, activation of CD4+ and CD8+ T cells, Treg percentages and very low-level viraemia. Causative interactions between Tregs and CD4+ T cells should now be explored prospectively in a large patients cohort. PMID:24460818

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

PubMed Central

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

2009-01-01

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

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

Rates of Initial Virological Suppression and Subsequent Virological Failure After Initiating Highly Active Antiretroviral Therapy: The Impact of Aboriginal Ethnicity and Injection Drug Use

PubMed Central

Martin, L.J.; Houston, S.; Yasui, Y.; Wild, T.C.; Saunders, L.D.

2010-01-01

Objectives: To compare rates of initial virological suppression and subsequent virological failure by Aboriginal ethnicity after starting highly active antiretroviral therapy (HAART). Methods: We conducted a retrospective cohort study of antiretroviral-naïve HIV-patients starting HAART in January 1999-June 2005 (baseline), followed until December 31, 2005 in Alberta, Canada. We compared the odds of achieving initial virological suppression (viral load <500 copies/mL) by Aboriginal ethnicity using logistic regression and, among those achieving suppression, rates of virological failure (the first of two consecutive viral loads > 1000 copies/mL) by Aboriginal ethnicity using cumulative incidence curves and Cox proportional hazards models. Sex, injection drug use as an HIV exposure category (IDU), baseline age, CD4 cell count, viral load, calendar year, and HAART regimen were considered as potential confounders. Results: Of 461 study patients, 37% were Aboriginal and 48% were IDUs; 71% achieved initial virological suppression and were followed for 730.4 person-years. After adjusting for confounding variables, compared to non-Aboriginals with other exposures, the odds of achieving initial virological suppression were lower for Aboriginal IDUs (odds ratio (OR)=0.33, 95% CI=0.19-0.60, p=0.0002), non-Aboriginal IDUs (OR=0.30, 95% CI=0.15-0.60, p=0.0006), and Aboriginals with other exposures (OR=0.38, 95% CI=0.21-0.67, p=0.0009). Among those achieving suppression, Aboriginals experienced higher virological failure rates ≥1 year after suppression (hazard ratio=3.35, 95% CI=1.68-6.65, p=0.0006). Conclusions: Future research should investigate adherence among Aboriginals and IDUs treated with HAART and explore their treatment experiences to assess ways to improve outcomes. PMID:21187007

Active site remodeling switches HIV specificity of antiretroviral TRIMCyp

PubMed Central

Price, Amanda J; Marzetta, Flavia; Lammers, Michael; Ylinen, Laura M J; Schaller, Torsten; Wilson, Sam J; Towers, Greg J; James, Leo C

2011-01-01

TRIMCyps are primate antiretroviral proteins that potently inhibit HIV replication. Here we describe how rhesus macaque TRIMCyp (RhTC) has evolved to target and restrict HIV-2. We show that the ancestral cyclophilin A (CypA) domain of RhTC targets HIV-2 capsid with weak affinity, which is strongly increased in RhTC by two mutations (D66N and R69H) at the expense of HIV-1 binding. These mutations disrupt a constraining intramolecular interaction in CypA, triggering the complete restructuring (>16 Å) of an active site loop. This new configuration discriminates between divergent HIV-1 and HIV-2 loop conformations mediated by capsid residue 88. Viral sensitivity to RhTC restriction can be conferred or abolished by mutating position 88. Furthermore, position 88 determines the susceptibility of naturally occurring HIV-1 sequences to restriction. Our results reveal the complex molecular, structural and thermodynamic changes that underlie the ongoing evolutionary race between virus and host. PMID:19767750

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.

Earlier initialization of highly active antiretroviral therapy is associated with long-term survival and is cost-effective: findings from a deterministic model of a 10-year Ugandan cohort.

PubMed

Mills, Fergal P; Ford, Nathan; Nachega, Jean B; Bansback, Nicholas; Nosyk, Bohdan; Yaya, Sanni; Mills, Edward J

2012-11-01

Raising the guidelines for the initiation of antiretroviral therapy in resource-limited settings at CD4 T-cell counts of 350 cells per microliter raises concerns about feasibility and cost. We examined costs of this shift using data from Uganda for almost 10 years. We projected total costs of earlier initiation with combined antiretroviral therapy, including inpatient and outpatient services, antiretroviral treatment and treatment for limited HIV-related opportunistic diseases, and benefits expressed in years-of-life-saved over 5- and 30-year time horizons using a deterministic economic model to examine the incremental cost-effectiveness ratio (ICER), expressed in cost per year-of-life-saved (YLS). The model generated ICERs for 5- and 30-year time horizons. Discounting both costs and benefits at 3% annually, for the 5-year analysis, the ICER was $695/YLS and $769 in the 30-year analysis. The results were most sensitive to program cost and the discount rate applied, but they were less sensitive to opportunistic infection treatment costs or the relative-risk reduction from earlier initiation. Program costs varied from 25% to 125%, and the ICER for the lower bound decreased to $491/YLS at 5-years and $574/YLS at 30 years. For the upper bound, the ICER increased to $899 for 5-years and $964 at 30-years. The budget impact of adoption, assuming the same level of program penetration in the community, is $261,651,942 for 5 years and $872,685,561 for 30 years. Our model showed that earlier initiation of combined antiretroviral therapy in Uganda is associated with improved long-term survival and is highly cost-effective, as defined by WHO-CHOICE.

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.

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.

Association between discordant immunological response to highly active anti-retroviral therapy, regulatory T cell percentage, immune cell activation and very low-level viraemia in HIV-infected patients.

PubMed

Saison, J; Ferry, T; Demaret, J; Maucort Boulch, D; Venet, F; Perpoint, T; Ader, F; Icard, V; Chidiac, C; Monneret, G

2014-06-01

The mechanisms sustaining the absence of complete immune recovery in HIV-infected patients upon long-term effective highly active anti-retroviral therapy (HAART) remain elusive. Immune activation, regulatory T cells (T(regs)) or very low-level viraemia (VLLV) have been alternatively suspected, but rarely investigated simultaneously. We performed a cross-sectional study in HIV-infected aviraemic subjects (mean duration of HAART: 12 years) to concomitantly assess parameters associated independently with inadequate immunological response. Patients were classified as complete immunological responders (cIR, n = 48) and inadequate immunological responders (iIR, n = 39), depending on the CD4(+) T cell count (> or < 500/mm(3)). Clinical and virological data (including very low-level viraemia) were collected. In parallel, immunophenotyping of CD4(+) lymphocytes, including T(reg) subsets, and CD8(+) T cells was performed. Percentages of activated CD4(+) T cells, T(regs), effector T(regs) and terminal effector T(regs) were found to be significantly elevated in iIR. Neither the percentage of activated CD8(+) T cells nor VLLV were found to be associated with iIR. In the multivariate analysis, nadir of CD4(+) T cell count and percentage of T(regs) were the only two parameters associated independently with iIR [odds ratio (OR) = 2·339, P = 0·001, and OR = 0·803, P = 0·041]. We present here the largest study investigating simultaneously the immune response to long-term HAART, activation of CD4(+) and CD8(+) T cells, T(reg) percentages and very low-level viraemia. Causative interactions between T(regs) and CD4(+) T cells should now be explored prospectively in a large patients cohort. © 2014 British Society for Immunology.

Antiretroviral Therapy Outcomes of HIV-infected children in the TREAT Asia Pediatric HIV Observational Database

PubMed Central

Hansudewechakul, Rawiwan; Sirisanthana, Virat; Kurniati, Nia; Puthanakit, Thanyawee; Lumbiganon, Pagakrong; Yusoff, Nik Khairulddin Nik; Fong, Siew Moy; Nallusamy, Revathy; Srasuebkul, Preeyaporn; Law, Matthew; Sohn, Annette H.; Chokephaibulkit, Kulkanya

2010-01-01

Introduction We report responses to combination antiretroviral therapy (cART) in the TREAT Asia Pediatric HIV Observational Database. Methods Children included were those who had received cART (i.e., ≥3 antiretrovirals) at <18 years. The analysis was intention-to-treat by the first cART regimen. Median values are provided with interquartile ranges; hazard ratios (HR) with 95% confidence intervals. Results Of the 1655 children included, 50.4% were male, with a median age at cART of 7.0 (3.9, 9.8) years and CD4 of 8 (2.0, 15)%; 92.5% were started on an NNRTI; median duration of follow-up was 2.9 (1.4, 4.6) years. Loss-to-follow-up and death rates were 4.2 (3.7, 4.8) and 2.1 (1.7, 2.5) per 100 person-years, respectively. At 36 months, median CD4 was 26 (21, 31)%; 81% of those with viral load (N=302) were <400 copies/mL. Children who reached CD4 ≥25% within five years were more likely to be females (HR 1.4; 1.2, 1.7), start before 18 months old (HR 3.8; 2.4, 6.2), lack a history of mono/dual-therapy (HR 1.7; 1.4, 2.5), and have a higher baseline CD4 (per 10% increase: HR 2; 1.9, 2.2). Conclusion These data underscore the need for early diagnosis and cART initiation to preserve immune function. PMID:20842043

Risk factors for treatment-limiting toxicities in patients starting nevirapine-containing antiretroviral therapy.

PubMed

Kesselring, Anouk M; Wit, Ferdinand W; Sabin, Caroline A; Lundgren, Jens D; Gill, M John; Gatell, Jose M; Rauch, Andri; Montaner, Julio S; de Wolf, Frank; Reiss, Peter; Mocroft, Amanda

2009-08-24

This collaboration of seven observational clinical cohorts investigated risk factors for treatment-limiting toxicities in both antiretroviral-naive and experienced patients starting nevirapine-based combination antiretroviral therapy (NVPc). Patients starting NVPc after 1 January 1998 were included. CD4 cell count at starting NVPc was classified as high (>400/microl/>250/microl for men/women, respectively) or low. Cox models were used to investigate risk factors for discontinuations due to hypersensitivity reactions (HSR, n = 6547) and discontinuation of NVPc due to treatment-limiting toxicities and/or patient/physician choice (TOXPC, n = 10,186). Patients were classified according to prior antiretroviral treatment experience and CD4 cell count/viral load at start NVPc. Models were stratified by cohort and adjusted for age, sex, nadir CD4 cell count, calendar year of starting NVPc and mode of transmission. Median time from starting NVPc to TOXPC and HSR were 162 days [interquartile range (IQR) 31-737] and 30 days (IQR 17-60), respectively. In adjusted Cox analyses, compared to naive patients with a low CD4 cell count, treatment-experienced patients with high CD4 cell count and viral load more than 400 had a significantly increased risk for HSR [hazard ratio 1.45, confidence interval (CI) 1.03-2.03] and TOXPC within 18 weeks (hazard ratio 1.34, CI 1.08-1.67). In contrast, treatment-experienced patients with high CD4 cell count and viral load less than 400 had no increased risk for HSR 1.10 (0.82-1.46) or TOXPC within 18 weeks (hazard ratio 0.94, CI 0.78-1.13). Our results suggest it may be relatively well tolerated to initiate NVPc in antiretroviral-experienced patients with high CD4 cell counts provided there is no detectable viremia.

Increased premotor cortex activation in high functioning autism during action observation.

PubMed

Perkins, Tom J; Bittar, Richard G; McGillivray, Jane A; Cox, Ivanna I; Stokes, Mark A

2015-04-01

The mirror neuron (MN) hypothesis of autism has received considerable attention, but to date has produced inconsistent findings. Using functional MRI, participants with high functioning autism or Asperger's syndrome were compared to typically developing individuals (n=12 in each group). Participants passively observed hand gestures that included waving, pointing, and grasping. Concerning the MN network, both groups activated similar regions including prefrontal, inferior parietal and superior temporal regions, with the autism group demonstrating significantly greater activation in the dorsal premotor cortex. Concerning other regions, participants with autism demonstrated increased activity in the anterior cingulate and medial frontal gyrus, and reduced activation in calcarine, cuneus, and middle temporal gyrus. These results suggest that during observation of hand gestures, frontal cortex activation is affected in autism, which we suggest may be linked to abnormal functioning of the MN system. Copyright © 2014 Elsevier Ltd. All rights reserved.

Access to antiretroviral drugs and AIDS management in Senegal.

PubMed

Desclaux, Alice; Ciss, Mounirou; Taverne, Bernard; Sow, Papa S; Egrot, Marc; Faye, Mame A; Lanièce, Isabelle; Sylla, Omar; Delaporte, Eric; Ndoye, Ibrahima

2003-07-01

Description and analysis of the Senegalese Antiretroviral Drug Access Initiative (ISAARV), the first governmental highly active antiretroviral therapy (HAART) treatment programme in Africa, launched in 1998. ISAARV was initially an experimental project designed to evaluate the feasibility, efficacy and acceptability of HAART in an African context. It was based on four principles: collective definition of the strategy, with involvement of the health professionals who would be called on to execute the programme; matching the objectives to available means (gradual enrollment according to drug availability); monitoring by several research programmes; and ongoing adaptation of treatment and follow-up according to the latest international recommendations. Persons qualifying for antiretroviral (ARV) therapy are selected on the basis of immunological and clinical criteria, regardless of economic and social considerations. A system of subsidies was created to favor access to ARV. Following the ARV price reductions that occurred in November 2000, 100% subsidies were created for the poorest participants. Optimal adherence was ensured by monthly follow-up by pharmacists and support groups held by social workers and patient associations. The chosen supply and distribution system allowed drug dispensing to be strictly controlled. The ISAARV programme demonstrates that HAART can be successfully prescribed in Africa. This experience has served as the basis for the creation of a national treatment programme in Senegal planned to treat 7000 patients by 2006.

Antiretroviral Treatment Effect on Immune Activation Reduces Cerebrospinal Fluid HIV-1 Infection

PubMed Central

Sinclair, Elizabeth; Ronquillo, Rollie; Lollo, Nicole; Deeks, Steven G.; Hunt, Peter; Yiannoutsos, Constantin T.; Spudich, Serena; Price, Richard W.

2012-01-01

Objective To define the effect of antiretroviral therapy (ART) on activation of T cells in cerebrospinal fluid (CSF) and blood, and interactions of this activation with CSF HIV-1 RNA concentrations. Design Cross-sectional analysis of 14 HIV-negative subjects and 123 neuroasymptomatic HIV-1–infected subjects divided into 3 groups: not on ART (termed “offs”), on ART with plasma HIV-1 RNA >500 copies/mL (“failures”), and on ART with plasma HIV-1 RNA ≤500 copies/mL (“successes”). T-cell activation was measured by coexpression of CD38 and human leukocyte antigen DR (HLA-DR). Other measurements included CSF neopterin and white blood cell (WBC) counts. Results CD8 T-cell activation in CSF and blood was highly correlated across all subjects and was highest in the offs, lower in the failures, and lower still in the successes. While CD8 activation was reduced in failures compared to offs across the range of plasma HIV-1, it maintained a coincident relation to CSF HIV-1 in both viremic groups. In addition to correlation with CSF HIV-1 concentrations, CD8 activation in blood and CSF correlated with CSF WBCs and CSF neopterin. Multivariate analysis confirmed the association of blood CD8 T-cell activation, along with plasma HIV-1 RNA and CSF neopterin, with CSF HIV-1 RNA levels. Conclusions The similarity of CD8 T-cell activation in blood and CSF suggests these cells move from blood to CSF with only minor changes in CD38/HLA-DR expression. Differences in the relation of CD8 activation to HIV-1 concentrations in the blood and CSF in the 2 viremic groups suggest that changes in immune activation not only modulate CSF HIV-1 replication but also contribute to CSF treatment effects. The magnitude of systemic HIV-1 infection and intrathecal macrophage activation are also important determinants of CSF HIV-1 RNA levels. PMID:18362693

Which factors hinder the decision of Polish HIV-positive patients to take up antiretroviral therapy?

PubMed

Rogowska-Szadkowska, D; Chlabicz, S; Oltarzewska, M A; Sawicka-Powierza, J

2009-03-01

The implementation of highly active antiretroviral therapy (HAART) in 1996 has significantly reduced mortality and morbidity for HIV-positive patients worldwide. However not all eligible persons start HAART. To identify reasons for therapy refusal by HIV-positive persons we performed a questionnaire study. The investigation was conducted among 321 HIV-positive individuals and focused on the decision to take up antiretroviral treatment. Out of 71 untreated patients, 34 (47.9%) admitted that in their case the therapy was not indicated, whereas 20 (28.3%) were afraid of potential side effects that might change their appearance, e.g. face lipoatrophy. Only the treated patients had been prepared to take up therapy, although 17 patients (6.0%) had not received any explanation of the therapy principles, aims or necessity to comply with medication regime. The therapy is generally not discussed with the patients for whom it is not currently indicated, which may contribute to the fixation of fears and prejudices. Doctors who treat HIV-positive patients should be aware of the prejudices and fears their patients have towards antiretroviral therapy in order to react properly and by means of the available antiretroviral drugs help prolong life and improve its quality.

Multi-wavelength and High-resolution Observations of Solar Eruptive Activities

NASA Astrophysics Data System (ADS)

Shen, Y. D.

2014-09-01

In recent years, various solar eruptive activities have been observed in the solar atmosphere, such as solar flares, filament eruptions, jets, coronal mass ejections (CMEs), and magnetohydrodynamics (MHD) waves. Previous observations have indicated that solar magnetic field plays a dominant role in the processes of all kinds of solar activities. Since many large-scale solar eruptive activities can cause significant effects on the space environment of the Earth as well as the human life, studying and forecasting the solar activities are urgent tasks for us. In addition, the Sun is the nearest star to the Earth, so that people can directly observe and study it in detail. Hence, studying the Sun can also provide a reference to study other stars in the universe. This thesis focuses on the multi-wavelength and high-resolution observations of three types of solar eruptive activities: filament eruptions, coronal jets, and coronal MHD waves. By analyzing various observations taken by ground-based and space-borne instruments, we try to understand the inherent physical mechanisms, and construct models to interpret different kinds of solar eruptive activities. The triggering mechanism and the cause of a failed filament eruption are studied in Chapter 3, which indicates that the energy released in the flare is a key factor to the fate of the filament. Two successive filament eruptions are studied in Chapter 4, which indicates that the magnetic implosion could be the physical linkage between them, and the structures of coronal magnetic fields are important for producing sympathetic eruptions. A magnetic unwinding jet and a blowout jet are studied in Chapters 5 and 6, respectively. The former exhibits obvious radial expansion, which undergoes three distinct phases: the slow expansion phase, the fast expansion phase, and the steady phase. In addition, calculation indicates that the non-potential magnetic field in the jet can supply sufficient energy for producing the unwinding

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

The Female Genital Tract Microbiome Is Associated With Vaginal Antiretroviral Drug Concentrations in Human Immunodeficiency Virus-Infected Women on Antiretroviral Therapy.

PubMed

Donahue Carlson, Renee; Sheth, Anandi N; Read, Timothy D; Frisch, Michael B; Mehta, C Christina; Martin, Amy; Haaland, Richard E; Patel, Anar S; Pau, Chou-Pong; Kraft, Colleen S; Ofotokun, Igho

2017-11-15

The female genital tract (FGT) microbiome may affect vaginal pH and other factors that influence drug movement into the vagina. We examined the relationship between the microbiome and antiretroviral concentrations in the FGT. Over one menstrual cycle, 20 human immunodeficiency virus (HIV)-infected women virologically suppressed on tenofovir (TFV) disoproxil fumarate/emtricitabine and ritonavir-boosted atazanavir (ATV) underwent serial paired cervicovaginal and plasma sampling for antiretroviral concentrations using high-performance liquid chromatography-tandem mass spectrometry. Analysis of 16S ribosomal RNA gene sequencing of cervicovaginal lavage clustered each participant visit into a unique microbiome community type (mCT). Participants were predominantly African American (95%), with a median age of 38 years. Cervicovaginal lavage sequencing (n = 109) resulted in a low-diversity mCT dominated by Lactobacillus (n = 40), and intermediate-diversity (n = 28) and high-diversity (n = 41) mCTs with abundance of anaerobic taxa. In multivariable models, geometric mean FGT:plasma ratios varied significantly by mCT for all 3 drugs. For both ATV and TFV, FGT:plasma was significantly lower in participant visits with high- and low-diversity mCT groups (all P < .02). For emtricitabine, FGT:plasma was significantly lower in participant visits with low- vs intermediate-diversity mCT groups (P = .002). Certain FGT mCTs are associated with decreased FGT antiretroviral concentrations. These findings are relevant for optimizing antiretrovirals used for biomedical HIV prevention in women. © The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.

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

Gender differences in clinical, immunological, and virological outcomes in highly active antiretroviral-treated HIV–HCV coinfected patients

PubMed Central

Emery, Joel; Pick, Neora; Mills, Edward J; Cooper, Curtis L

2010-01-01

Objective: The influence of biological sex on human immunodeficiency virus (HIV) antiretroviral treatment outcome is not well described in HIV–hepatitis C (HCV) coinfection. Methods: We assessed patients’ clinical outcomes of HIV–HCV coinfected patients initiating antiretroviral therapy attending the Ottawa Hospital Immunodeficiency Clinic from January 1996 to June 2008. Results: We assessed 144 males and 39 females. Although similar in most baseline characteristics, the CD4 count was higher in females (375 vs 290 cells/μL). Fewer females initiated ritonavir-boosted regimens. The median duration on therapy before interruption or change was longer in males (10 versus 4 months) (odds ratio [OR] 1.40 95% confidence interval: 0.95–2.04; P = 0.09). HIV RNA suppression was frequent (74%) and mean CD4 count achieved robust (over 400 cells/μL) at 6 months, irrespective of sex. The primary reasons for therapy interruption in females and males included: gastrointestinal intolerance (25% vs 19%; P = 0.42); poor adherence (22% vs 15%; P = 0.31); neuropsychiatric symptoms (19% vs 5%; P = 0.003); and lost to follow-up (3% vs 13%; P = 0.08). Seven males (5%) and no females discontinued therapy for liver-specific complications. Death rate was higher in females (23% vs 7%; P = 0.003). Conclusion: There are subtle differences in the characteristics of female and male HIV–HCV coinfected patients that influence HIV treatment decisions. The reasons for treatment interruption and change differ by biological sex. This knowledge should be considered when starting HIV therapy and in efforts to improve treatment outcomes. PMID:20517470

[Sustainability of Brazilian policy for access to antiretroviral drugs].

PubMed

Grangeiro, Alexandre; Teixeira, Luciana; Bastos, Francisco I; Teixeira, Paulo

2006-04-01

The expense of acquiring antiretroviral drugs in Brazil has given rise to debate about the sustainability of the policy of universal access to AIDS medications, despite the evident benefits. The objective of this study was to analyze the evolution of the Ministry of Health's spending on acquiring antiretroviral drugs from 1998 to 2005, the determining factors and the medium-term sustainability of this policy (2006-2008). The study on the evolution of spending on antiretrovirals included analysis of their prices, the year-by-year expenditure, the number of patients utilizing the medication, the mean expenditure per patient and the strategies for reducing the prices maintained during this period. To analyze the sustainability of the policy for access to antiretrovirals, the cost of acquiring the drugs over the period from 2006 to 2008 was estimated, along with the proportion of gross domestic product and federal health expenditure represented by this spending. The data were collected from the Ministry of Health, the Brazilian Institute for Geography and Statistics (IBGE) and the Ministry of Planning. The expenditure on antiretrovirals increased by 66% in 2005, breaking the declining trend observed over the period from 2000 to 2004. The main factors associated with this increase were the weakening of the national generics industry and the unsatisfactory results from the process of negotiating with pharmaceutical companies. The Brazilian policy for universal access is unsustainable at the present growth rates of the gross domestic product, unless the country compromises its investments in other fields.

When to Start Antiretroviral Therapy

MedlinePlus

... pregnant should continue taking HIV medicines throughout their pregnancies. When HIV infection is diagnosed during pregnancy, ART should be ... States: Recommendations for Use of Antiretroviral Drugs During Pregnancy: ... with HIV Who Are Currently Receiving Antiretroviral Therapy , and Pregnant ...

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

PubMed Central

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

2014-01-01

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

Health and federal budgetary effects of increasing access to antiretroviral medications for HIV by expanding Medicaid.

PubMed

Kahn, J G; Haile, B; Kates, J; Chang, S

2001-09-01

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. 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. 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 5,816 years of life. Net federal costs for all programs are $739 million (full benefits) and $480 million (limited benefits); for Medicaid alone, the costs are $1.43 and $1.17 billion, respectively. Results were sensitive to awareness of serostatus, highly active antiretroviral therapy cost, and participation rate. Strategies for federal cost neutrality include Medicaid HIV drug price reductions as low as 9% and private insurance buy-ins. Expansion of the Medicaid eligibility to increase access to antiretroviral therapy would have substantial health benefits at affordable costs.

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

PubMed Central

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

2005-01-01

Human immunodeficiency virus (HIV)-1 infection influences natural killer (NK) cell expression of inhibitory NK receptors and activating natural cytotoxicity receptors. It is unknown whether expression of the co-stimulatory NK cell receptor 2B4 (CD244) on NK cells and CD3+ CD8+ cells are affected by highly active antiretroviral therapy (HAART), low-level viraemia, proviral-DNA or immune activation in HIV-1 infected patients. A total of 101 HAART-treated HIV-1 infected patients with ≤ 200 HIV-RNA copies/ml were followed prospectively for 24 months. HIV-RNA was investigated 3-monthly and 2B4 expression on CD3− CD16+ NK cells and CD3+ CD8+ cells, proviral-DNA and plasma soluble tumour necrosis factor receptor (sTNFr)-II were investigated 6-monthly. For comparison, 2B4 expression was investigated in 20 healthy individuals. The concentration of 2B4+ NK cells was initially reduced in HIV-1 infected patients (P < 0·001) but increased to a normal level during the 24 months’ follow-up. The concentration of CD3+ CD8+ 2B4+ cells in HIV-1 infected patients was normal and did not change during follow-up. The relative fluorescence intensity (RFI) of 2B4 increased on both NK cells and CD3+ CD8+ cells during follow-up (both P < 0·001). Higher levels of proviral-DNA carrying cells and plasma sTNFrII were associated with reductions in the concentration of 2B4+ NK cells (all P < 0·05). HIV-RNA had no effect on 2B4 expression on NK cells or CD3+ CD8+ cells. These findings demonstrate that the concentration of 2B4+ NK cells normalizes during long-term HAART in HIV-1 infected patients. The finding that proviral-DNA and sTNFrII were associated negatively with the concentration of 2B4+ NK cells suggests that immune activation in HIV-1 infected patients receiving HAART influences the target cell recognition by NK cells. PMID:16045743

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

PubMed

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

2005-09-01

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

Mitochondrial Toxicity Studied with the PBMC of Children from the Chinese National Pediatric Highly Active Antiretroviral Therapy Cohort

PubMed Central

Liu, Daojie; Yin, Jiming; Qiao, Luxin; Shi, Ying; Dong, Yaowu; Li, Ning; Zhang, Fujie; Chen, Dexi

2013-01-01

As the backbone of highly active antiretroviral therapy (HAART), nucleoside reverse transcriptase inhibitors (NRTIs) have effectively improved outcomes for HIV-infected patients. However, long-term treatment with NRTIs can cause a series of pathologies associated with mitochondrial toxicity. To date, the status and mechanism of mitochondrial toxicity induced by NRTIs are still not clear, especially in HIV-infected children. As part of the national pediatric HAART program in China, our study focused on mitochondrial toxicity and its potential mechanism in HIV-1-infected children who were divided into two groups based on their duration of treatment with NRTIs: one group received treatment for less than 36 months and one group was treated for 36 to 72 months. The control group comprised age-matched non-HIV-infected children. Blood lactic acid and ATP levels in peripheral blood mononuclear cells (PBMCs) were measured to evaluate mitochondrial function, and mtDNA copies and mutations in PBMCs were determined for detecting mtDNA lesions. Simultaneously, TK2 and P53R2 gene expression in PBMC was measured. As compared with the control group, blood lactic acid levels in both NRTI treatment groups were significantly higher, whereas ATP levels and mtDNA mutation rates in PBMCs did not differ between the control and the two NRTI treatment groups. Both NRTI treatment groups exhibited significant mtDNA loss. N Moreover, we found that P53R2 mRNA expression and protein levels were significantly reduced in both treatment groups and that TK2 mRNA expression and protein levels were induced in the long-term NRTI treatment group. These results suggest that mitochondrial toxicity occurs in long-term HAART patients and that P53R2 and TK2 levels in PBMCs are useful biomarkers for detecting mitochondrial toxicity in patients on long-term treatment with NRTIs. PMID:23468942

Elevated serum uric acid levels are associated with endothelial dysfunction in HIV patients receiving highly-active antiretroviral therapy.

PubMed

Pirro, Matteo; Bianconi, Vanessa; Schiaroli, Elisabetta; Francisci, Daniela; Mannarino, Massimo R; Bagaglia, Francesco; Sahebkar, Amirhossein; Merriman, Tony; Baldelli, Franco

2018-05-01

Elevated serum uric acid (SUA) levels may be associated with endothelial dysfunction. Increased rates of metabolic syndrome (MS) and elevated SUA levels were described in human immunodeficiency virus (HIV) infected patients. We investigated whether SUA levels are associated with endothelial dysfunction in HIV positive patients receiving highly-active antiretroviral therapy (HAART) irrespective of MS. In this cross-sectional study of 250 HIV positive patients receiving stable HAART, we evaluated the relationship between MS, SUA levels and endothelial function. SUA levels and brachial artery flow-mediated dilation (bFMD) were measured. The relationship between logarithmic (LG)-transformed SUA levels and bFMD was evaluated after correction for MS. MS was detected in 28.4% of patients and elevated SUA levels (≥6 mg/dL) in 25.2%. MS was associated with higher LG-SUA levels (age-, gender- and glomerular filtration rate-adjusted beta = 0.204, p = 0.001). The crude linear association between LG-SUA levels and LG-bFMD (beta = -0.166, p = 0.008) was abolished after correction for MS (beta = -0.089, p = 0.172). When SUA levels were used as a categorical variable (≥6 mg/dL or <6 mg/dL and SUA quartiles, respectively), the association between LG-SUA levels and LG-bFMD remained significant after adjustment for MS (beta = -0.142, p = 0.022 and beta = -0.163, p = 0.010, respectively). MS significantly affects SUA levels in HAART-treated HIV infected patients. The negative association between SUA and bFMD is independent of MS only for elevated SUA levels. Copyright © 2018 Elsevier B.V. All rights reserved.

Durability of Adherence to Antiretroviral Therapy on Initial and Subsequent Regimens

PubMed Central

GARDNER, EDWARD M.; BURMAN, WILLIAM J.; MARAVI, MOISES E.; DAVIDSON, ARTHUR J.

2007-01-01

There is uncertainty regarding the durability of adherence to antiretroviral therapy. This study is a retrospective review of previously antiretroviral naïve patients initiating therapy between 1997 and 2002. Antiretroviral adherence was calculated using prescription refill data and was analyzed over time on an initial regimen and on sequential antiretroviral regimens. Three hundred forty-four patients were included. The median lengths of the first, second, and third regimens were stable at 1.7 years, 1.2 years, and 1.5 years, respectively (p = 0.10). In multivariate analysis the factor most significantly associated with earlier initial regimen termination was poor adherence. On an initial regimen, adherence decreased over time and declined most rapidly in patients with the shortest regimens (4 to <16 months, −43% per year), followed by patients with intermediate regimen duration (16 to <28 months, −19% per year), and then patients with longer regimens (≥28 months, −5% per year). In patients progressing to a third regimen, there was a trend toward decreasing adherence over successive regimens. In conclusion, sequential antiretroviral regimens are of similar lengths, with adherence being highly associated with first regimen duration. Adherence decreases during an initial regimen and on sequential antiretroviral regimens. Effective and durable interventions to prevent declining adherence are needed. PMID:16987049

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

PubMed

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.

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

[Non-antiretroviral drugs uses among HIV-infected persons receiving antiretroviral therapy in Senegal: Costs and factors associated with prescription].

PubMed

Diouf, A; Youbong, T J; Maynart, M; Ndoye, M; Diéye, F L; Ndiaye, N A; Koita-Fall, M B; Ndiaye, B; Seydi, M

2017-08-01

In addition to antiretroviral therapy, non-antiretroviral drugs are necessary for the appropriate care of people living with HIV. The costs of such drugs are totally or partially supported by the people living with HIV. We aimed to evaluate the overall costs, the costs supported by the people living with HIV and factors associated with the prescription of non-antiretroviral drugs in people living with HIV on antiretroviral therapy in Senegal. We conducted a retrospective cohort study on 331 people living with HIV who initiated antiretroviral therapy between 2009 and 2011 and followed until March 2012. The costs of non-antiretroviral drugs were those of the national pharmacy for essential drugs; otherwise they were the lowest costs in the private pharmacies. Associated factors were identified through a logistic regression model. The study population was 61 % female. At baseline, 39 % of patients were classified at WHO clinical stage 3 and 40 % at WHO clinical stage 4. Median age, body mass index and CD4 cells count were 41 years, 18kg/m 2  and 93 cells/μL, respectively. After a mean duration of 11.4 months of antiretroviral therapy, 85 % of patients received at least one prescription for a non-antiretroviral drug. Over the entire study period, the most frequently prescribed non-antiretroviral drugs were cotrimoxazole (78.9 % of patients), iron (33.2 %), vitamins (21.1 %) and antibiotics (19.6 %). The mean cost per patient was 34 Euros and the mean cost supported per patient was 14 Euros. The most expensive drugs per treated patient were antihypertensives (168 Euros), anti-ulcer agents (12 Euros), vitamins (8.5 Euros) and antihistamines (7 Euros). The prescription for a non-antiretroviral drug was associated with advanced clinical stage (WHO clinical stage 3/4 versus stage 1/2): OR=2.25; 95 % CI=1.11-4.57 and viral type (HIV-2 versus HIV-1/HIV-1+HIV-2): OR=0.36; 95 % CI=0.14-0.89. Non-antiretroviral drugs are frequently prescribed to

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

Subclinical herpesvirus shedding among HIV-1-infected men on antiretroviral therapy.

PubMed

Agudelo-Hernandez, Arcadio; Chen, Yue; Bullotta, Arlene; Buchanan, William G; Klamar-Blain, Cynthia R; Borowski, Luann; Riddler, Sharon A; Rinaldo, Charles R; Macatangay, Bernard J C

2017-09-24

We evaluated the subclinical shedding of six different herpesviruses in antiretroviral drug-treated HIV-positive [HIV(+)] MSM, and determined how this is associated with markers of inflammation and immune activation. We obtained blood, semen, throat washing, urine, and stool from 15 antiretroviral-treated HIV-1-infected MSM with CD4 T-cell reconstitution, and 12 age-matched HIV-negative [HIV (-)] MSM from the Multicenter AIDS Cohort Study at four timepoints over 24 weeks to measure DNA levels of cytomegalovirus (CMV), Epstein-Barr virus (EBV), herpes simplex virus 1 and 2, human herpesvirus 6 (HHV6), and HHV8. T-cell activation and plasma levels of soluble markers of inflammation and activation were also measured at the corresponding timepoints. HIV(+) participants had a trend for higher total herpesvirus shedding rate. HIV(+) participants also had a significantly higher rate of shedding EBV and CMV compared with the HIV(-) group. Herpesvirus shedding was mostly seen in throat washings. In the HIV(+) group, herpesvirus shedding rate inversely correlated with plasma levels of interferon γ-induced protein 10 and soluble CD163. CMV DNA levels negatively correlated with levels of T-cell activation. There was a trend for a positive correlation between EBV shedding rate and plasma soluble CD14. HHV6 shedding rate negatively correlated with plasma levels of interleukin-6, soluble CD163, and interferon gamma-induced protein 10. Correlations were not observed among HIV(-) individuals. Among treated HIV-infected MSM, there are higher subclinical shedding rates of some herpesviruses that occur in different body compartments and negatively correlate with levels of inflammation and immune activation.

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

Cellular and humoral immune responses to a tetanus toxoid booster in perinatally HIV-1-infected children and adolescents receiving highly active antiretroviral therapy (HAART).

PubMed

Ching, Natascha; Deville, Jaime G; Nielsen, Karin A; Ank, Bonnie; Wei, Lian S; Sim, Myung Shin; Wolinsky, Steven M; Bryson, Yvonne J

2007-01-01

Human immunodeficiency virus type 1 (HIV-1) infected children treated with highly active antiretroviral therapy (HAART) may develop a significant reduction of plasma viremia associated with an increase in CD4+ T-cell counts. Functional capacity of this reconstituted immune system in response to recall antigens is important to maintain protective immunity to vaccine-preventable diseases. We therefore determined cellular and humoral immune responses to tetanus toxoid (TT) booster in perinatally HIV-1-infected children and adolescents receiving HAART. Immune responses were prospectively evaluated pre- and post-tetanus booster using lymphocyte proliferation assay (LPA) stimulation index (SI > or = 3.0) and tetanus antibody (TAb > or = 0.15) in 15 patients. The median interval from primary tetanus immunization series was 6 years (range 2-12 years). We compared patients by their virological response to HAART (complete responders, CR, n=7; incomplete responders, ICR, n=8). There were no significant differences in median age 12.6 years (CR: 12.9; ICR: 10.6) or median CD4 T-cell pre-booster (CR: 35%/819; ICR: 26%/429) between groups. Tetanus LPA responses were observed in one patient prior to booster and in seven patients post-booster. In contrast, 38% of patients had protective TAb pre-booster, but 92% developed protective TAb post-booster. All of the CR and 5/6 ICR patients developed protective TAb. HIV-1-infected children and adolescents had modest LPA responses to tetanus following booster, similar to HIV-1-infected adults. However, the majority of patients developed protective TAb levels after booster and maintained the response. Shorter intervals may need to be considered for TT immunization boosters in HIV-1-infected pediatric patients, as only 38% had protective TAb at baseline.

Cancer survival in patients with HIV/AIDS in the era of highly active antiretroviral therapy in Taiwan: a population-based cohort study.

PubMed

Lin, Chih-Shin; Lin, Charlene; Weng, Shih-Feng; Lin, Shih-Wei; Lin, Yung-Song

2013-10-01

HIV-related immunosuppression has been associated with the development of AIDS-defining malignancies. We examined the overall survival of HIV-infected patients who developed cancer. A retrospective cohort study. Using the Taiwan Longitudinal Health Insurance Database, we compared patients diagnosed with HIV (n=9918) between January 1, 2002, and December 31, 2007 with age-matched controls (n=99,180). Each patient was followed until the end of 2009 (least 2 years after the initial HIV diagnosis) to evaluate the incidence of malignancies. The risk of overall malignancies in the HIV-infected cohort was 1.88 times higher than the risk of a first malignancy in the age-matched non-HIV infected cohort (incidence rate ratio [IRR])=2.05, p<0.0001). The diagnosis of a malignancy was negatively correlated with survival in the HIV-infected cohort (p<0.0011), and HIV infection had a synergistic effect on the survival of patients with malignancies compared with the non-HIV infected cohort, all of who had been newly diagnosed with cancer (p<0.0001). However, the difference in the risk of developing nasopharyngeal carcinoma (NPC), a highly prevalent malignancy in Taiwan, between the two cohorts was not significant (IRR=0.22, 95% CI=0.03-1.65). The risk of cancer in HIV-infected patients in Taiwan has increased significantly in the era of highly active antiretroviral therapy. A history of HIV significantly affected the survival of the patients in our study cohort after they developed cancer. Evidence level: 2B. Copyright © 2013 Elsevier Ltd. All rights reserved.

Does short-term virologic failure translate to clinical events in antiretroviral-naïve patients initiating antiretroviral therapy in clinical practice?

PubMed

Mugavero, Michael J; May, Margaret; Harris, Ross; Saag, Michael S; Costagliola, Dominique; Egger, Matthias; Phillips, Andrew; Günthard, Huldrych F; Dabis, Francois; Hogg, Robert; de Wolf, Frank; Fatkenheuer, Gerd; Gill, M John; Justice, Amy; D'Arminio Monforte, Antonella; Lampe, Fiona; Miró, Jose M; Staszewski, Schlomo; Sterne, Jonathan A C

2008-11-30

To determine whether differences in short-term virologic failure among commonly used antiretroviral therapy (ART) regimens translate to differences in clinical events in antiretroviral-naïve patients initiating ART. Observational cohort study of patients initiating ART between January 2000 and December 2005. The Antiretroviral Therapy Cohort Collaboration (ART-CC) is a collaboration of 15 HIV cohort studies from Canada, Europe, and the United States. A total of 13 546 antiretroviral-naïve HIV-positive patients initiating ART with efavirenz, nevirapine, lopinavir/ritonavir, nelfinavir, or abacavir as third drugs in combination with a zidovudine and lamivudine nucleoside reverse transcriptase inhibitor backbone. Short-term (24-week) virologic failure (>500 copies/ml) and clinical events within 2 years of ART initiation (incident AIDS-defining event, death, and a composite measure of these two outcomes). Compared with efavirenz as initial third drug, short-term virologic failure was more common with all other third drugs evaluated; nevirapine (adjusted odds ratio = 1.87, 95% confidence interval (CI) = 1.58-2.22), lopinavir/ritonavir (1.32, 95% CI = 1.12-1.57), nelfinavir (3.20, 95% CI = 2.74-3.74), and abacavir (2.13, 95% CI = 1.82-2.50). However, the rate of clinical events within 2 years of ART initiation appeared higher only with nevirapine (adjusted hazard ratio for composite outcome measure 1.27, 95% CI = 1.04-1.56) and abacavir (1.22, 95% CI = 1.00-1.48). Among antiretroviral-naïve patients initiating therapy, between-ART regimen, differences in short-term virologic failure do not necessarily translate to differences in clinical outcomes. Our results should be interpreted with caution because of the possibility of residual confounding by indication.

[Ocular manifestations in patients with human immunodeficiency virus infection before and after the introduction of highly active antiretroviral therapy].

PubMed

Mesarić, Branko; Lisić, Miroslav; Kniewald, Tihana; Ugrinović, Nikola; Begovac, Josip

2005-01-01

The aim of this study was to determine and compare the incidence of various ophthalmlogic changes before anfd after the initiation of highly active antiretroviral therapy (HAART) in HIV-infected patients treated at the University Hospital for Infectious Diseases "Dr. Fran Mihaljević" in Zagreb. This retrospective longitudinal analysis included all adult patients with confirmed HIV-1 infection divided into two groups: period before HAART (1995-1997) and period after HAART (1998-2000). Only those patients who underwent at least two ophthalmologic examinations in any of the two or in both periods were considered eligible. In total, 85 patients were enrolled in the study, 50 during the 1995-1997 period and 47 in the period 1998-2000 (12 patients were monitored in both periods). The mortality rate was significantly lower in patients treated during the HAART era, with an average decrease in mortality rates of 59.3%. During the period of ophthalmologic monitoing from 1995 to 1997, only 9 (18%) patients received HAART, and 33 (70.2%) in the period 1998-2000. In total, 208 ophthalmic abnormalities were recorded, 132 (63.5%) in the first and 76 (36.5%) in the second period. Vascular changes were most frequently diagnosed (113/208 or 54.3% cases) of which cotton-wool exudates in 55 and microaneurysms in 54 cases. Cytomegalovirus (CMV) retinitis was most commonly diagnosed among infectious ocular complications (altogether 39 episodes). Changes in the anterior segment were observed in only 11/208 (5.3%) cases, while neuro-ophthalmic manifestations were sees in 39/208 patients (18.7%). The incidence of CMV-retinitis episodes in the first monitored period was 57.2 (95% CI, 38.5-86.6) per 100 years of follow-up and in the HAART era 7.6 (95% CI, 1.6-22.4; p<0.0001) per 100 years of follow-up. The visual acuity in patients from the HAART era was significantly more frequently preserved than in patients from the pre HAART era on follow-up examinations (p<0.001). Our study showed that

Calculating the affordability of antiretrovirals in St Lucia.

PubMed

Reddock, J R; Grignon, M

2013-01-01

The cost of antiretrovirals is borne by donors in many low- and middle-income countries, including St Lucia. Although donor involvement has facilitated access to antiretrovirals, donor engagement in HIV/AIDS has changed over the years. This paper assesses the affordability of antiretrovirals at the individual level if donors were no longer available to fund the cost of first and second-line antiretrovirals and a prospective third-line regimen. Various conceptions of affordability are reviewed using different assumptions of what is required to maintain a standard of living that would avoid individuals descending into poverty as a result of antiretroviral purchases. These concepts of affordability are operationalized using data from the Household Budgeting Survey conducted in St Lucia in 2005/2006. While there is a range of results for the affordability of first and second-line antiretrovirals depending on which standard of affordability is used, third-line antiretrovirals are unaffordable to more than 80% of the population across the four standards of affordability used - the national poverty line, 50% of median annual consumption, 10% of annual consumption and a proposed reasonable minimum standard.

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

Antiretroviral therapy potentiates high-fat diet induced obesity and glucose intolerance.

PubMed

Pepin, Mark E; Padgett, Lindsey E; McDowell, Ruth E; Burg, Ashley R; Brahma, Manoja K; Holleman, Cassie; Kim, Teayoun; Crossman, David; Kutsch, Olaf; Tse, Hubert M; Wende, Adam R; Habegger, Kirk M

2018-06-01

Breakthroughs in HIV treatment, especially combination antiretroviral therapy (ART), have massively reduced AIDS-associated mortality. However, ART administration amplifies the risk of non-AIDS defining illnesses including obesity, diabetes, and cardiovascular disease, collectively known as metabolic syndrome. Initial reports suggest that ART-associated risk of metabolic syndrome correlates with socioeconomic status, a multifaceted finding that encompasses income, race, education, and diet. Therefore, determination of causal relationships is extremely challenging due to the complex interplay between viral infection, ART, and the many environmental factors. In the current study, we employed a mouse model to specifically examine interactions between ART and diet that impacts energy balance and glucose metabolism. Previous studies have shown that high-fat feeding induces persistent low-grade systemic and adipose tissue inflammation contributing to insulin resistance and metabolic dysregulation via adipose-infiltrating macrophages. Studies herein test the hypothesis that ART potentiates the inflammatory effects of a high-fat diet (HFD). C57Bl/6J mice on a HFD or standard chow containing ART or vehicle, were subjected to functional metabolic testing, RNA-sequencing of epididymal white adipose tissue (eWAT), and array-based kinomic analysis of eWAT-infiltrating macrophages. ART-treated mice on a HFD displayed increased fat mass accumulation, impaired glucose tolerance, and potentiated insulin resistance. Gene set enrichment and kinomic array analyses revealed a pro-inflammatory transcriptional signature depicting granulocyte migration and activation. The current study reveals a HFD-ART interaction that increases inflammatory transcriptional pathways and impairs glucose metabolism, energy balance, and metabolic dysfunction. Copyright © 2018 The Authors. Published by Elsevier GmbH.. All rights reserved.

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

PubMed Central

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

2010-01-01

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

Reasons and predictors for antiretroviral therapy change among HIV-infected adults at South West Ethiopia.

PubMed

Mekonnen, Endalkachew; Workicho, Abdulhalik; Hussein, Nezif; Feyera, Teka

2018-06-05

This retrospective cohort study is aimed to assess reasons and predictors of regimen change from initial highly active antiretroviral therapy among 1533 Human Immunodeficiency virus-infected adult patients at the Jimma University Tertiary Hospital. One in two (47.7%) adults changed their antiretroviral therapy regimen. Patients who were above the primary level of education [Hazard ratio (HR) 1.241 (95% CI 1.070-1.440)] and with human immunodeficiency virus/tuberculosis co-infection [HR 1.405 (95% CI 1.156-1.708)] had the higher risk of regimen change than their comparator. Individuals on Efavirenz [HR 0.675 (95% CI 0.553-0.825)] and non-stavudine [HR 0.494 (95% CI 0.406-0.601)] based regimens had lower risk of regimen change.

Early versus delayed initiation of antiretroviral therapy for Indian HIV-Infected individuals with tuberculosis on antituberculosis treatment.

PubMed

Sinha, Sanjeev; Shekhar, Rahul C; Singh, Gurjeet; Shah, Nipam; Ahmad, Hafiz; Kumar, Narendra; Sharma, Surendra K; Samantaray, J C; Ranjan, Sanjai; Ekka, Meera; Sreenivas, Vishnu; Mitsuyasu, Ronald T

2012-07-31

For antiretroviral therapy (ART) naive human immunodeficiency virus (HIV) infected adults suffering from tuberculosis (TB), there is uncertainty about the optimal time to initiate highly active antiretroviral therapy (HAART) after starting antituberculosis treatment (ATT), in order to minimize mortality, HIV disease progression, and adverse events. In a randomized, open label trial at All India Institute of Medical Sciences, New Delhi, India, eligible HIV positive individuals with a diagnosis of TB were randomly assigned to receive HAART after 2-4 or 8-12 weeks of starting ATT, and were followed for 12 months after HAART initiation. Participants received directly observed therapy short course (DOTS) for TB, and an antiretroviral regimen comprising stavudine or zidovudine, lamivudine, and efavirenz. Primary end points were death from any cause, and progression of HIV disease marked by failure of ART. A total of 150 patients with HIV and TB were initiated on HAART: 88 received it after 2-4 weeks (early ART) and 62 after 8-12 weeks (delayed ART) of starting ATT. There was no significant difference in mortality between the groups after the introduction of HAART. However, incidence of ART failure was 31% in delayed versus 16% in early ART arm (p = 0.045). Kaplan Meier disease progression free survival at 12 months was 79% for early versus 64% for the delayed ART arm (p = 0.05). Rates of adverse events were similar. Early initiation of HAART for patients with HIV and TB significantly decreases incidence of HIV disease progression and has good tolerability. CTRI/2011/12/002260.

High prevalence of lipoatrophy in pre-pubertal South African children on antiretroviral therapy: a cross-sectional study.

PubMed

Innes, Steve; Cotton, Mark F; Haubrich, Richard; Conradie, Maria M; van Niekerk, Margaret; Edson, Clair; Rabie, Helena; Jain, Sonia; Sun, Xiaoying; Zöllner, Ekkehard W; Hough, Stephen; Browne, Sara H

2012-11-23

Despite changes in WHO guidelines, stavudine is still used extensively for treatment of pediatric HIV in the developing world. Lipoatrophy in sub-Saharan African children can be stigmatizing and have far-reaching consequences. The severity and extent of lipoatrophy in pre-pubertal children living in sub-Saharan Africa is unknown. In this cross-sectional study, children who were 3-12 years old, on antiretroviral therapy and pre-pubertal were recruited from a Family HIV Clinic in South Africa. Lipoatrophy was identified and graded by consensus between two HIV pediatricians using a standardized grading scale. A professional dietician performed formal dietary assessment and anthropometric measurements of trunk and limb fat. Previous antiretroviral exposures were recorded. In a Dual-Energy X-ray Absorbtiometry (DXA) substudy body composition was determined in 42 participants. Among 100 recruits, the prevalence of visually obvious lipoatrophy was 36% (95% CI: 27%-45%). Anthropometry and DXA measurements corroborated the clinical diagnosis of lipoatrophy: Both confirmed significant, substantial extremity fat loss in children with visually obvious lipoatrophy, when adjusted for age and sex. Adjusted odds ratio for developing lipoatrophy was 1.9 (95% CI: 1.3 - 2.9) for each additional year of accumulated exposure to standard dose stavudine. Cumulative time on standard dose stavudine was significantly associated with reductions in biceps and triceps skin-fold thickness (p=0.008). The prevalence of visually obvious lipoatrophy in pre-pubertal South African children on antiretroviral therapy is high. The amount of stavudine that children are exposed to needs review. Resources are needed to enable low-and-middle-income countries to provide suitable pediatric-formulated alternatives to stavudine-based pediatric regimens. The standard stavudine dose for children may need to be reduced. Diagnosis of lipoatrophy at an early stage is important to allow timeous antiretroviral

Time to viral load suppression in antiretroviral-naive and -experienced HIV-infected pregnant women on highly active antiretroviral therapy: implications for pregnant women presenting late in gestation.

PubMed

Aziz, N; Sokoloff, A; Kornak, J; Leva, N V; Mendiola, M L; Levison, J; Feakins, C; Shannon, M; Cohan, D

2013-11-01

To compare time to achieve viral load <400 copies/ml and <1000 copies/ml in HIV-infected antiretroviral (ARV) -naive versus ARV-experienced pregnant women on highly active antiretroviral therapy (HAART). Retrospective cohort study. Three university medical centers, USA. HIV-infected pregnant women initiated or restarted on HAART during pregnancy. We calculated time to viral load <400 copies/ml and <1000 copies/ml in HIV-infected pregnant women on HAART who reported at least 50% adherence, stratifying based on previous ARV exposure history. Time to HIV viral load <400 copies/ml and <1000 copies/ml. We evaluated 138 HIV-infected pregnant women, comprising 76 ARV-naive and 62 ARV-experienced. Ninety-three percent of ARV-naive women achieved a viral load < 400 copies/ml during pregnancy compared with 92% of ARV-experienced women (P = 0.82). The median number of days to achieve a viral load < 400 copies/ml in the ARV-naive cohort was 25.0 (range 3.5-133; interquartile range 16-34) days compared with 27.0 (range 8-162.5; interquartile range 18.5-54.3) days in the ARV-experienced cohort (P = 0.02). In a multiple predictor analysis, women with higher adherence (adjusted relative hazard [aRH] per 10% increase in adherence 1.29, 95% confidence interval [CI] 1.08-1.54, P = 0.01) and receiving a non-nucleotide reverse transcriptase inhibitor (NNRTI) -based regimen (aRH 2.48, 95% CI 1.33-4.63, P = 0.01) were more likely to achieve viral load <400 copies/ml earlier. Increased baseline HIV log10 viral load was associated with a later time of achieving viral load <400 copies/ml (aRH 0.60, 95% CI 0.39-0.92, P = 0.02). In a corresponding model of time to achieve viral load <1000 copies/ml, adherence (aRH per 10% increase in adherence 1.79, 95% CI 1.34-2.39, P < 0.001), receipt of NNRTI (aRH 2.95, 95% CI 1.23-7.06, P = 0.02), and CD4 cell count (aRH per 50 count increase in CD4 1.12, 95% CI 1.03-1.22, P = 0.01) were associated with an earlier time to achieve viral load below this

Antiretroviral drug treatment of CNS HIV-1 infection.

PubMed

Yilmaz, Aylin; Price, Richard W; Gisslén, Magnus

2012-02-01

The advent of combination antiretroviral treatment has had a profound impact on CNS HIV infection and its clinical complications, but neurological impairment still occurs in patients on systemically effective combination therapy, and in some patients it may be important to consider antiretroviral drug entry and effects within the CNS. There are now data on the CNS exposure for most antiretroviral drugs. This review focuses on the CNS pharmacokinetics and pharmacodynamics of antiretroviral drugs in humans, and also discusses controversies in this field.

Sexual risk behavior among people living with HIV and AIDS on antiretroviral therapy at the regional hospital of Sokodé, Togo

PubMed Central

2014-01-01

Background Several studies on the sexual risk behaviors in sub-Saharan Africa have reported that the initiation of antiretroviral therapy leads to safer sexual behaviors. There is however a persistence of risky sexual behavior which is evidenced by a high prevalence of sexually transmitted infections among people living with HIV and AIDS (PLWHA). We sought to determine the factors associated with risky sex among PLWHA on antiretroviral therapy in Togo. Methods An analytical cross-sectional survey was conducted from May to July 2013 at regional hospital of Sokodé, Togo, and targeted 291 PLWHA on antiretroviral therapy for at least three months. Results From May to July 2013, 291 PLWHA on antiretroviral treatment were surveyed. The mean age of PLWHA was 37.3 years and the sex ratio (male/female) was 0.4. Overall, 217 (74.6%) PLWHA were sexually active since initiation of antiretroviral treatment, of which, 74 (34.6%) had risky sexual relations. In multivariate analysis, the factors associated with risky sex were: the duration of antiretroviral treatment (1 to 3 years: aOR = 27.08; p = 0.003; more than 3 years: aOR = 10.87; p = 0.028), adherence of antiretroviral therapy (aOR = 2.56; p = 0.014), alcohol consumption before sex (aOR = 3.59; p = 0.013) and level of education (primary school: aOR = 0.34 p = 0.011; secondary school: aOR = 0.23 p = 0.003; high school: aOR = 0.10; p = 0.006). Conclusion There was a high prevalence of unsafe sex among PLWHA receiving ART at the hospital of Sokodé. Factors associated with sexual risk behaviors were: low education level, non-adherence to ART, alcohol consumption before sex and the duration of ART. It is important to strengthen the implementation of secondary prevention strategies among this population group. PMID:24952380

Immune control of HIV-1 infection after therapy interruption: immediate versus deferred antiretroviral therapy

PubMed Central

2009-01-01

Background The optimal stage for initiating antiretroviral therapies in HIV-1 bearing patients is still a matter of debate. Methods We present computer simulations of HIV-1 infection aimed at identifying the pro et contra of immediate as compared to deferred Highly Active Antiretroviral Therapy (HAART). Results Our simulations highlight that a prompt specific CD8+ cytotoxic T lymphocytes response is detected when therapy is delayed. Compared to very early initiation of HAART, in deferred treated patients CD8+ T cells manage to mediate the decline of viremia in a shorter time and, at interruption of therapy, the virus experiences a stronger immune pressure. We also observe, however, that the immunological effects of the therapy fade with time in both therapeutic regimens. Thus, within one year from discontinuation, viral burden recovers to the value at which it would level off in the absence of therapy. In summary, simulations show that immediate therapy does not prolong the disease-free period and does not confer a survival benefit when compared to treatment started during the chronic infection phase. Conclusion Our conclusion is that, since there is no therapy to date that guarantees life-long protection, deferral of therapy should be preferred in order to minimize the risk of adverse effects, the occurrence of drug resistances and the costs of treatment. PMID:19840392

TLR7 agonists induce transient viremia and reduce the viral reservoir in SIV-infected rhesus macaques on antiretroviral therapy

DOE PAGES

Lim, So-Yon; Osuna, Christa E.; Hraber, Peter T.; ...

2018-05-02

Antiretroviral therapy can halt HIV-1 replication, but fails to target the long-lived latent viral reservoir. Several pharmacological compounds have been evaluated for their ability to reverse HIV-1 latency, but none have demonstrably reduced the latent HIV-1 reservoir, or impacted viral rebound following the interruption of antiretroviral therapy. Here, we evaluate orally administered selective tolllike receptor 7 agonists GS-986 and GS-9620 for their ability to induce transient viremia in simian immunodeficiency virus-infected rhesus monkeys on suppressive antiretroviral therapy. In an initial doseescalation study, and a subsequent dose-optimization study, we found that toll-like receptor 7 agonists activate multiple innate and adaptive immunemore » cell populations in addition to inducing SIV RNA. We also observed toll-like receptor 7 agonist-induced reductions in SIV DNA and ex vivo inducible virus from treated animals. In a second study, after stopping antiretroviral therapy, two of nine treated animals have remained aviremic for more than two years, even after in vivo CD8+ lymphocyte depletion. Moreover, adoptive transfer of cells from aviremic animals could not induce de novo infection in naive recipient macaques. These findings suggest that toll-like receptor agonists may facilitate reservoir reduction in a subset of individuals.« less

TLR7 agonists induce transient viremia and reduce the viral reservoir in SIV-infected rhesus macaques on antiretroviral therapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lim, So-Yon; Osuna, Christa E.; Hraber, Peter T.

Antiretroviral therapy can halt HIV-1 replication, but fails to target the long-lived latent viral reservoir. Several pharmacological compounds have been evaluated for their ability to reverse HIV-1 latency, but none have demonstrably reduced the latent HIV-1 reservoir, or impacted viral rebound following the interruption of antiretroviral therapy. Here, we evaluate orally administered selective tolllike receptor 7 agonists GS-986 and GS-9620 for their ability to induce transient viremia in simian immunodeficiency virus-infected rhesus monkeys on suppressive antiretroviral therapy. In an initial doseescalation study, and a subsequent dose-optimization study, we found that toll-like receptor 7 agonists activate multiple innate and adaptive immunemore » cell populations in addition to inducing SIV RNA. We also observed toll-like receptor 7 agonist-induced reductions in SIV DNA and ex vivo inducible virus from treated animals. In a second study, after stopping antiretroviral therapy, two of nine treated animals have remained aviremic for more than two years, even after in vivo CD8+ lymphocyte depletion. Moreover, adoptive transfer of cells from aviremic animals could not induce de novo infection in naive recipient macaques. These findings suggest that toll-like receptor agonists may facilitate reservoir reduction in a subset of individuals.« less

Synergy against drug-resistant HIV-1 with the microbicide antiretrovirals, dapivirine and tenofovir, in combination.

PubMed

Schader, Susan M; Colby-Germinario, Susan P; Schachter, Jordana R; Xu, Hongtao; Wainberg, Mark A

2011-08-24

To evaluate the candidate antiretroviral microbicide compounds, dapivirine (DAP) and tenofovir (TFV), alone and in combination against the transmission of wild-type and nonnucleoside reverse transcriptase inhibitor (NNRTI)-resistant HIV-1 from different subtypes. We determined single-drug efficacy of the RTIs, DAP and TFV, against subtype B and non-B wild-type and NNRTI-resistant HIV-1 in vitro. To assess breadth of activity, compounds were tested alone and in combination against wild-type and NNRTI-resistant subtype C primary HIV-1 isolates and complimentary clonal HIV-1 from subtypes B, C and CRF02_AG to control for viral variation. Early infection was quantified by counting light units emitted from TZM-bl cells less than 48-h postinfection. Combination ratios were based on drug inhibitory concentrations (IC(50)s) and combined effects were determined by calculating combination indices. Both candidate microbicide antiretrovirals demonstrated potent anti-NNRTI-resistant HIV-1 activity in vitro, albeit the combination protected better than the single-drug treatments. Of particular interest, the DAP with TFV combination exhibited synergy (50% combination index, CI(50) = 0.567) against subtype C NNRTI-resistant HIV-1, whereas additivity (CI(50) = 0.987) was observed against the wild-type counterpart from the same patient. The effect was not compounded by the presence of subdominant viral fractions, as experiments using complimentary clonal subtype C wild-type (CI(50) = 0.968) and NNRTI-resistant (CI(50) = 0.672) HIV-1, in lieu of the patient quasispecies, gave similar results. This study supports the notion that antiretroviral drug combinations may retain antiviral activity against some drug-resistant HIV-1 despite subtype classification and quasispecies diversity.

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

PubMed

Dimala, Christian Akem; Blencowe, Hannah

2017-03-09

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. 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 I 2 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. 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 available especially to national HIV/AIDS committees formulating

Cost-efficacy analysis of the MONET trial using UK antiretroviral drug prices.

PubMed

Gazzard, Brian; Hill, Andrew; Anceau, Anne

2011-07-01

In virologically suppressed patients, switching to darunavir/ritonavir (DRV/r) monotherapy maintains HIV RNA suppression, and could also lower treatment costs. The purpose of this analysis was to calculate the potential cost savings from the use of DRV/r monotherapy in the UK. In the MONET trial, 256 patients with HIV RNA < 50 copies/mL on current highly active antiretroviral therapy (HAART) for over 24 weeks (non-nucleoside reverse-transcriptase inhibitor [NNRTI] based [43%] or protease inhibitor [PI] based [57%]), switched to DRV/r 800/100 mg once daily, either as monotherapy (n = 127) or with two NRTIs (n = 129). The UK costs per patient with HIV RNA < 50 copies/mL at week 48 (responders) were calculated using a 'switch included' analysis to account for additional antiretrovirals taken after initial treatment failure. By this analysis, efficacy was 93.5% versus 95.1% in the DRV/r monotherapy and triple therapy arms, respectively. British National Formulary 2009 values were used. Before the trial, the mean annual cost of antiretrovirals was £6906 for patients receiving NNRTI-based HAART, and £8348 for patients receiving PI-based HAART. During the MONET trial, the mean annual per-patient cost of antiretrovirals was £8642 in the triple therapy arm, of which 55% was from NRTIs and 45% from PIs. The mean per-patient cost in the monotherapy arm was £4126, a saving of 52% versus triple therapy. The mean cost per responder was £9085 in the triple therapy arm versus £4413 in the DRV/r monotherapy arm. Based on the MONET results, the lower cost of DRV/r monotherapy versus triple therapy in the UK would allow more patients to be treated for fixed budgets, while maintaining HIV RNA suppression at < 50 copies/mL. If all patients meeting the inclusion criteria of the MONET trial in the UK were switched to DRV/r monotherapy, there is the potential to save up to £60 million in antiretroviral drug costs from the UK NHS budget.

Vitamin D Deficiency in HIV-Infected Women on Antiretroviral Therapy Living in the Tropics.

PubMed

Conrado, Tereza; Miranda-Filho, Demócrito de Barros; Ximenes, Ricardo Arraes de Alencar; Albuquerque, Maria de Fátima; Lacerda, Heloísa Ramos; Ramos, Regina Coeli F; Araújo, Paulo Sérgio Ramos de; Montarroyos, Ulisses; Bandeira, Francisco

2011-01-01

The effects of HIV/AIDS and antiretroviral drugs on vitamin D metabolism are still mostly unknown. This was a cross-sectional study to estimate the prevalence of vitamin D deficiency and identify its association with the clinical and metabolic parameters among 214 HIV-positive female patients on antiretroviral therapy (ART) in Brazil. The prevalence of vitamin D deficiency (< 30 ng/ml) was 40.65% (87/214). Hypercholesterolemia, high LDL-c, duration of use of current antiretroviral regimen, hypertriglyceridemia, body mass index, age, hypertension, time with AIDS ≥ 10 years and hyperglycemia were selected for multivariate analysis (p < 0.20). After this analysis, hypercholesterolemia and use of current antiretroviral regimen ≥ 3 years remained independently associated with vitamin D deficiency. There was an inverse statistically significant correlation between total cholesterol and serum 25(OH)D levels. High prevalence of vitamin D deficiency was found among HIV-positive women on ART and was independently associated with its prolonged use and with hypercholesterolemia.

CARMENES input catalogue of M dwarfs. III. Rotation and activity from high-resolution spectroscopic observations

NASA Astrophysics Data System (ADS)

Jeffers, S. V.; Schöfer, P.; Lamert, A.; Reiners, A.; Montes, D.; Caballero, J. A.; Cortés-Contreras, M.; Marvin, C. J.; Passegger, V. M.; Zechmeister, M.; Quirrenbach, A.; Alonso-Floriano, F. J.; Amado, P. J.; Bauer, F. F.; Casal, E.; Alonso, E. Diez; Herrero, E.; Morales, J. C.; Mundt, R.; Ribas, I.; Sarmiento, L. F.

2018-06-01

CARMENES is a spectrograph for radial velocity surveys of M dwarfs with the aim of detecting Earth-mass planets orbiting in the habitable zones of their host stars. To ensure an optimal use of the CARMENES guaranteed time observations, in this paper we investigate the correlation of activity and rotation for approximately 2200 M dwarfs, ranging in spectral type from M0.0 V to M9.0 V. We present new high-resolution spectroscopic observations with FEROS, CAFE, and HRS of approximately 500 M dwarfs. For each new observation, we determined its radial velocity and measured its Hα activity index and its rotation velocity. Additionally, we have multiple observations of many stars to investigate if there are any radial velocity variations due to multiplicity. The results of our survey confirm that early-M dwarfs are Hα inactive with low rotational velocities and that late-M dwarfs are Hα active with very high rotational velocities. The results of this high-resolution analysis comprise the most extensive catalogue of rotation and activity in M dwarfs currently available. Based on observations made at the Calar Alto Observatory, Spain, the European Southern Observatory, La Silla, Chile and McDonald Observatory, USA.Tables A.1-A.3 are only available at the CDS via anonymous ftp to http://cdsarc.u-strasbg.fr (ftp://130.79.128.5) or via http://cdsarc.u-strasbg.fr/viz-bin/qcat?J/A+A/614/A76

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.

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

Technology-based self-care methods of improving antiretroviral adherence: a systematic review.

PubMed

Saberi, Parya; Johnson, Mallory O

2011-01-01

As HIV infection has shifted to a chronic condition, self-care practices have emerged as an important topic for HIV-positive individuals in maintaining an optimal level of health. Self-care refers to activities that patients undertake to maintain and improve health, such as strategies to achieve and maintain high levels of antiretroviral adherence. Technology-based methods are increasingly used to enhance antiretroviral adherence; therefore, we systematically reviewed the literature to examine technology-based self-care methods that HIV-positive individuals utilize to improve adherence. Seven electronic databases were searched from 1/1/1980 through 12/31/2010. We included quantitative and qualitative studies. Among quantitative studies, the primary outcomes included ARV adherence, viral load, and CD4+ cell count and secondary outcomes consisted of quality of life, adverse effects, and feasibility/acceptability data. For qualitative/descriptive studies, interview themes, reports of use, and perceptions of use were summarized. Thirty-six publications were included (24 quantitative and 12 qualitative/descriptive). Studies with exclusive utilization of medication reminder devices demonstrated less evidence of enhancing adherence in comparison to multi-component methods. This systematic review offers support for self-care technology-based approaches that may result in improved antiretroviral adherence. There was a clear pattern of results that favored individually-tailored, multi-function technologies, which allowed for periodic communication with health care providers rather than sole reliance on electronic reminder devices.

Antiretroviral Agents Effectively Block HIV Replication after Cell-to-Cell Transfer

PubMed Central

Permanyer, Marc; Ballana, Ester; Ruiz, Alba; Badia, Roger; Riveira-Munoz, Eva; Gonzalo, Encarna; Clotet, Bonaventura

2012-01-01

Cell-to-cell transmission of HIV has been proposed as a mechanism contributing to virus escape to the action of antiretrovirals and a mode of HIV persistence during antiretroviral therapy. Here, cocultures of infected HIV-1 cells with primary CD4+ T cells or lymphoid cells were used to evaluate virus transmission and the effect of known antiretrovirals. Transfer of HIV antigen from infected to uninfected cells was resistant to the reverse transcriptase inhibitors (RTIs) zidovudine (AZT) and tenofovir, but was blocked by the attachment inhibitor IgGb12. However, quantitative measurement of viral DNA production demonstrated that all anti-HIV agents blocked virus replication with similar potency to cell-free virus infections. Cell-free and cell-associated infections were equally sensitive to inhibition of viral replication when HIV-1 long terminal repeat (LTR)-driven green fluorescent protein (GFP) expression in target cells was measured. However, detection of GFP by flow cytometry may incorrectly estimate the efficacy of antiretrovirals in cell-associated virus transmission, due to replication-independent Tat-mediated LTR transactivation as a consequence of cell-to-cell events that did not occur in short-term (48-h) cell-free virus infections. In conclusion, common markers of virus replication may not accurately correlate and measure infectivity or drug efficacy in cell-to-cell virus transmission. When accurately quantified, active drugs blocked proviral DNA and virus replication in cell-to-cell transmission, recapitulating the efficacy of antiretrovirals in cell-free virus infections and in vivo. PMID:22696642

CD4+ T cells spontaneously producing human immunodeficiency virus type I in breast milk from women with or without antiretroviral drugs

PubMed Central

2011-01-01

Background Transmission of human immunodeficiency virus type 1 (HIV-1) through breast-feeding may involve both cell-free and cell-associated virus. This latter viral reservoir remains, however, to be fully explored. CD4+ T cell-associated virus production in breast milk was therefore investigated. Methods The ex vivo spontaneous production of HIV-1 antigen and HIV-1 RNA by CD4+ T cells was measured in paired blood and breast milk samples from 15 HIV-1 infected women treated or not with antiretroviral drugs. Spontaneous antigen secreting cells (HIV-1-AgSCs) from breast milk and blood were enumerated by an ELISpot assay, and cell-associated HIV-1 RNA was quantified by real-time PCR in supernatants of CD4+ T cells cultured for 18 hours without addition of polyclonal activators. Results Among the CD4+ T cells present in breast milk, memory cells expressing high levels of cell-surface activation markers were predominant. Spontaneous HIV-1-AgSCs were detected and enumerated in the breast milk of all 15 women, with a median number of 13.0 and 9.5 HIV-1- AgSCs/106 CD4+ T cells in aviremic (n = 7) and viremic (n = 8) women, respectively. Cell- associated HIV-1 RNA was detected in cell-free supernatants from 4/7 aviremic and 5/8 viremic individuals at median levels of 190 and 245 copies/ml, respectively. Conclusions Activated CD4+ T cells producing HIV-1 are detected in the breast milk of untreated individuals as well as those receiving highly active antiretroviral therapy. This finding strongly suggests that HIV-1 replication occurs in latently infected CD4+ T cells that, upon spontaneous activation, revert to productively infected cells. These cells might be responsible for a residual breast milk transmission despite maternal highly active antiretroviral therapy. PMID:21569457

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

PubMed

2004-03-01

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

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.

Interventions for Enhancing Adherence to Antiretroviral Therapy (ART): A Systematic Review of High Quality Studies

PubMed Central

Sivaramalingam, Bhairavi; Navarro, Tamara; Hobson, Nicholas; Keepanasseril, Arun; Wilczynski, Nancy J.; Haynes, R. Brian

2015-01-01

Abstract We sought to review the effectiveness of interventions designed to improve adherence to antiretroviral therapy (ART) from studies included in a recent Cochrane review that reported a clinical and an adherence outcome, with at least 80% follow-up for 6 months or more. Data were extracted independently and in duplicate, with an adjudicator for disagreements. Risk of bias was assessed using the Cochrane Risk of Bias tool. Of 182 relevant studies in the Cochrane review, 49 were related to ART. Statistical pooling was not warranted due to heterogeneity in interventions, participants, treatments, adherence measures and outcomes. Many studies had high risk of bias in elements of design and outcome ascertainment. Only 10 studies improved both adherence and clinical outcomes. These used the following interventions: adherence counselling (two studies); a once-daily regimen (compared to twice daily); text messaging; web-based cognitive behavioral intervention; face-to-face multi-session intensive behavioral interventions (two studies); contingency management; modified directly observed therapy; and nurse-delivered home visits combined with telephone calls. Patient-related adherence interventions were the most frequently tested. Uniform adherence measures and higher quality studies of younger populations are encouraged. PMID:25825938

Contribution of 20 single nucleotide polymorphisms of 13 genes to dyslipidemia associated with antiretroviral therapy.

PubMed

Arnedo, Mireia; Taffé, Patrick; Sahli, Roland; Furrer, Hansjakob; Hirschel, Bernard; Elzi, Luigia; Weber, Rainer; Vernazza, Pietro; Bernasconi, Enos; Darioli, Roger; Bergmann, Sven; Beckmann, Jacques S; Telenti, Amalio; Tarr, Philip E

2007-09-01

HIV-1 infected individuals have an increased cardiovascular risk which is partially mediated by dyslipidemia. Single nucleotide polymorphisms in multiple genes involved in lipid transport and metabolism are presumed to modulate the risk of dyslipidemia in response to antiretroviral therapy. The contribution to dyslipidemia of 20 selected single nucleotide polymorphisms of 13 genes reported in the literature to be associated with plasma lipid levels (ABCA1, ADRB2, APOA5, APOC3, APOE, CETP, LIPC, LIPG, LPL, MDR1, MTP, SCARB1, and TNF) was assessed by longitudinally modeling more than 4400 plasma lipid determinations in 438 antiretroviral therapy-treated participants during a median period of 4.8 years. An exploratory genetic score was tested that takes into account the cumulative contribution of multiple gene variants to plasma lipids. Variants of ABCA1, APOA5, APOC3, APOE, and CETP contributed to plasma triglyceride levels, particularly in the setting of ritonavir-containing antiretroviral therapy. Variants of APOA5 and CETP contributed to high-density lipoprotein-cholesterol levels. Variants of CETP and LIPG contributed to non-high-density lipoprotein-cholesterol levels, a finding not reported previously. Sustained hypertriglyceridemia and low high-density lipoprotein-cholesterol during the study period was significantly associated with the genetic score. Single nucleotide polymorphisms of ABCA1, APOA5, APOC3, APOE, and CETP contribute to plasma triglyceride and high-density lipoprotein-cholesterol levels during antiretroviral therapy exposure. Genetic profiling may contribute to the identification of patients at risk for antiretroviral therapy-related dyslipidemia.

Effects of Hydroxychloroquine on Immune Activation and Disease Progression Among HIV-Infected Patients Not Receiving Antiretroviral Therapy A Randomized Controlled Trial

PubMed Central

Paton, Nicholas I.; Goodall, Ruth L.; Dunn, David T.; Franzen, Samuel; Collaco-Moraes, Yolanda; Gazzard, Brian G.; Williams, Ian G.; Fisher, Martin J.; Winston, Alan; Fox, Julie; Orkin, Chloe; Herieka, Elbushra A.; Ainsworth, Jonathan G.; Post, Frank A.; Wansbrough-Jones, Mark; Kelleher, Peter

2013-01-01

Context Therapies to decrease immune activation might be of benefit in slowing HIV disease progression. Objective To determine whether hydroxychloroquine decreases immune activation and slows CD4 cell decline. Design, Setting, and Patients Randomized, double-blind, placebo-controlled trial performed at 10 HIV outpatient clinics in the United Kingdom between June 2008 and February 2011. The 83 patients enrolled had asymptomatic HIV infection, were not taking antiretroviral therapy, and had CD4 cell counts greater than 400 cells/μL. Intervention Hydroxychloroquine, 400 mg, or matching placebo once daily for 48 weeks. Main Outcome Measures The primary outcome measure was change in the proportion of activated CD8 cells (measured by the expression of CD38 and HLA-DR surface markers), with CD4 cell count and HIV viral load as secondary outcomes. Analysis was by intention to treat using mixed linear models. Results There was no significant difference in CD8 cell activation between the 2 groups (−4.8% and −4.2% in the hydroxychloroquine and placebo groups, respectively, at week 48; difference, −0.6%; 95% CI, −4.8% to 3.6%; P=.80). Decline in CD4 cell count was greater in the hydroxychloroquine than placebo group (−85 cells/μL vs −23 cells/μL at week 48; difference, −62 cells/μL; 95% CI, −115 to −8; P=.03). Viral load increased in the hydroxychloroquine group compared with placebo (0.61 log10 copies/mL vs 0.23 log10 copies/mL at week 48; difference, 0.38 log10 copies/mL; 95% CI, 0.13 to 0.63; P=.003). Antiretroviral therapy was started in 9 patients in the hydroxychloroquine group and 1 in the placebo group. Trial medication was well tolerated, but more patients reported influenza-like illness in the hydroxychloroquine group compared with the placebo group (29% vs 10%; P=.03). Conclusion Among HIV-infected patients not taking antiretroviral therapy, the use of hydroxychloroquine compared with placebo did not reduce CD8 cell activation but did result in

[Pulmonary hypertension in human immunodeficiency virus-infected patients: the role of antiretroviral therapy].

PubMed

Olalla, Julián; Urdiales, Daniel; Pombo, Marta; del Arco, Alfonso; de la Torre, Javier; Prada, José Luis

2014-03-20

Pulmonary arterial hypertension (PAH) is a serious disorder, more prevalent in patients infected with human immunodeficiency virus (HIV). It is not entirely clear what role is played by highly active antiretroviral therapy (HAART) in PAH development or course. Our aim was to describe PAH prevalence in a series of HIV-infected patients and identify possible links with cumulative and current use of different antiretrovirals. Cross-sectional study of a cohort of HIV-infected patients attending a hospital in southern Spain. Demographic data, data on HIV infection status and on cumulative and recent antiretroviral treatment were recorded. Transthoracic echocardiography was performed in all study participants. PAH was defined as pulmonary artery systolic pressure of 36mmHg or more. A total of 400 patients participated in the study; 178 presented with tricuspid regurgitation and 22 of these presented with PAH (5.5%). No differences were encountered in age, sex, CD4 lymphocytes, proportion of naive patients or patients with AIDS. No differences were encountered in cumulative use of antiretrovirals. However, recent use of lamivudine was associated with a greater presence of PAH, whereas recent use of tenofovir and emtricitabine was associated with a lower presence of PAH. Logistic regression analysis was performed including the use of lamivudine, emtricitabine and tenofovir. Only recent use of tenofovir was associated with a lower presence of PAH (odds ratio 0.31; 95% confidence interval: 0.17-0.84). PAH prevalence in our study was similar to others series. Current use of tenofovir may be associated with lower PAH prevalence. Copyright © 2012 Elsevier España, S.L. All rights reserved.

Hidden costs of antiretroviral treatment: the public health efficiency of drug packaging.

PubMed

Andreu-Crespo, Àngels; Llibre, Josep M; Cardona-Peitx, Glòria; Sala-Piñol, Ferran; Clotet, Bonaventura; Bonafont-Pujol, Xavier

2015-01-01

While the overall percentage of unused antiretroviral medicines returned to the hospital pharmacy is low, their cost is quite high. Adverse events, treatment failure, pharmacokinetic interactions, pregnancy, or treatment simplification are common reasons for unplanned treatment changes. Socially inefficient antiretroviral packages prevent the reuse of drugs returned to the hospital pharmacy. We defined antiretroviral package categories based on the excellence of drug packaging and analyzed the number of pills and costs of drugs returned during a period of 1 year in a hospital-based HIV unit attending to 2,413 treated individuals. A total of 6,090 pills (34% of all returned antiretrovirals) - with a cost of 47,139.91 € - would be totally lost, mainly due to being packed up in the lowest efficiency packages. Newer treatments are packaged in low-excellence categories of packages, thus favoring the maintenance of these hidden costs in the near future. Therefore, costs of this low-efficiency drug packaging, where medication packages are started but not completed, in high-cost medications are substantial and should be properly addressed. Any improvement in the packaging by the manufacturer, and favoring the choice of drugs supplied through efficient packages (when efficacy, toxicity, and convenience are similar), should minimize the treatment expenditures paid by national health budgets.

Hidden costs of antiretroviral treatment: the public health efficiency of drug packaging

PubMed Central

Andreu-Crespo, Àngels; Llibre, Josep M; Cardona-Peitx, Glòria; Sala-Piñol, Ferran; Clotet, Bonaventura; Bonafont-Pujol, Xavier

2015-01-01

While the overall percentage of unused antiretroviral medicines returned to the hospital pharmacy is low, their cost is quite high. Adverse events, treatment failure, pharmacokinetic interactions, pregnancy, or treatment simplification are common reasons for unplanned treatment changes. Socially inefficient antiretroviral packages prevent the reuse of drugs returned to the hospital pharmacy. We defined antiretroviral package categories based on the excellence of drug packaging and analyzed the number of pills and costs of drugs returned during a period of 1 year in a hospital-based HIV unit attending to 2,413 treated individuals. A total of 6,090 pills (34% of all returned antiretrovirals) – with a cost of 47,139.91€ – would be totally lost, mainly due to being packed up in the lowest efficiency packages. Newer treatments are packaged in low-excellence categories of packages, thus favoring the maintenance of these hidden costs in the near future. Therefore, costs of this low-efficiency drug packaging, where medication packages are started but not completed, in high-cost medications are substantial and should be properly addressed. Any improvement in the packaging by the manufacturer, and favoring the choice of drugs supplied through efficient packages (when efficacy, toxicity, and convenience are similar), should minimize the treatment expenditures paid by national health budgets. PMID:26273190

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

Associations between highly active antiretroviral therapy and the presence of HPV, premalignant and malignant cervical lesions in sub-Saharan Africa, a systematic review: current evidence and directions for future research

PubMed Central

Menon, Sonia; Rossi, Rodolfo; Zdraveska, Natasha; Kariisa, Mbabazi; Acharya, Sushama D; Vanden Broeck, Davy; Callens, Steven

2017-01-01

Objectives In sub-Saharan Africa, substantial international funding along with evidence-based clinical practice have resulted in an unparalleled scale-up of access to antiretroviral treatment at a higher CD4 count. The role and timing of highly active antiretroviral therapy (HAART) in mediating cervical disease remains unclear. The aim of this article is to systematically review all evidence pertaining to Africa and identify research gaps regarding the epidemiological association between HAART use and the presence of premalignant/malignant cervical lesions. Method Five databases were searched until January 2017 to retrieve relevant literature from sub-Saharan Africa. Publications were included if they addressed prevalence, incidence or clearance of human papillomavirus (HPV) infection in women undergoing HAART as well as cytological or histological neoplastic abnormalities. Results 22 studies were included, of which seven were prospective studies. Women receiving HAART are less likely to develop squamous intraepithelial lesions (SILs). There is evidence that duration of HAART along with the CD4 count may reduce the prevalence of high-risk HPV (HR-HPV), suggesting that without HAART, severe immunosuppression increases the risk of becoming or remaining infected with HR-HPV. Furthermore, according to existent literature, the CD4 count, rather than HAART coverage or its duration, plays a central role in the prevalence of cervical intraepithelial neoplasia (CIN) 2 and CIN 3. Conclusion Our findings suggest a positive impact of HAART duration, in conjunction and interaction with CD4 count, on reducing the prevalence of HR-HPV. The greatest treatment effect might be seen among women starting at the lowest CD4 count, which may have a more instrumental role in cervical oncogenesis than either HAART use or the treatment duration on the prevalence of CIN 2 and CIN 3. There is still insufficient evidence to show a clear association between HAART coverage and the incidence of

[Assessment on depressive status and the therapeutic effects of highly active antiretroviral therapy among anti-HIV-1(+) population].

PubMed

Zhang, Li; Yang, Di; Zhao, Hong-xin; Han, Ning; Xiao, Jiang; Chen, Yu-fang; Han, Zhu; Li, Yan-mei; Wei, Kai; Zhang, Wen; Gao, Gui-ju

2013-05-01

To assess the depressive status and its influence on Chinese HIV-1(+) population, and how it was influenced by highly active antiretroviral therapy (HAART) and the CD4(+) T cell count. Anti-HIV-1(+) patients (age between 18 and 65 years old) who had met the criteria to commence the anti-HIV treatment but had not yet started, were selected from the Beijing Ditan Hospital between March 2011 and June 2012. BDI-II (Beck Depression Inventory) and a self-designed questionnaire were used to evaluate the baseline and the status of 48 weeks post the HAART treatment. Statistically, t test and the Wilcoxon rank sum test were used to compare the BDI scores under different conditions and before/after the HAART. (1) Of 100 subjects: male to female ratio was 99:1; the average age was 31.37 ± 5.58 years; the average education background was of 13.13 ± 3.51 years; the unemployed percentage was 4%; time before being identified as anti-HIV-1(+) was 5.0 (1.0 - 21.0) months; the percentage being infected through homosexual contact was 83%. The baseline BDI score was 6.0 (3 - 10.25). (2) There was no significant difference (P > 0.05) in BDI score between those subjects having had education less or more than 12 years; the BDI score of patients whose anti-HIV-1(+) was significantly higher (P < 0.05) among those discovered within the past 6 months than those more than 6 months. The BDI score of patients whose baseline CD4(+) T cell count below 200 cells/µl was significantly higher (P < 0.05) than those with baseline CD4(+) T cell count greater than 200 cells/µl. The CD4(+) T cell count was significantly high (P < 0.001) after 48 weeks of anti-viral treatment, but the BDI score was not significantly different (P > 0.05). There was no significant change (P > 0.05) in the proportion of patients with different degrees of BDI score before and after 48 weeks of antiviral treatment. Depression in HIV patients was most overt in the first six months when they were aware of the infection. The

[Antiretroviral treatment for HIV infection. Where we are and where we are going?].

PubMed

Sierra-Madero, Juan G; Franco-San-Sebastián, Dennise

2004-01-01

Antiretroviral treatment for HIV infection has evolved importantly during the last few years. Eradication of HIV is currently not a realistic target of antiretroviral therapy; however, long term virologic control is possible with current antiviral combinations in the majority of patients. This has resulted in a dramatic reduction in complications and mortality associated with AIDS, even though significant challenges remain. Some of them are the limited access to antiretroviral drugs that exist in most of the affected countries because of the elevated costs of the drugs, the high level of adherence needed for efficacy and the short term and long term toxicity. It is important that antiretroviral access programs financed with public funds consider the following points in their design: specialized prescription that optimizes the use of these resources, integration of prevention to care, evaluation of costs in a global perspective, and integration of research with medical care.

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.

Mortality and its predictors among highly active antiretroviral therapy naive hiv-infected individuals: data from prospective cohort study in Ukraine.

PubMed

Zhyvytsia, D

2014-01-01

There is little information from Ukraine about the effect of Highly active antiretroviral therapy (HAART) on survival of HIV-infected patients. Our objective was to identify predictors of mortality in HIV-infected patients initiating HAART at the Zaporizhzhya AIDS Center, Ukraine. Prospective cohort study of HIV-infected patients from January 2005 to December 2008 in a Zaporizhzhya AIDS Center, and were tracked for 60 months after start HAART. Unvaried and multivariate analysis and constructed Kaplan-Meier curves to assess predictors. To identify predictors of mortality were used to build a regression Cox proportional hazards model.Two hundred and seventy two patients were studied (mean age 34 years, 42% female, median CD4 count 120 cell/μL). In 60 months of HAART 36 patients died. The probability of survival was 87%. In the univariate analysis, mortality was strongly associated with male gender (HR 6,28; 95% CI 2,22-17,78), IDU route of HIV transmission (HR 2,90; 95% CI 1,32-6,36), WHO clinical stage 4 (HR 3,45 95% CI 1,7-7,0). Mortality was also strongly associated with anemia (HR 2,24 95% CI 1,02-4,92) and HBsAg seropositivity (HR 6,26 95% CI 3,01-13,02). In the multivariate analysis independent factors associated with mortality were WHO clinical stage 4 (HR 2,66 95% CI 1,26-5,58) and HBsAg seropositivity (HR 4,35 95% CI 2,05-9,23). HAART significantly increased probability of survival and reduced the risk of death for HIV-infected patients in Ukraine. Simple clinical and laboratory data independently predict mortality and allow for risk stratification in HIV-infected patients in Ukraine.

Relationship of long-term highly active antiretroviral therapy on salivary flow rate and CD4 Count among HIV-infected patients.

PubMed

Kumar, J Vijay; Baghirath, P Venkat; Naishadham, P Parameswar; Suneetha, Sujai; Suneetha, Lavanya; Sreedevi, P

2015-01-01

To determine if long-term highly active antiretroviral therapy (HAART) therapy alters salivary flow rate and also to compare its relation of CD4 count with unstimulated and stimulated whole saliva. A cross-sectional study was performed on 150 individuals divided into three groups. Group I (50 human immunodeficiency virus (HIV) seropositive patients, but not on HAART therapy), Group II (50 HIV-infected subjects and on HAART for less than 3 years called short-term HAART), Group III (50 HIV-infected subjects and on HAART for more than or equal to 3 years called long-term HAART). Spitting method proposed by Navazesh and Kumar was used for the measurement of unstimulated and stimulated salivary flow rate. Chi-square test and analysis of variance (ANOVA) were used for statistical analysis. The mean CD4 count was 424.78 ± 187.03, 497.82 ± 206.11 and 537.6 ± 264.00 in the respective groups. Majority of the patients in all the groups had a CD4 count between 401 and 600. Both unstimulated and stimulated whole salivary (UWS and SWS) flow rates in Group I was found to be significantly higher than in Group II (P < 0.05). Unstimulated salivary flow rate between Group II and III subjects were also found to be statistically significant (P < 0.05). ANOVA performed between CD4 count and unstimulated and stimulated whole saliva in each group demonstrated a statistically significant relationship in Group II (P < 0.05). There were no significant results found between CD4 count and stimulated whole saliva in each groups. The reduction in CD4 cell counts were significantly associated with salivary flow rates of HIV-infected individuals who are on long-term HAART.

Virtual Elimination of Mother-to-Child Transmission of Human Immunodeficiency Virus in Mothers on Highly Active Antiretroviral Therapy in Enugu, South-Eastern Nigeria.

PubMed

Okafor, Ii; Ugwu, Eo; Obi, Sn; Odugu, Bu

2014-07-01

With the current World Health Organization (WHO) "Option B+" for prevention of mother to child transmission (PMTCT) of human immunodeficiency virus (HIV), virtual elimination of mother to child transmission (eMTCT) is highly achievable. The aim of this study is to determine the rate of MTCT of HIV from mothers who started highly active antiretroviral therapy (HAART) for life from diagnosis during pregnancy to the exposed babies who had daily nevirapine in the first 6 weeks of life. HIV positive mothers and their exposed babies who enrolled for the hospital PMTCT protocol from January 1, 2009 to December 31, 2011 were studied. The babies were tested for HIV using deoxyribo nucleic acid polymerase chain reaction test at 6 weeks, and then HIV rapid tests at 18 months. A total of 5,946 booked mothers had HIV testing and counseling (HTC) within the study period. Two hundred and twenty-three (223/5946, 3.7%) were positive, out of which 188 (188/223, 84.3%) enrolled for the PMTCT interventions while 35 (35/223, 15.7%) did not enroll. Three of the enrollees were lost to follow up and two were referred to another PMCT center. Of the remaining 183 enrolled HIV positive mothers, one gave birth to a set of twins, giving a total of 184 exposed babies. There were two cases of intrauterine fetal death of unknown fetal HIV status. None of the 182 remaining babies evaluated for HIV testing tested positive to HIV. With adequate suppression of maternal viral replication with HAART using the WHO Option B+, eMTCT of HIV is achievable in a developing country like Nigeria where infant breastfeeding is a norm.

Free software to analyse the clinical relevance of drug interactions with antiretroviral agents (SIMARV®) in patients with HIV/AIDS.

PubMed

Giraldo, N A; Amariles, P; Monsalve, M; Faus, M J

Highly active antiretroviral therapy has extended the expected lifespan of patients with HIV/AIDS. However, the therapeutic benefits of some drugs used simultaneously with highly active antiretroviral therapy may be adversely affected by drug interactions. The goal was to design and develop a free software to facilitate analysis, assessment, and clinical decision making according to the clinical relevance of drug interactions in patients with HIV/AIDS. A comprehensive Medline/PubMed database search of drug interactions was performed. Articles that recognized any drug interactions in HIV disease were selected. The publications accessed were limited to human studies in English or Spanish, with full texts retrieved. Drug interactions were analyzed, assessed, and grouped into four levels of clinical relevance according to gravity and probability. Software to systematize the information regarding drug interactions and their clinical relevance was designed and developed. Overall, 952 different references were retrieved and 446 selected; in addition, 67 articles were selected from the citation lists of identified articles. A total of 2119 pairs of drug interactions were identified; of this group, 2006 (94.7%) were drug-drug interactions, 1982 (93.5%) had an identified pharmacokinetic mechanism, and 1409 (66.5%) were mediated by enzyme inhibition. In terms of clinical relevance, 1285 (60.6%) drug interactions were clinically significant in patients with HIV (levels 1 and 2). With this information, a software program that facilitates identification and assessment of the clinical relevance of antiretroviral drug interactions (SIMARV ® ) was developed. A free software package with information on 2119 pairs of antiretroviral drug interactions was designed and developed that could facilitate analysis, assessment, and clinical decision making according to the clinical relevance of drug interactions in patients with HIV/AIDS. Copyright © 2016 Elsevier Inc. All rights reserved.

Association of child care burden and household composition with adherence to highly active antiretroviral therapy in the Women's Interagency HIV Study.

PubMed

Merenstein, Daniel; Schneider, Michael F; Cox, Christopher; Schwartz, Rebecca; Weber, Kathleen; Robison, Esther; Gandhi, Monica; Richardson, Jean; Plankey, Michael W

2009-04-01

Our objective was to describe the association that childcare burden, household composition, and health care utilization have with adherence to highly active antiretroviral therapy (HAART) among women in the United States. The primary outcome was 95% or more adherence to HAART evaluated at 10,916 semiannual visits between October 1998 and March 2006 among 1419 HIV-infected participants enrolled in the Women's Interagency HIV Study. HAART adherence levels of 95% or more were reported at 76% of the semiannual visits. At only 4% of the person-visits did women report either quite a bit or extreme difficulty in caring for child; at 52% of the person-visits women reported at least one child 18 years of age or older living in the household. We found a one-unit increase in the difficulty in caring for children (childcare burden was assessed on a 5-point scale: not difficult [1] to extremely difficult [5]) was associated with a 6% decreased odds of 95% or more HAART adherence (adjusted odds ratio [OR] = 0.94; p = 0.07). Each additional child 18 years of age or less living in the household was associated with an 8% decreased odds of 95% or more adherence (adjusted OR = 0.92, p = 0.03). Both the number and type of adult living in the household, as well as health care utilization were not associated with HAART adherence. Greater child care burden and number of children 18 years old or younger living in household were both inversely associated with HAART adherence. Assessing patients' difficulties in caring for children and household composition are important factors to consider when addressing adherence to HAART.

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

Long-Acting Antiretrovirals: Where Are We now?

PubMed

Nyaku, Amesika N; Kelly, Sean G; Taiwo, Babafemi O

2017-04-01

Current HIV treatment options require daily use of combination antiretroviral drugs. Many persons living with HIV experience treatment fatigue and suboptimal adherence as a result. Long-acting antiretroviral drugs are being developed to expand options for HIV treatment. Here, we review the agents in development, and evaluate data from recent clinical trials. In addition, we anticipate challenges to successful widespread use of long-acting antiretrovirals. Parenteral nanosuspensions of cabotegravir and rilpivirine, and dapivirine vaginal ring are the farthest in clinical development. Long-acting modalities in earlier development stages employ drug-loaded implants, microparticles, or targeted mutagenesis, among other innovations. Long-acting antiretroviral drugs promise new options for HIV prevention and treatment, and ways to address poor adherence and treatment fatigue. Further studies will identify the long-acting agents or combinations that are suitable for routine use. Creative solutions will be needed for anticipated implementation challenges.

The Indigenous Red Ribbon Storytelling Study: What does it mean for Indigenous peoples living with HIV and a substance use disorder to access antiretroviral therapy in Saskatchewan?

PubMed Central

Nowgesic, Earl; Meili, Ryan; Stack, Sandra; Myers, Ted

2016-01-01

Indigenous peoples living with HIV are less likely than non-Indigenous peoples living with HIV to access antiretroviral therapy; however, there is not enough contextual information surrounding this issue. The Indigenous Red Ribbon Storytelling Study was conducted in part to examine how Indigenous peoples living with HIV construct and understand their experiences accessing antiretroviral therapy. Our study design was critical Indigenous qualitative research, using the Behavioral Model of Health Services Use and community-based participatory research approaches. The study was conducted in partnership with Indigenous and non-Indigenous organizations. Study participants were adults from two Canadian cities. The study methods included 20 individual and two Indigenous sharing circle interviews, six participant observation sessions, a short survey and thematic analysis. Accessing antiretroviral therapy within the context of living with a substance use disorder was an overarching theme. Indigenous peoples living with HIV felt they had to choose between living with their active substance use disorder and accessing antiretroviral therapy. They felt misunderstood as a person living with a substance use disorder and often felt coerced into using antiretroviral therapy. Despite these challenges, they persevered as Indigenous peoples living with HIV and a substance use disorder. Further research on antiretroviral therapy access among Indigenous peoples living with HIV and a substance use disorder, particularly from the perspective of health service providers, is needed. PMID:27867444

The Indigenous Red Ribbon Storytelling Study: What does it mean for Indigenous peoples living with HIV and a substance use disorder to access antiretroviral therapy in Saskatchewan?

PubMed

Nowgesic, Earl; Meili, Ryan; Stack, Sandra; Myers, Ted

2015-01-01

Indigenous peoples living with HIV are less likely than non-Indigenous peoples living with HIV to access antiretroviral therapy; however, there is not enough contextual information surrounding this issue. The Indigenous Red Ribbon Storytelling Study was conducted in part to examine how Indigenous peoples living with HIV construct and understand their experiences accessing antiretroviral therapy. Our study design was critical Indigenous qualitative research, using the Behavioral Model of Health Services Use and community-based participatory research approaches. The study was conducted in partnership with Indigenous and non-Indigenous organizations. Study participants were adults from two Canadian cities. The study methods included 20 individual and two Indigenous sharing circle interviews, six participant observation sessions, a short survey and thematic analysis. Accessing antiretroviral therapy within the context of living with a substance use disorder was an overarching theme. Indigenous peoples living with HIV felt they had to choose between living with their active substance use disorder and accessing antiretroviral therapy. They felt misunderstood as a person living with a substance use disorder and often felt coerced into using antiretroviral therapy. Despite these challenges, they persevered as Indigenous peoples living with HIV and a substance use disorder. Further research on antiretroviral therapy access among Indigenous peoples living with HIV and a substance use disorder, particularly from the perspective of health service providers, is needed.

High-resolution Observation of Moving Magnetic Features in Active Regions

NASA Astrophysics Data System (ADS)

Li, Qin; Deng, Na; Jing, Ju; Wang, Haimin

2017-08-01

Moving magnetic features (MMFs) are small photospheric magnetic elements that emerge and move outward toward the boundary of moat regions mostly during a sunspot decaying phase, in a serpent wave-like magnetic topology. Studies of MMFs and their classification (e.g., unipolar or bipolar types) strongly rely on the high spatiotemporal-resolution observation of photospheric magnetic field. In this work, we present a detailed observation of a sunspot evolution in NOAA active region (AR) 12565, using exceptionally high resolution Halpha images from the 1.6 New Solar telescope (NST) at Big Bear Solar Observatory (BBSO) and the UV images from the Interface Region Imaging Spectrograph (IRIS). The spectropolarimetric measurements of photospheric magnetic field are obtained from the NST Near InfraRed Imaging Spectropolarimeter (NIRIS) at Fe I 1.56 um line. We investigate the horizontal motion of the classified MMFs and discuss the clustering patterns of the geometry and motion of the MMFs. We estimate the rate of flux generation by appearance of MMFs and the role MMFs play in sunspot decaying phase. We also study the interaction between the MMFs and the existing magnetic field features and its response to Ellerman bombs and IRIS bombs respectively at higher layers.

Prevalence of Dyslipidemia Among Antiretroviral-Naive HIV-Infected Individuals in China

PubMed Central

Shen, Yinzhong; Wang, Jiangrong; Wang, Zhenyan; Qi, Tangkai; Song, Wei; Tang, Yang; Liu, Li; Zhang, Renfang; Lu, Hongzhou

2015-01-01

Abstract Little is known about the epidemiological features of dyslipidemia among antiretroviral-naive HIV-infected individuals in China. We used a cross-sectional study design to estimate the prevalence of dyslipidemia in this population, and to identify risk factors associated with the presence of dyslipidemia. One thousand five hundred and eighteen antiretroviral-naive HIV-infected individuals and 347 HIV-negative subjects in China were enrolled during 2009 to 2010. Demographics and medical histories were recorded. After an overnight fast, serum samples were collected to measure lipid levels. Factors associated with the presence of dyslipidemia were analyzed by logistic regression. Mean total cholesterol (TC), low-density lipoprotein cholesterol (LDL), high-density lipoprotein cholesterol (HDL) levels were lower in HIV-positive than HIV-negative subjects, but mean triglyceride (TG) was higher in HIV-positive subjects. The overall prevalence of dyslipidemia in HIV-positive and HIV-negative groups did not differ (75.6% vs. 73.7%, P = 0.580). However, the prevalence of high TC (8.4% vs. 28.2%, P < 0.001) and high LDL (8.5% vs. 62.6%, P < 0.001) was lower in HIV-positive than HIV-negative subjects, and the prevalence of high TG (33.9% vs. 17.0%, P < 0.001) and low HDL (59.6% vs. 11.2%, P < 0.001) was higher in HIV-positive than HIV-negative subjects. Logistic analysis showed that HIV positivity was significantly associated with both an increased risk of high TG and low HDL and a decreased risk of high TC and high LDL. The mean levels of TC, of LDL and of HDL showed an increasing trend with increasing CD4 count in HIV-positive subjects. Multivariable logistic regression found that lower CD4 count was significantly associated with both an increased risk of high TG and low HDL and a decreased risk of high TC in HIV-positive subjects. Among antiretroviral-naive HIV-infected Chinese adults, there was a high prevalence of dyslipidemia characterized by

HIV Infection Is Associated With Poor Outcomes for Patients With Anal Cancer in the Highly Active Antiretroviral Therapy Era.

PubMed

Grew, David; Bitterman, Danielle; Leichman, Cynthia G; Leichman, Lawrence; Sanfilippo, Nicholas; Moore, Harvey G; Du, Kevin

2015-12-01

HIV status may affect outcomes after definitive chemoradiotherapy for anal cancer. Here, we report a large series in the highly active antiretroviral therapy era comparing outcomes between HIV-positive and HIV-negative patients with anal cancer. This was a retrospective chart review. The study was conducted at an outpatient oncology clinic at large academic center. A total of 107 patients were reviewed, 39 HIV positive and 68 HIV negative. All of the patients underwent definitive chemoradiation for anal cancer. Data on patient characteristics, treatment, toxicity, and outcomes were collected. Overall survival, colostomy-free survival, local recurrence-free survival, and distant metastasis-free survival were analyzed. Median follow-up was 15 months. HIV-positive patients were younger (median, 52 vs 64 years; p < 0.001) and predominantly men (82% men vs 49% men; p = 0.001). There were no significant differences in T, N, or stage groups. HIV-positive patients had a significantly longer duration from biopsy to start of chemoradiation (mean number of days, 82 vs 54; p = 0.042). There were no differences in rates of acute toxicities including diarrhea, fatigue, or dermatitis. HIV-positive patients had significantly higher rates of hospitalization (33% vs 15%; p = 0.024). The 3-year overall survival rate was 42% in HIV-positive and 76% in HIV-negative patients (p = 0.037; HR, 2.335 (95% CI, 1.032-5.283)). Three-year colostomy-free survival was 67% in HIV-positive and 88% in HIV-negative patients (p = 0.036; HR, 3.231 (95% CI, 1.014-10.299)). Differences in overall survival rates were not significant on multivariate analysis. This study was limited by its retrospective design and small patient numbers. In this cohort, HIV-positive patients had significantly worse overall and colostomy-free survival rates than HIV-negative patients. However, differences in survival were not significant on multivariate analysis. Additional studies are necessary to establish the etiology of

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

Dosing antiretroviral medication when crossing time zones: a review

PubMed Central

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

2016-01-01

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

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

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

PubMed Central

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

2013-01-01

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

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

PubMed

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

2010-04-01

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

An overview of the antiretroviral market.

PubMed

Camponeschi, Geannan; Fast, Jessica; Gauval, Marianne; Guerra, Katherine; Moore, Meredith; Ravinutala, Siddharth; Ripin, David; Shepel, Vadim

2013-11-01

An understanding of the current state of the antiretroviral marketplace is an important context in which to consider drug optimization work. The antiretroviral marketplace has undergone a remarkable evolution over the past 11 years, expanding from serving less than 300 000 patients in low and middle-income countries in 2002 to almost 10 million patients today. In addition to dramatic growth, a steady and rapid improvement in the drugs and drug regimens used to treat patients has characterized a rapidly changing market. The antiretroviral marketplace has been characterized by rapid growth and a succession of improving drugs and regimens over the past 11 years. The dynamic and innovative marketplace provides a strong platform from which to introduce new, optimized drugs and regimens to better serve patients' health needs.

High-spectral resolution solar microwave observations

NASA Technical Reports Server (NTRS)

Hurford, G. J.

1986-01-01

The application of high-spectral resolution microwave observations to the study of solar activity is discussed with particular emphasis on the frequency dependence of microwave emission from solar active regions. A shell model of gyroresonance emission from active regions is described which suggest that high-spectral resolution, spatially-resolved observations can provide quantitative information about the magnetic field distribution at the base of the corona. Corresponding observations of a single sunspot with the Owens Valley frequency-agile interferometer at 56 frequencies between 1.2 and 14 Ghs are presented. The overall form of the observed size and brightness temperature spectra was consistent with expectations based on the shell model, although there were differences of potential physical significance. The merits and weaknesses of microwave spectroscopy as a technique for measuring magnetic fields in the solar corona are briefly discussed.

[HIV-1 resistance to antiretroviral drugs in pregnant women from Buenos Aires metropolitan area].

PubMed

Zapiola, Inés; Cecchini, Diego; Fernández Giuliano, Silvina; Martínez, Marina; Rodríguez, Claudia; Bouzas, María Belén

The study aimed to determine the prevalence of antiretroviral resistance associated mutations in HIV-1 infected pregnant woman treated in Buenos Aires metropolitan area (period 2008-2014). A total of 136 women with viral load = 500 copies/ml were included: 77 (56.6%) were treatment-naïve and 59 (43.4%) were antiretroviral-experienced patients either with current (n: 24) or previous (n = 35) antiretroviral therapy. Genotypic baseline resistance was investigated in plasma of antiretroviral-naïve patients and antiretroviral-experienced patients. The resistance mutations were identified according to the lists of the World Health Organization and the International Antiviral Society, respectively. Frequencies of resistance associated mutations detected in 2008-2011 and 2012-2014 were compared. A total of 37 (27.2%) women presented at least one resistance associated mutation: 25/94 (26.5%) in 2008-2011 and 12/42 (28.5%) in 2012-2014 (p > 0.05). Among naïves, 15 (19.5%) had at least one mutation: 10/49 (20.4%) in the period 2008-2011 and 5/28 (17.8%) in 2012-2014 (p > 0.05). The resistance mutations detected in naïves were associated with non nucleoside reverse transcriptase inhibitors, being K103N the most common mutation in both periods. In antiretroviral experienced patients, 22/59 (37.3%) had at least one resistance mutation. This study demonstrates a high frequency of resistance associated mutations which remained stable in the period analyzed. These levels suggest an increased circulation of HIV-1 antiretroviral resistant strains in our setting compared to previous reports from Argentina.

Reconstitution of Intestinal CD4 and Th17 T Cells in Antiretroviral Therapy Suppressed HIV-Infected Subjects: Implication for Residual Immune Activation from the Results of a Clinical Trial

PubMed Central

d'Ettorre, Gabriella; Baroncelli, Silvia; Micci, Luca; Ceccarelli, Giancarlo; Andreotti, Mauro; Sharma, Prachi; Fanello, Gianfranco; Fiocca, Fausto; Cavallari, Eugenio Nelson; Giustini, Noemi; Mallano, Alessandra; Galluzzo, Clementina M.; Vella, Stefano; Mastroianni, Claudio M.; Silvestri, Guido; Paiardini, Mirko; Vullo, Vincenzo

2014-01-01

Introduction During HIV infection the severe depletion of intestinal CD4+ T-cells is associated with microbial translocation, systemic immune activation, and disease progression. This study examined intestinal and peripheral CD4+ T-cell subsets reconstitution under combined antiretroviral therapy (cART), and systemic immune activation markers. Methods This longitudinal single-arm pilot study evaluates CD4+ T cells, including Th1 and Th17, in gut and blood and soluble markers for inflammation in HIV-infected individuals before (M0) and after eight (M8) months of cART. From January 2010 to December 2011, 10 HIV-1 naïve patients were screened and 9 enrolled. Blood and gut CD4+ T-cells subsets and cellular immune activation were determined by flow-cytometry and plasma soluble CD14 by ELISA. CD4+ Th17 cells were detected in gut biopsies by immunohistochemistry. Microbial translocation was measured by limulus-amebocyte-lysate assay to detect bacterial lipopolysaccharide (LPS) and PCR Real Time to detect plasma bacterial 16S rDNA. Results Eight months of cART increased intestinal CD4+ and Th17 cells and reduced levels of T-cell activation and proliferation. The magnitude of intestinal CD4+ T-cell reconstitution correlated with the reduction of plasma LPS. Importantly, the magnitude of Th17 cells reconstitution correlated directly with blood CD4+ T-cell recovery. Conclusion Short-term antiretroviral therapy resulted in a significant increase in the levels of total and Th17 CD4+ T-cells in the gut mucosa and in decline of T-cell activation. The observation that pre-treatment levels of CD4+ and of CD8+ T-cell activation are predictors of the magnitude of Th17 cell reconstitution following cART provides further rationale for an early initiation of cART in HIV-infected individuals. Trial Registration ClinicalTrials.gov NCT02097381 PMID:25340778

Unresolved antiretroviral treatment management issues in HIV-infected children.

PubMed

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

2012-02-01

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

[Companion Diagnostics for Selecting Antiretroviral Drugs against HIV-1].

PubMed

Fukutake, Katsuyuki

2015-11-01

Currently, the treatment of human immunodeficiency virus involves combination therapy, as antiretroviral therapy(ART). The treatment has improved steadily since the advent of potent combination therapy in 1996. New drugs that offer new mechanisms of action, improvements in potency and activity even against multidrug-resistant viruses, dosing convenience, and tolerability have been approved. Among ART with useful drugs, there are two important examinations before starting the treatment using the two kinds of drug. CCR5 co-receptor antagonists, maraviroc, prevent HIV entry into target cells by binding to CCR5 receptors. Genotypic assays have been developed that can determine or predict the co-receptor tropism(i.e., CCR5, CXCR4, or both) of the patient's dominant virus population. The assay for HIV-1 co-receptor usage should be performed whenever the use of a CCR5 antagonist is being considered. One of the nucleoside/nucleotide reverse transcriptase inhibitors (NRTIs), abacavir, is an important agent to develop recommended regimens for antiretroviral therapy. Serious and sometimes fatal hypersensitivity reactions have been associated with abacavir-containing products, ZIAGEN, Epzicom, and Triumeq. Patients who carry the HLA-B*5701 allele are at high-risk of a hypersensitivity reaction to abacavir. Prior to initiating therapy with abacavir, performing a screening test for the HLA-B*5701 allele is recommended. [Review].

Potential drug interactions in patients given antiretroviral therapy

PubMed Central

dos Santos, Wendel Mombaque; Secoli, Silvia Regina; Padoin, Stela Maris de Mello

2016-01-01

ABSTRACT Objective: to investigate potential drug-drug interactions (PDDI) in patients with HIV infection on antiretroviral therapy. Methods: a cross-sectional study was conducted on 161 adults with HIV infection. Clinical, socio demographic, and antiretroviral treatment data were collected. To analyze the potential drug interactions, we used the software Micromedex(r). Statistical analysis was performed by binary logistic regression, with a p-value of ≤0.05 considered statistically significant. Results: of the participants, 52.2% were exposed to potential drug-drug interactions. In total, there were 218 potential drug-drug interactions, of which 79.8% occurred between drugs used for antiretroviral therapy. There was an association between the use of five or more medications and potential drug-drug interactions (p = 0.000) and between the time period of antiretroviral therapy being over six years and potential drug-drug interactions (p < 0.00). The clinical impact was prevalent sedation and cardiotoxicity. Conclusions: the PDDI identified in this study of moderate and higher severity are events that not only affect the therapeutic response leading to toxicity in the central nervous and cardiovascular systems, but also can interfere in tests used for detection of HIV resistance to antiretroviral drugs. PMID:27878224

CROI 2016: Advances in Antiretroviral Therapy.

PubMed

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

2016-01-01

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

Quality of life, anxiety and depression in patients with HIV/AIDS who present poor adherence to antiretroviral therapy: a cross-sectional study in Salvador, Brazil.

PubMed

Betancur, Mónica Narváez; Lins, Liliane; Oliveira, Irismar Reis de; Brites, Carlos

The introduction of highly active antiretroviral therapy marked a major gain in efficacy of HIV/AIDS treatment and a reduction in morbidity and mortality of the infected patients. However, high levels of adherence are required to obtain virologic suppression. In Brazil, the policy of free and universal access to antiretroviral therapy has been in place since 1996, although there are reports of poor adherence. To define the clinical, demographic and psychological characteristics, and quality of life of patients with HIV/AIDS who present poor adherence to highly active antiretroviral therapy. This was a cross-sectional study. To be included in the study patients had to be 18 through 65 years old, diagnosed with HIV/AIDS, having the two previous viral loads above 500 copies, a surrogate for poor adherence to antiretrovirals. The following instruments were applied to all eligible patients: the sociodemographic questionnaire "Adherence Follow-up Questionnaire", the Beck Depression Inventory (BDI-II), the Beck Anxiety Inventory (BAI), and the 36-Item Short Form Survey. 47 patients were evaluated, 70.2% were female, mean age of 41.9 years (±10.5), 46.8% were single, 51.1% self-reported adherence ≥95%, 46.8% mentioned depression as the main reason for not taking the medication, 59.5% presented symptoms of moderate to severe depression, and 44.7% presented symptoms of moderate to severe anxiety. Finally, regarding health-related quality of life these patients obtained low scores in all dimensions, physical component summary of 43.96 (±9.64) and mental component summary of 33.19 (±13.35). The psychological component is considered to be fundamental in the management of HIV/AIDS patients. Psychoeducation should be conducted at the initial evaluation to reduce negative beliefs regarding antiretroviral therapy Assessment of anxiety and depression symptoms should be done throughout therapy as both psycological conditions are associated with patient adherence, success of

Attitudes toward antiretroviral therapy among African American women.

PubMed

Richter, Donna L; Sowell, Richard L; Pluto, Delores M

2002-01-01

To examine attitudes and beliefs of African American women of childbearing age, living with HIV, about pregnancy and antiretroviral therapy. Focus groups were conducted using an exploratory design with a convenience sample of HIV-infected women in 2 southeastern cities. Thirty-three African American women of childbearing age participated in 5 focus groups. Attitudes and beliefs about antiretroviral therapy were related to the women's willingness to comply with treatment. The challenge for health care providers is to counter women's willingness to "play the odds" of having a noninfected baby without taking antiretrovirals.

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.

Pre-Antiretroviral Therapy Serum Selenium Concentrations Predict WHO Stages 3, 4 or Death but not Virologic Failure Post-Antiretroviral Therapy

PubMed Central

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

2014-01-01

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

Antiretroviral Drug Susceptibility Among HIV-Infected Adults Failing Antiretroviral Therapy in Rakai, Uganda

PubMed Central

Laeyendecker, Oliver; Nakigozi, Gertrude; Gallant, Joel E.; Huang, Wei; Hudelson, Sarah E.; Quinn, Thomas C.; Newell, Kevin; Serwadda, David; Gray, Ronald H.; Wawer, Maria J.; Eshleman, Susan H.

2012-01-01

Abstract We analyzed antiretroviral drug susceptibility in HIV-infected adults failing first- and second-line antiretroviral treatment (ART) in Rakai, Uganda. Samples obtained from participants at baseline (pretreatment) and at the time of failure on first-line ART and second-line ART were analyzed using genotypic and phenotypic assays for antiretroviral drug resistance. Test results were obtained from 73 samples from 38 individuals (31 baseline samples, 36 first-line failure samples, and six second-line failure samples). Four (13%) of the 31 baseline samples had mutations associated with resistance to nucleoside or nonnucleoside reverse transcriptase inhibitors (NRTIs and NNRTIs, respectively). Among the 36 first-line failure samples, 31 (86%) had NNRTI resistance mutations and 29 (81%) had lamivudine resistance mutations; only eight (22%) had other NRTI resistance mutations. None of the six individuals failing a second-line protease inhibitor (PI)-based regimen had PI resistance mutations. Six (16%) of the participants had discordant genotypic and phenotypic test results. Genotypic resistance to drugs included in first-line ART regimens was detected prior to treatment and among participants failing first-line ART. PI resistance was not detected in individuals failing second-line ART. Surveillance for transmitted and acquired drug resistance remains a priority for scale-up of ART. PMID:22443282

Differences in National Antiretroviral Prescribing Patterns between Black and White Patients with HIV/AIDS, 1996–2006

PubMed Central

Oramasionwu, Christine U.; Brown, Carolyn M.; Lawson, Kenneth A.; Ryan, Laurajo; Skinner, Jeff; Frei, Christopher R.

2011-01-01

Objectives The benefit of improved health outcomes for blacks receiving highly active antiretroviral therapy (HAART) lags behind that of whites. This project therefore sought to determine whether the reason for this discrepancy in health outcomes could be attributed to disparities in use of antiretroviral therapy between black and white patients with HIV. Materials and Methods The 1996–2006 National Hospital Ambulatory Medical Care Surveys were used to identify hospital outpatient visits that documented antiretrovirals. Patients younger than 18 years, of nonblack or nonwhite race, and lacking documentation of antiretrovirals were excluded. A multivariable logistic regression model was constructed with race as the independent variable and use of HAART as the dependent variable. Results Approximately 3 million HIV/AIDS patient visits were evaluated. Blacks were less likely than whites to use HAART and protease inhibitors (odds ratio, 95% CI 0.81 [0.81–0.82] and 0.67 [0.67–0.68], respectively). More blacks than whites used non-nucleoside reverse transcriptase inhibitors (odds ratio, 95% CI 1.18 [1.17–1.18]). In 1996, the crude rates of HAART were relatively low for both black and white cohorts (5% vs 6%). The rise in HAART for blacks appeared to lag behind that of whites for several years, until 2002, when the proportion of blacks receiving HAART slightly exceeded the proportion of whites receiving HAART. In later years, the rates of HAART were similar for blacks and whites (81% vs 82% in 2006). Blacks appeared less likely than whites to use protease inhibitors and more likely than whites to use non-nucleoside reverse transcriptase inhibitors from 2000 to 2004. Conclusions Blacks experienced a lag in the use of antiretrovirals at the beginning of the study; this discrepancy dissipated in more recent years. PMID:22089356

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

Discussion and revision of the mathematical modeling tool described in the previously published article "Modeling HIV Transmission risk among Mozambicans prior to their initiating highly active antiretroviral therapy".

PubMed

Cassels, Susan; Pearson, Cynthia R; Kurth, Ann E; Martin, Diane P; Simoni, Jane M; Matediana, Eduardo; Gloyd, Stephen

2009-07-01

Mathematical models are increasingly used in social and behavioral studies of HIV transmission; however, model structures must be chosen carefully to best answer the question at hand and conclusions must be interpreted cautiously. In Pearson et al. (2007), we presented a simple analytically tractable deterministic model to estimate the number of secondary HIV infections stemming from a population of HIV-positive Mozambicans and to evaluate how the estimate would change under different treatment and behavioral scenarios. In a subsequent application of the model with a different data set, we observed that the model produced an unduly conservative estimate of the number of new HIV-1 infections. In this brief report, our first aim is to describe a revision of the model to correct for this underestimation. Specifically, we recommend adjusting the population-level sexually transmitted infection (STI) parameters to be applicable to the individual-level model specification by accounting for the proportion of individuals uninfected with an STI. In applying the revised model to the original data, we noted an estimated 40 infections/1000 HIV-positive persons per year (versus the original 23 infections/1000 HIV-positive persons per year). In addition, the revised model estimated that highly active antiretroviral therapy (HAART) along with syphilis and herpes simplex virus type 2 (HSV-2) treatments combined could reduce HIV-1 transmission by 72% (versus 86% according to the original model). The second aim of this report is to discuss the advantages and disadvantages of mathematical models in the field and the implications of model interpretation. We caution that simple models should be used for heuristic purposes only. Since these models do not account for heterogeneity in the population and significantly simplify HIV transmission dynamics, they should be used to describe general characteristics of the epidemic and demonstrate the importance or sensitivity of parameters in the

High Resolution Active Optics Observations from the Kepler Follow-up Observation Program

NASA Astrophysics Data System (ADS)

Gautier, Thomas N.; Ciardi, D. R.; Marcy, G. W.; Hirsch, L.

2014-01-01

The ground based follow-up observation program for candidate exoplanets discovered with the Kepler observatory has supported a major effort for high resolution imaging of candidate host stars using adaptive optics wave-front correction (AO), speckle imaging and lucky imaging. These images allow examination of the sky as close as a few tenths of an arcsecond from the host stars to detect background objects that might be the source of the Kepler transit signal instead of the host star. This poster reports on the imaging done with AO cameras on the Keck, Palomar 5m and Shane 3m (Lick Observatory) which have been used to obtain high resolution images of over 500 Kepler Object of Interest (KOI) exoplanet candidate host stars. All observations were made at near infrared wavelengths in the J, H and K bands, mostly using the host target star as the AO guide star. Details of the sensitivity to background objects actually attained by these observations and the number of background objects discovered are presented. Implications to the false positive rate of the Kepler candidates are discussed.

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

Incomplete IgG response to HIV-1 proteins and low avidity levels in recently converted HIV patients treated with early antiretroviral therapy.

PubMed

Re, Maria Carla; Schiavone, Pasqua; Bon, Isabella; Vitone, Francesca; De Crignis, Elisa; Biagetti, Carlo; Gibellini, Davide

2010-11-01

To evaluate the evolution of antibody avidity and Western blot reactivity in recently infected HIV-1 subjects and to study the impact of highly active antiretroviral therapy (HAART) on avidity maturation of HIV-1-specific immunoglobulin G (IgG) in patients with recent HIV-1 infection. Thirty-six HIV-1 seroconverters were enrolled in this study and followed longitudinally over 24 months to evaluate if the administration of antiretroviral therapy during primary infection affects Western blot reactivity and the evolution of antibody avidity. The patients were divided into two groups; group A consisted of 19 HIV-1-untreated patients who did not receive any drug treatment during our follow-up period; group B consisted of 17 subjects who were treated early with an association of two nucleoside reverse transcriptase inhibitors (NRTI) and one non-nucleoside reverse transcriptase inhibitor (NNRTI) within 3 months after seroconversion. At diagnosis, Western blot analysis and avidity index (mean value) were exactly matched in untreated and treated patients; subsequently, however, a significantly lower reactivity to HIV-1 pol and gag proteins and a lower avidity index (mean values) were observed in HAART-treated patients up until the end of the follow-up period. The impaired production and maturation of the humoral immunological response in antiretroviral-treated patients might be related to a rapid suppression of HIV replication, driven by HAART. These results could have important implications in understanding the complex mechanism of the immune response during HIV infection. Copyright © 2010 International Society for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

The study of brain activity during the observation of commercial advertising by using high resolution EEG techniques.

PubMed

Vecchiato, Giovanni; Astolfi, Laura; De Vico Fallani, Fabrizio; Salinari, Serenella; Cincotti, Febo; Aloise, Fabio; Mattia, Donatella; Marciani, Maria Grazia; Bianchi, Luigi; Soranzo, Ramon; Babiloni, Fabio

2009-01-01

In this paper we illustrate the capability of tracking brain activity during the observation of commercial TV spots by using advanced high resolution EEG statistical techniques in time and frequency domains. In particular, we analyzed the statistically significant cortical spectral power activity in different frequency bands during the observation of a commercial video clip related to the use of a beer in a group of 13 normal subjects. In addition, a TV speech of the prime minister of Italy was analyzed in two groups of swing and "supporter" voters. Results suggested that the cortical activity during the observation of commercial spots could vary consistently across the spot. This fact suggest the possibility to remove the part of the spot that are not particularly attractive by using those cerebral indexes. The cortical activity during the observation of the political speech indicated a major cortical activity in the supporters group when compared to the swing voters. In this case, it is possible to conclude that the communication proposed has failed to raise attention or interest on swing voters. In conclusions, high resolution EEG have been proved able to generate useful insights about the particular fruition of TV messages, related to both commercial as well as political fields.

Association Between the Occurrence of Adverse Drug Events and Modification of First-Line Highly Active Antiretroviral Therapy in Ghanaian HIV Patients.

PubMed

Tetteh, Raymond A; Nartey, Edmund T; Lartey, Margaret; Mantel-Teeuwisse, Aukje K; Leufkens, Hubert G M; Yankey, Barbara A; Dodoo, Alexander N O

2016-11-01

Patients initiated on highly active antiretroviral therapy (HAART) generally remain on medication indefinitely. A modification in the HAART regimen may become necessary because of possible acute or chronic toxicities, concomitant clinical conditions, development of virological failure or the advent of adverse drug events. The study documents adverse drug events of HIV-positive Ghanaian patients with HAART modifications. It also investigates the association between documented adverse drug events and HAART modification using an unmatched case-control study design. The study was conducted in the Fevers Unit of the Korle Bu Teaching Hospital and involved patients who attended the HIV Care Clinic between January 2004 and December 2009. Data from 298 modified therapy patients (cases) were compared with 298 continuing therapy patients (controls) who had been on treatment for at least 1 month before the end of study. Controls were sampled from the same database of a cohort of HIV-positive patients on HAART, at the time a case occurred, in terms of treatment initiation ±1 month. Data were obtained from patients' clinical folders and the HIV clinic database linked to the pharmacy database. The nature of the documented adverse drug events of the cases was described and the association between the documented adverse drug events and HAART modification was determined by logistic regression with reported odds ratios (ORs) and their 95 % confidence interval (CI). Among the 298 modified therapy patients sampled in this study, 52.7 % of them had at least one documented adverse drug event. The most documented adverse drug event was anaemia, recorded in 18.5 % of modified therapy patients, all of whom were on a zidovudine-based regimen. The presence of documented adverse drug events was significantly associated with HAART modification [adjusted OR = 2.71 (95 % CI 2.11-3.48), p < 0.001]. Among HIV patients on HAART, adverse drug events play a major role in treatment

Current Perspectives on HIV-1 Antiretroviral Drug Resistance

PubMed Central

Iyidogan, Pinar; Anderson, Karen S.

2014-01-01

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

Understanding the disparity: predictors of virologic failure in women using highly active antiretroviral therapy vary by race and/or ethnicity.

PubMed

McFall, Allison M; Dowdy, David W; Zelaya, Carla E; Murphy, Kerry; Wilson, Tracey E; Young, Mary A; Gandhi, Monica; Cohen, Mardge H; Golub, Elizabeth T; Althoff, Keri N

2013-11-01

Stark racial/ethnic disparities in health outcomes exist among those living with HIV in the United States. One of 3 primary goals of the National HIV/AIDS Strategy is to reduce HIV-related disparities and health inequities. Using data from HIV-infected women participating in the Women's Interagency HIV Study from April 2006 to March 2011, we measured virologic failure (HIV RNA >200 copies/mL) after suppression (HIV RNA < 80 copies/mL) on highly active antiretroviral therapy. We identified predictors of virologic failure using discrete time survival analysis and calculated racial/ethnic-specific population-attributable fractions (PAFs). Of 887 eligible women, 408 (46%) experienced virologic failure during the study period. Hispanic and white women had significantly lower hazards of virologic failure than African American women [Hispanic hazard ratio, (HR) = 0.8, 95% confidence interval: (0.6 to 0.9); white HR = 0.7 (0.5 to 0.9)]. The PAF of virologic failure associated with low income was higher in Hispanic [adjusted hazard ratios (aHR) = 2.2 (0.7 to 6.5), PAF = 49%] and African American women [aHR = 1.8 (1.1 to 3.2), PAF = 38%] than among white women [aHR = 1.4 (0.6 to 3.4), PAF = 16%]. Lack of health insurance compared with public health insurance was associated with virologic failure only among Hispanic [aHR = 2.0 (0.9 to 4.6), PAF = 22%] and white women [aHR = 1.9 (0.7 to 5.1), PAF = 13%]. By contrast, depressive symptoms were associated with virologic failure only among African-American women [aHR = 1.6 (1.2 to 2.2), PAF = 17%]. In this population of treated HIV-infected women, virologic failure was common, and correlates of virologic failure varied by race/ethnicity. Strategies to reduce disparities in HIV treatment outcomes by race/ethnicity should address racial/ethnic-specific barriers including depression and low income to sustain virologic suppression.

HIV-associated neurocognitive disorders persist in the era of potent antiretroviral therapy

PubMed Central

Heaton, R.K.; Clifford, D.B.; Franklin, D.R.; Woods, S.P.; Ake, C.; Vaida, F.; Ellis, R.J.; Letendre, S.L.; Marcotte, T.D.; Atkinson, J.H.; Rivera-Mindt, M.; Vigil, O.R.; Taylor, M.J.; Collier, A.C.; Marra, C.M.; Gelman, B.B.; McArthur, J.C.; Morgello, S.; Simpson, D.M.; McCutchan, J.A.; Abramson, I.; Gamst, A.; Fennema-Notestine, C.; Jernigan, T.L.; Wong, J.; Grant, I.

2010-01-01

Objectives: This is a cross-sectional, observational study to determine the frequency and associated features of HIV-associated neurocognitive disorders (HAND) in a large, diverse sample of infected individuals in the era of combination antiretroviral therapy (CART). Methods: A total of 1,555 HIV-infected adults were recruited from 6 university clinics across the United States, with minimal exclusions. We used standardized neuromedical, psychiatric, and neuropsychological (NP) examinations, and recently published criteria for diagnosing HAND and classifying 3 levels of comorbidity (minimal to severe non-HIV risks for NP impairment). Results: Fifty-two percent of the total sample had NP impairment, with higher rates in groups with greater comorbidity burden (40%, 59%, and 83%). Prevalence estimates for specific HAND diagnoses (excluding severely confounded cases) were 33% for asymptomatic neurocognitive impairment, 12% for mild neurocognitive disorder, and only 2% for HIV-associated dementia (HAD). Among participants with minimal comorbidities (n = 843), history of low nadir CD4 was a strong predictor of impairment, and the lowest impairment rate on CART occurred in the subset with suppressed plasma viral loads and nadir CD4 ≥200 cells/mm3 (30% vs 47% in remaining subgroups). Conclusions: The most severe HAND diagnosis (HAD) was rare, but milder forms of impairment remained common, even among those receiving CART who had minimal comorbidities. Future studies should clarify whether early disease events (e.g., profound CD4 decline) may trigger chronic CNS changes, and whether early CART prevents or reverses these changes. GLOSSARY ANI = asymptomatic neurocognitive impairment; CART = combination antiretroviral therapy; CHARTER = CNS HIV Antiretroviral Therapy Effects Research; CIDI = Composite International Diagnostic Interview; CLIA = Clinical Laboratory Improvement Amendments; CPE = CNS penetration effectiveness; HAD = HIV-associated dementia; HAND = HIV

A Comparison of Adverse Drug Reaction Profiles in Patients on Antiretroviral and Antitubercular Treatment in Zimbabwe.

PubMed

Masuka, Josiah T; Chipangura, Precious; Nyambayo, Priscilla P; Stergachis, Andy; Khoza, Star

2018-01-01

Few studies describe the adverse drug event profiles in patients simultaneously receiving antiretroviral and anti-tubercular medicines in resource-limited countries. To describe and compare the adverse drug reaction profiles in patients on highly active antiretroviral therapy only (HAART), HAART and isoniazid preventive therapy (HHART), and HAART and antitubercular treatment (ATTHAART). We analysed individual case safety reports (ICSRs) for patients on antiretroviral therapy and antitubercular treatment submitted to the national pharmacovigilance centre during the targeted spontaneous reporting (TSR) programme from 1 September 2012 through 31 August 2016. All reports considered certain, probable or possible were included in the analysis. A total of 1076 ICSRs were included in the analysis. Most of the reports were from the HAART only group (n = 882; 82.0%), followed by patients on HHART (n = 132; 12.3%), and ATTHAART (n = 62; 5.7%). The ATTHAART (35.5%) and HHAART (34.1%) had a higher frequency of hepatic disorders than the HAART group (5.0%) (p < 0.0001). A higher frequency of rash was reported in the HHAART (35.6%) and HAART groups (29.4%) than the ATTHAART group (14.5%) (p = 0.011). Peripheral neuropathy occurred more frequently in the ATTHAART group (19.3%) than other groups (p = 0.001) while Stevens-Johnson syndrome (14.7%; p < 0.001), gynaecomastia (18.2%; p < 0.001), and lipodystrophy (4.5%; p = 0.012) occurred more frequently in the HAART group. The HHAART group was associated with a higher frequency of psychosis (4.5%; p = 0.002). Antiretroviral therapy was associated with a higher frequency of Stevens-Johnson syndrome, gynaecomastia, and lipodystrophy. Co-administration of antiretroviral and antitubercular medicines was associated with a higher frequency of drug-induced liver injury and peripheral neuropathy. Similarly, co-administration of isoniazid preventive therapy and antiretroviral drugs was associated with a higher risk for

The treatment outcomes of antiretroviral substitutions in routine clinical settings in Asia; data from the TREAT Asia HIV Observational Database (TAHOD).

PubMed

Jung, In Young; Boettiger, David; Wong, Wing Wai; Lee, Man Po; Kiertiburanakul, Sasisopin; Chaiwarith, Romanee; Avihingsanon, Anchalee; Tanuma, Junko; Kumarasamy, Nagalingeswaran; Kamarulzaman, Adeeba; Zhang, Fujie; Kantipong, Pacharee; Ng, Oon Tek; Sim, Benedict Lim Heng; Law, Matthew; Ross, Jeremy; Choi, Jun Yong

2017-12-01

Although substitutions of antiretroviral regimen are generally safe, most data on substitutions are based on results from clinical trials. The objective of this study was to evaluate the treatment outcomes of substituting antiretroviral regimen in virologically suppressed HIV-infected patients in non-clinical trial settings in Asian countries. The study population consisted of HIV-infected patients enrolled in the TREAT Asia HIV Observational Database (TAHOD). Individuals were included in this analysis if they started combination antiretroviral treatment (cART) after 2002, were being treated at a centre that documented a median rate of viral load monitoring ≥0.8 tests/patient/year among TAHOD enrolees, and experienced a minor or major treatment substitution while on virally suppressive cART. The primary endpoint to evaluate outcomes was clinical or virological failure (VF), followed by an ART class change. Clinical failure was defined as death or an AIDS diagnosis. VF was defined as confirmed viral load measurements ≥400 copies/mL followed by an ART class change within six months. Minor regimen substitutions were defined as within-class changes and major regimen substitutions were defined as changes to a drug class. The patterns of substitutions and rate of clinical or VF after substitutions were analyzed. Of 3994 adults who started ART after 2002, 3119 (78.1%) had at least one period of virological suppression. Among these, 1170 (37.5%) underwent a minor regimen substitution, and 296 (9.5%) underwent a major regimen substitution during suppression. The rates of clinical or VF were 1.48/100 person years (95% CI 1.14 to 1.91) in the minor substitution group, 2.85/100 person years (95% CI 1.88 to 4.33) in the major substitution group and 2.53/100 person years (95% CI 2.20 to 2.92) among patients that did not undergo a treatment substitution. The rate of clinical or VF was low in both major and minor substitution groups, showing that regimen substitution is

Low-abundance HIV drug-resistant viral variants in treatment-experienced persons correlate with historical antiretroviral use.

PubMed

Le, Thuy; Chiarella, Jennifer; Simen, Birgitte B; Hanczaruk, Bozena; Egholm, Michael; Landry, Marie L; Dieckhaus, Kevin; Rosen, Marc I; Kozal, Michael J

2009-06-29

historical antiretroviral use. Ultra-deep sequencing can provide important historical resistance information for clinicians when planning subsequent antiretroviral regimens for highly treatment-experienced patients, particularly when their prior treatment histories and longitudinal genotypes are not available.

Low-Abundance HIV Drug-Resistant Viral Variants in Treatment-Experienced Persons Correlate with Historical Antiretroviral Use

PubMed Central

Le, Thuy; Chiarella, Jennifer; Simen, Birgitte B.; Hanczaruk, Bozena; Egholm, Michael; Landry, Marie L.; Dieckhaus, Kevin; Rosen, Marc I.; Kozal, Michael J.

2009-01-01

genotyping. The majority of unrecognized resistant mutations correlate with historical antiretroviral use. Ultra-deep sequencing can provide important historical resistance information for clinicians when planning subsequent antiretroviral regimens for highly treatment-experienced patients, particularly when their prior treatment histories and longitudinal genotypes are not available. PMID:19562031

CROI 2017: Advances in Antiretroviral Therapy

PubMed Central

Jones, Joyce; Taylor, Barbara S.; Tieu, Hong-Van; Wilkin, Timothy J.

2017-01-01

The 2017 Conference on Retroviruses and Opportunistic Infections (CROI) featured exciting preclinical data on investigational antiretroviral agents with good in vitro efficacy and long half-lives. Investigational medications, including bictegravir, demonstrated excellent efficacy and tolerability, as did dual-agent therapy with dolutegravir paired with rilpivirine or with lamivudine. Dolutegravir monotherapy proved inadvisable due to virologic failure and resistance. The gap between high- and low-income settings along the HIV care continuum is narrowing, with Zimbabwe, Malawi, and Zambia approaching the 90-90-90 targets established by the joint United Nations Programme on HIV/AIDS (UNAIDS), whereas communities in the Southern United States are falling behind. Innovative strategies to improve outcomes include 2-way text messaging, home-based HIV testing, peer navigation, and New York City's realignment of services into comprehensive sexual health programs. A high prevalence of resistance was documented in low- and middle-income settings and policy considerations were modeled to address increasing resistance rates. Novel resistance mutations to integrase strand transfer inhibitors and nucleoside analogue reserve transcriptase inhibitors were identified, but the clinical implications are unclear and require further investigation. Several studies provided insights on dosing and safety of antiretroviral therapy to prevent mother-to-child transmission through pharmacokinetic analysis. A special session devoted to Zika virus included a study of its effects on the central nervous system and a promising animal study of a Zika vaccine. PMID:28598790

The impact of HIV infection and antiretroviral therapy on the predicted risk of Down syndrome.

PubMed

Charlton, Thomas G; Franklin, Jamie M; Douglas, Melanie; Short, Charlotte E; Mills, Ian; Smith, Rachel; Clarke, Amanda; Smith, John; Tookey, Pat A; Cortina-Borja, Mario; Taylor, Graham P

2014-02-01

The aim of this study was to assess predicted Down syndrome risk, based on three serum analytes (triple test), with HIV infection status and antiretroviral therapy regimen. Screening results in 72 HIV-positive women were compared with results from age-matched and race-matched HIV-negative controls. Mean concentrations of each analyte were compared by serostatus and antiretroviral therapy. Observed Down syndrome incidence in the offspring of HIV-positive women was calculated from national HIV surveillance data. Overall, women with HIV had a significantly higher probability of receiving a 'high-risk' result than uninfected controls (p = 0.002). Compared with matched uninfected controls, women with HIV infection had significantly higher human chorionic gonadotrophin, lower unconjugated estriol, and higher overall predicted risk of their infant having Down syndrome (1/6250 vs. 1/50 000 p = < 0.001). National surveillance data show no evidence of higher than expected incidence of Down syndrome in the offspring of HIV-positive women. HIV infection impacts the serum analytes used to assay for Down syndrome risk resulting in a high rate of 'high risk' results. However, there is no population-based association between maternal HIV infection and Down syndrome. Care should be taken when interpreting high-risk serum screening results in HIV-positive women to avoid unnecessary invasive diagnostic procedures. © 2013 John Wiley & Sons, Ltd.

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

PubMed Central

Jabs, Douglas A.; Ahuja, Alka; Van Natta, Mark; Dunn, JP; Yeh, Steven

2012-01-01

Purpose To describe the outcomes of different treatment approaches for cytomegalovirus (CMV) retinitis in the era of highly active antiretroviral therapy (HAART). Design Prospective cohort study, the Longitudinal Study of the Ocular Complications of AIDS. Participants 250 patients with CMV retinitis and CD4+ T cells <100 cells/µL (n=221) at enrollment or incident retinitis (n=29) during cohort follow-up. Methods 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. Main Outcome Measures Mortality, CMV dissemination, retinitis progression, treatment side effects. Results 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), 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 to those using only intraocular therapy (implants or injections). Compared to 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 ½ 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, and for loss ½ 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 among those treated with intravitreal injections was 0.017/EY (95% CI =0.006, 0.05) and among those treated with an implant 0.01/EY (95% CI =0.002, 0.04). Conclusions In the HAART era

Effect of HIV Infection and Highly Active Antiretroviral Therapy on Hearing Function: A Prospective Case-Control Study From Cameroon.

PubMed

Fokouo, Jean Valentin F; Vokwely, Jean Espoir E; Noubiap, Jean Jacques N; Nouthe, Brice Enid; Zafack, Joseline; Minka Ngom, Esthelle Stéphanie; Dalil, Asmaou Bouba; Ngo Nyeki, Adèle-Rose; Bengono, Géneviève; Njock, Richard

2015-05-01

Human immunodeficiency virus (HIV) infection remains a major cause of morbidity and mortality worldwide. Many studies have found a higher prevalence of hearing impairment among HIV-positive individuals. To investigate the effect of HIV and highly active antiretroviral treatment (HAART) on the hearing function in a Cameroonian population. We conducted a prospective case-control study from March 1, 2012, through January 31, 2013. The study took place at the National Social Insurance Fund Hospital in Yaoundé, Cameroon, a public health facility. We included 90 HIV-positive case patients and 90 HIV-negative control patients aged 15 to 49 years without any history of hearing loss or treatment with a known ototoxic drug. The case group was further divided into 3 subgroups: 30 HAART-naive patients, 30 patients receiving first-line HAART, and 30 patients receiving second-line HAART. Hearing function was assessed by pure-tone audiometry and classified according to the criteria of the Bureau International d'Audio-Phonologie. Hearing loss due to HIV and HAART. The HIV-positive patients had more otologic symptoms (hearing loss, dizziness, tinnitus, and otalgia) than HIV-negative patients (41 vs 13, P = .04). There were 49 cases (27.2%) of hearing loss in the HIV-positive group vs 10 (5.6%) in the HIV-negative group (P = .04). Compared with HIV-negative individuals, the odds of hearing loss were higher among HIV-infected HAART-naive patients (right ear: odds ratio [OR], 6.7; 95% CI, 4.3-9.7; P = .004; left ear: OR, 6.2; 95% CI, 3.5-8.3; P = .006), patients receiving first-line HAART (right ear: OR, 5.6; 95% CI, 1.9-10.5; P = .01; left ear: OR, 12.5; 95% CI, 8.5-15.4; P < .001), and patients receiving second-line HAART (right ear: OR, 6.7; 95% CI, 3.3-9.6; P = .004; left ear: OR, 3.7; 95% CI, 3.0-5.0; P = .08). Hearing loss is more frequent in HIV-infected patients compared with uninfected patients. Therefore, HIV-infected patients need special

Short-Term Clinical Disease Progression in HIV-Infected Patients Receiving Combination Antiretroviral Therapy: Results from the TREAT Asia HIV Observational Database

PubMed Central

Srasuebkul, Preeyaporn; Lim, Poh Lian; Lee, Man Po; Kumarasamy, Nagalingeswaran; Zhou, Jialun; Sirisanthana, Thira; Li, Patrick C. K.; Kamarulzaman, Adeeba; Oka, Shinichi; Phanuphak, Praphan; Vonthanak, Saphonn; Merati, Tuti P.; Chen, Yi-Ming A.; Sungkanuparph, Somnuek; Tau, Goa; Zhang, Fujie; Lee, Christopher K. C.; Ditangco, Rossana; Pujari, Sanjay; Choi, Jun Y.; Smith, Jeffery; Law, Matthew G.

2009-01-01

Objective The aim of our study was to develop, on the basis of simple clinical data, predictive short-term risk equations for AIDS or death in Asian patients infected with human immunodeficiency virus (HIV) who were included in the TREAT Asia HIV Observational Database. Methods Inclusion criteria were highly active antiretroviral therapy initiation and completion of required laboratory tests. Predictors of short-term AIDS or death were assessed using Poisson regression. Three different models were developed: a clinical model, a CD4 cell count model, and a CD4 cell count and HIV RNA level model. We separated patients into low-risk, high-risk, and very high-risk groups according to the key risk factors Identified. Results In the clinical model, patients with severe anemia or a body mass index (BMI; calculated as the weight in kilograms divided by the square of the height in meters) ≤18 were at very high risk, and patients who were aged <40 years or were male and had mild anemia were at high risk. In the CD4 cell count model, patients with a CD4 cell count <50 cells/µL, severe anemia, or a BMI ≤18 were at very high risk, and patients who had a CD4 cell count of 51–200 cells/µL, were aged <40 years, or were male and had mild anemia were at high risk. In the CD4 cell count and HIV RNA level model, patients with a CD4 cell count <50 cells/µL, a detectable viral load, severe anemia, or a BMI ≤18 were at very high risk, and patients with a CD4 cell count of 51–200 cells/µL and mild anemia were at high risk. The incidence of new AIDS or death in the clinical model was 1.3, 4.9, and 15.6 events per 100 person-years in the low-risk, high-risk, and very high-risk groups, respectively. In the CD4 cell count model the respective incidences were 0.9, 2.7, and 16.02 events per 100 person-years; in the CD4 cell count and HIV RNA level model, the respective incidences were 0.8, 1.8, and 6.2 events per 100 person-years. Conclusions These models are simple enough for

Cost-effectiveness of Newer Antiretroviral Drugs in Treatment-Experienced Patients with Multi-drug Resistant HIV Disease

PubMed Central

Bayoumi, Ahmed M.; Barnett, Paul G.; Joyce, Vilija R.; Griffin, Susan C.; Sun, Huiying; Bansback, Nick J.; Holodniy, Mark; Sanders, Gillian; Brown, Sheldon T.; Kyriakides, Tassos C.; Angus, Brian; Cameron, D. William; Anis, Aslam H.; Sculpher, Mark; Owens, Douglas K.

2014-01-01

Objective Newer antiretroviral drugs provide substantial benefits but are expensive. We determined the cost-effectiveness of using antiretroviral drugs in combination for patients with multi-drug resistant HIV disease. Design We built a cohort state-transition model representing treatment-experienced patients with low CD4 counts, high viral load levels, and multi-drug resistant virus. We estimated the effectiveness of newer drugs (those approved in 2005 or later) from published randomized trials. We estimated other parameters from a randomized trial and from the literature. The model had a lifetime time horizon and used the perspective of an ideal insurer in the United States. The interventions were combination antiretroviral therapy, consisting of two newer drugs and one conventional drug, compared to three conventional drugs. Outcome measures were life-years, quality-adjusted life-years (QALYs), costs, and incremental cost-effectiveness. Results Substituting newer antiretroviral drugs increased expected survival by 3.9 years in advanced HIV disease. The incremental cost-effectiveness ratio of newer, compared to conventional, antiretroviral drugs was $75,556/QALY gained. Sensitivity analyses showed that substituting only one newer antiretroviral drug cost $54,559 to $68,732/QALY, depending on assumptions about efficacy. Substituting three newer drugs cost $105,956 to $117,477/QALY. Cost-effectiveness ratios were higher if conventional drugs were not discontinued. Conclusions In treatment-experienced patients with advanced HIV disease, use of newer antiretroviral agents can be cost effective, given a cost-effectiveness threshold in the range of $50,000 to $75,000 per QALY gained. Newer antiretroviral agents should be used in carefully selected patients for whom less expensive options are clearly inferior. PMID:24129369

Acute hypophosphataemia and hypokalaemia in a patient starting antiretroviral therapy in Zambia—a new context for refeeding syndrome?

PubMed Central

Nyirenda, Christopher; Zulu, Isaac; Kabagambe, Edmond K; Bagchi, Shashwatee; Potter, Dara; Bosire, Claire; Krishnasami, Zipporah; Heimburger, Douglas C

2009-01-01

High mortality rates have been reported in the first 90 days of antiretroviral therapy in Zambia and other low-income countries. We report a case of acute hypophosphataemia and hypokalaemia in the first week of antiretroviral therapy in a patient with extreme AIDS wasting. Given its occurrence in an extremely wasted patient, it may be physiologically similar to refeeding syndrome but other causes could be relevant as well. Acute hypophosphataemia may contribute to early antiretroviral therapy associated mortality in low-income countries. PMID:21686792

Antiretroviral chemoprophylaxis in children and adolescents victims of rape in Abidjan.

PubMed

Ehui, E; Couitchéré, L S; Kouakou, G A; Doumbia, A; Kassi, A N; Mossou, C M; Guié, P Y; Eholié, S

2015-08-01

We described the use of antiretroviral drugs to prevent HIV transmission among children and adolescents victims of rape in Abidjan (Ivory Coast). We conducted a retrospective and descriptive study on children (0-9 years) and adolescents (10-19 years) victims of rape between 2000 and 2013. We analyzed the patients' socio-demographic characteristics and the modality of the chemoprophylaxis. We included 10 children and 89 adolescents in the study. The median age was 16 years old (3-19 years). The median time to consultation was 23.5 hours (5-152 hours). The antiretroviral chemoprophylaxis was administered to 92 patients (93%). No HIV and HBV seroconversion was observed after a 3-month follow-up. A better management of rape victims is required in Abidjan. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

An information-motivation-behavioral skills model of adherence to antiretroviral therapy.

PubMed

Fisher, Jeffrey D; Fisher, William A; Amico, K Rivet; Harman, Jennifer J

2006-07-01

HIV-positive persons who do not maintain consistently high levels of adherence to often complex and toxic highly active antiretroviral therapy (HAART) regimens may experience therapeutic failure and deterioration of health status and may develop multidrug-resistant HIV that can be transmitted to uninfected others. The current analysis conceptualizes social and psychological determinants of adherence to HAART among HIV-positive individuals. The authors propose an information-motivation-behavioral skills (IMB) model of HAART adherence that assumes that adherence-related information, motivation, and behavioral skills are fundamental determinants of adherence to HAART. According to the model, adherence-related information and motivation work through adherence-related behavioral skills to affect adherence to HAART. Empirical support for the IMB model of adherence is presented, and its application in adherence-promotion intervention efforts is discussed.

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

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

PubMed

Vairo, Francesco; Nicastri, Emanuele; Liuzzi, Giuseppina; Chaula, Zainab; Nguhuni, Boniface; Bevilacqua, Nazario; Forbici, Federica; Amendola, Alessandra; Fabeni, Lavinia; De Nardo, Pasquale; Perno, Carlo Federico; Cannas, Angela; Sakhoo, Calistus; Capobianchi, Maria Rosaria; Ippolito, Giuseppe

2013-09-21

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

High Prevalence of Tuberculosis and Serious Bloodstream Infections in Ambulatory Individuals Presenting for Antiretroviral Therapy in Malawi

PubMed Central

Bedell, Richard A.; Anderson, Suzanne T. B.; van Lettow, Monique; Åkesson, Ann; Corbett, Elizabeth L.; Kumwenda, Moses; Chan, Adrienne K.; Heyderman, Robert S.; Zachariah, Rony; Harries, Anthony D.; Ramsay, Andrew R.

2012-01-01

Background Tuberculosis (TB) and serious bloodstream infections (BSI) may contribute to the high early mortality observed among patients qualifying for antiretroviral therapy (ART) with unexplained weight loss, chronic fever or chronic diarrhea. Methods and Findings A prospective cohort study determined the prevalence of undiagnosed TB or BSI among ambulatory HIV-infected adults with unexplained weight loss and/or chronic fever, or diarrhea in two routine program settings in Malawi. Subjects with positive expectorated sputum smears for AFB were excluded. Investigations Bacterial and mycobacterial blood cultures, cryptococcal antigen test (CrAg), induced sputum (IS) for TB microscopy and solid culture, full blood count and CD4 lymphocyte count. Among 469 subjects, 52 (11%) had microbiological evidence of TB; 50 (11%) had a positive (non-TB) blood culture and/or positive CrAg. Sixty-five additional TB cases were diagnosed on clinical and radiological grounds. Nontyphoidal Salmonellae (NTS) were the most common blood culture pathogens (29 cases; 6% of participants and 52% of bloodstream isolates). Multivariate analysis of baseline clinical and hematological characteristics found significant independent associations between oral candidiasis or lymphadenopathy and TB, marked CD4 lymphopenia and NTS infection, and severe anemia and either infection, but low positive likelihood ratios (<2 for all combinations). Conclusions We observed a high prevalence of TB and serious BSI, particularly NTS, in a program cohort of chronically ill HIV-infected outpatients. Baseline clinical and hematological characteristics were inadequate predictors of infection. HIV clinics need better rapid screening tools for TB and BSI. Clinical trials to evaluate empiric TB or NTS treatment are required in similar populations. PMID:22761767

The impact of methadone or buprenorphine treatment and ongoing injection on highly active antiretroviral therapy (HAART) adherence: evidence from the MANIF2000 cohort study.

PubMed

Roux, Perrine; Carrieri, M Patrizia; Villes, Virgine; Dellamonica, Pierre; Poizot-Martin, Isabelle; Ravaux, Isabelle; Spire, Bruno

2008-11-01

To date, no data exist assessing the impact of either methadone or buprenorphine on adherence to highly active antiretroviral therapy (HAART) in the long term. This study was conducted in order to evaluate whether receiving take-home methadone and buprenorphine may ensure better adherence to HAART in individuals infected with human immunodeficiency virus (HIV) through injection drug use (IDU). Longitudinal data on adherence, opioid substitution treatment (OST) and patient behaviours starting from their first HAART prescription were collected for 276 individuals HIV-infected through drug use (n=1558 visits). Out-patient hospital services delivering HIV care in Marseilles, Avignon, Nice and Ile de France. At any given visit, patients were classified both according to the type of OST received and ongoing injection. Patients who reported no injection and no OST over the whole study period were considered as 'abstinent' and used as a reference category. A logit model based on generalized estimation equations (GEE) was used to identify predictors of non-adherence. After adjustment for alcohol consumption, depression and self-reported side effects, patients ceasing injection during OST and abstinent patients exhibited comparable adherence. Patients reporting injection, on OST or not, had a twofold and threefold risk, respectively, of non-adherence compared with abstinent patients (P<0.01 linear trend). Duration on OST without injecting was associated significantly with virological success. Both access to and effectiveness of OST contribute to sustaining adherence to HAART in HIV-infected IDUs. These results advocate strongly the need of wider use of OST in countries scaling-up HAART where HIV is driven by IDUs.

Broadening the use of antiretroviral therapy: the case for feline leukemia virus

PubMed Central

Greggs, Willie M; Clouser, Christine L; Patterson, Steven E; Mansky, Louis M

2011-01-01

Antiretroviral drugs have saved and extended the lives of millions of individuals infected with HIV. The major classes of anti-HIV drugs include reverse transcriptase inhibitors, protease inhibitors, integrase inhibitors, and entry/fusion inhibitors. While antiretroviral drug regimens are not commonly used to treat other types of retroviral infections, there are instances where there is a perceived need for re-evaluation of the benefits of antiretroviral therapy. One case in point is that of feline leukemia virus (FeLV), an infection of companion felines. While vaccines exist to prevent FeLV infection and spread, they have not eliminated FeLV infection. For FeLV-infected felines and their human companions, antiretroviral therapy would be desirable and of practical importance if good options were available. Here, we discuss FeLV biology and current treatment options, and propose that there is a need for antiretroviral treatment options for FeLV infection. The comparative use and analysis of antiretroviral therapy can provide new insights into the mechanism of antiretroviral drug action. PMID:21479142

Broad spectrum antiretroviral activity of 2',3'-dideoxynucleosides.

PubMed Central

Dahlberg, J E; Mitsuya, H; Blam, S B; Broder, S; Aaronson, S A

1987-01-01

Certain dideoxynucleosides have been shown to markedly inhibit the infectivity of human T-lymphotropic virus type III/lymphadenopathy-associated virus, the causative agent of acquired immunodeficiency syndrome (AIDS). Our present studies demonstrate that these drugs are broad spectrum antiretroviral agents capable of inhibiting the infectivity of evolutionarily divergent mammalian type C and animal lentiviruses. Under some conditions, virus infectivity could be inhibited by more than six orders of magnitude. However, the potency of these agents was shown to be greatly influenced by cell-specified determinants. Drug exposure during the initial 24 hr was almost as effective as prolonged treatment on the inhibition of a single cycle of virus infection and expression. Moreover, virus infection was shown directly to be inhibited at the level of proviral DNA synthesis. Thus the time period during which reverse transcription and provirus integration occur is the critical period required for drug action. Our findings have implications concerning strategies to be considered in attempts to utilize 2',3'-dideoxynucleosides in control and treatment of retrovirus-induced diseases of animals and humans. Images PMID:3470806

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.

Depression among patients attending antiretroviral treatment program in public health facilities in Bahir Dar City, Ethiopia.

PubMed

Tareke, Minale; Addisu, Fikir; Abate, Andargie

2018-05-01

The magnitude of depression is not well investigated among people living with HIV/AIDS. Thus, this research aimed to assess the magnitude of depression and its influencing factors among people living with HIV/AIDS attending government institutions in Bahir Dar City, North West, Ethiopia. institution based-cross-sectional study was done among randomly selected 415 people living with HIV/AIDS attending antiretroviral therapy program in Bahir Dar city, Ethiopia. Socio-demographic data and medical histories for all respondents were collected using interviewer-administered structured questionnaire. We assessed the odds of association of patient characteristics with depression was assessed using multiple logistic regression. The relative effect estimates of the respective factors were presented with odds ratio accompanied by their 95% uncertainty intervals. From 407 people living with HIV/AIDS interviewed, 198(48.6%) of them had depression. Social support, HIV clinical staging, total daily pill burden, treatment regimen and adherence to highly active antiretroviral therapy were significantly associated with depression. The magnitude of depression among people living with HIV/AIDS was found to be high. Early mental health screening should be done for people living with HIV/AIDS. Copyright © 2018 Elsevier B.V. All rights reserved.

[Antiretroviral therapy for HIV-infected patients with schizophrenia. Coordinated multidisciplinary management (7 cases)].

PubMed

Leclerc, Stéphanie; Brunschwig, Olivier; Berki-Benhaddad, Zhora; Soyris, Dominique; Grataud, Christian; Breton, Guillaume; Leport, Catherine; Vildé, Jean-Louis

2005-03-26

Schizophrenia might appear to be an obstacle to the initiation of and especially compliance with antiretroviral therapy for HIV-infected patients. The aims of this study were to describe the clinical, immunologic and virologic course after initiation of antiretroviral therapy in 7 HIV patients with schizophrenia (according to DSM-IV-R criteria), and to analyse the possibilities of an adequate antiretroviral therapy for those patients. Multidisciplinary management by specialists in infectious diseases, addiction-related disorders, treatment adherence and compliance, and psychiatrists, as well as social workers, home care agencies, and patient advocacy and assistance groups, was organized with coordinated medical-psychiatric follow-up at least once a month. The patients, 6 men and 1 woman, were aged from 26 to 48 years; schizophrenia had been diagnosed in 5 patients 6 months to 20 years before the HIV infection was discovered; diagnoses of both diseases were essentially simultaneous for the other 2. All patients took long-term neuroleptics for their schizophrenia. Two were active drug addicts who received drug substitution treatment. Before antiretroviral treatment began, 6 patients had advanced infection: stage C with peak CD4 cell counts ranging from 6 to 70/mm3; they began treatment with protease inhibitors between May 1996 and August 1997. The seventh patient was first seen during primary HIV infection in July 1998, and treatment began then. Response to antiretroviral treatment with protease inhibitors was slow for all patients, but viral load became undetectable for 6 of the 7, after 5 months to 4 years; 3 had opportunistic infections. Follow-up ended in January 2002: 5 patients still had undetectable viral loads,, with CD4 cell counts ranging from 45 to 1 000/mm3. One patient died from mixed terminal cirrhosis (alcohol abuse and hepatitis C); the viral load in another was only partially controlled (10 000 copies/ml), because of poor treatment adherence

Scientific Production about the Adherence to Antiretroviral Therapy

PubMed Central

de Oliveira, Regina Célia; de Andrade Moraes, Danielle Chianca; Santos, Cleytiane Stephany Silva; da Silva Monteiro, Gicely Regina Sobral; da Rocha Cabral, Juliana; Beltrão, Roberta Andrade; da Silva, Calos Roberto Lyra

2017-01-01

Objective To identify the elite of authors about the subject adherence to antiretroviral therapy; to identify the journals turned to publishing articles about adherence to antiretroviral therapy; and to identify and analyze the most commonly used words in abstracts of articles about adherence to antiretroviral therapy. Method A bibliometric study conducted through the Scopus base. We used articles published between 1996 and 2014, after application of the eligibility criteria, there were composed the sample with 24 articles. The data were analyzed descriptively. Were used the laws of bibliometric (Lotka, Bradford and Zipf) and the conceptual cloud map of words, through the program Cmap tools. Results Lotka’s Law identified the 5 authors more productive (46% of the total published). Bradford is impaired in this study. Concerning Zipf, 3 zones were determined, 31.47% of the words with in the first zone, 26.46% in the second and 42.06% in the third. In the conceptual map, the words/factors that positively and negatively influence adherence were emphasized, among them the need for more research in the health services. Conclusion There are few publications about the accession to antiretroviral therapy, and the scientific production is in the process of maturation. One can infer that the theme researched is not yet an obsolete topic. It should be noted that the Bibliometric was a relevant statistic tool to generate information about the publications about the antiretroviral therapy. PMID:28979571

Cost analysis of initial highly active antiretroviral therapy regimens for managing human immunodeficiency virus-infected patients according to clinical practice in a hospital setting.

PubMed

Colombo, Giorgio L; Castagna, Antonella; Di Matteo, Sergio; Galli, Laura; Bruno, Giacomo; Poli, Andrea; Salpietro, Stefania; Carbone, Alessia; Lazzarin, Adriano

2014-01-01

In the study reported here, single-tablet regimen (STR) versus (vs) multi-tablet regimen (MTR) strategies were evaluated through a cost analysis in a large cohort of patients starting their first highly active antiretroviral therapy (HAART). Adult human immunodeficiency virus (HIV) 1-naïve patients, followed at the San Raffaele Hospital, Milan, Italy, starting their first-line regimen from June 2008 to April 2012 were included in the analysis. The most frequently used first-line HAART regimens (>10%) were grouped into two classes: 1) STR of tenofovir disoproxil fumarate (TDF) + emtricitabine (FTC) + efavirenz (EFV) and 2) MTR including TDF + FTC + EFV, TDF + FTC + atazanavir/ritonavir (ATV/r), TDF + FTC + darunavir/ritonavir (DRV/r), and TDF + FTC + lopinavir/ritoavir (LPV/r). Data were analyzed from the point of view of the Lombardy Regional Health Service. HAART, hospitalizations, visits, medical examinations, and other concomitant non-HAART drug costs were evaluated and price variations included. Descriptive statistics were calculated for baseline demographic, clinical, and laboratory characteristics; associations between categorical variables and type of antiretroviral strategy (STR vs MTR) were examined using chi-square or Fisher's exact tests. At multivariate analysis, the generalized linear model was used to identify the predictive factors of the overall costs of the first-line HAART regimens. A total of 474 naïve patients (90% male, mean age 42.2 years, mean baseline HIV-RNA 4.50 log 10 copies/mL, and cluster of differentiation 4 [CD4+] count of 310 cells/μL, with a mean follow-up of 28 months) were included. Patients starting an STR treatment were less frequently antibody-hepatitis C virus positive (4% vs 11%, P=0.040), and had higher mean CD4+ values (351 vs 297 cells/μL, P=0.004) than MTR patients. The mean annual cost per patient in the STR group was €9,213.00 (range: €6,574.71-€33,570.00) and €14,277.00 (range: €5,908.89-€82

Cost analysis of initial highly active antiretroviral therapy regimens for managing human immunodeficiency virus-infected patients according to clinical practice in a hospital setting

PubMed Central

Colombo, Giorgio L; Castagna, Antonella; Di Matteo, Sergio; Galli, Laura; Bruno, Giacomo; Poli, Andrea; Salpietro, Stefania; Carbone, Alessia; Lazzarin, Adriano

2014-01-01

Objective In the study reported here, single-tablet regimen (STR) versus (vs) multi-tablet regimen (MTR) strategies were evaluated through a cost analysis in a large cohort of patients starting their first highly active antiretroviral therapy (HAART). Adult human immunodeficiency virus (HIV) 1-naïve patients, followed at the San Raffaele Hospital, Milan, Italy, starting their first-line regimen from June 2008 to April 2012 were included in the analysis. Methods The most frequently used first-line HAART regimens (>10%) were grouped into two classes: 1) STR of tenofovir disoproxil fumarate (TDF) + emtricitabine (FTC) + efavirenz (EFV) and 2) MTR including TDF + FTC + EFV, TDF + FTC + atazanavir/ritonavir (ATV/r), TDF + FTC + darunavir/ritonavir (DRV/r), and TDF + FTC + lopinavir/ritoavir (LPV/r). Data were analyzed from the point of view of the Lombardy Regional Health Service. HAART, hospitalizations, visits, medical examinations, and other concomitant non-HAART drug costs were evaluated and price variations included. Descriptive statistics were calculated for baseline demographic, clinical, and laboratory characteristics; associations between categorical variables and type of antiretroviral strategy (STR vs MTR) were examined using chi-square or Fisher’s exact tests. At multivariate analysis, the generalized linear model was used to identify the predictive factors of the overall costs of the first-line HAART regimens. Results A total of 474 naïve patients (90% male, mean age 42.2 years, mean baseline HIV-RNA 4.50 log 10 copies/mL, and cluster of differentiation 4 [CD4+] count of 310 cells/μL, with a mean follow-up of 28 months) were included. Patients starting an STR treatment were less frequently antibody-hepatitis C virus positive (4% vs 11%, P=0.040), and had higher mean CD4+ values (351 vs 297 cells/μL, P=0.004) than MTR patients. The mean annual cost per patient in the STR group was €9,213.00 (range: €6,574.71–€33,570.00) and €14,277.00 (range

Alcohol use and HIV serostatus of partner predict high-risk sexual behavior among patients receiving antiretroviral therapy in South Western Uganda.

PubMed

Bajunirwe, Francis; Bangsberg, David R; Sethi, Ajay K

2013-05-03

Antiretroviral treatment restores the physical and immunological function for patients with HIV/AIDS and the return of sexual desire. The frequency and correlates of sexual activity among patients receiving ART have not been widely studied. There is concern that widespread availability of ART may result in sexual disinhibition including practice of high-risk sexual behavior. We determined the correlates of sexual activity and high-risk sexual behavior in an ART-treated population in rural and urban Uganda. We conducted a cross-sectional study among 329 ART-treated adult patients at two hospitals, one located in rural and another in urban western Uganda. We collected data on sexual activity, frequency of condom use, pregnancy, viral load (VL) and CD4. Patients were considered sexually active if they had had sexual intercourse in the last 6 months. Any unprotected sex was considered high-risk sex. A two-stage logistic regression was performed to determine factors associated with sexual activity and high-risk sex among those sexually active. Overall, 222 (67%) patients were women, 138 (41.2%) had been on ART for at least one year, and 168 (51.4%) were sexually active of whom 127 (75.6%) used condoms at the last intercourse. Younger age (<=30 years) (Odds ratio; OR=2.3, 95% CI 1.2, 4.2), higher monthly income (OR=4.1, 95% CI 2.4, 7.4), and being married (OR=22.7, 95% CI 8.2, 62.9) were associated with being sexually active. Undetectable VL, CD4 count and treatment duration were not significantly associated with sexual activity. Among the sexually active, alcohol consumption (OR=3.3, 95% CI 1.2, 9.1) and unknown serostatus of partner (OR=5.8, 95% CI 1.5, 21.4) were significant predictors of high-risk sexual behavior. The frequency of unprotected sex at the last intercourse was 25.9% and 22.1% among the men and women respectively and was not significantly different (p value for chi square test =0.59). Younger persons receiving ART are more likely to be sexually active

Alcohol use and HIV serostatus of partner predict high-risk sexual behavior among patients receiving antiretroviral therapy in South Western Uganda

PubMed Central

2013-01-01

Background Antiretroviral treatment restores the physical and immunological function for patients with HIV/AIDS and the return of sexual desire. The frequency and correlates of sexual activity among patients receiving ART have not been widely studied. There is concern that widespread availability of ART may result in sexual disinhibition including practice of high-risk sexual behavior. We determined the correlates of sexual activity and high-risk sexual behavior in an ART-treated population in rural and urban Uganda. Methods We conducted a cross-sectional study among 329 ART-treated adult patients at two hospitals, one located in rural and another in urban western Uganda. We collected data on sexual activity, frequency of condom use, pregnancy, viral load (VL) and CD4. Patients were considered sexually active if they had had sexual intercourse in the last 6 months. Any unprotected sex was considered high-risk sex. A two-stage logistic regression was performed to determine factors associated with sexual activity and high-risk sex among those sexually active. Results Overall, 222 (67%) patients were women, 138 (41.2%) had been on ART for at least one year, and 168 (51.4%) were sexually active of whom 127 (75.6%) used condoms at the last intercourse. Younger age (<=30 years) (Odds ratio; OR=2.3, 95% CI 1.2, 4.2), higher monthly income (OR=4.1, 95% CI 2.4, 7.4), and being married (OR=22.7, 95% CI 8.2, 62.9) were associated with being sexually active. Undetectable VL, CD4 count and treatment duration were not significantly associated with sexual activity. Among the sexually active, alcohol consumption (OR=3.3, 95% CI 1.2, 9.1) and unknown serostatus of partner (OR=5.8, 95% CI 1.5, 21.4) were significant predictors of high-risk sexual behavior. The frequency of unprotected sex at the last intercourse was 25.9% and 22.1% among the men and women respectively and was not significantly different (p value for chi square test =0.59). Conclusion Younger persons receiving ART

Impact of an antiretroviral stewardship strategy on medication error rates.

PubMed

Shea, Katherine M; Hobbs, Athena Lv; Shumake, Jason D; Templet, Derek J; Padilla-Tolentino, Eimeira; Mondy, Kristin E

2018-05-02

The impact of an antiretroviral stewardship strategy on medication error rates was evaluated. This single-center, retrospective, comparative cohort study included patients at least 18 years of age infected with human immunodeficiency virus (HIV) who were receiving antiretrovirals and admitted to the hospital. A multicomponent approach was developed and implemented and included modifications to the order-entry and verification system, pharmacist education, and a pharmacist-led antiretroviral therapy checklist. Pharmacists performed prospective audits using the checklist at the time of order verification. To assess the impact of the intervention, a retrospective review was performed before and after implementation to assess antiretroviral errors. Totals of 208 and 24 errors were identified before and after the intervention, respectively, resulting in a significant reduction in the overall error rate ( p < 0.001). In the postintervention group, significantly lower medication error rates were found in both patient admissions containing at least 1 medication error ( p < 0.001) and those with 2 or more errors ( p < 0.001). Significant reductions were also identified in each error type, including incorrect/incomplete medication regimen, incorrect dosing regimen, incorrect renal dose adjustment, incorrect administration, and the presence of a major drug-drug interaction. A regression tree selected ritonavir as the only specific medication that best predicted more errors preintervention ( p < 0.001); however, no antiretrovirals reliably predicted errors postintervention. An antiretroviral stewardship strategy for hospitalized HIV patients including prospective audit by staff pharmacists through use of an antiretroviral medication therapy checklist at the time of order verification decreased error rates. Copyright © 2018 by the American Society of Health-System Pharmacists, Inc. All rights reserved.

Antiretroviral treatment of adult HIV infection: 2008 recommendations of the International AIDS Society-USA panel.

PubMed

Hammer, Scott M; Eron, Joseph J; Reiss, Peter; Schooley, Robert T; Thompson, Melanie A; Walmsley, Sharon; Cahn, Pedro; Fischl, Margaret A; Gatell, Jose M; Hirsch, Martin S; Jacobsen, Donna M; Montaner, Julio S G; Richman, Douglas D; Yeni, Patrick G; Volberding, Paul A

2008-08-06

The availability of new antiretroviral drugs and formulations, including drugs in new classes, and recent data on treatment choices for antiretroviral-naive and -experienced patients warrant an update of the International AIDS Society-USA guidelines for the use of antiretroviral therapy in adult human immunodeficiency virus (HIV) infection. To summarize new data in the field and to provide current recommendations for the antiretroviral management and laboratory monitoring of HIV infection. This report provides guidelines in key areas of antiretroviral management: when to initiate therapy, choice of initial regimens, patient monitoring, when to change therapy, and how best to approach treatment options, including optimal use of recently approved drugs (maraviroc, raltegravir, and etravirine) in treatment-experienced patients. A 14-member panel with expertise in HIV research and clinical care was appointed. Data published or presented at selected scientific conferences since the last panel report (August 2006) through June 2008 were identified. Data that changed the previous guidelines were reviewed by the panel (according to section). Guidelines were drafted by section writing committees and were then reviewed and edited by the entire panel. Recommendations were made by panel consensus. New data and considerations support initiating therapy before CD4 cell count declines to less than 350/microL. In patients with 350 CD4 cells/microL or more, the decision to begin therapy should be individualized based on the presence of comorbidities, risk factors for progression to AIDS and non-AIDS diseases, and patient readiness for treatment. In addition to the prior recommendation that a high plasma viral load (eg, >100,000 copies/mL) and rapidly declining CD4 cell count (>100/microL per year) should prompt treatment initiation, active hepatitis B or C virus coinfection, cardiovascular disease risk, and HIV-associated nephropathy increasingly prompt earlier therapy. The initial

Early antiretroviral therapy: rationale, protease inhibitor-sparing regimens and once daily dosing.

PubMed

Gatell, J M

1998-01-01

In 1998 it seems reasonable and widely accepted that all human immunodeficiency virus type 1 (HIV-1)-infected patients willing to be treated may benefit from receiving antiretroviral therapy. Only those with undetectable plasma HIV-1 RNA, normal CD4 lymphocyte counts and lack of markers of immunological system activation may be possible exceptions. The rationale supporting the early initiation of antiretroviral therapy are (i) data on viral dynamics; (ii) preliminary data pointing toward a better and a quicker restoration of immune function when treatment is initiated in very early stages (during or within a few weeks or months of acute symptomatic or asymptomatic HIV-1 infection); (iii) the lack of a stable viral load set-point even in patients in the early stages (CD4 > 500 cells/mm3) who have a very low viral load (< 5000 copies/ml); (iv) the relatively high likelihood of clinical progression at mid-term of the approximately 50-75% of patients in very early disease stages (CD4 > 500 cells/mm3) who have a plasma viral load above 5000 to 10,000 HIV-1 RNA copies/ml; (v) data from the Spanish Earth-1 study, which used a composite endpoint (virological, immunological or clinical progression), demonstrating that even in these very early stages of HIV-1 disease any antiretroviral therapy (double or triple combination) was better than no treatment. Even in early disease stages, a triple combination is needed to achieve a durable and profound virological and immunological response. In addition, the combination of stavudine plus didanosine has several advantages and can be considered one of the best double nucleoside combinations to combine with a protease inhibitor or with a non-nucleoside reverse transcriptase inhibitor. The INCAS study and the preliminary results of the ongoing Spanish SCAN study have demonstrated the possibility of protease inhibitor-sparing combinations for initial antiretroviral treatment, at least in selected patient subsets, such as those with a

Time from HIV seroconversion to death: a collaborative analysis of eight studies in six low and middle-income countries before highly active antiretroviral therapy

PubMed Central

Todd, Jim; Glynn, Judith R.; Marston, Milly; Lutalo, Tom; Biraro, Sam; Mwita, Wambura; Suriyanon, Vinai; Rangsin, Ram; Nelson, Kenrad E.; Sonnenberg, Pam; Fitzgerald, Dan; Karita, Etienne; Żaba, Basia

2018-01-01

Objectives To estimate survival patterns after HIV infection in adults in low and middle-income countries. Design An analysis of pooled data from eight different studies in six countries. Methods HIV seroconverters were included from eight studies (three population-based, two occupational, and three clinic cohorts) if they were at least 15 years of age, and had no more than 4 years between the last HIV-negative and subsequent HIV-positive test. Four strata were defined: East African cohorts; South African miners cohort; Thai cohorts; Haitian clinic cohort. Kaplan–Meier functions were used to estimate survival patterns, and Weibull distributions were used to model and extend survival estimates. Analyses examined the effect of site, age, and sex on survival. Results From 3823 eligible seroconverters, 1079 deaths were observed in 19 671 person-years of follow-up. Survival times varied by age and by study site. Adjusting to age 25–29 years at seroconversion, the median survival was longer in South African miners: 11.6 years [95% confidence interval (CI) 9.8–13.7] and East African cohorts: 11.1 years (95% CI 8.7–14.2) than in Haiti: 8.3 years (95% CI 3.2–21.4) and Thailand: 7.5 years (95% CI 5.4–10.4). Survival was similar for men and women, after adjustment for age at seroconversion and site. Conclusion Without antiretroviral therapy, overall survival after HIV infection in African cohorts was similar to survival in high-income countries, with a similar pattern of faster progression at older ages at seroconversion. Survival appears to be significantly worse in Thailand where other, unmeasured factors may affect progression. PMID:18032940

Novel antiretroviral combinations in treatment-experienced patients with HIV infection: rationale and results.

PubMed

Taiwo, Babafemi; Murphy, Robert L; Katlama, Christine

2010-09-10

Novel antiretroviral drugs offer different degrees of improvement in activity against drug-resistant HIV, short- and long-term tolerability, and dosing convenience compared with earlier drugs. Those drugs approved more recently and commonly used in treatment-experienced patients include the entry inhibitor enfuvirtide, protease inhibitors (PIs) [darunavir and tipranavir], a C-C chemokine receptor (CCR) type 5 antagonist (maraviroc), an integrase inhibitor (raltegravir) and etravirine, a non-nucleoside reverse transcriptase inhibitor (NNRTI). Novel agents in earlier stages of development include a CCR5 monoclonal antibody (PRO 140) administered subcutaneously once weekly, once-daily integrase inhibitors (elvitegravir and S/GSK1349572), and several nucleoside (nucleotide) reverse transcriptase inhibitors and NNRTIs. Bevirimat, a maturation inhibitor, has compromised activity in the presence of relatively common Gag polymorphisms. Viral suppression is necessary to control the evolution of drug resistance, reduce chronic immune activation that probably underlies the excess morbidity and mortality in HIV-infected patients, and reduce viral transmission, including transmitted drug resistance. In general, the proportion of viraemic patients who achieve suppression increases with the number of active pharmacokinetically compatible antiretroviral drugs in the regimen. In the ANRS139-TRIO trial, 86% of highly treatment-experienced patients treated with darunavir-ritonavir, etravirine and raltegravir had HIV RNA <50 copies/mL at 48 weeks. In patients who had received at least 12 weeks of a stable regimen and had no darunavir resistance-associated mutations, once-daily darunavir boosted with ritonavir 100 mg was virologically noninferior with better lipid effects than with the twice-daily dosing, which requires a 200 mg total daily dose of ritonavir. Raltegravir plus a boosted PI is being investigated for second-line therapy in patients not responding to NNRTI-based first

Determinants of access to experimental antiretroviral drugs in an Italian cohort of patients with HIV: a multilevel analysis.

PubMed

Girardi, Enrico; Scognamiglio, Paola; Angeletti, Claudio; Gori, Andrea; Buonfrate, Dora; Arlotti, Massimo; Mazzarello, Giovanni; Castagna, Antonella; Andreoni, Massimo; d'Arminio Monforte, Antonella; Antinori, Andrea; Ippolito, Giuseppe

2012-02-15

Identification of the determinants of access to investigational drugs is important to promote equity and scientific validity in clinical research. We aimed to analyze factors associated with the use of experimental antiretrovirals in Italy. We studied participants in the Italian Cohort of Antiretroviral-Naive Patients (ICoNA). All patients 18 years or older who had started cART (≥ 3 drugs including at least two NRTI) after their enrolment and during 1997-2007 were included in this analysis. We performed a random effect logistic regression analysis to take into account clustering observations within clinical units. The outcome variable was the use of an experimental antiretroviral, defined as an antiretroviral started before commercial availability, in any episode of therapy initiation/change. Use of an experimental antiretroviral obtained through a clinical trial or an expanded access program (EAP) was also analyzed separately. A total of 9,441 episodes of therapy initiation/change were analyzed in 3,752 patients. 392 episodes (360 patients) involved an experimental antiretroviral. In multivariable analysis, factors associated with the overall use of experimental antiretrovirals were: number of experienced drugs (≥ 8 drugs versus "naive": adjusted odds ratio [AOR] = 3.71) or failed antiretrovirals(3-4 drugs and ≥ 5 drugs versus 0-2 drugs: AOR = 1.42 and 2.38 respectively); calendar year (AOR = 0.80 per year) and plasma HIV-RNA copies/ml at therapy change (≥ 4 log versus < 2 log: AOR = 1.55). The probability of taking an experimental antiretroviral through a trial was significantly lower for patients suffering from liver co-morbidity(AOR = 0.65) and for those who experienced 3-4 drugs (vs naive) (AOR = 0.55), while it increased for multi-treated patients(AOR = 2.60). The probability to start an experimental antiretroviral trough an EAP progressively increased with the increasing number of experienced and of failed drugs and also increased for patients with

Identification of 1-Aryl-1H-1,2,3-triazoles as Potential New Antiretroviral Agents.

PubMed

Gonzaga, Daniel T G; Souza, Thiago M L; Andrade, Viviane M M; Ferreira, Vitor F; de C da Silva, Fernando

2018-01-01

Low molecular weight 1-Aryl-1H-1,2,3-triazoles are endowed with various types of biological activities, such as against cancer, HIV and bacteria. Despite the existence of six different classes of antiretroviral drugs in clinical use, HIV/AIDS continue to be an on growing public health problem. In the present study, we synthesized and evaluated thirty 1-Aryl-1H-1,2,3-triazoles against HIV replication. The compounds were prepared by Huisgen 1,3-dipolar cycloaddition protocol catalyzed by Cu(I) between aryl azides and propargylic alcohol followed by further esterification and etherification from a nucleophilic substitution with acid chlorides or alkyl bromides in good yields. The compounds were submitted to the inhibition of HIV replication and evaluation of their cytotoxicity. Initially, the compounds were screened at 10 µM and the most active were further evaluated in order to obtain some pharmacological parameters. Thirty molecules were evaluated, six were selected - because they inhibited more than 80% HIV replication. We further showed that two of these compounds are 8-times more potent, and less cytotoxic, than nevirapine, an antiretroviral drug in clinical use. We identified very simple triazoles with promissing antiretroviral activities that led to the development of new drugs against AIDS. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Racial, gender and geographic disparities of antiretroviral treatment among US Medicaid enrolees in 1998

PubMed Central

King, WD; Minor, P; Ramirez Kitchen, C; Oré, LE; Shoptaw, S; Victorianne, GD; Rust, G

2016-01-01

Background In 1998, highly active antiretroviral therapy (HAART) was widespread, but the diffusion of these lifesaving treatments was not uniform. As half of all AIDS patients in the USA have Medicaid coverage, this study of a multistate Medicaid claims dataset was undertaken to assess disparities in the rates of HAART. Methods Data came from 1998 Medicaid claims files from five states with varying HIV prevalence. ICD-9 codes were used to identify people with a diagnosis of HIV/AIDS or AIDS-defining illness. Multivariate analyses assessed associations between age, gender, race and state of residence for antiretroviral regimens consistent with HAART, as defined by 1998 Centers for Disease Control and Prevention (CDC) guidelines. Results Among 7202 Medicaid enrolees with a diagnosis of HIV/AIDS or AIDS, 62% received HAART and 25% received no antiretroviral therapy. Multivariate analyses showed that age, race, gender and state were all significant predictors of receiving HAART: white, non-Hispanic patients were most likely to receive HAART (68.3%), with lower rates in Hispanic and black, non-Hispanic segments of the population (59.3% and 57.5%, respectively, p<0.001). Women were less likely to receive HAART than men (51.8% vs 69.3%, p<0.001). Conclusion Despite similar insurance coverage and drug benefits, life-saving treatments for HIV/AIDS diffused at widely varying rates in different segments of the Medicaid population. Research is needed to determine the extent to which racial, gender, interstate and region disparities currently correspond to barriers to such care. PMID:18701730

Five Antiretroviral Drug Class-Resistant HIV-1 in a Treatment-Naïve Patient Successfully Suppressed with Optimized Antiretroviral Drug Selection.

PubMed

Volpe, Joseph M; Ward, Douglas J; Napolitano, Laura; Phung, Pham; Toma, Jonathan; Solberg, Owen; Petropoulos, Christos J; Walworth, Charles M

2015-01-01

Transmitted HIV-1 exhibiting reduced susceptibility to protease and reverse transcriptase inhibitors is well documented but limited for integrase inhibitors and enfuvirtide. We describe here a case of transmitted 5 drug class-resistance in an antiretroviral (ARV)-naïve patient who was successfully treated based on the optimized selection of an active ARV drug regimen. The value of baseline resistance testing to determine an optimal ARV treatment regimen is highlighted in this case report. © The Author(s) 2015.

Guidelines for using antiretroviral agents among HIV-infected adults and adolescents.

PubMed

Dybul, Mark; Fauci, Anthony S; Bartlett, John G; Kaplan, Jonathan E; Pau, Alice K

2002-09-03

, treatment should be offered to persons who have <350 CD4+ T cells/mm3 or plasma HIV ribonucleic acid (RNA) levels of >55,000 copies/mL (by b-deoxyribonucleic acid [bDNA] or reverse transcriptase-polymerase chain reaction [RT-PCR] assays). The recommendation to treat asymptomatic patients should be based on the willingness and readiness of the person to begin therapy; the degree of existing immunodeficiency as determined by the CD4+ T cell count; the risk for disease progression as determined by the CD4+ T cell count and level of plasma HIV RNA; the potential benefits and risks of initiating therapy in an asymptomatic person; and the likelihood, after counseling and education, of adherence to the prescribed treatment regimen. Treatment goals should be maximal and durable suppression of viral load, restoration and preservation of immunologic function, improvement of quality of life, and reduction of HIV-related morbidity and mortality. Results of therapy are evaluated through plasma HIV RNA levels, which are expected to indicate a 1.0 log10 decrease at 2-8 weeks and no detectable virus (<50 copies/mL) at 4-6 months after treatment initiation. Failure of therapy at 4-6 months might be ascribed to nonadherence, inadequate potency of drugs or suboptimal levels of antiretroviral agents, viral resistance, and other factors that are poorly understood. Patients whose therapy fails in spite of a high level of adherence to the regimen should have their regimen changed; this change should be guided by a thorough drug treatment history and the results of drug-resistance testing. Because of limitations in the available alternative antiretroviral regimens that have documented efficacy, optimal changes in therapy might be difficult to achieve for patients in whom the preferred regimen has failed. These decisions are further confounded by problems with adherence, toxicity, and resistance. For certain patients, participating in a clinical trial with or without access to new drugs or using a

Antiretroviral drug use and HIV drug resistance among MSM and transgender women in sub-Saharan Africa.

PubMed

Zhang, Yinfeng; Fogel, Jessica M; Guo, Xu; Clarke, William; Breaud, Autumn; Cummings, Vanessa; Hamilton, Erica L; Ogendo, Arthur; Kayange, Noel; Panchia, Ravindre; Dominguez, Karen; Chen, Ying Q; Sandfort, Theodorus; Eshleman, Susan H

2018-06-19

To analyze antiretroviral drug use and HIV drug resistance among HIV-infected MSM and transgender women who were screened for participation in the HIV Prevention Trials Network 075 study. A qualitative assay was used to detect 20 antiretroviral drugs in five drug classes; this assay is based on liquid chromatography coupled with high-resolution accurate-mass mass spectrometry. HIV viral load testing was performed using the RealTime HIV-1 Viral Load Assay. HIV drug resistance testing was performed using the ViroSeq HIV-1 Genotyping System. Logistic regression was used to evaluate factors associated with study outcomes. Antiretroviral drugs were detected in 63 (34.4%) of 183 participants who had confirmed HIV infection at screening; 11 (17.5%) of the 63 participants were not virally suppressed. Six (54.5%) of the 11 participants had drug-resistant HIV, including four who had multiclass resistance. Seven (63.6%) of the 11 were at risk of acquiring resistance to additional antiretroviral drugs. In multivariate model, antiretroviral drugs were more frequently detected in older participants, those recruited from Kisumu, Kenya, and those who reported ever having been in HIV care or on antiretroviral therapy (ART). Most of HIV-infected persons screened for participation in HIV Prevention Trials Network 075 were not on ART, and many of those who were on ART were not virally suppressed. Many of those participants had drug-resistant HIV. These findings highlight the need for improved HIV care for African MSM and transgender women.

Linking HIV and antiretroviral drug resistance surveillance in Peru: a model for a third-generation HIV sentinel surveillance.

PubMed

Lama, Javier R; Sanchez, Jorge; Suarez, Luis; Caballero, Patricia; Laguna, Alberto; Sanchez, Jose L; Whittington, William L H; Celum, Connie; Grant, Robert M

2006-08-01

HIV drug resistance surveillance is limited by recruitment and selection bias and by limited information regarding HIV incidence rates, secondary resistance, and treatment prevalence. A second-generation HIV sentinel surveillance among men who have sex with men (MSM), regardless of prior history of HIV screening, serostatus, or treatment, was conducted in Peru in 2002. Recent HIV infection was estimated using sensitive/less sensitive enzyme immunoassay testing. Genotypic resistance testing was performed. HIV prevalence was 13.9% (456 HIV positive of 3280 participants). HIV incidence was estimated to be 5.1 per 100 person-years (95% confidence interval: 3.1-8.3). Among 143 MSM who were aware of their HIV infection before testing, only 20 (14.0%) were receiving antiretrovirals (ARV). Mutations conferring ARV resistance were found in 12 (3.3%) of 359 treatment-naive and 5 (31.3%) of 16 treatment-experienced participants with successful genotyping. One recently infected man from Lima demonstrated 3-class multidrug resistance. The most frequently observed mutations in treatment-naive, chronically infected persons from Lima were M184V (1.7%), D30N (1.3%), L90M (1.3%), and L10I (1.3%). The prevalence of ARV resistance among treatment-naive MSM in Peru is low, reflecting limited access to treatment before 2004, and contrasts with the history of ARV treatment in developed countries, where high levels of nucleoside reverse transcriptase inhibitor resistance occurred before introduction of highly active antiretroviral therapy. Linking ARV resistance and HIV sentinel surveillance in developing settings is feasible and should be considered in third-generation HIV sentinel surveillance programs.

Erythrocyte Inosine triphosphatase activity: A potential biomarker for adverse events during combination antiretroviral therapy for HIV

PubMed Central

Bierau, Jörgen; Bakker, Jaap A.; Schippers, Jolanda A.; Lowe, Selwyn H.; Paulussen, Aimée D. C.; van den Bosch, Bianca J. C.; Leers, Mathie P. G.; Hansen, Bettina E.; Verbon, Annelies

2018-01-01

The purine analogues tenofovir and abacavir are precursors of potential substrates for the enzyme Inosine 5’-triphosphate pyrophosphohydrolase (ITPase). Here, we investigated the association of ITPase activity and ITPA genotype with the occurrence of adverse events (AEs) during combination antiretroviral therapy (cART) for human immunodeficiency virus (HIV) infection. In 393 adult HIV-seropositive patients, AEs were defined as events that led to stop of cART regimen. ITPase activity ≥4 mmol IMP/mmol Hb/hour was considered as normal. ITPA genotype was determined by testing two ITPA polymorphisms: c.94C>A (p.Pro32Thr, rs1127354) and c.124+21A>C (rs7270101). Logistic regression analysis determined odds ratios for developing AEs. In tenofovir-containing regimens decreased ITPase activity was associated with less AEs (p = 0.01) and longer regimen duration (p = 0.001). In contrast, in abacavir-containing regimens decreased ITPase activity was associated with more AEs (crude p = 0.02) and increased switching of medication due to AEs (p = 0.03). ITPA genotype wt/wt was significantly associated with an increase in the occurrence of AEs in tenofovir-containing regimens. Decreased ITPase activity seems to be protective against occurrence of AEs in tenofovir-containing cART, while it is associated with an increase in AEs in abacavir-containing regimens. PMID:29329318

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.

Cerebral signal intensity abnormalities on T2-weighted MR images in HIV patients with highly active antiretroviral therapy: relationship with clinical parameters and interval changes.

PubMed

Hanning, Uta; Husstedt, Ingo W; Niederstadt, Thomas-Ulrich; Evers, Stefan; Heindel, Walter; Kloska, Stephan P

2011-09-01

The aim of this study was to assess the relationship between immune state and cerebral signal intensity abnormalities (SIAs) on T2-weighted magnetic resonance images in subjects with human immunodeficiency virus type 1 infection and highly active antiretroviral therapy. Thirty-two subjects underwent a total of 109 magnetic resonance studies. The presence of human immunodeficiency virus-associated neurocognitive disorder, categorized CD4(+) T lymphocyte count, and plasma viral load were assessed for relationship with the severity and interval change of SIAs for different anatomic locations of the brain. Subjects with multifocal patterns of SIAs had CD4(+) cell counts < 200 cells/μL in 66.0%, whereas subjects with diffuse patterns of SIAs had CD4(+) cell counts < 200 cells/μL in only 31.4% (P < .001). Subjects without SIAs in the basal ganglia had CD4(+) cell counts < 200 cells/μL in 37.0%, whereas subjects with minor and moderate SIAs in the basal ganglia had CD4(+) cell counts < 200 cells/μL in 78.3% and 80.0%, respectively (P < .005). The percentage of subjects with CD4(+) cell counts < 200 cells/μL was 85.7% when there were progressive periventricular SIA changes and 45.5% when periventricular SIA changes were stable in follow-up (P < .05). The presence and progression of cerebral SIAs on T2-weighted magnetic resonance images reflecting cerebral infection with human immunodeficiency virus are significantly related to impaired immune state as measured by CD4(+) cell count. Copyright © 2011 AUR. Published by Elsevier Inc. All rights reserved.

Decreased mitochondrial DNA content in subcutaneous fat from HIV-infected women taking antiretroviral therapy as measured at delivery.

PubMed

Nasi, Milena; Pinti, Marcello; Chiesa, Elisabetta; Fiore, Simona; Manzini, Serena; Del Giovane, Cinzia; D'Amico, Roberto; Palai, Nicoletta; Campatelli, Carlo; Sabbatini, Francesca; Roccio, Marianna; Tibaldi, Cecilia; Masuelli, Giulia; Mussini, Cristina; Ferrazzi, Enrico; d'Arminio Monforte, Antonella; Cossarizza, Andrea

2011-01-01

Increasing numbers of pregnant HIV-positive women are receiving combination antiretroviral regimens for preventing mother-to-child virus transmission or for treating the infection itself. Several studies have demonstrated that nucleoside reverse transcriptase inhibitors (NRTIs) induce mitochondrial toxicity by several mechanisms, including depletion of mitochondrial DNA (mtDNA). By the quantification of mtDNA levels, we studied mitochondrial toxicity in HIV-positive women at delivery and the possible correlations with antiretroviral regimens, viroimmunological and metabolic parameters. We analysed 68 HIV-positive women enrolled in the Italian Prospective Cohort Study on Efficacy and Toxicity of Antiretroviral in Pregnancy (TARGET Study); all were taking ≥1 NRTI. We quantified mtDNA copies per cell in subcutaneous fat samples collected during delivery. At the 3rd, 6th and 9th month of pregnancy, we collected data concerning CD4(+) T-cell count, plasma HIV RNA, total and high-density lipoprotein (HDL) cholesterol, fasting plasma glucose and triglycerides. As a control, we analysed mtDNA levels in abdominal subcutaneous fat samples from 23 HIV-seronegative women at delivery. mtDNA content was significantly lower in HIV-infected women when compared with HIV-negative controls. mtDNA content varied independently from viroimmunological, lipid and glucose parameters at the different months, with the exceptions of triglycerides at the 9th month and of HDL at the 6th month of pregnancy. In subcutaneous tissue from women taking NRTI-based antiretroviral regimens, we observed a significant decrease of mtDNA content, compared with uninfected women not on antiviral treatment. Moreover, a significant correlation was noted between mtDNA content and HDL cholesterol and triglycerides.

Genetic characterization and antiretroviral resistance mutations among treatment-naive HIV-infected individuals in Jiaxing, China.

PubMed

Guo, Jinlei; Yan, Yong; Zhang, Jiafeng; Ji, Jimei; Ge, Zhijian; Ge, Rui; Zhang, Xiaofei; Wang, Henghui; Chen, Zhongwen; Luo, Jianyong

2017-03-14

The aim of this study was to characterize HIV-1 genotypes and antiretroviral resistance mutations among treatment-naive HIV-infected individuals in Jiaxing, China. The HIV-1 partial polymerase (pol) genes in 93 of the 99 plasma samples were successfully amplified and analyzed. Phylogenetic analysis revealed the existence of five HIV-1 genotypes, of which the most prevalent genotype was CRF01_AE (38.7%), followed by CRF07_BC (34.4%), CRF08_BC (16.1%), subtype B/B' (5.4%), and CRF55_01B (2.1%). Besides, three types of unique recombination forms (URFs) were also observed, including C/F2/A1, CRF01_AE/B, and CRF08_BC/CRF07_BC. Among 93 amplicons, 46.2% had drug resistance-associated mutations, including 23.7% for protease inhibitors (PIs) mutations, 1.1% for nucleoside reverse transcriptase inhibitors (NRTIs) mutations, and 20.4% for non-nucleoside reverse transcriptase inhibitors (NNRTIs) mutations. Six (6.5%) out of 93 treatment-naive subjects were identified to be resistant to one or more NNRTIs, while resistance to NRTIs or PIs was not observed. Our study showed the genetic diversity of HIV-1 strains circulating in Jiaxing and a relative high proportion of antiretroviral resistance mutations among treatment-naive patients, indicating a serious challenge for HIV prevention and treatment program.

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

The Track of Brain Activity during the Observation of TV Commercials with the High-Resolution EEG Technology

PubMed Central

Astolfi, Laura; Vecchiato, Giovanni; De Vico Fallani, Fabrizio; Salinari, Serenella; Cincotti, Febo; Aloise, Fabio; Mattia, Donatella; Marciani, Maria Grazia; Bianchi, Luigi; Soranzo, Ramon; Babiloni, Fabio

2009-01-01

We estimate cortical activity in normal subjects during the observation of TV commercials inserted within a movie by using high-resolution EEG techniques. The brain activity was evaluated in both time and frequency domains by solving the associate inverse problem of EEG with the use of realistic head models. In particular, we recover statistically significant information about cortical areas engaged by particular scenes inserted within the TV commercial proposed with respect to the brain activity estimated while watching a documentary. Results obtained in the population investigated suggest that the statistically significant brain activity during the observation of the TV commercial was mainly concentrated in frontoparietal cortical areas, roughly coincident with the Brodmann areas 8, 9, and 7, in the analyzed population. PMID:19584910

Impaired lipoprotein processing in HIV patients on antiretroviral therapy: aberrant high-density lipoprotein lipids, stability, and function.

PubMed

Gillard, Baiba K; Raya, Joe L; Ruiz-Esponda, Raul; Iyer, Dinakar; Coraza, Ivonne; Balasubramanyam, Ashok; Pownall, Henry J

2013-07-01

HIV patients on antiretroviral therapy (HIV/ART) exhibit a unique atherogenic dyslipidemic profile with hypertriglyceridemia (HTG) and low plasma concentrations of high-density lipoprotein (HDL) cholesterol. In the Heart Positive Study of HIV/ART patients, a hypolipidemic therapy of fenofibrate, niacin, diet, and exercise reduced HTG and plasma non-HDL cholesterol concentrations and raised plasma HDL cholesterol and adiponectin concentrations. We tested the hypothesis that HIV/ART HDL have abnormal structures and properties and are dysfunctional. Hypolipidemic therapy reduced the TG contents of low-density lipoprotein and HDL. At baseline, HIV/ART low-density lipoproteins were more triglyceride (TG)-rich and HDL were more TG- and cholesteryl ester-rich than the corresponding lipoproteins from normolipidemic (NL) subjects. Very-low-density lipoproteins, low-density lipoprotein, and HDL were larger than the corresponding lipoproteins from NL subjects; HIV/ART HDL were less stable than NL HDL. HDL-[(3)H]cholesteryl ester uptake by Huh7 hepatocytes was used to assess HDL functionality. HIV/ART plasma were found to contain significantly less competitive inhibition activity for hepatocyte HDL-cholesteryl ester uptake than NL plasma were found to contain (P<0.001). Compared with NL subjects, lipoproteins from HIV/ART patients are larger and more neutral lipid-rich, and their HDL are less stable and less receptor-competent. On the basis of this work and previous studies of lipase activity in HIV, we present a model in which plasma lipolytic activities or hepatic cholesteryl ester uptake are impaired in HIV/ART patients. These findings provide a rationale to determine whether the distinctive lipoprotein structure, properties, and function of HIV/ART HDL predict atherosclerosis as assessed by carotid artery intimal medial thickness.

Adipocytes Impair Efficacy of Antiretroviral Therapy

PubMed Central

Couturier, Jacob; Winchester, Lee C.; Suliburk, James W.; Wilkerson, Gregory K.; Podany, Anthony T.; Agarwal, Neeti; Chua, Corrine Ying Xuan; Nehete, Pramod N.; Nehete, Bharti P.; Grattoni, Alessandro; Sastry, K. Jagannadha; Fletcher, Courtney V.; Lake, Jordan E.; Balasubramanyan, Ashok; Lewis, Dorothy E.

2018-01-01

Adequate distribution of antiretroviral drugs to infected cells in HIV patients is critical for viral suppression. In humans and primates, HIV- and SIV-infected CD4 T cells in adipose tissues have recently been identified as reservoirs for infectious virus. To better characterize adipose tissue as a pharmacological sanctuary for HIV-infected cells, in vitro experiments were conducted to assess antiretroviral drug efficacy in the presence of adipocytes, and drug penetration in adipose tissue cells (stromal-vascular-fraction cells and mature adipocytes) was examined in treated humans and monkeys. Co-culture experiments between HIV-1-infected CD4 T cells and primary human adipocytes showed that adipocytes consistently reduced the antiviral efficacy of the nucleotide reverse transcriptase inhibitor tenofovir and its prodrug forms tenofovir disoproxil fumarate (TDF) and tenofovir alafenamide (TAF). In HIV-infected persons, LC-MS/MS analysis of intracellular lysates derived from adipose tissue stromal-vascular-fraction cells or mature adipocytes suggested that integrase inhibitors penetrate adipose tissue, whereas penetration of nucleoside/nucleotide reverse transcriptase inhibitors such as TDF, emtricitabine, abacavir, and lamivudine is restricted. The limited distribution and functions of key antiretroviral drugs within fat depots may contribute to viral persistence in adipose tissue. PMID:29630975

The impact of herbal remedies on adverse effects and quality of life in HIV-infected individuals on antiretroviral therapy

PubMed Central

Bepe, Nyasha; Madanhi, Nathan; Mudzviti, Tinashe; Gavi, Samuel; Maponga, Charles Chiedza; Morse, Gene D

2012-01-01

Introduction Use of herbal remedies among HIV-infected individuals in Africa increased in the past decade, mainly due to traditional beliefs and at times inconsistent access to antiretroviral drugs. In Zimbabwe, accessibility and availability of antiretroviral drugs has increased in recent years; however, the use of herbal remedies remains high. This study was conducted to determine the impact of concomitant use of herbal remedies with antiretroviral drugs on adverse events and on quality of life. Methodology A convenient sample of HIV positive patients at Parirenyatwa group of hospitals' Family Care Clinic (Harare, Zimbabwe) was enrolled. A questionnaire was used to collect data on the adverse event experiences of the patients using herbal remedies for their HIV, as well as the types of herbal remedy used. Quality of life index was measured using an HIV/AIDS targeted quality of life (HAT-QOL) tool developed by the World Health Organization. Results Abdominal pain (odds ratio = 2.7, p-value = 0.01) and rash (odds ratio = 2.5, p-value = 0.02) had significant associations with using herbal remedies during antiretroviral therapy. Improved quality of life index was not significantly associated with herbal remedy use during antiretroviral therapy. Conclusions There is evidence to suggest that some traditional herbal remedies used in Zimbabwe may increase incidence of certain types of adverse events when used in combination with antiretroviral drugs. Use of herbal drugs in combination with antiretroviral therapy does not significantly improve quality of life index in comparison to antiretroviral drug use only. PMID:21330740

Virgin coconut oil extract mitigates testicular-induced toxicity of alcohol use in antiretroviral therapy.

PubMed

Ogedengbe, O O; Naidu, E C S; Akang, E N; Offor, U; Onanuga, I O; Peter, A I; Jegede, A I; Azu, O O

2018-04-14

The consumption of alcohol by people living with HIV/AIDS is associated with a graver prognosis. Long-term use of antiretrovirals may have certain health challenges that may be aggravated by concomitant alcohol use. This study investigated virgin coconut oil (VCO) as an adjuvant to the deleterious effects of highly active antiretroviral therapy (HAART) and alcohol on the cyto-architecture and functioning of the testis. Forty adult male Sprague-Dawley rats, weighing 165~176 g, were divided into eight groups and treated according to protocol. Testicular histology, stereological parameters, seminal fluid, testosterone, luteinizing hormone, follicle-stimulating hormone, the antioxidants marker malondialdehyde (MDA), and antioxidant glutathione (GSH) were examined. The use of ethanol alone and ethanol + HAART showed extensive degeneration in the seminiferous epithelium, decreased semen quality, disorganized basement membrane and widened, hypocellular interstitium. GSH was significantly decreased in the ethanol alone treated group with no significant effect on testosterone, LH, and MDA levels. Adjuvant treatment with VCO at low dose (2.5 mL/kg/bw) improved sperm motility with a partial restoration of the histopathological alterations. High doses of VCO (5.0 mL/kg/bw) showed greater improvement with respect to sperm counts, increased FSH hormonal and GSH antioxidant levels, and a well-preserved testicular cyto-architecture. © 2018 American Society of Andrology and European Academy of Andrology.

Comparison of anti-retroviral therapy treatment strategies in prevention of mother-to-child transmission in a teaching hospital in Ethiopia.

PubMed

Kumela, Kabaye; Amenu, Demisew; Chelkeba, Legese

2015-01-01

More than 90% of Human immunodeficiency virus (HIV) infection in children is acquired due to mother-to-child transmission, which is spreading during pregnancy, delivery or breastfeeding. To determine the effectiveness of highly active antiretroviral and short course antiretroviral regimens in prevention of mother-to-child transmission of HIV and associated factors Jimma University Specialized Hospital (JUSH). A hospital based retrospective cohort study was conducted on HIV infected pregnant mothers who gave birth and had follow up at anti-retroviral therapy (ART) clinic for at least 6 months during a time period paired with their infants. The primary and secondary outcomes were rate of infant infection by HIV at 6 weeks and 6 months respectively. The Chi-square was used for the comparison of categorical data multivariate logistic regression model was used to identify the determinants of early mother-to-child transmission of HIV at 6 weeks. Cox proportional hazard model was used to analyze factors that affect the 6 month HIV free survival of infants born to HIV infected mothers. A total of 180 mother infant pairs were considered for the final analysis, 90(50%) mothers received single dose nevirapine (sdNVP) designated as regimen-3, 67 (37.2%) mothers were on different types of ARV regimens commonly AZT + 3TC + NVP (regimen-1), while the rest 23 (12.8%) mothers were on short course dual regimen AZT + 3TC + sdNVP (regimen-2). Early mother-to-child transmission rate at 6 weeks for regimens 1, 2 and 3 were 5.9% (4/67), 8.6% (2/23), and 15.5% (14/90) respectively. The late cumulative mother-to-child transmission rate of HIV at 6 months regardless of regimen type was 15.5% (28/180). Postnatal transmission at 6 months was 28.5% (8/28) of infected children. Factors that were found to be associated with high risk of early mother-to-child transmission of HIV include duration of ARV regimen shorter than 2 months during pregnancy (OR=4.3, 95%CI =1.38-13.46), base line CD4 less

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

PubMed Central

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

2015-01-01

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

Human papillomavirus prevalence, viral load and pre-cancerous lesions of the cervix in women initiating highly active antiretroviral therapy in South Africa: a cross-sectional study.

PubMed

Moodley, Jennifer R; Constant, Deborah; Hoffman, Margaret; Salimo, Anna; Allan, Bruce; Rybicki, Ed; Hitzeroth, Inga; Williamson, Anna-Lise

2009-08-07

Cervical cancer and infection with human immunodeficiency virus (HIV) are both important public health problems in South Africa (SA). The aim of this study was to determine the prevalence of cervical squamous intraepithelial lesions (SILs), high-risk human papillomavirus (HR-HPV), HPV viral load and HPV genotypes in HIV positive women initiating anti-retroviral (ARV) therapy. A cross-sectional survey was conducted at an anti-retroviral (ARV) treatment clinic in Cape Town, SA in 2007. Cervical specimens were taken for cytological analysis and HPV testing. The Digene Hybrid Capture 2 (HC2) test was used to detect HR-HPV. Relative light units (RLU) were used as a measure of HPV viral load. HPV types were determined using the Roche Linear Array HPV Genotyping test. Crude associations with abnormal cytology were tested and multiple logistic regression was used to determine independent risk factors for abnormal cytology. The median age of the 109 participants was 31 years, the median CD4 count was 125/mm3, 66.3% had an abnormal Pap smear, the HR-HPV prevalence was 78.9% (Digene), the median HPV viral load was 181.1 RLU (HC2 positive samples only) and 78.4% had multiple genotypes. Among women with abnormal smears the most prevalent HR-HPV types were HPV types 16, 58 and 51, all with a prevalence of 28.5%. On univariate analysis HR-HPV, multiple HPV types and HPV viral load were significantly associated with the presence of low and high-grade SILs (LSIL/HSIL). The multivariate logistic regression showed that HPV viral load was associated with an increased odds of LSIL/HSIL, odds ratio of 10.7 (95% CI 2.0 - 57.7) for those that were HC2 positive and had a viral load of 181.1 RLU. Women initiating ARVs have a high prevalence of abnormal Pap smears and HR-HPV. Our results underscore the need for locally relevant, rigorous screening protocols for

Physical Activity in Public Parks of High and Low Socioeconomic Status in Colombia Using Observational Methods.

PubMed

Camargo, Diana Marina; Ramírez, Paula Camila; Quiroga, Vanesa; Ríos, Paola; Férmino, Rogério César; Sarmiento, Olga L

2018-03-28

Public parks are an important resource for the promotion of physical activity (PA). This is the first study in Colombia and the fourth in Latin America to describe the characteristics of park users and their levels of PA using objective measures. A systematic observation assessed sex, age, and the level of PA of users of 10 parks in an intermediate-size city in Colombia, classified in low (5 parks) and high (5 parks) socioeconomic status (SES). A total of 10 daily observations were conducted, in 5 days of the week during 3 periods: morning, afternoon, and evening. In total, 16,671 observations were completed, recording 46,047 users. A higher number of users per park, per day, were recorded in high SES (1195) versus low SES (647). More men were observed in low-SES than high-SES parks (70.1% vs 54.2%), as well as more children were observed in low-SES than high-SES parks (30.1% vs 15.9%). Older adults in high-SES parks were more frequent (9.5% vs 5.2%). Moderate to vigorous PA was higher in low-SES parks (71.7% vs 63.2%). Low-SES parks need more green spaces, walk/bike trails, and areas for PA. All parks need new programs to increase the number of users and their PA level, considering sex, age group, and period of the week.

Access to antiretroviral therapy among HIV/AIDS patients in Chiang Mai province, Thailand

PubMed Central

Himakalasa, Woraluck; Grisurapong, Siriwan; Phuangsaichai, Sasipen

2013-01-01

The objective of this study is to investigate the access to antiretroviral treatment among human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS) patients in Chiang Mai province, Thailand. Access to antiretroviral treatment is defined in terms of availability, affordability, and acceptability. The data for the study were collected during the period of April 1, 2012–May 31, 2012 from a sample of 380 HIV/AIDS patients in eight hospitals who had received antiretroviral treatment for more than 6 months at the time of data collection. The results of the study show that for most patients, the average traveling time to access health care was acceptable, but the nearly half day waiting time caused them to be absent from their work. In particular, it took longer for patients in the rural and lower income groups to access the treatment than the other groups. Their travel times and food costs relating to the treatment were found to be relatively high and therefore these patients had a higher tendency to borrow or seek financial assistance from their relatives. However, due to improvements in the access to treatment, most patients were satisfied with the services they received. The results imply that policy should be implemented to raise the potential of subdistrict hospitals where access to antiretroviral treatment is available, with participating HIV/AIDS patients acting as volunteers in providing services and other forms of health promotion to new patients. Privacy issues could be reduced if the antiretroviral treatment was isolated from other health services. Additionally, efforts to educate HIV/AIDS patients and society at large should be made. PMID:23986652

Access to antiretroviral therapy among HIV/AIDS patients in Chiang Mai province, Thailand.

PubMed

Himakalasa, Woraluck; Grisurapong, Siriwan; Phuangsaichai, Sasipen

2013-01-01

The objective of this study is to investigate the access to antiretroviral treatment among human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS) patients in Chiang Mai province, Thailand. Access to antiretroviral treatment is defined in terms of availability, affordability, and acceptability. The data for the study were collected during the period of April 1, 2012-May 31, 2012 from a sample of 380 HIV/AIDS patients in eight hospitals who had received antiretroviral treatment for more than 6 months at the time of data collection. The results of the study show that for most patients, the average traveling time to access health care was acceptable, but the nearly half day waiting time caused them to be absent from their work. In particular, it took longer for patients in the rural and lower income groups to access the treatment than the other groups. Their travel times and food costs relating to the treatment were found to be relatively high and therefore these patients had a higher tendency to borrow or seek financial assistance from their relatives. However, due to improvements in the access to treatment, most patients were satisfied with the services they received. The results imply that policy should be implemented to raise the potential of subdistrict hospitals where access to antiretroviral treatment is available, with participating HIV/AIDS patients acting as volunteers in providing services and other forms of health promotion to new patients. Privacy issues could be reduced if the antiretroviral treatment was isolated from other health services. Additionally, efforts to educate HIV/AIDS patients and society at large should be made.

Surveillance of HIV antiretroviral drug resistance in treated individuals in England: 1998-2000.

PubMed

Scott, Paul; Arnold, Eve; Evans, Barry; Pozniak, Anton; Moyle, Graeme; Shahmenesh, Mohsen; White, David; Shirley, Jane; Cane, Patricia; Pillay, Deenan

2004-03-01

To establish a surveillance programme for HIV drug resistance within the UK covering the years from 1998 to 2000, following the introduction of triple combination antiretroviral therapy. Sentinel sites included large, medium sized and small clinical centres. Data were analysed until December 2000. Of nearly 300 samples tested, results from 91, 92 and 92 patients, respectively in 1998, 1999 and 2000, who were receiving HIV therapy with a viral load >2000 copies/mL, the majority had viruses with some degree of drug resistance. Overall, the presence of any resistance increased between 1998 and 1999, and fell again in 2000 (69% versus 88% versus 55%). However, major differences were observed between drug classes, such that non-nucleoside analogue reverse transcriptase inhibitor (NNRTI) resistance rose dramatically over the period studied. We show that this correlated with increased NNRTI prescribing. Furthermore, an overall increase in prevalence of viruses with resistance to one or more drugs within all three available classes was observed. A higher prevalence of drug resistance was observed in patients from smaller clinical centres. This is the first such sentinel surveillance dataset from the UK, and is unique in correlating these data with national antiretroviral prescribing patterns. Our findings are relevant to the increased transmission of HIV drug resistance observed over this period.

Changing rates and patterns of drug resistance mutations in antiretroviral-experienced HIV-infected patients.

PubMed

de Mendoza, Carmen; Garrido, Carolina; Corral, Angelica; Ramírez-Olivencia, German; Jiménez-Nacher, Inmaculada; Zahonero, Natalia; Gonzalez-Lahoz, Juan; Soriano, Vincent

2007-07-01

Surveillance of drug resistance mutations in antiretroviral-experienced HIV(+) patients may provide useful information regarding options available for rescue interventions. All resistance tests performed from 1999 to 2005 on antiretroviral-experienced individuals at one reference laboratory in Madrid were examined. Only mutations associated with drug resistance recorded at the September 2006 IAS-USA list were considered. A total of 2137 specimens were analyzed. Overall, 71.1% showed resistance mutations to at least one drug class, 56.1% to at least two, and 21% to all three drug families. Resistance mutations were 65% for NRTI, 44.4% for NNRTI, and 42.5% for PI. Mutations T215Y/F, M184V, and M41L were the most frequent for NRTI. Their rate significantly declined since 1999. K65R significantly increased since 1999 (0.8%) to 2003 (7.3%) but declined up to 3.3% in 2005. For NNRTI, K103N significantly increased from 21.8% in 1999 to 29.5% in 2005 (p < 0.01). The most frequent PI resistance mutations were L90M (24.3%), V82X (19.9%), M46I/L (19.5%), and I54V (17.1%). The presence of five or more was 58.8% in 1999 but declined to 22.2% in 2005. The rate of drug resistance mutations causing NRTI and PI resistance has steadily declined in antiretroviral-experienced patients since 1999. The availability of a large number and/or more convenient NRTI as well as the wide use of ritonavir-boosted PI could explain these observations. However, broad PI cross-resistance was seen in nearly 25% of antiretroviral-experienced patients in 2005. Therefore, there is a still need for new antiretrovirals with different resistance profiles.

Cohort Profile: HAART Observational Medical Evaluation and Research (HOMER) Cohort

PubMed Central

Patterson, Sophie; Cescon, Angela; Samji, Hasina; Cui, Zishan; Yip, Benita; Lepik, Katherine J; Moore, David; Lima, Viviane D; Nosyk, Bohdan; Harrigan, P Richard; Montaner, Julio SG; Shannon, Kate; Wood, Evan; Hogg, Robert S

2015-01-01

Since 1986, antiretroviral therapy (ART) has been available free of charge to individuals living with HIV in British Columbia (BC), Canada, through the BC Centre of Excellence in HIV/AIDS (BC-CfE) Drug Treatment Program (DTP). The Highly Active Antiretroviral Therapy (HAART) Observational Medical Evaluation and Research (HOMER) cohort was established in 1996 to maintain a prospective record of clinical measurements and medication profiles of a subset of DTP participants initiating HAART in BC. This unique cohort provides a comprehensive data source to investigate mortality, prognostic factors and treatment response among people living with HIV in BC from the inception of HAART. Currently over 5000 individuals are enrolled in the HOMER cohort. Data captured include socio-demographic characteristics (e.g. sex, age, ethnicity, health authority), clinical variables (e.g. CD4 cell count, plasma HIV viral load, AIDS-defining illness, hepatitis C co-infection, mortality) and treatment variables (e.g. HAART regimens, date of treatment initiation, treatment interruptions, adherence data, resistance testing). Research findings from the HOMER cohort have featured in numerous high-impact peer-reviewed journals. The HOMER cohort collaborates with other HIV cohorts on both national and international scales to answer complex HIV-specific research questions, and welcomes input from external investigators regarding potential research proposals or future collaborations. For further information please contact the principal investigator, Dr Robert Hogg (robert_hogg@sfu.ca). PMID:24639444

Broad, Intense Anti-Human Immunodeficiency Virus (HIV) Ex Vivo CD8+ Responses in HIV Type 1-Infected Patients: Comparison with Anti-Epstein-Barr Virus Responses and Changes during Antiretroviral Therapy

PubMed Central

Dalod, Marc; Dupuis, Marion; Deschemin, Jean-Christophe; Sicard, Didier; Salmon, Dominique; Delfraissy, Jean-Francois; Venet, Alain; Sinet, Martine; Guillet, Jean-Gerard

1999-01-01

The ex vivo antiviral CD8+ repertoires of 34 human immunodeficiency virus (HIV)-seropositive patients with various CD4+ T-cell counts and virus loads were analyzed by gamma interferon enzyme-linked immunospot assay, using peptides derived from HIV type 1 and Epstein-Barr virus (EBV). Most patients recognized many HIV peptides, with markedly high frequencies, in association with all the HLA class I molecules tested. We found no correlation between the intensity of anti-HIV CD8+ responses and the CD4+ counts or virus load. In contrast, the polyclonality of anti-HIV CD8+ responses was positively correlated with the CD4+ counts. The anti-EBV responses were significantly less intense than the anti-HIV responses and were positively correlated with the CD4+ counts. Longitudinal follow-up of several patients revealed the remarkable stability of the anti-HIV and anti-EBV CD8+ responses in two patients with stable CD4+ counts, while both antiviral responses decreased in two patients with obvious progression toward disease. Last, highly active antiretroviral therapy induced marked decreases in the number of anti-HIV CD8+ T cells, while the anti-EBV responses increased. These findings emphasize the magnitude of the ex vivo HIV-specific CD8+ responses at all stages of HIV infection and suggest that the CD8+ hyperlymphocytosis commonly observed in HIV infection is driven mainly by virus replication, through intense, continuous activation of HIV-specific CD8+ T cells until ultimate progression toward disease. Nevertheless, highly polyclonal anti-HIV CD8+ responses may be associated with a better clinical status. Our data also suggest that a decrease of anti-EBV CD8+ responses may occur with depletion of CD4+ T cells, but this could be restored by highly active antiretroviral treatment. PMID:10438796

Treatment and prevention of HIV infection with long-acting antiretrovirals.

PubMed

Benítez-Gutiérrez, Laura; Soriano, Vicente; Requena, Silvia; Arias, Ana; Barreiro, Pablo; de Mendoza, Carmen

2018-05-01

Current antiretroviral therapy allows to achieve and sustain maximal suppression of HIV replication in most treated patients. As result, the life expectancy of HIV-infected persons has improved dramatically and is nowadays similar to that of the HIV-negative population. However, oral antiretrovirals have to be taken daily and indefinitely to avoid resumption of HIV replication and selection of drug resistance. Unfortunately, drug adherence is often suboptimal and tends to decline over time. Areas covered: New drugs, formulations and delivery systems are being developed for extended-release of antiretrovirals. At this time, intramuscular cabotegravir and rilpivirine, dapivirine vaginal rings and tenofovir alafenamide subdermal implants are the products in more advanced stages of clinical development. Their pharmacokinetics/dynamics and safety/efficacy are reviewed. Expert commentary: In the absence of eradicative therapy for individuals with HIV infection and protective vaccines for persons at risk, long-term antiretroviral therapy is the best approach for preventing disease progression in patients and halting transmissions, either as result of 'treatment as prevention' for HIV carriers or 'pre-exposure prophylaxis' for uninfected individuals at risk. In all these scenarios, the advent of long-acting antiretrovirals will expand options for overcoming the challenge of suboptimal drug adherence and reduce the burden of HIV infection.

Dietary diversity and associated factors among HIV positive adults attending antiretroviral therapy clinics at Hiwot Fana and Dilchora Hospitals, eastern Ethiopia.

PubMed

Weldegebreal, Fitsum; Digaffe, Tesfaye; Mesfin, Frehiwot; Mitiku, Habtamu

2018-01-01

Nutritional care is considered a crucial component of comprehensive care for people living with HIV/AIDS (PLWHA), particularly in resource-limited settings where malnutrition and food insecurity are endemic problems, and low quality monotonous diets are the norm. The findings of this study provide baseline information on dietary diversity and related factors for health care providers so that they will be able to improve nutritional care and support activity. Therefore, the aim of this study was to assess dietary diversity and associated factors among HIV positive adults (18-65 years old) attending antiretroviral therapy (ART) clinics at Hiwot Fana and Dilchora Hospitals, eastern Ethiopia. An institution-based cross-sectional study was conducted from November 2015 to February 2016 at the ART clinics of Hiwot Fana and Dilchora Hospitals. Using a systematic random sampling technique, a total of 303 patients were selected from all adults attending the ART clinics. The data were collected with a 95% CI used to show association between dietary diversity and independent factors. A total of 303 adult HIV positive individuals on ART participated in the study and 62.4% were females. The largest numbers of participants (49.5%) were 30-40 years of age. Eighty-seven (28.7%) participants had low dietary diversity (≤4 food groups). Duration of anti-retroviral treatment was the factor significantly associated with dietary diversity: respondents with a duration of antiretroviral treatment of more than 2 years were almost two times more likely to have high dietary diversity compared with those with less than a year of antiretroviral treatment (adjusted odds ratio =0.490; 95% CI: 0.091, 0.978). Low dietary diversity was found to be a nutritional problem among HIV positive adults. Duration of antiretroviral treatment was the predictor of low dietary diversity. Therefore, appropriate dietary management of side effects of ART is important.

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.

Prevalence of antiretroviral drug resistance and resistance-associated mutations in antiretroviral therapy-naïve HIV-infected individuals from 40 United States cities.

PubMed

Ross, Lisa; Lim, Michael L; Liao, Qiming; Wine, Brian; Rodriguez, Allan E; Weinberg, Winkler; Shaefer, Mark

2007-01-01

Transmission of drug-resistant HIV strains to antiretroviral therapy (ART)-naïve subjects can negatively impact therapy response. As treatment strategies and utilization of antiretroviral drugs evolve, patterns of transmitted mutations may shift. Paired genotypic and phenotypic susceptibility data were retrospectively analyzed for 317 ART-naïve, HIV-infected subjects from 40 small and major metropolitan cities in the Northeastern, Midwestern, Southern, Southwestern, and Northwestern United States during 2003. Using current (January 2007) PhenoSense cutoffs, HIV-from 8% of subjects had reduced susceptibility to > or = 1 drug. By class, < 1% had reduced susceptibility to protease inhibitors (PIs), and 1% had reduced susceptibility to nucleoside reverse transcriptase inhibitors (NRTIs); reduced susceptibility to > or = 1 non-nucleoside reverse transcriptase inhibitor (NNRTIs) was seen in 7% of subjects, with 4% of all subjects having reduced susceptibility to all NNRTIs. IAS-USA-defined NRTI, NNRTI, and/or major PI HIV-drug resistance-associated mutations were detected for 0% of the subjects. HIV risk factors included homosexual contact (74%), heterosexual contact (28%), and injectable drug use/transfusion/other (7%). Reduced susceptibility to > or = 1 drug was significantly higher (p = .034) for white subjects than African Americans and Hispanics/others. The high prevalence of drug resistance in these ART-naïve subjects suggests that transmitted resistance is occurring widely within the United States. HIV genotyping and/or phenotyping for antiretroviral-naïve patients seeking treatment should be considered, especially if the therapy will include an NNRTI.

HIV Treatment and Prevention: An Overview of Recommendations From the 2016 IAS–USA Antiretroviral Guidelines Panel

PubMed Central

Volberding, Paul A.

2017-01-01

Updated recommendations from the IAS–USA Antiretroviral Guidelines Panel on antiretroviral therapy for the treatment and prevention of HIV infection in adults were published in the Journal of the American Medical Association in 2016. The updated, evidence-based recommendations address when to initiate antiretroviral therapy, recommended initial antiretroviral regimens, including integrase strand transfer inhibitor (InSTI)-based regimens, recommended regimens for persons in whom an InSTI is not an option, and special treatment considerations. The interface between antiretroviral therapy and opportunistic infections, when and how to switch antiretroviral therapy, laboratory monitoring, engagement in care, adherence to antiretroviral therapy, and use of antiretroviral therapy as HIV prevention are also discussed, as well as future directions in HIV treatment. This article summarizes an IAS–USA continuing education webinar presented by Paul A. Volberding, MD, in August 2016. PMID:28402930

Improving antiretroviral therapy scale-up and effectiveness through service integration and decentralization.

PubMed

Suthar, Amitabh B; Rutherford, George W; Horvath, Tara; Doherty, Meg C; Negussie, Eyerusalem K

2014-03-01

Current service delivery systems do not reach all people in need of antiretroviral therapy (ART). In order to inform the operational and service delivery section of the WHO 2013 consolidated antiretroviral guidelines, our objective was to summarize systematic reviews on integrating ART delivery into maternal, newborn, and child health (MNCH) care settings in countries with generalized epidemics, tuberculosis (TB) treatment settings in which the burden of HIV and TB is high, and settings providing opiate substitution therapy (OST); and decentralizing ART into primary health facilities and communities. A summary of systematic reviews. The reviewers searched PubMed, Embase, PsycINFO, Web of Science, CENTRAL, and the WHO Index Medicus databases. Randomized controlled trials and observational cohort studies were included if they compared ART coverage, retention in HIV care, and/or mortality in MNCH, TB, or OST facilities providing ART with MNCH, TB, or OST facilities providing ART services separately; or primary health facilities or communities providing ART with hospitals providing ART. The reviewers identified 28 studies on integration and decentralization. Antiretroviral therapy integration into MNCH facilities improved ART coverage (relative risk [RR] 1.37, 95% confidence interval [CI] 1.05-1.79) and led to comparable retention in care. ART integration into TB treatment settings improved ART coverage (RR 1.83, 95% CI 1.48-2.23) and led to a nonsignificant reduction in mortality (RR 0.55, 95% CI 0.29-1.05). The limited data on ART integration into OST services indicated comparable rates of ART coverage, retention, and mortality. Partial decentralization into primary health facilities improved retention (RR 1.05, 95% CI 1.01-1.09) and reduced mortality (RR 0.34, 95% CI 0.13-0.87). Full decentralization improved retention (RR 1.12, 95% CI 1.08-1.17) and led to comparable mortality. Community-based ART led to comparable rates of retention and mortality. Integrating ART

Adipocytes impair efficacy of antiretroviral therapy.

PubMed

Couturier, Jacob; Winchester, Lee C; Suliburk, James W; Wilkerson, Gregory K; Podany, Anthony T; Agarwal, Neeti; Xuan Chua, Corrine Ying; Nehete, Pramod N; Nehete, Bharti P; Grattoni, Alessandro; Sastry, K Jagannadha; Fletcher, Courtney V; Lake, Jordan E; Balasubramanyam, Ashok; Lewis, Dorothy E

2018-06-01

Adequate distribution of antiretroviral drugs to infected cells in HIV patients is critical for viral suppression. In humans and primates, HIV- and SIV-infected CD4 T cells in adipose tissues have recently been identified as reservoirs for infectious virus. To better characterize adipose tissue as a pharmacological sanctuary for HIV-infected cells, in vitro experiments were conducted to assess antiretroviral drug efficacy in the presence of adipocytes, and drug penetration in adipose tissue cells (stromal-vascular-fraction cells and mature adipocytes) was examined in treated humans and monkeys. Co-culture experiments between HIV-1-infected CD4 T cells and primary human adipocytes showed that adipocytes consistently reduced the antiviral efficacy of the nucleotide reverse transcriptase inhibitor tenofovir and its prodrug forms tenofovir disoproxil fumarate (TDF) and tenofovir alafenamide (TAF). In HIV-infected persons, LC-MS/MS analysis of intracellular lysates derived from adipose tissue stromal-vascular-fraction cells or mature adipocytes suggested that integrase inhibitors penetrate adipose tissue, whereas penetration of nucleoside/nucleotide reverse transcriptase inhibitors such as TDF, emtricitabine, abacavir, and lamivudine is restricted. The limited distribution and functions of key antiretroviral drugs within fat depots may contribute to viral persistence in adipose tissue. Copyright © 2018 Elsevier B.V. All rights reserved.

Emerging Trends of HIV Drug Resistance in Chinese HIV-Infected Patients Receiving First-Line Highly Active Antiretroviral Therapy: A Systematic Review and Meta-Analysis

PubMed Central

Liu, Huixin; Ma, Ye; Su, Yingying; Smith, M. Kumi; Liu, Ying; Jin, Yantao; Gu, Hongqiu; Wu, Jing; Zhu, Lin; Wang, Ning

2014-01-01

Background. Highly active antiretroviral therapy (HAART) has led to a dramatic decrease in AIDS-related morbidity and mortality through sustained suppression of human immunodeficiency virus (HIV) replication and reconstitution of the immune response. Settings like China that experienced rapid HAART rollout and relatively limited drug selection face considerable challenges in controlling HIV drug resistance (DR). Methods. We conducted a systematic review and meta-analysis to describe trends in emergent HIV DR to first-line HAART among Chinese HIV-infected patients, as reflected in the point prevalence of HIV DR at key points and fixed intervals after treatment initiation, using data from cohort studies and cross-sectional studies respectively. Results. Pooled prevalence of HIV DR from longitudinal cohorts studies was 10.79% (95% confidence interval [CI], 5.85%–19.07%) after 12 months of HAART and 80.58% (95% CI, 76.6%–84.02%) after 72 months of HAART. The HIV DR prevalence from cross-sectional studies was measured in treatment intervals; during the 0–12-month HAART treatment interval, the pooled prevalence of HIV DR was 11.1% (95% CI, 7.49%–16.14%), which increased to 22.92% at 61–72 months (95% CI, 9.45%–45.86%). Stratified analyses showed that patients receiving a didanosine-based regimen had higher HIV DR prevalence than those not taking didanosine (15.82% vs 4.97%). Patients infected through former plasma donation and those receiving AIDS treatment at village clinics had higher HIV DR prevalence than those infected through sexual transmission or treated at a county-level hospital. Conclusions. Our findings indicate higher prevalence of HIV DR for patients with longer cumulative HAART exposure, highlighting important subgroups for future HIV DR surveillance and control. PMID:25053721

A prospective study of endothelial activation biomarkers, including plasma angiopoietin-1 and angiopoietin-2, in Kenyan women initiating antiretroviral therapy.

PubMed

Graham, Susan M; Rajwans, Nimerta; Tapia, Kenneth A; Jaoko, Walter; Estambale, Benson B A; McClelland, R Scott; Overbaugh, Julie; Liles, W Conrad

2013-06-04

HIV-1-related inflammation is associated with increased levels of biomarkers of vascular adhesion and endothelial activation, and may increase production of the inflammatory protein angiopoietin-2 (ANG-2), an adverse prognostic biomarker in severe systemic infection. We hypothesized that antiretroviral therapy (ART) initiation would decrease endothelial activation, reducing plasma levels of ANG-2. Antiretroviral-naïve Kenyan women with advanced HIV infection were followed prospectively. Endothelial activation biomarkers including soluble intercellular adhesion molecule-1 (ICAM-1), vascular adhesion molecule-1 (VCAM-1), and E-selectin, and plasma ANG-2 and angiopoietin-1 (ANG-1) were tested in stored plasma samples from 0, 6, and 12 months after ART initiation. We used Wilcoxon matched-pairs signed rank tests to compare endothelial activation biomarkers across time-points, generalized estimating equations to analyze associations with change in log10-transformed biomarkers after ART initiation, and Cox proportional-hazards regression to analyze associations with mortality. The 102 HIV-1-seropositive women studied had advanced infection (median CD4 count, 124 cells/μL). Soluble ICAM-1 and plasma ANG-2 levels decreased at both time-points after ART initiation, with concomitant increases in the beneficial protein ANG-1. Higher ANG-2 levels after ART initiation were associated with higher plasma HIV-1 RNA, oral contraceptive pill use, pregnancy, severe malnutrition, and tuberculosis. Baseline ANG-2 levels were higher among five women who died after ART initiation than among women who did not (median 2.85 ng/mL [inter-quartile range (IQR) 2.47-5.74 ng/mL] versus median 1.32 ng/mL [IQR 0.35-2.18 ng/mL], p = 0.01). Both soluble ICAM-1 and plasma ANG-2 levels predicted mortality after ART initiation. Biomarkers of endothelial activation decreased after ART initiation in women with advanced HIV-1 infection. Changes in plasma ANG-2 were associated with HIV-1 RNA

Antiretroviral Therapy in Simian Immunodeficiency Virus-Infected Sooty Mangabeys: Implications for AIDS Pathogenesis

PubMed Central

Calascibetta, Francesca; Micci, Luca; Carnathan, Diane; Lawson, Benton; Vanderford, Thomas H.; Bosinger, Steven E.; Easley, Kirk; Chahroudi, Ann; Mackel, Joseph; Keele, Brandon F.; Long, Samuel; Lifson, Jeffrey; Paiardini, Mirko

2016-01-01

ABSTRACT Simian immunodeficiency virus (SIV)-infected sooty mangabeys (SMs) do not develop AIDS despite high levels of viremia. Key factors involved in the benign course of SIV infection in SMs are the absence of chronic immune activation and low levels of infection of CD4+ central memory (TCM) and stem cell memory (TSCM) T cells. To better understand the role of virus replication in determining the main features of SIV infection in SMs, we treated 12 SMs with a potent antiretroviral therapy (ART) regimen for 2 to 12 months. We observed that ART suppressed viremia to <60 copies/ml of plasma in 10 of 12 animals and induced a variable decrease in the level of cell-associated SIV DNA in peripheral blood (average changes of 0.9-, 1.1-, 1.5-, and 3.7-fold for CD4+ transitional memory [TTM], TCM, effector memory [TEM], and TSCM cells, respectively). ART-treated SIV-infected SMs showed (i) increased percentages of circulating CD4+ TCM cells, (ii) increased levels of CD4+ T cells in the rectal mucosa, and (iii) significant declines in the frequencies of HLA-DR+ CD8+ T cells in the blood and rectal mucosa. In addition, we observed that ART interruption resulted in rapid viral rebound in all SIV-infected SMs, indicating that the virus reservoir persists for at least a year under ART despite lower infection levels of CD4+ TCM and TSCM cells than those seen in pathogenic SIV infections of macaques. Overall, these data indicate that ART induces specific immunological changes in SIV-infected SMs, thus suggesting that virus replication affects immune function even in the context of this clinically benign infection. IMPORTANCE Studies of natural, nonpathogenic simian immunodeficiency virus (SIV) infection of African monkeys have provided important insights into the mechanisms responsible for the progression to AIDS during pathogenic human immunodeficiency virus (HIV) infection of humans and SIV infection of Asian macaques. In this study, for the first time, we treated SIV

Effects of fish oil on lipid profile and other metabolic outcomes in HIV-infected patients on antiretroviral therapy: a randomized placebo-controlled trial.

PubMed

Oliveira, Julicristie M; Rondó, Patrícia H C; Yudkin, John S; Souza, José M P; Pereira, Tatiane N; Catalani, Andrea W; Picone, Camila M; Segurado, Aluisio A C

2014-02-01

Although antiretroviral therapy has revolutionized the care of HIV-infected patients, it has been associated with metabolic abnormalities. Hence, this study was planned to investigate the effects of fish oil on lipid profile, insulin resistance, and body fat distribution in HIV-infected Brazilian patients on antiretroviral therapy, considering that marine omega-3 fatty acids seem to improve features of the metabolic syndrome. We conducted a randomized, parallel, placebo-controlled trial that assessed the effects of 3 g fish oil/day (540 mg of eicosapentaenoic acid plus 360 mg of docosahexaenoic acid) or 3 g soy oil/day (placebo) on 83 HIV-infected Brazilian men and non-pregnant women on antiretroviral therapy. No statistically significant relationships between fish oil supplementation and longitudinal changes in triglyceride (p = 0.335), low-density lipoprotein cholesterol (p = 0.078), high-density lipoprotein cholesterol (p = 0.383), total cholesterol (p = 0.072), apolipoprotein B (p = 0.522), apolipoprotein A1 (p = 0.420), low-density lipoprotein cholesterol/apolipoprotein B ratio (p = 0.107), homeostasis model assessment for insulin resistance index (p = 0.387), body mass index (p = 0.068), waist circumference (p = 0.128), and waist/hip ratio (p = 0.359) were observed. A low dose of fish oil did not alter lipid profile, insulin resistance, and body fat distribution in HIV-infected patients on antiretroviral therapy.

Trends in drug resistance mutations in antiretroviral-naïve intravenous drug users of Rio de Janeiro.

PubMed

Maia Teixeira, Sylvia Lopes; Bastos, Francisco Inácio; Hacker, Mariana A; Guimarães, Monick Lindenmeyer; Morgado, Mariza Gonçalves

2006-06-01

DNA sequencing of a pol gene fragment from drug-naive injecting drug users samples obtained at two time points of the Brazilian AIDS epidemic (Pre-HAART era: 1994 to early 1997, n = 27; post-HAART era: 1999-2001, n = 38) was undertaken to assess HIV-1 antiretroviral drug resistance mutations and subtyping profiles. Genotypic analysis revealed the presence of PR primary L90M, D30N, M46I, and V82A mutations in 7.9% of the post-HAART group, and a high frequency of secondary mutations (84.2%). Nucleoside RT-associated mutations were observed in 13.2%. In the pre-HAART group, a higher frequency of RT mutations was observed (22.2%) and no PR primary mutations were found, in agreement with the introduction of protease inhibitors (PIs) in therapy during the same period. The identification of 7.9% of drug-naive injecting drug users already bearing RT/PR primary resistance mutations in the post-HAART era group constitutes a major concern in terms of dissemination of drug resistant viruses. The resistance mutations profile of the individuals may reflect the context of antiretroviral treatment in Brazil at the sample collection periods (1994-1997 and 1999-2001). In spite of the differences observed in the drug resistance profiles, similar frequencies of subtype B (63.0 vs. 73.7%), F (22.2 vs. 10.5%), and recombinant B/F (14.8 vs. 15.8%) viruses were found, respectively, in the pre- and post-HAART groups.

Frequency of Antiretroviral Resistance Mutations among Infants Exposed to Single-Dose Nevirapine and Short Course Maternal Antiretroviral Regimens: ACTG A5207.

PubMed

Hitti, Jane; Halvas, Elias K; Zheng, Lu; Panousis, Constantinos G; Kabanda, Joseph; Taulo, Frank; Kumarasamy, Nagalingeswaran; Pape, Jean William; Lalloo, Umesh; Sprenger, Heather; Klingman, Karin L; Chan, Ellen S; McMahon, Deborah; Mellors, John W

2014-11-01

Intrapartum single-dose nevirapine (sdNVP) reduces HIV-1 perinatal transmission but selects NVP resistance among mothers and infants. We evaluated the frequency of antiretroviral resistance among infants with intrauterine HIV-1 infection exposed to sdNVP and maternal antenatal or breastfeeding antiretroviral therapy. This analysis included 429 infants from sub-Saharan Africa, India and Haiti whose 422 mothers received sdNVP plus maternal study treatment. At entry mothers had CD4>250/μL and were ART-naïve except for antenatal ZDV per local standard of care. Maternal study treatment started intrapartum and included ZDV/3TC, TDF/FTC or LPV/r for 7 or 21 days in a randomized factorial design. Infants received sdNVP study treatment and ZDV if local standard of care. Infant HIV RNA or DNA PCR and samples for genotype were obtained at birth and weeks 2, 4 and 12; infants who ever breast-fed were also tested at weeks 16, 24, 48 and 96. Samples from HIV-1-infected infants were tested for drug resistance by population genotype (ViroSeq). NVP or NRTI resistance mutations were assessed using the IAS-USA mutation list. Perinatal HIV-1 transmission occurred in 17 (4.0%) infants including 12 intrauterine infections. Resistance mutations were detected among 5 (42%) intrauterine-infected infants; of these, 3 had mutations conferring resistance to NVP alone, 1 had resistance to NRTI alone, and 1 had dual-class resistance mutations. Among the 2 infants with NRTI mutations, one (K70R) was likely maternally transmitted and one (K65R) occurred in the context of breastfeeding exposure to maternal antiretroviral therapy. Infants with intrauterine HIV infection are at risk of acquiring resistance mutations from exposure to maternal antiretroviral medications intrapartum and/or during breastfeeding. New approaches are needed to lower the risk of antiretroviral resistance in these infants.

Factors affecting high-density lipoprotein cholesterol in HIV-infected patients on nevirapine-based antiretroviral therapy

PubMed Central

Padmapriyadarsini, C.; Ramesh, K.; Sekar, L.; Ramachandran, Geetha; Reddy, Devaraj; Narendran, G.; Sekar, S.; Chandrasekar, C.; Anbarasu, D.; Wanke, Christine; Swaminathan, Soumya

2017-01-01

Background & objectives: Cardiovascular disease (CVD) risk with low high-density lipoprotein cholesterol (HDL-C) and high triglycerides is common in the general population in India. As nevirapine (NVP)-based antiretroviral therapy (ART) tends to increase HDL-C, gene polymorphisms associated with HDL-C metabolism in HIV-infected adults on stable NVP-based ART were studied. Methods: A cross-sectional study was conducted between January 2013 and July 2014 among adults receiving NVP-based ART for 12-15 months. Blood lipids were estimated and gene polymorphisms in apolipoprotein C3 (APOC3), cholesteryl ester transfer protein (CETP) and lipoprotein lipase (LPL) genes were analyzed by real-time polymerase chain reaction. Framingham's 10-yr CVD risk score was estimated. Logistic regression was done to show factors related to low HDL-C levels. Results: Of the 300 patients included (mean age: 38.6±8.7 yr; mean CD4 count 449±210 cell/μl), total cholesterol (TC) >200 mg/dl was observed in 116 (39%) patients. Thirty nine per cent males and 47 per cent females had HDL-C levels below normal while 32 per cent males and 37 per cent females had TC/HDL ratio of 4.5 and 4.0, respectively. Body mass index [adjusted odds ratio (aOR)=1.70, 95% confidence interval (CI) 1.01-2.84, P=0.04] and viral load (aOR=3.39, 95% CI: 1.52-7.52, P=0.003) were negatively associated with serum HDL-C levels. The 10-yr risk score of developing CVD was 11-20 per cent in 3 per cent patients. Allelic variants of APOC3 showed a trend towards low HDL-C. Interpretation & conclusions: High-risk lipid profiles for atherosclerosis and cardiovascular disease were common among HIV-infected individuals, even after 12 months of NVP-based ART. Targeted interventions to address these factors should be recommended in the national ART programmes. PMID:28948955

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

PubMed Central

2014-01-01

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

The Association between HIV Infection, Antiretroviral Therapy and Cervical Squamous Intraepithelial Lesions in South Western Nigerian Women

PubMed Central

Ezechi, Oliver Chukwujekwu; Pettersson, Karen Odberg; Okolo, Clement Abu; Ujah, Innocent Achaya O.; Ostergren, Per Olof

2014-01-01

Introduction Findings from studies that evaluated the effect of antiretroviral drug use on the development of cervical squamous intraepithelial lesion differed in their conclusions. This study investigated the association between HIV infection, antiretroviral drug use and cervical squamous intraepithelial lesion in a high HIV and cervical cancer burden setting- Nigeria. Methods A cross sectional study among 1140 women of known HIV status enrolled in a randomised study to determine the test characteristics of visual inspection in detecting cytology diagnosed squamous intraepithelial lesion. Multivariate analysis was used to determine the association between HIV infection, antiretroviral drug use and the twin outcome variables of cervical squamous intraepithelial lesion (SIL) and High grade squamous intraepithelial lesion (HSIL) while controlling for confounders. Results Prevalence of cervical squamous intraepithelial lesion was 8.5%, with a higher prevalence of 14.3% in HIV positive compared to 3.3% in HIV negative women (aOR: 5.4; 95% CI: 2.9–8.8). Not using antiretroviral drugs was found to be associated with an increased risk of SIL (aOR: 2.1; 95% CI: 1.4–3.5) and HSIL (aOR: 2.6; 95% CI: 1.1–6.4). Participants who had a CD4 cell count <200 cells/mm3, were also found to be at increased risk for SIL (aOR: 1.9; 95% CI: 1.1–5.9) and HSIL (aOR: 5.7; 95% CI: 1.1–7.2). Conclusion HIV infection and severe immunosuppression were found to be associated with increased risk of cervical squamous intraepithelial lesion but not viral load. For the first time, in the West African sub-region with specific HIV type and strains, we established the protective effect of antiretroviral drug use against the development of SIL. Integration of cervical cancer screening programme into HIV services and early initiation of antiretroviral drug in HIV positive women especially those with severe immune-suppression could therefore prove to be useful in preventing and controlling

Adverse effects of antiretroviral therapy for HIV infection.

PubMed

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

2004-01-20

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

Adverse effects of antiretroviral therapy for HIV infection

PubMed Central

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

2004-01-01

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

Prevalence and predictors of anaemia in patients with HIV infection at the initiation of combined antiretroviral therapy in Xinjiang, China.

PubMed

Mijiti, Peierdun; Yuexin, Zhang; Min, Liu; Wubuli, Maimaitili; Kejun, Pan; Upur, Halmurat

2015-03-01

We retrospectively analysed routinely collected baseline data of 2252 patients with HIV infection registered in the National Free Antiretroviral Treatment Program in Xinjiang province, China, from 2006 to 2011 to estimate the prevalence and predictors of anaemia at the initiation of combined antiretroviral therapy. Anaemia was diagnosed using the criteria set forth by the World Health Organisation, and univariate and multivariate logistic regression analyses were performed to determine its predictors. The prevalences of mild, moderate, and severe anaemia at the initiation of combined antiretroviral therapy were 19.2%, 17.1%, and 2.6%, respectively. Overall, 38.9% of the patients were anaemic at the initiation of combined antiretroviral therapy. The multivariate logistic regression analysis indicated that Uyghur ethnicity, female gender, lower CD4 count, lower body mass index value, self-reported tuberculosis infection, and oral candidiasis were associated with a higher prevalence of anaemia, whereas higher serum alanine aminotransferase level was associated with a lower prevalence of anaemia. The results suggest that the overall prevalence of anaemia at the initiation of combined antiretroviral therapy in patients with HIV infection is high in Xinjiang, China, but severe anaemia is uncommon. Patients in China should be routinely checked for anaemia prior to combined antiretroviral therapy initiation, and healthcare providers should carefully select the appropriate first-line combined antiretroviral therapy regimens for anaemic patients. © The Author(s) 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

Simultaneous determination of antiretroviral drugs in human hair with liquid chromatography-electrospray ionization-tandem mass spectrometry.

PubMed

Wu, Yan; Yang, Jin; Duan, Cailing; Chu, Liuxi; Chen, Shenghuo; Qiao, Shan; Li, Xiaoming; Deng, Huihua

2018-04-15

The determination of the concentrations of antiretroviral drugs in hair is believed to be an important means for the assessment of the long-term adherence to highly active antiretroviral therapy. At present, the combination of tenofovir, lamivudine and nevirapine is widely used in China. However, there was no research reporting simultaneous determination of the three drugs in hair. The present study aimed to develop a sensitive method for simultaneous determination of the three drugs in 2-mg and 10-mg natural hair (Method 1 and Method 2). Hair samples were incubated in methanol at 37 °C for 16 h after being rinsed with methanol twice. The analysis was performed on high performance liquid chromatography tandem mass spectrometry with electronic spray ionization in positive mode and multiple reactions monitoring. Method 1 and Method 2 showed the limits of detection at 160 and 30 pg/mg for tenofovir, at 5 and 6 pg/mg for lamivudine and at 15 and 3 pg/mg for nevirapine. The two methods showed good linearity with the square of correlation coefficient >0.99 at the ranges of 416-5000 and 77-5000 pg/mg for tenofovir, 12-5000 and 15-5000 pg/mg for lamivudine and 39-50,000 and 6-50,000 pg/mg for nevirapine. They gave intra-day and inter-day coefficient of variation <15% and the recoveries ranging from 80.6 to 122.3% and from 83.1 to 114.4%. Method 2 showed LOD and LOQ better than Method 1 for tenofovir and nevirapine and matched Method 1 for lamivudine, but there was high consistency between them in the determination of the three drugs in hair. The population analysis with Method 2 revealed that the concentrations in hair were decreased with the distance of hair segment away from the scalp for the three antiretroviral drugs. Copyright © 2018 Elsevier B.V. All rights reserved.

Effects of HIV, antiretroviral therapy and prebiotics on the active fraction of the gut microbiota.

PubMed

Deusch, Simon; Serrano-Villar, Sergio; Rojo, David; Martínez-Martínez, Mónica; Bargiela, Rafael; Vázquez-Castellanos, Jorge F; Sainz, Talía; Barbas, Coral; Moya, Andrés; Moreno, Santiago; Gosalbes, María J; Estrada, Vicente; Seifert, Jana; Ferrer, Manuel

2018-06-19

In a recent blinded randomized study, we found that in HIV-infected individuals a short supplementation with prebiotics (scGOS/lcFOS/glutamine) ameliorates dysbiosis of total gut bacteria, particularly among viremic untreated patients. Our study goal was to determine the fraction of the microbiota that becomes active during the intervention and that could provide additional functional information. A total of six healthy individuals, and 16 HIV-infected patients comprising viremic untreated patients (n = 5) and antiretroviral therapy-treated patients that are further divided into immunological responders (n = 7) and immunological nonresponders (n = 4) completed the 6-week course of prebiotic treatment, including six patients receiving a placebo. Alpha and beta diversity of potentially active and total gut microbiota was evaluated using shotgun proteomics and 16S rRNA gene sequencing. HIV infection decreased dormancy and increased alpha diversity of active bacteria in comparison with the healthy controls, whose richness was not further influenced by the prebiotic intervention. The effect of the prebiotics was most evident at the beta-diversity of active bacteria, particularly within viremic untreated patients. We found that the prebiotics did not only ameliorate dysbiosis of total bacteria in viremic untreated patients but also increased the abundance of active bacteria with strong immunomodulatory properties and amino acids metabolism, namely Bifidobacteriaceae, at similar levels to those in healthy individuals. This effect was attenuated in ART-treated individuals. The effect of prebiotics was greater among ART-naive HIV-infected individuals than in ART-treated patients and healthy controls. This highlights the importance of therapies aimed at manipulating the microbiome in this group of patients.

The antiretrovirals in pregnancy registry: a fifteenth anniversary celebration.

PubMed

Tilson, Hugh H; Doi, Peggy A; Covington, Deborah L; Parker, Artist; Shields, Kristine; White, Alice

2007-02-01

The year 2007 marks the fifteenth anniversary year of the founding of a landmark effort in drug safety risk management, the formation of the first monitoring effort of an antiretroviral (ARV) drug in pregnancy which has become the Antiretrovirals in Pregnancy Registry, the APR. This multicompany, multi-national voluntary collaborative registry monitors pregnancy exposure to a class of highly important drugs for any indication of an increase in the postexposure incidence of birth defects in the offspring of these pregnancies. To recognize the anniversary, the Steering Committee of the APR has commissioned this review of the contributions and lessons learned over the past decade and a half and, in the spirit of continuous process improvement, has committed to apply these lessons for the next fifteen years. This retrospective examines the antecedents to this registry and the context in which the APR was formed; the early efforts to establish technical and organizational procedures and policies; the evolving experiences with enrollment and follow-up, patient and participant protections, information management and oversight; public and regulatory dissemination; and of course, the accomplishments and lessons learned. Obstetricians & Gynecologists, Family Physicians. After completion of this article, the reader should be able to explain the value of a drug registry in determining safety risk management; summarize that the Antiretroviral (ARV) drugs in Pregnancy Registry (APR) is a very successful multinational, multicompany collaborative effort that has been in place for 15 years; and state that it has been an ideal public interest effort dealing with the devastating pandemic of human immunodeficiency viral disease.

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

PubMed

Álvaro-Meca, Alejandro; Jensen, Julia; Micheloud, Dariela; Díaz, Asunción; Gurbindo, Dolores; Resino, Salvador

2013-03-04

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. 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. 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, both non-ICM and ICM rates

[New and "old" antiretroviral drugs in Pediatrics: new doses, formulations and associations].

PubMed

Villarroel B, Julia

2010-10-01

Of the 25 antiretroviral drugs available in the market, only 16 are allowed for prescription in the pediatric patients. The antiretroviral, pertaining to the first three families, used for two decades, remain valid and are important components of antiretroviral therapy in naive children. We describe doses, presentations and current associations for these drugs in children, and also discuss new co-formulations that will reduce the number of doses, improve tolerance and therefore achieve better adherence of pediatric patients.

Predictors of mortality among HIV infected patients taking antiretroviral treatment in Ethiopia: a retrospective cohort study

PubMed Central

2012-01-01

Background Studies indicate that there is high early mortality among patients starting antiretroviral treatment in sub-Saharan Africa. However, there is paucity of evidence on long term survival of patients on anti-retroviral treatment in the region. The objective of this study is to examine mortality and its predictors among a cohort of HIV infected patients on anti-retroviral treatment retrospectively followed for five years. Methods A retrospective cohort study was conducted among HIV infected patients on ART in eastern Ethiopia. Cox regression and Kaplan-Meier analyses were performed to investigate factors that influence time to death and survival over time. Result A total of 1540 study participants were included in the study. From the registered patients in the cohort, the outcome of patients as active, deceased, lost to follow up and transfer out was 1005 (67.2%), 86 (5.9%), 210 (14.0%) and 192 (12.8%) respectively. The overall mortality rate provides an incidence density of 2.03 deaths per 100 person years (95% CI 1.64 - 2.50). Out of a total of 86 deaths over 60 month period; 63 (73.3%) died during the first 12 months, 10 (11.6%) during the second year, and 10 (11.6%) in the third year of follow up. In multivariate analysis, the independent predictors for mortality were loss of more 10% weight loss, bedridden functional status at baseline, ≤ 200 CD4 cell count/ml, and advanced WHO stage patients. Conclusion A lower level of mortality was detected among the cohort of patients on antiretroviral treatment in eastern Ethiopia. Previous history of weight loss, bedridden functional status at baseline, low CD4 cell count and advanced WHO status patients had a higher risk of death. Early initiation of ART, provision of nutritional support and strengthening of the food by prescription initiative, and counseling of patients for early presentation to treatment is recommended. PMID:22606951

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

High-resolution observations of active region moss and its dynamics

DOE Office of Scientific and Technical Information (OSTI.GOV)

Morton, R. J.; McLaughlin, J. A., E-mail: richard.morton@northumbria.ac.uk

2014-07-10

The High Resolution Coronal Imager has provided the sharpest view of the EUV corona to date. In this paper, we exploit its impressive resolving power to provide the first analysis of the fine-scale structure of moss in an active region. The data reveal that the moss is made up of a collection of fine threads that have widths with a mean and standard deviation of 440 ± 190 km (FWHM). The brightest moss emission is located at the visible head of the fine-scale structure and the fine structure appears to extend into the lower solar atmosphere. The emission decreases alongmore » the features, implying that the lower sections are most likely dominated by cooler transition region plasma. These threads appear to be the cool, lower legs of the hot loops. In addition, the increased resolution allows for the first direct observation of physical displacements of the moss fine structure in a direction transverse to its central axis. Some of these transverse displacements demonstrate periodic behavior, which we interpret as a signature of kink (Alfvénic) waves. Measurements of the properties of the transverse motions are made and the wave motions have means and standard deviations of 55 ± 37 km for the transverse displacement amplitude, 77 ± 33 s for the period, and 4.7 ± 2.5 km s{sup –1} for the velocity amplitude. The presence of waves in the transition region of hot loops could have important implications for the heating of active regions.« less

Investigational Antiretroviral Drugs: What is Coming Down the Pipeline.

PubMed

Gulick, Roy M

2018-04-01

Over the past 30 years, antiretroviral drug regimens for treating HIV infection have become more effective, safer, and more convenient. Despite 31 currently approved drugs, the pipeline of investigational HIV drugs remains full. Investigational antiretroviral drugs include the nucleoside analogue reverse transcriptase translocation inhibitor (NRTTI) MK-8591, a long-acting compound that could be dosed once weekly. Investigational nonnucleoside analogue reverse transcriptase inhibitors (NNRTIs) include doravirine, which is active in vitro against NNRTI-resistant HIV and was potent and well-tolerated when used in combination with a dual-nucleoside analogue RTI (nRTI) backbone in treatment-naive individuals.New integrase strand transfer inhibitors (InSTIs) include recently approved bictegravir, which is active against InSTI-resistant viral strains in vitro and was potent and well-tolerated in combination regimens in treatment-naive individuals, and investigational cabotegravir, which is being studied with monthly parenteral dosing for HIV maintenance treatment and with bimonthly dosing for HIV preexposure prophylaxis (PrEP). Investigational HIV entry inhibitors include the new CD4 attachment inhibitor fostemsavir, which targets HIV envelope glycoprotein 120, and recently approved ibalizumab, which binds the CD4 receptor. This article summarizes presentations by Roy M. Gulick, MD, MPH, at the IAS-USA continuing education program, Improving the Management of HIV Disease, held in Los Angeles, California, in April 2017, and at the 2017 Ryan White HIV/AIDS Program Clinical Conference, held in San Antonio, Texas, in August 2017.

Impact of antiretroviral drugs on the microbiome: unknown answers to important questions

PubMed Central

Pinto-Cardoso, Sandra; Klatt, Nichole R.; Reyes-Terán, Gustavo

2018-01-01

Purpose of review Little is known on how different antiretroviral (ARV) drugs affect the gut microbiome in HIV infection; and conflicting data exists on the effect of ARV drugs on residual inflammation/immune activation and microbial translocation. Recent findings Gut microbiome involvement in the transmission and pathogenesis of HIV infection is increasingly being recognized. Various studies have shown that antiretroviral therapy (ART) is unable to restore gut health despite effective suppression of plasma HIV viremia. Indeed, the resolution of residual inflammation and gut microbial translocation is partial under ART. Very recent studies have provided new evidence that ARV combinations can differentially affect the gut microbiome, immune activation and microbial translocation. Furthermore, a recent article uncovered a link between drug metabolism and specific microbial species indicating that microbes can directly metabolically degrade ARV drugs when administered topically. Summary There are still many unanswered questions regarding ARVs and the gut microbiome. It is, therefore, critical for researchers to address the effect of distinct ARV drugs on the microbiome and vice versa: the effects of the microbiome on ARV drug metabolism, and speculate about possible therapeutic avenues. PMID:29028667

High Dose Atorvastatin Decreases Cellular Markers of Immune Activation Without Affecting HIV-1 RNA Levels: Results of a Double-Blind Randomized Placebo Controlled Clinical Trial

DTIC Science & Technology

2011-02-15

M A J O R A R T I C L E High Dose Atorvastatin Decreases Cellular Markers of Immune Activation without Affecting HIV-1 RNA Levels: Results of a... atorvastatin on HIV-1 RNA (primary objective) and cellular markers of immune activation (secondary objective). HIV-infected individuals not receiving...antiretroviral therapy were randomized to receive either 8 weeks of atorvastatin (80 mg) or placebo daily. After a 4–6 week washout phase, participants

Dyslipidemia, Diet and Physical Exercise in Children on Treatment With Antiretroviral Medication in El Salvador: A Cross-sectional Study.

PubMed

Sonego, Michela; Sagrado, Maria José; Escobar, Gustavo; Lazzerini, Marzia; Rivas, Estefanie; Martín-Cañavate, Rocio; Pérez de López, Elsy; Ayala, Sandra; Castaneda, Luis; Aparicio, Pilar; Custodio, Estefanía

2016-10-01

Dyslipidemias are common in HIV-infected children, especially if treated with protease inhibitors, but there are few data on how to treat dyslipidemias in this population. We estimated the dyslipidemia prevalence and its association with treatment, diet and physical exercise in children on antiretroviral treatment at the El Salvador reference center for pediatric HIV care (CENID). Information was gathered regarding socio-demographic characteristics, treatment, diet and physical activity of 173 children aged 5-18 years and receiving antiretroviral therapy. Triglycerides, total cholesterol, low-density lipoprotein (LDL-C), high-density lipoprotein (HDL-C), viral load and CD4 T-lymphocytes were measured. Abnormal concentrations were defined as triglycerides ≥130 mg/dL in 10- to 18-year olds and ≥100 mg/dL in <10-year olds; total cholesterol ≥200 mg/dL; LDL-C ≥130 mg/dL and HDL-C ≤35 mg/dL. We adjusted 4 different multivariate models to assess the independent association of each type of dyslipidemia with protease inhibitors, diet and physical exercise. Of the 173 children, 83 (48%) had hypertriglyceridemia and 25 (14.5%) hypercholesterolemia. High LDL-C concentrations were observed in 17 children (9.8%) and low HDL-C in 38 (22%). Treatment with protease inhibitors was significantly associated with hypertriglyceridemia [prevalence ratio (PR) 2.8; 95% confidence interval (CI): 2.0-3.8] and hypercholesterolemia (PR 9.0; 95% CI: 3.6-22.2). Higher adherence to a "high fat/sugar diet" was associated with hypercholesterolemia (PR 1.6; 95% CI: 1.1-2.3) and high LDL-C (PR 1.7; 95% CI: 1.0-2.9). Compared with those exercising <3 times/week, children exercising ≥7 times were less likely to have low HDL-C (PR = 0.4; 95% CI: 0.2-0.7). These results suggest that a healthy diet and exercise habits can contribute to controlling some aspects of the lipid profile in this population.

Postpartum weight change among HIV-infected mothers by antiretroviral prophylaxis and infant feeding modality in a research setting.

PubMed

Cames, Cecile; Cournil, Amandine; de Vincenzi, Isabelle; Gaillard, Philippe; Meda, Nicolas; Luchters, Stanley; Nduati, Ruth; Naidu, Kevindra; Newell, Marie-Louise; Read, Jennifer S; Bork, Kirsten

2014-01-02

To assess the relationship between infant feeding, triple-antiretroviral prophylaxis and weight from 2 weeks (baseline) to 6 months postpartum among HIV-infected mothers in a mother-to-child transmission (MTCT) of HIV-prevention trial in five sub-Saharan African sites. HIV-infected pregnant women with CD4 cell counts of 200-500 cells/μl were counselled to choose breastfeeding to 6 months or replacement feeding from delivery. They were randomized to receive perinatal zidovudine and single-dose nevirapine or triple-antiretroviral MTCT prophylaxis until breastfeeding cessation. Mixed-effect linear models were used to compare maternal weight trajectories over time by infant feeding mode. Antiretroviral prophylaxis and BMI at baseline were examined as potential effect modifiers. Among 797 mothers, 620 (78%) initiated breastfeeding. Wasting (BMI <18.5) was rare at baseline (2%), whereas overweight/obesity (BMI ≥ 25) was common (40%). In the model including all women, breastfeeding was not associated with weight loss up to 6 months, irrespective of baseline BMI and antiretroviral prophylaxis. Triple-antiretroviral prophylaxis was associated with weight gain among replacement-feeding mothers with baseline BMI at least 25 (+0.54 kg/month; P < 0.0001). In the model including breastfeeding mothers only, triple-antiretroviral prophylaxis was associated with weight gain among mothers with baseline BMI at least 25 who ceased breastfeeding before 3 months postpartum (+0.33 kg/month; P = 0.03). The results suggest that breastfeeding up to 6 months postpartum is not detrimental for postpartum weight among well nourished HIV-infected mothers at intermediate-disease stage. In the absence of breastfeeding or after weaning, triple-antiretroviral prophylaxis is associated with weight gain among women with high BMI, even after cessation of prophylaxis.

Methods Development for Blood Borne Macrophage Carriage of Nanoformulated Antiretroviral Drugs

PubMed Central

Roy, Upal; Martinez-Skinner, Andrea; McMillan, JoEllyn; Gendelman, Howard E.

2010-01-01

Nanoformulated drugs can improve pharmacodynamics and bioavailability while serving also to reduce drug toxicities for antiretroviral (ART) medicines. To this end, our laboratory has applied the principles of nanomedicine to simplify ART regimens and as such reduce toxicities while improving compliance and drug pharmacokinetics. Simple and reliable methods for manufacturing nanoformulated ART (nanoART) are shown. Particles of pure drug are encapsulated by a thin layer of surfactant lipid coating and produced by fractionating larger drug crystals into smaller ones by either wet milling or high-pressure homogenization. In an alternative method free drug is suspended in a droplet of a polymer. Herein, drug is dissolved within a polymer then agitated by ultrasonication until individual nanosized droplets are formed. Dynamic light scattering and microscopic examination characterize the physical properties of the particles (particle size, charge and shape). Their biologic properties (cell uptake and retention, cytotoxicity and antiretroviral efficacy) are determined with human monocyte-derived macrophages (MDM). MDM are derived from human peripheral blood monocytes isolated from leukopacks using centrifugal elutriation for purification. Such blood-borne macrophages may be used as cellular transporters for nanoART distribution to human immunodeficiency virus (HIV) infected organs. We posit that the repackaging of clinically available antiretroviral medications into nanoparticles for HIV-1 treatments may improve compliance and positively affect disease outcomes. PMID:21178968

Supervision, monitoring and evaluation of nationwide scale-up of antiretroviral therapy in Malawi.

PubMed Central

Libamba, Edwin; Makombe, Simon; Mhango, Eustice; de Ascurra Teck, Olga; Limbambala, Eddie; Schouten, Erik J.; Harries, Anthony D.

2006-01-01

OBJECTIVE: To describe the supervision, monitoring and evaluation strategies used to assess the delivery of antiretroviral therapy during nationwide scale-up of treatment in Malawi. METHODS: In the first quarter of 2005, the HIV Unit of the Ministry of Health and its partners (the Lighthouse Clinic; Médecins Sans Frontières-Belgium, Thyolo district; and WHO's Country Office) undertook structured supervision and monitoring of all public sector health facilities in Malawi delivering antiretroviral therapy. FINDINGS: Data monitoring showed that by the end of 2004, there were 13,183 patients (5274 (40%) male, 12 527 (95%) adults) who had ever started antiretroviral therapy. Of patients who had ever started, 82% (10 761/13,183) were alive and taking antiretrovirals; 8% (1026/13,183) were dead; 8% (1039/13,183) had been lost to follow up; <1% (106/13,183) had stopped treatment; and 2% (251/13,183) had transferred to another facility. Of those alive and on antiretrovirals, 98% (7098/7258) were ambulatory; 85% (6174/7258) were fit to work; 10% (456/4687) had significant side effects; and, based on pill counts, 96% (6824/7114) had taken their treatment correctly. Mistakes in the registration and monitoring of patients were identified and corrected. Drug stocks were checked, and one potential drug stock-out was averted. As a result of the supervisory visits, by the end of March 2005 recruitment of patients to facilities scheduled to start delivering antiretroviral therapy had increased. CONCLUSION: This report demonstrates the importance of early supervision for sites that are starting to deliver antiretroviral therapy, and it shows the value of combining data collection with supervision. Making regular supervisory and monitoring visits to delivery sites are essential for tracking the national scale-up of delivery of antiretrovirals. PMID:16628306

Cohort Profile: HAART Observational Medical Evaluation and Research (HOMER) cohort.

PubMed

Patterson, Sophie; Cescon, Angela; Samji, Hasina; Cui, Zishan; Yip, Benita; Lepik, Katherine J; Moore, David; Lima, Viviane D; Nosyk, Bohdan; Harrigan, P Richard; Montaner, Julio S G; Shannon, Kate; Wood, Evan; Hogg, Robert S

2015-02-01

Since 1986, antiretroviral therapy (ART) has been available free of charge to individuals living with HIV in British Columbia (BC), Canada, through the BC Centre of Excellence in HIV/AIDS (BC-CfE) Drug Treatment Program (DTP). The Highly Active Antiretroviral Therapy (HAART) Observational Medical Evaluation and Research (HOMER) cohort was established in 1996 to maintain a prospective record of clinical measurements and medication profiles of a subset of DTP participants initiating HAART in BC. This unique cohort provides a comprehensive data source to investigate mortality, prognostic factors and treatment response among people living with HIV in BC from the inception of HAART. Currently over 5000 individuals are enrolled in the HOMER cohort. Data captured include socio-demographic characteristics (e.g. sex, age, ethnicity, health authority), clinical variables (e.g. CD4 cell count, plasma HIV viral load, AIDS-defining illness, hepatitis C co-infection, mortality) and treatment variables (e.g. HAART regimens, date of treatment initiation, treatment interruptions, adherence data, resistance testing). Research findings from the HOMER cohort have featured in numerous high-impact peer-reviewed journals. The HOMER cohort collaborates with other HIV cohorts on both national and international scales to answer complex HIV-specific research questions, and welcomes input from external investigators regarding potential research proposals or future collaborations. For further information please contact the principal investigator, Dr Robert Hogg (robert_hogg@sfu.ca). © The Author 2014; all rights reserved. Published by Oxford University Press on behalf of the International Epidemiological Association.

Use of Third Line Antiretroviral Therapy in Latin America

PubMed Central

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

2014-01-01

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

Antiretrovirals and safer conception for HIV-serodiscordant couples

PubMed Central

Matthews, Lynn T.; Smit, Jennifer A.; Cu-Uvin, Susan; Cohan, Deborah

2013-01-01

Purpose of review Many men and women living with HIV and their uninfected partners attempt to conceive children. HIV-prevention science can be applied to reduce sexual transmission risk while respecting couples’ reproductive goals. Here we discuss antiretrovirals as prevention in the context of safer conception for HIV-serodiscordant couples. Recent findings Antiretroviral therapy (ART) for the infected partner and pre-exposure prophylaxis (PrEP) for the uninfected partner reduce the risk of heterosexual HIV transmission. Several demonstration projects suggest the feasibility and acceptability of antiretroviral (ARV)s as periconception HIV-prevention for HIV-serodiscordant couples. The application of ARVs to periconception risk reduction may be limited by adherence. Summary For male-infected (M+F−) couples who cannot access sperm processing and female-infected (F+M−) couples unwilling to carry out insemination without intercourse, ART for the infected partner, PrEP for the uninfected partner, combined with treatment for sexually transmitted infections, sex limited to peak fertility, and medical male circumcision (for F+M couples) provide excellent, well tolerated options for reducing the risk of periconception HIV sexual transmission. PMID:23032734

Deferred modification of antiretroviral regimen following documented treatment failure in Asia: results from the TREAT Asia HIV Observational Database (TAHOD)

PubMed Central

Zhou, J; Li, PCK; Kumarasamy, N; Boyd, M; Chen, YMA; Sirisanthana, T; Sungkanuparph, S; Oka, S; Tau, G; Phanuphak, P; Saphonn, V; Zhang, FJ; Omar, SFS; Lee, CKC; Ditangco, R; Merati, TP; Lim, PL; Choi, JY; Law, MG; Pujari, S

2010-01-01

Objective The aim of the study was to examine the rates and predictors of treatment modification following combination antiretroviral therapy (cART) failure in Asian patients with HIV enrolled in the TREAT Asia HIV Observational Database (TAHOD). Methods Treatment failure (immunological, virological and clinical) was defined by World Health Organization criteria. Countries were categorized as high or low income by World Bank criteria. Results Among 2446 patients who initiated cART, 447 were documented to have developed treatment failure over 5697 person-years (7.8 per 100 person-years). A total of 253 patients changed at least one drug after failure (51.6 per 100 person-years). There was no difference between patients from high- and low-income countries [adjusted hazard ratio (HR) 1.02; P = 0.891]. Advanced disease stage [Centers for Disease Control and Prevention (CDC) category C vs. A; adjusted HR 1.38, P = 0.040], a lower CD4 count (≥ 51 cells/μL vs. ≤ 50 cells/μL; adjusted HR 0.61, P = 0.022) and a higher HIV viral load (≥ 400 HIV-1 RNA copies/mL vs. < 400 copies/mL; adjusted HR 2.69, P < 0.001) were associated with a higher rate of treatment modification after failure. Compared with patients from low-income countries, patients from high-income countries were more likely to change two or more drugs (67% vs. 49%; P = 0.009) and to change to a protease-inhibitor-containing regimen (48% vs. 16%; P< 0.001). Conclusions In a cohort of Asian patients with HIV infection, nearly half remained on the failing regimen in the first year following documented treatment failure. This deferred modification is likely to have negative implications for accumulation of drug resistance and response to second-line treatment. There is a need to scale up the availability of second-line regimens and virological monitoring in this region. PMID:19601993

Antiretroviral prophylaxis for HIV prevention in heterosexual men and women.

PubMed

Baeten, Jared M; Donnell, Deborah; Ndase, Patrick; Mugo, Nelly R; Campbell, James D; Wangisi, Jonathan; Tappero, Jordan W; Bukusi, Elizabeth A; Cohen, Craig R; Katabira, Elly; Ronald, Allan; Tumwesigye, Elioda; Were, Edwin; Fife, Kenneth H; Kiarie, James; Farquhar, Carey; John-Stewart, Grace; Kakia, Aloysious; Odoyo, Josephine; Mucunguzi, Akasiima; Nakku-Joloba, Edith; Twesigye, Rogers; Ngure, Kenneth; Apaka, Cosmas; Tamooh, Harrison; Gabona, Fridah; Mujugira, Andrew; Panteleeff, Dana; Thomas, Katherine K; Kidoguchi, Lara; Krows, Meighan; Revall, Jennifer; Morrison, Susan; Haugen, Harald; Emmanuel-Ogier, Mira; Ondrejcek, Lisa; Coombs, Robert W; Frenkel, Lisa; Hendrix, Craig; Bumpus, Namandjé N; Bangsberg, David; Haberer, Jessica E; Stevens, Wendy S; Lingappa, Jairam R; Celum, Connie

2012-08-02

Antiretroviral preexposure prophylaxis is a promising approach for preventing human immunodeficiency virus type 1 (HIV-1) infection in heterosexual populations. We conducted a randomized trial of oral antiretroviral therapy for use as preexposure prophylaxis among HIV-1-serodiscordant heterosexual couples from Kenya and Uganda. The HIV-1-seronegative partner in each couple was randomly assigned to one of three study regimens--once-daily tenofovir (TDF), combination tenofovir-emtricitabine (TDF-FTC), or matching placebo--and followed monthly for up to 36 months. At enrollment, the HIV-1-seropositive partners were not eligible for antiretroviral therapy, according to national guidelines. All couples received standard HIV-1 treatment and prevention services. We enrolled 4758 couples, of whom 4747 were followed: 1584 randomly assigned to TDF, 1579 to TDF-FTC, and 1584 to placebo. For 62% of the couples followed, the HIV-1-seronegative partner was male. Among HIV-1-seropositive participants, the median CD4 count was 495 cells per cubic millimeter (interquartile range, 375 to 662). A total of 82 HIV-1 infections occurred in seronegative participants during the study, 17 in the TDF group (incidence, 0.65 per 100 person-years), 13 in the TDF-FTC group (incidence, 0.50 per 100 person-years), and 52 in the placebo group (incidence, 1.99 per 100 person-years), indicating a relative reduction of 67% in the incidence of HIV-1 with TDF (95% confidence interval [CI], 44 to 81; P<0.001) and of 75% with TDF-FTC (95% CI, 55 to 87; P<0.001). Protective effects of TDF-FTC and TDF alone against HIV-1 were not significantly different (P=0.23), and both study medications significantly reduced the HIV-1 incidence among both men and women. The rate of serious adverse events was similar across the study groups. Eight participants receiving active treatment were found to have been infected with HIV-1 at baseline, and among these eight, antiretroviral resistance developed in two during the

[Injecting drug users and antiretroviral therapy: perceptions of pharmacy teams].

PubMed

Yokaichiya, Chizuru Minami; Figueiredo, Wagner dos Santos; Schraiber, Lilia Blima

2007-12-01

To understand the perceptions of pharmacy teams about their role in the healthcare assistance challenges and adherence to antiretroviral therapy by injecting drug users living with HIV/AIDS. Qualitative study through focus groups and thematic discourse analysis of pharmacists, technicians and assistants with more than six months of experience with medication supply, in 15 assisting units for STD/AIDS in the city of São Paulo, in 2002. Three groups were formed, totaling 29 participants, originating from 12 out of the 15 existing services, and including 12 university level professionals and 17 high-school level professionals. The groups concluded that the pharmacy has an important role in the antiretroviral drug supply, which is reflected in the treatment adherence, because trust-based relationships can be built up through their procedures. In spite of this, they pointed out that such building-up does not take place through excessively bureaucratic activities. This has negative repercussions for all patients, especially for injecting drug users, considered "difficult people". Such concept sums up their behavior: they are supposed to be confused and incapable to adhere to treatment, and have limited understanding. Staff members, however, affirm they treat these patients equally. They do not realize that, by this acting, the specific needs of injecting drug users may become invisible in the service. There is also the possibility that stigmatizing stereotypes may be created, resulting in yet another barrier to the work on adherence. Although the pharmacy is recommended as a potentially favorable place to listen to and form bonds with users, the results show objective and subjective obstacles to render it suitable for the work on adherence.

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

NASA Astrophysics Data System (ADS)

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

2013-10-01

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

Simultaneous quantification of four antiretroviral drugs in breast milk samples from HIV-positive women by an ultra-high performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) method

PubMed Central

Rodríguez-Delgado, Rosa Georgina; Figueroa-Damián, Ricardo; Domínguez-Castro, Mauricio; López-Martínez, Margarita; Flores-García, Zayra

2018-01-01

The primary strategy to avoid mother-to-child transmission of human immunodeficiency virus (HIV) through breastfeeding is administration of highly active antiretroviral therapy (HAART) to HIV-positive pregnant women. Because significant changes in the pharmacokinetics of antiretroviral (ARV) drugs occur during pregnancy, quantifying HAART and the viral load in breast milk in this population is essential. Here, we developed an analytical assay for the simultaneous quantification of four ARV drugs in breast milk using ultra-performance liquid chromatography coupled to tandem mass spectrometry. We validated this method following Mexican and international guidelines. ARV drugs. We extracted the ARV drugs from 200 μL samples of breast milk and detected these drugs in a triple quadrupole mass spectrometer with positive electrospray ionization. The validated concentration ranges (ng/mL) for zidovudine, lamivudine, lopinavir, and ritonavir were 12.5–750, 50–2500, 100–5000 and 5 to 250, respectively. Additionally, the absolute recovery percentages (and matrix effects) were 91.4 (8.39), 88.78 (28.75), 91.38 (11.77) and 89.78 (12.37), respectively. We determined that ARV drugs are stable for 24 h at 8°C and 24°C for 15 days at –80°C. This methodology had the capacity for simultaneous detection; separation; and accurate, precise quantification of ARV drugs in human breast milk samples according to Mexican standard laws and United States Food and Drug Administration guidelines. PMID:29351333

HIV-1 genetic diversity and antiretroviral drug resistance among individuals from Roraima state, northern Brazil

PubMed Central

Leão, Renato Augusto Carvalho; Granja, Fabiana; Naveca, Felipe Gomes

2017-01-01

The HIV-1 epidemic in Brazil has spread towards the Northern country region, but little is known about HIV-1 subtypes and prevalence of HIV strains with resistance mutations to antiretrovirals in some of the Northern states. HIV-1 protease (PR) and reverse transcriptase (RT) sequences were obtained from 73 treatment-naive and -experienced subjects followed between 2013 and 2014 at a public health reference unit from Roraima, the northernmost Brazilian state. The most prevalent HIV-1 clade observed in the study population was the subtype B (91%), followed by subtype C (9%). Among 12 HIV-1 strains from treatment-naïve patients, only one had a transmitted drug resistance mutation for NNRTI. Among 59 treatment-experienced patients, 12 (20%) harbored HIV-1 strains with acquired drug resistance mutations (ADRM) that reduce the susceptibility to two classes of antiretroviral drugs (NRTI and NNRTI or NRTI and PI), and five (8%) harbored HIV-1 strains with ADRM that reduced susceptibility to only one class of antiretroviral drugs (NNRTI or PI). No patients harboring HIV strains with reduced susceptibility to all three classes of antiretroviral drugs were detected. A substantial fraction of treatment-experienced patients with (63%) and without (70%) ADRM had undetectable plasma viral loads (<40 copies/ml) at the time of sampling. Among treatment-experienced with plasma viral loads above 2,000 copies/ml, 44% displayed no ADRM. This data showed that the HIV-1 epidemic in Roraima displayed a much lower level of genetic diversity and a lower prevalence of ADRM than that described in other Brazilian states. PMID:28301548

Clinical Outcomes of Retinal Detachment Surgery following Cytomegalovirus Retinitis in Patients on Highly Active Anti-retroviral Therapy for Acquired Immune Deficiency Syndrome.

PubMed

Mathur, Gaurav; Ratra, Dhanashree; Bhuibhar, Sagar Sudhakar; Roy, Rupak

2015-01-01

The objective of this study is to describe the surgical outcomes of patients of HIV on HAART who underwent surgery for CMV retinitis related retinal detachment. A retrospective analysis of the medical records of 40 eyes of 35 consecutive HIV positive patients who underwent surgical repair for CMV retinitis associated rhegmatogenous retinal detachment between January 2000 to August 2010 was done. All patients had an adequate follow up of atleast 6 months. Favourable anatomical outcome was achieved in 78 % of eyes with the eyes having a attached retina, clear media and controlled intraocular pressure.Favourable functional outcome (vision >3/60) was achieved in 56%. Though anatomical outcomes have not changed from the pre HAART era but there has been an increase in favorable functional outcomes possibly due to effects of antiretroviral therapy.

Impact of medical and nonmedical factors on physician decision making for HIV/AIDS antiretroviral treatment.

PubMed

Bogart, L M; Kelly, J A; Catz, S L; Sosman, J M

2000-04-15

To examine influences of medical factors (e.g., viral load) and nonmedical factors (e.g., patient characteristics) on treatment decisions for highly active antiretroviral therapy (HAART), we sent a survey to a random sample of 995 infectious disease physicians who treat patients with HIV/AIDS in the United States in August, 1998. The response rate was 53%. Respondents were asked to report their current practices with respect to antiretroviral treatment and the extent to which each of three medical and 17 nonmedical factors would influence them for or against prescribing HAART to a hypothetical HIV-positive patient. Most reported initiating HAART with findings of low CD4+ cell counts and high viral loads, and weighing CD4+ cell counts, viral load, and opportunistic infection heavily in their decisions to prescribe HAART. Patients' prior history of poor adherence was weighed very much against initiating HAART. Patient homelessness, heavy alcohol use, injection drug use, and prior psychiatric hospitalization were cited by most physicians as weighing against HAART initiation. Thus, most physicians in this sample follow guidelines for the use of HAART, and nonmedical factors related to patients' life situations are weighed as heavily as disease severity in treatment decisions. As HIV increasingly becomes a disease associated with economic disadvantage and other social health problems, it will be essential to develop interventions and care support systems to enable patients experiencing these problems to benefit from HIV treatment advances.

HEROES Observations of a Quiescent Active Region

NASA Astrophysics Data System (ADS)

Shih, A. Y.; Christe, S.; Gaskin, J.; Wilson-Hodge, C.

2014-12-01

Hard X-ray (HXR) observations of solar flares reveal the signatures of energetic electrons, and HXR images with high dynamic range and high sensitivity can distinguish between where electrons are accelerated and where they stop. Even in the non-flaring corona, high-sensitivity HXR measurements may be able to detect the presence of electron acceleration. The High Energy Replicated Optics to Explore the Sun (HEROES) balloon mission added the capability of solar observations to an existing astrophysics balloon payload, HERO, which used grazing-incidence optics for direct HXR imaging. HEROES measures HXR emission from ~20 to ~75 keV with an angular resolution of 33" HPD. HEROES launched on 2013 September 21 from Fort Sumner, New Mexico, and had a successful one-day flight. We present the detailed analysis of the 7-hour observation of AR 11850, which sets new upper limits on the HXR emission from a quiescent active region, with corresponding constraints on the numbers of tens of keV energetic electrons present. Using the imaging capability of HEROES, HXR upper limits are also obtained for the quiet Sun surrounding the active region. We also discuss what can be achieved with new and improved HXR instrumentation on balloons.

Antiretroviral therapy as HIV prevention: status and prospects.

PubMed

Mayer, Kenneth H; Venkatesh, Kartik K

2010-10-01

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

Concurrent chemoradiotherapy with 5-fluorouracil and mitomycin C for anal carcinoma: are there differences between HIV-positive and HIV-negative patients in the era of highly active antiretroviral therapy?

PubMed

Fraunholz, Ingeborg; Rabeneck, Daniela; Gerstein, Johanna; Jäck, Katharina; Haberl, Annette; Weiss, Christian; Rödel, Claus

2011-01-01

To report treatment compliance, toxicity and clinical outcome of chemoradiotherapy (CRT) for anal carcinoma in HIV-negative vs. HIV-positive patients treated with highly active antiretroviral therapy. Between 1997 and 2008, 25 HIV-positive and 45 HIV-negative patients received CRT (50.4 Gy at 1.8 Gy/fraction plus 5.4-10.8 Gy boost; 5-fluorouracil, 1000 mg/m(2), Days 1-4 and 29-32, mitomycin C, 10 mg/m(2), Days 1 and 29). Median follow-up was 51 (range, 3-235) months. HIV-positive patients were significantly younger (mean age, 47 vs. 57 years, p<0.001) and predominantly male (92% vs. 29%, p<0.001). CRT could be completed in all patients with a reduction of chemotherapy and/or RT-interruption in 28% and 8%, respectively, in HIV-positive patients, and in 9% and 11%, respectively, in HIV-negative patients. Acute Grade 3/4-toxicity occurred in 44% vs. 49% (p=0.79). Initial complete response (84% vs. 93%, p=0.41), 5-year rates of local control (65% vs. 78%, p=0.44), cancer-specific (78% vs. 90%, p=0.17) and overall survival (71% vs. 77%, p=0.76) were not significantly different. HIV-positive patients with anal cancer can be treated with standard CRT, with the same tolerability and toxicity as HIV-negative patients. Long-term local control and survival rates are not significantly different between these groups. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

Pharmacokinetics and Disposition of Rilpivirine (TMC278) Nanosuspension as a Long-Acting Injectable Antiretroviral Formulation▿

PubMed Central

van ′t Klooster, Gerben; Hoeben, Eva; Borghys, Herman; Looszova, Adriana; Bouche, Marie-Paule; van Velsen, Frans; Baert, Lieven

2010-01-01

The next-generation human immunodeficiency virus type 1 (HIV-1) nonnucleoside reverse transcriptase inhibitor rilpivirine (TMC278) was administered in rats and dogs as single intramuscular (IM) or subcutaneous (SC) injections, formulated as a 200-nm nanosuspension. The plasma pharmacokinetics, injection site concentrations, disposition to lymphoid tissues, and tolerability were evaluated in support of its potential use as a once-monthly antiretroviral agent in humans. Rilpivirine plasma concentration-time profiles showed sustained and dose-proportional release over 2 months in rats and over 6 months in dogs. The absolute bioavailability approached 100%, indicating a complete release from the depot, in spite of rilpivirine concentrations still being high at the injection site(s) 3 months after administration in dogs. For both species, IM administration was associated with higher initial peak plasma concentrations and a more rapid washout than SC administration, which resulted in a stable plasma-concentration profile over at least 6 weeks in dogs. The rilpivirine concentrations in the lymph nodes draining the IM injection site exceeded the plasma concentrations by over 100-fold 1 month after administration, while the concentrations in the lymphoid tissues decreased to 3- to 6-fold the plasma concentrations beyond 3 months. These observations suggest uptake of nanoparticles by macrophages, which generates secondary depots in these lymph nodes. Both SC and IM injections were generally well tolerated and safe, with observations of a transient inflammatory response at the injection site. The findings support clinical investigations of rilpivirine nanosuspension as a long-acting formulation to improve adherence during antiretroviral therapy and for preexposure prophylaxis. PMID:20160045

Influence of the number of daily pills and doses on adherence to antiretroviral treatment: a 7-year study.

PubMed

Hernández Arroyo, M J; Cabrera Figueroa, S E; Sepúlveda Correa, R; Valverde Merino, M P; Luna Rodrigo, G; Domínguez-Gil Hurlé, A

2016-02-01

Antiretroviral treatment (ART) is hampered by complicated regimens, high pill burden, drug-drug interactions, and frequent short- and long-term adverse effects, leading to decreased adherence. Over recent years, considerable effort has been directed at developing regimens that are less burdening. We undertook a 7-year retrospective study of the records of 264 HIV-infected subjects enrolled in a pharmaceutical care programme to document the progress made and to study the influence of the number of ART pills and doses on the level of treatment adherence. Antiretroviral dispensing records were analysed for the number of pills and doses administered and the ART adherence rate estimated. In 2005, the patients took a mean of 6·2 pills daily (CI 95%: 5·9-6·6), and 92·9% of them were on a twice-a-day (BID) dosage regimen. By 2012, the mean number of pills was reduced to 4·1 (CI 95%: 3·8-4·4), and only 50·9% were on a BID regimen. No statistically significant relation was observed between number of daily pills and doses and ART adherence reached by the patients in any of the analyses performed. There has been a continuous reduction in the number of pills and doses of antiretrovirals taken by individual patients over the last 7 years due largely to the introduction of improved treatments and regimens. More daily pills or doses was not associated with worse ART adherence in our pharmaceutical care programme. © 2015 John Wiley & Sons Ltd.

Reduced sTWEAK and Increased sCD163 Levels in HIV-Infected Patients: Modulation by Antiretroviral Treatment, HIV Replication and HCV Co-Infection

PubMed Central

Beltrán, Luis M.; García Morillo, José S.; Egido, Jesús; Noval, Manuel Leal; Ferrando-Martinez, Sara; Blanco-Colio, Luis M.; Genebat, Miguel; Villar, José R.; Moreno-Luna, Rafael; Moreno, Juan Antonio

2014-01-01

Background Patients infected with the human immunodeficiency virus (HIV) have an increased risk of cardiovascular disease due to increased inflammation and persistent immune activation. CD163 is a macrophage scavenger receptor that is involved in monocyte-macrophage activation in HIV-infected patients. CD163 interacts with TWEAK, a member of the TNF superfamily. Circulating levels of sTWEAK and sCD163 have been previously associated with cardiovascular disease, but no previous studies have fully analyzed their association with HIV. Objective The aim of this study was to analyze circulating levels of sTWEAK and sCD163 as well as other known markers of inflammation (hsCRP, IL-6 and sTNFRII) and endothelial dysfunction (sVCAM-1 and ADMA) in 26 patients with HIV before and after 48 weeks of antiretroviral treatment (ART) and 23 healthy subjects. Results Patients with HIV had reduced sTWEAK levels and increased sCD163, sVCAM-1, ADMA, hsCRP, IL-6 and sTNFRII plasma concentrations, as well as increased sCD163/sTWEAK ratio, compared with healthy subjects. Antiretroviral treatment significantly reduced the concentrations of sCD163, sVCAM-1, hsCRP and sTNFRII, although they remained elevated when compared with healthy subjects. Antiretroviral treatment had no effect on the concentrations of ADMA and sTWEAK, biomarkers associated with endothelial function. The use of protease inhibitors as part of antiretroviral therapy and the presence of HCV-HIV co-infection and/or active HIV replication attenuated the ART-mediated decrease in sCD163 plasma concentrations. Conclusion HIV-infected patients showed a proatherogenic profile characterized by increased inflammatory, immune-activation and endothelial-dysfunction biomarkers that partially improved after ART. HCV-HIV co-infection and/or active HIV replication enhanced immune activation despite ART. PMID:24594990

Toll-Like Receptor 7 Agonist GS-9620 Induces HIV Expression and HIV-Specific Immunity in Cells from HIV-Infected Individuals on Suppressive Antiretroviral Therapy.

PubMed

Tsai, Angela; Irrinki, Alivelu; Kaur, Jasmine; Cihlar, Tomas; Kukolj, George; Sloan, Derek D; Murry, Jeffrey P

2017-04-15

maintained in reservoirs of latently infected cells. Consequently, lifelong therapy is required to maintain viral suppression. Ultimately, new therapies that specifically target and eliminate the latent HIV reservoir are needed. Toll-like receptor agonists are potent enhancers of innate antiviral immunity that can also improve the adaptive immune response. Here, we show that a highly selective TLR7 agonist, GS-9620, activated HIV from peripheral blood mononuclear cells isolated from HIV-infected individuals with suppressed infection. GS-9620 also improved immune effector functions that specifically targeted HIV-infected cells. Previously published studies on the compound in other chronic viral infections show that it can effectively induce immune activation at safe and tolerable clinical doses. Together, the results of these studies suggest that GS-9620 may be useful for treating HIV-infected individuals on suppressive antiretroviral therapy. Copyright © 2017 Tsai et al.

Toll-Like Receptor 7 Agonist GS-9620 Induces HIV Expression and HIV-Specific Immunity in Cells from HIV-Infected Individuals on Suppressive Antiretroviral Therapy

PubMed Central

Tsai, Angela; Irrinki, Alivelu; Kaur, Jasmine; Cihlar, Tomas; Kukolj, George

2017-01-01

persistently maintained in reservoirs of latently infected cells. Consequently, lifelong therapy is required to maintain viral suppression. Ultimately, new therapies that specifically target and eliminate the latent HIV reservoir are needed. Toll-like receptor agonists are potent enhancers of innate antiviral immunity that can also improve the adaptive immune response. Here, we show that a highly selective TLR7 agonist, GS-9620, activated HIV from peripheral blood mononuclear cells isolated from HIV-infected individuals with suppressed infection. GS-9620 also improved immune effector functions that specifically targeted HIV-infected cells. Previously published studies on the compound in other chronic viral infections show that it can effectively induce immune activation at safe and tolerable clinical doses. Together, the results of these studies suggest that GS-9620 may be useful for treating HIV-infected individuals on suppressive antiretroviral therapy. PMID:28179531

Simultaneous observations of reaction kinetics, creep behavior, and AE activities during syndeformational antigorite dehydration at high pressures

NASA Astrophysics Data System (ADS)

Kubo, T.; Iwasato, T.; Higo, Y.; Kato, T.; Kaneshima, S.; Uehara, S.; Koizumi, S.; Imamura, M.; Tange, Y.

2015-12-01

Intermediate-depth earthquakes are seismic activities in Wadati-Benioff zone at depths from 60 km to 300 km, where subducting plates deform plastically rather than brittle failure. Although it has been reported that unstable faulting occurred during antigorite dehydration even at higher pressures than ~2 GPa (e.g., Jung et al., 2009), the recent study by Chernak and Hirth (2011) revealed that the syndefromational antigorite dehydration does not produces stick-slip instabilities but stable fault slip. In the present study, we newly developed an AE monitoring system for high-pressure reaction-deformation processes combined with D-DIA and synchrotron monochromatic X-ray to observe reaction kinetics, creep behaviors, and AE activities simultaneously. We applied this technique to investigate shear instability during syndeformational antigorite dehydration. High-pressure deformation experiments were conducted up to ~8 GPa, ~1050 K, and strain rates of 3.4-9.2 x 10-5 s-1 in compression using a D-DIA type apparatus installed at BL-04B1, SPring-8. 50 keV mono X-ray were used to measure reaction kinetics and stress-strain data. To monitor shear instabilities by detecting AEs, six piezoelectric devices were positioned between first and second stage anvils of MA 6-6 type system. We used three kinds of starting materials of polycrystalline antigorite, fine-grained forsterite polycrystal, and two-phase mixtures of antigorite and San Carlos olivine (10%, 30%, and 50%atg). Clear contrasts were observed in AE activities between forsterite and antigorite samples. AE activities detected within the forsterite polycrystal suggested (semi) brittle behaviors at low pressures during the cold compression stage.
Almost no AEs were detected within the antigorite samples during any stages of cold compression, ramping, deformation, and syndeformational dehydration although localized deformation textures were observed in recovered samples. Instead, we detected some AEs outside the sample

Antiretroviral therapy during pregnancy and the risk of an adverse outcome.

PubMed

Tuomala, Ruth E; Shapiro, David E; Mofenson, Lynne M; Bryson, Yvonne; Culnane, Mary; Hughes, Michael D; O'Sullivan, M J; Scott, Gwendolyn; Stek, Alice M; Wara, Diane; Bulterys, Marc

2002-06-13

Some studies suggest that combination antiretroviral therapy in pregnant women with human immunodeficiency virus type 1 (HIV-1) infection increases the risk of premature birth and other adverse outcomes of pregnancy. We studied pregnant women with HIV-1 infection who were enrolled in seven clinical studies and delivered their infants from 1990 through 1998. The cohort comprised 2123 women who received antiretroviral therapy during pregnancy (monotherapy in 1590, combination therapy without protease inhibitors in 396, and combination therapy with protease inhibitors in 137) and 1143 women who did not receive antiretroviral therapy. After standardization for the CD4+ cell count and use or nonuse of tobacco, alcohol, and illicit drugs, the rate of premature delivery (<37 weeks of gestation) was similar among the women who received antiretroviral therapy and those who did not (16 percent and 17 percent, respectively); the rate of low birth weight (<2500 g) was 16 percent among the infants born to both groups; and the rate of very low birth weight (<1500 g) was 2 percent for the group that received antiretroviral therapy and 1 percent for the group that did not. The rates of low Apgar scores (<7) and stillbirth were also similar or the same in the two groups. After adjustment for multiple risk factors, combination antiretroviral therapy was not associated with an increased risk of premature delivery as compared with monotherapy (odds ratio, 1.08; 95 percent confidence interval, 0.71 to 1.62) or delivery of an infant with low birth weight (odds ratio, 1.03; 95 percent confidence interval, 0.64 to 1.63). Seven of the women who received combination therapy with protease inhibitors (5 percent) had infants with very low birth weight, as compared with nine women who received combination therapy without protease inhibitors (2 percent) (adjusted odds ratio, 3.56; 95 percent confidence interval, 1.04 to 12.19). As compared with no antiretroviral therapy or monotherapy

From Radio with Love: An Overview of the Role of Radio Observations in Understanding High-Energy Emission from Active Galaxies

NASA Technical Reports Server (NTRS)

Ojha, Roopesh

2012-01-01

The gamma-ray satellite Fermi and the ground based TeV facilities MAGIC, VERITAS and HESS have ushered in a new era in the observation of high-energy emission from active galaxies. The energy budgets of these objects have a major contribution from gamma-rays and it is simply not possible to understand their physics without high-energy observations. Though the exact mechanisms for high-energy production in galaxies remains an open question, gamma-rays typically result from interactions between high-energy particles. Via different interactions these same particles can produce radio emission. Thus the non-thermal nature of gamma-ray emission practically guarantees that high-energy emitters are also radio loud. Aside from their obvious role as a component of multiwavelength analysis, radio observations provide two crucial elements essential to understanding the source structure and physical processes of high-energy emitters: very high timing resolution and very high spatial resolution. A brief overview of the unique role played by radio observations in unraveling the mysteries of the high energy Universe as presented here.

Characteristics and outcomes of older HIV-infected patients receiving antiretroviral therapy in Malawi: A retrospective observation cohort study.

PubMed

Tweya, Hannock; Feldacker, Caryl; Heller, Tom; Gugsa, Salem; Ng'ambi, Wingston; Nthala, Omisher; Kalulu, Mike; Chiwoko, Jane; Banda, Rabecca; Makwinja, Agness; Phiri, Sam

2017-01-01

To estimate patients enrolling on antiretroviral therapy (ART) over time; describe trends in baseline characteristics; and compare immunological response, loss to follow-up (LTFU), and mortality by three age groups (25-39, 40-49 and ≥50 years). A retrospective observation cohort study. This study used routine ART data from two public clinics in Lilongwe, Malawi. All HIV-infected individuals, except pregnant or breastfeeding women, aged ≥ 25 years at ART initiation between 2006 and 2015 were included. Poisson regression models estimated risk of mortality, stratified by age groups. Of 37,378 ART patients, 3,406 were ≥ 50 years old. Patients aged ≥ 50 years initiated ART with more advanced WHO clinical stage and lower CD4 cell count than their younger counterparts. Older patients had a significantly slower immunological response to ART in the first 18 months on ART compared to patients aged 25-39 years (p = 0.04). Overall mortality rates were 2.3 (95% confidence Interval (CI) 2.2-2.4), 2.9 (95% CI 2.7-3.2) and 4.6 (95% CI 4.2-5.1) per 100 person-years in patients aged 25-39 years, 40-49 years and 50 years and older, respectively. Overall LTFU rates were 6.3 (95% CI 6.1-6.5), 4.5 (95% CI 4.2-4.7), and 5.6 (95% CI 5.1-6.1) per 100 person years among increasing age cohorts. The proportion of patients aged ≥ 50 years and newly enrolling into ART care remained stable at 9% while the proportion of active ART patients aged ≥50 years increased from 10% in 2006 to 15% in 2015. Older people had slower immunological response and higher mortality. Malawi appears to be undergoing a demographic shift in people living with HIV. Increased consideration of long-term ART-related problems, drug-drug interactions and age-related non-communicable diseases is warranted.

Characteristics and outcomes of older HIV-infected patients receiving antiretroviral therapy in Malawi: A retrospective observation cohort study

PubMed Central

Tweya, Hannock; Feldacker, Caryl; Heller, Tom; Gugsa, Salem; Ng’ambi, Wingston; Nthala, Omisher; Kalulu, Mike; Chiwoko, Jane; Banda, Rabecca; Makwinja, Agness; Phiri, Sam

2017-01-01

Objective To estimate patients enrolling on antiretroviral therapy (ART) over time; describe trends in baseline characteristics; and compare immunological response, loss to follow-up (LTFU), and mortality by three age groups (25–39, 40–49 and ≥50 years). Design A retrospective observation cohort study. Methods This study used routine ART data from two public clinics in Lilongwe, Malawi. All HIV-infected individuals, except pregnant or breastfeeding women, aged ≥ 25 years at ART initiation between 2006 and 2015 were included. Poisson regression models estimated risk of mortality, stratified by age groups. Results Of 37,378 ART patients, 3,406 were ≥ 50 years old. Patients aged ≥ 50 years initiated ART with more advanced WHO clinical stage and lower CD4 cell count than their younger counterparts. Older patients had a significantly slower immunological response to ART in the first 18 months on ART compared to patients aged 25–39 years (p = 0.04). Overall mortality rates were 2.3 (95% confidence Interval (CI) 2.2–2.4), 2.9 (95% CI 2.7–3.2) and 4.6 (95% CI 4.2–5.1) per 100 person-years in patients aged 25–39 years, 40–49 years and 50 years and older, respectively. Overall LTFU rates were 6.3 (95% CI 6.1–6.5), 4.5 (95% CI 4.2–4.7), and 5.6 (95% CI 5.1–6.1) per 100 person years among increasing age cohorts. The proportion of patients aged ≥ 50 years and newly enrolling into ART care remained stable at 9% while the proportion of active ART patients aged ≥50 years increased from 10% in 2006 to 15% in 2015. Conclusion Older people had slower immunological response and higher mortality. Malawi appears to be undergoing a demographic shift in people living with HIV. Increased consideration of long-term ART-related problems, drug-drug interactions and age-related non-communicable diseases is warranted. PMID:28686636

Antiretroviral Chemoprophylaxis: State of Evidence and the Research Agenda

PubMed Central

Mayer, Kenneth H.

2014-01-01

Oral antiretroviral preexposure prophylaxis (PrEP) has been shown to decrease human immunodeficiency virus (HIV) incidence in studies of men who have sex with men, heterosexual men and women, and injecting drug users. One study of pericoital tenofovir gel demonstrated that it reduced HIV incidence in South African women. However, other studies of African women failed to demonstrate protection with either oral tenofovir or tenofovir-emtricitabine, or daily tenofovir gel. The magnitude of PrEP protection appears to be highly correlated with medication adherence. New studies are evaluating whether different antiretrovirals, including dapivirine, rilpivirine, maraviroc, and new integrase inhibitors. Different formulations are also being evaluated, including gels, films, vaginal rings, and injectable medication. Although PrEP efficacy has been demonstrated, and several normative bodies (eg, the US Food and Drug Administration) have approved PrEP for clinical use, uptake has been slow. Reasons may include lack of sufficient provider and consumer education, residual concerns about costs, potential long-term toxicities, and behavioral disinhibition. Additional work is under way to determine how to best educate consumers and providers about optimal adherence and to use PrEP in conjunction with risk mitigation. PMID:24926034

miR-34a is a common link in both HIV- and antiretroviral therapy-induced vascular aging.

PubMed

Zhan, Jiaxin; Qin, Shanshan; Lu, Lili; Hu, Xiamin; Zhou, Jun; Sun, Yeying; Yang, Jian; Liu, Ying; Wang, Zunzhe; Tan, Ning; Chen, Jiyan; Zhang, Chunxiang

2016-11-26

Both HIV and antiretroviral therapy could induce vascular aging with unclear mechanisms. In this study, via microarray analysis, we identified, for the first time, that miR-34a expression was significantly increased in both HIV-infected, and antiretroviral agents-treated vessels and vascular endothelial cells (ECs) from these vessels. In cultured ECs, miR-34a expression was significantly increased by HIV-Tat protein and by the antiretroviral agents, lopinavir/ritonavir. Both HIV-Tat protein and antiretroviral agents could induce EC senescence, which was inhibited by miR-34a inhibition. In contrast, EC senescence was exacerbated by miR-34a overexpression. In addition, the vascular ECs isolated from miR-34a knockout mice were resistant to HIV and antiretroviral agents-mediated senescence. In vivo, miR-34a expression in mouse vascular walls and their ECs was increased by antiretroviral therapy and by HIV-1 Tat transgenic approach. miR-34a inhibition could effectively inhibit both HIV-Tat protein and antiretroviral therapy-induced vascular aging in mice. The increased miR-34a was induced via p53, whereas Sirt1 was a downstream target gene of miR-34a in both HIV-Tat protein and antiretroviral agents-treated ECs and vessels. The study has demonstrated that miR-34a is a common link in both HIV and antiretroviral therapy-mediated vascular aging.

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

Adverse reactions associated with first-line regimens in patient initiating antiretroviral therapy.

PubMed

Mendes, Jullye Campos; Bonolo, Palmira de Fátima; Ceccato, Maria das Graças Braga; Costa, Juliana de Oliveira; Reis, Adriano Max Moreira; Dos Santos, Henrique; Silveira, Micheline Rosa

2018-05-08

To evaluate the prevalence of adverse drug reactions (ADR) and associated factors during the use of Highly Active Antiretroviral Therapy (HAART) in patients initiating treatment. This is a cross-sectional analysis of a prospective study conducted in three public referral services specialized in HIV/AIDS care in Belo Horizonte, Brazil. Self-reported ADR and explanatory variables were obtained from face-to-face interview and from Information Systems. Associated factors with ADR were evaluated by logistic regression in SPSS software v.22. We included 399 patients, of which 85.5% reported at least one and 72.7% up to 5 ADRs after HAART initiation. Neurological reactions were the most frequent, with self-reported ADRs being distinct according to HAART regimen used. The global model showed higher chance of ADRs among females (OR = 3.52) and illicit drug users (OR = 2.28). Lower chance of ADRs was found for patients aged > 33 years (OR = 0.37), DTG/TDF/3TC users (OR = 0.41), and higher physical domain of quality of life (OR = 0.78). The model restricted to patients using the single-tablet regimen EFV/TDF/3TC showed lower ADRs among patients with CD4+ T lymphocyte count > 200 cells/mm 3 (OR = 0.23) and higher independence domain of quality of life (OR = 0.74). The model restricted to DTG/TDF/3TC and to other regimens showed lower ADRs with higher physical domain of quality of life (OR = 0.74 and OR = 0.55, respectively). The prevalence of self-reported ADRs to first-line antiretroviral regimens was high and patients using DTG/TDF/3TC had a smaller number of ADRs. In addition to HAART regimen, sociodemographic, clinical, and quality of life characteristics were associated with ADRs.

Immunological changes in peripheral blood and in lymphoid tissue after treatment of HIV-infected subjects with highly active anti-retroviral therapy (HAART) or HAART + IL-2

PubMed Central

Zanussi, S; Simonelli, C; Bortolin, M T; D'Andrea, M; Crepaldi, C; Vaccher, E; Nasti, G; Politi, D; Barzan, L; Tirelli, U; De Paoli, P

1999-01-01

This study presents the immunophenotypic and functional analysis of lymphocyte subsets obtained from peripheral blood and lymphoid tissue from HIV+ individuals treated with highly active anti-retroviral therapy (HAART) alone or in combination with 6 million units international (MUI) s.c. IL-2. Before treatment, the HIV+ patients had reduced CD4 and increased CD8 values in the peripheral blood and lymphoid tissue and impaired cytokine production by peripheral blood mononuclear cells (PBMC). After 24 weeks of treatment, all the HIV+ patients demonstrated increased CD4 values in peripheral blood and lymphoid tissue. The use of IL-2 did not promote an additional CD4 expansion compared with HAART alone; increased ‘naive’ and CD26+ CD4 cells and reduced CD8 cells were found in the peripheral blood and lymphoid tissue of the IL-2-treated, but not of the HAART-treated patients. Both types of treatment induced a significant reduction of the CD8/CD38+ cells. While HAART alone had negligible effects on cytokine production by PBMC, the combined use of HAART + IL-2 was unable to increase the endogenous production of IL-2, but caused an increase of IL-4, IL-13 and interferon-gamma (IFN-γ) and a reduction of monocyte chemoattractant protein-1 (MCP-1) production. These data suggest that, although in this schedule IL-2 has minimal efficacy on CD4 recovery when compared with HAART alone, it produces an increase of ‘naive’ and CD26+CD4 cells and a partial restoration of cytokine production. These data may be used to better define clinical trials aiming to improve the IL-2-dependent immunological reconstitution of HIV-infected subjects. PMID:10361239

Cytomegalovirus Replication in Semen Is Associated with Higher Levels of Proviral HIV DNA and CD4+ T Cell Activation during Antiretroviral Treatment

PubMed Central

Massanella, Marta; Richman, Douglas D.; Little, Susan J.; Spina, Celsa A.; Vargas, Milenka V.; Lada, Steven M.; Daar, Eric S.; Dube, Michael P.; Haubrich, Richard H.; Morris, Sheldon R.; Smith, Davey M.

2014-01-01

ABSTRACT Asymptomatic cytomegalovirus (CMV) replication occurs frequently in the genital tract in untreated HIV-infected men and is associated with increased immune activation and HIV disease progression. To determine the connections between CMV-associated immune activation and the size of the viral reservoir, we evaluated the interactions between (i) asymptomatic seminal CMV replication, (ii) levels of T cell activation and proliferation in blood, and (iii) the size and transcriptional activity of the HIV DNA reservoir in blood from 53 HIV-infected men on long-term antiretroviral therapy (ART) with suppressed HIV RNA in blood plasma. We found that asymptomatic CMV shedding in semen was associated with significantly higher levels of proliferating and activated CD4+ T cells in blood (P < 0.01). Subjects with detectable CMV in semen had approximately five times higher average levels of HIV DNA in blood CD4+ T cells than subjects with no CMV. There was also a trend for CMV shedders to have increased cellular (multiply spliced) HIV RNA transcription (P = 0.068) compared to participants without CMV, but it is unclear if this transcription pattern is associated with residual HIV replication. In multivariate analysis, the presence of seminal plasma CMV (P = 0.04), detectable 2-long terminal repeat (2-LTR), and lower nadir CD4+ (P < 0.01) were independent predictors of higher levels of proviral HIV DNA in blood. Interventions aimed at reducing seminal CMV and associated immune activation may be important for HIV curative strategies. Future studies of anti-CMV therapeutics will help to establish causality and determine the mechanisms underlying these described associations. IMPORTANCE Almost all individuals infected with HIV are also infected with cytomegalovirus (CMV), and the replication dynamics of the two viruses likely influence each other. This study investigated interactions between asymptomatic CMV replication within the male genital tract, levels of inflammation in

Estimated mortality of adult HIV-infected patients starting treatment with combination antiretroviral therapy

PubMed Central

Yiannoutsos, Constantin Theodore; Johnson, Leigh Francis; Boulle, Andrew; Musick, Beverly Sue; Gsponer, Thomas; Balestre, Eric; Law, Matthew; Shepherd, Bryan E; Egger, Matthias

2012-01-01

Objective To provide estimates of mortality among HIV-infected patients starting combination antiretroviral therapy. Methods We report on the death rates from 122 925 adult HIV-infected patients aged 15 years or older from East, Southern and West Africa, Asia Pacific and Latin America. We use two methods to adjust for biases in mortality estimation resulting from loss from follow-up, based on double-sampling methods applied to patient outreach (Kenya) and linkage with vital registries (South Africa), and apply these to mortality estimates in the other three regions. Age, gender and CD4 count at the initiation of therapy were the factors considered as predictors of mortality at 6, 12, 24 and >24 months after the start of treatment. Results Patient mortality was high during the first 6 months after therapy for all patient subgroups and exceeded 40 per 100 patient years among patients who started treatment at low CD4 count. This trend was seen regardless of region, demographic or disease-related risk factor. Mortality was under-reported by up to or exceeding 100% when comparing estimates obtained from passive monitoring of patient vital status. Conclusions Despite advances in antiretroviral treatment coverage many patients start treatment at very low CD4 counts and experience significant mortality during the first 6 months after treatment initiation. Active patient tracing and linkage with vital registries are critical in adjusting estimates of mortality, particularly in low- and middle-income settings. PMID:23172344

Follow-up on long-term antiretroviral therapy for cats infected with feline immunodeficiency virus.

PubMed

Medeiros, Sheila de Oliveira; Abreu, Celina Monteiro; Delvecchio, Rodrigo; Ribeiro, Anísia Praxedes; Vasconcelos, Zilton; Brindeiro, Rodrigo de Moraes; Tanuri, Amilcar

2016-04-01

Feline immunodeficiency virus (FIV) is a lentivirus that induces AIDS-like disease in cats. Some of the antiretroviral drugs available to treat patients with HIV type 1 are used to treat FIV-infected cats; however, antiretroviral therapy (ART) is not used in cats as a long-term treatment. In this study, the effects of long-term ART were evaluated in domestic cats treated initially with the nucleoside transcriptase reverse inhibitor (NTRI) zidovudine (AZT) over a period ranging from 5-6 years, followed by a regimen of the NTRI lamivudine (3TC) plus AZT over 3 years. Viral load, sequencing of pol (reverse transcriptase [RT]) region and CD4:CD8 lymphocyte ratio were evaluated during and after treatment. Untreated cats were evaluated as a control group. CD4:CD8 ratios were lower, and uncharacterized resistance mutations were found in the RT region in the group of treated cats. A slight increase in viral load was observed in some cats after discontinuing treatment. The data strongly suggest that treated cats were resistant to therapy, and uncharacterized resistance mutations in the RT gene of FIV were selected for by AZT. Few studies have been conducted to evaluate the effect of long-term antiretroviral therapy in cats. To date, resistance mutations have not been described in vivo. © ISFM and AAFP 2015.

Can the generic antiretroviral industry support access to a universal antiretroviral regimen?

PubMed

Amole, Carolyn D; Middlecote, Caroline; Prabhu, Vineet R; Kumarasamy, N

2017-07-01

The generic antiretroviral (ARV) industry played a critical role in the massive scale-up of HIV treatment in low-income and middle-income countries since 2000. As the global community looks ahead to a universal antiretroviral regimen, this article considers the industry's role in supporting universal access to affordable, simpler, more durable, and tolerable HIV treatment regimens. Generic manufacturers made treatment scale-up in low-income and middle-income countries possible through reducing prices, combining molecules from different originator companies to develop optimal fixed-dose combinations, and investing in production capacity to meet escalating demand. Achieving scale-up of a universal regimen will require continued partnership in these areas. Collaboration on the demand and supply sides of the ARV marketplace will be required to foster a healthy and sustainable marketplace for new regimens. This includes clear priority setting from the global treatment community on priority products; predictable demand; regulatory prioritization of optimal products; effective tendering and procurement practices that enable multiple suppliers to participate in the market; coordinated product introduction efforts between Ministries of Health, partners, and civil society; and transparency from both buyers and suppliers to promote and monitor supply security. New regimens will benefit people living with HIV, as well as buyers and generic suppliers, by maximizing existing production capacity and treatment budgets to reach the 90-90-90 goals.

Phase II Study of Bevacizumab in Patients With HIV-Associated Kaposi's Sarcoma Receiving Antiretroviral Therapy

PubMed Central

Uldrick, Thomas S.; Wyvill, Kathleen M.; Kumar, Pallavi; O'Mahony, Deirdre; Bernstein, Wendy; Aleman, Karen; Polizzotto, Mark N.; Steinberg, Seth M.; Pittaluga, Stefania; Marshall, Vickie; Whitby, Denise; Little, Richard F.; Yarchoan, Robert

2012-01-01

Purpose Alternatives to cytotoxic agents are desirable for patients with HIV-associated Kaposi's sarcoma (KS). Vascular endothelial growth factor-A (VEGF-A) contributes to KS pathogenesis. We evaluated the humanized anti–VEGF-A monoclonal antibody, bevacizumab, in patients with HIV-KS. Patients and Methods Patients with HIV-KS who either experienced progression while receiving highly active antiretroviral therapy (HAART) for at least 1 month or did not regress despite HAART for at least 4 months were administered bevacizumab 15 mg/kg intravenously on days 1 and 8 and then every 3 weeks. The primary objective was assessment of antitumor activity using modified AIDS Clinical Trial Group (ACTG) criteria for HIV-KS. HIV-uninfected patients were also eligible and observed separately. Results Seventeen HIV-infected patients were enrolled. Fourteen patients had been receiving effective HAART for at least 6 months (median, 1 year). Thirteen patients had advanced disease (ACTG T1), 13 patients had received prior chemotherapy for KS, and seven patients had CD4 count less than 200 cells/μL. Median number of cycles was 10 (range, 1 to 37 cycles); median follow-up was 8.3 months (range, 3 to 36 months). Of 16 assessable patients, best tumor responses observed were complete response (CR) in three patients (19%), partial response (PR) in two patients (12%), stable disease in nine patients (56%), and progressive disease in two patients (12%). Overall response rate (CR + PR) was 31% (95% CI, 11% to 58.7%). Four of five responders had received prior chemotherapy for KS. Over 202 cycles, grade 3 to 4 adverse events at least possibly attributed to therapy included hypertension (n = 7), neutropenia (n = 5), cellulitis (n = 3), and headache (n = 2). Conclusion Bevacizumab is tolerated in patients with HIV-KS and has activity in a subset of patients. PMID:22430271

High-level cross-resistance to didanosine observed in South African children failing an abacavir- or stavudine-based 1st-line regimen.

PubMed

Steegen, Kim; Levin, Leon; Ketseoglou, Irene; Bronze, Michelle; Papathanasopoulos, Maria A; Carmona, Sergio; Stevens, Wendy

2014-01-01

The knowledge-base of emerging drug resistance profiles in children exposed to abacavir-based antiretroviral regimens in South Africa is very limited. This study investigated the suitability of didanosine-based 2nd-line regimens for children in the context of antiretroviral drug resistance patterns emerging after 1st-line virologic failure. A retrospective dataset of 354 antiretroviral drug resistant genotypes from children failing either abacavir (n = 81) or stavudine (n = 273) based 1st-line regimens, was analysed. Samples were sent to the HIV genotyping laboratory at Charlotte Maxeke Johannesburg Academic Hospital, for routine testing. Pol sequences were submitted to the Stanford HIV drug resistance database for genotypic predictions. Children were exposed to abacavir or stavudine-based 1st-line regimens for an average of 21 and 36 months, respectively. The frequency of reduced susceptibility to didanosine was substantial in the abacavir-exposed group (69.1%).This reduced susceptibility was commonly attributed to L74V/I (n = 44) and to a lesser extent K65R (n = 10) mutations. Didanosine resistance was observed in 43.2% of patients exposed to stavudine-based regimens. In contrast, most children remained susceptible to stavudine regardless of exposure to abacavir (77.8%) or stavudine (74.7%). At least 80% of children remained susceptible to zidovudine irrespective of stavudine or abacavir-exposure. The presence of the K65R mutation was more common after abacavir pressure (12.3% vs 1.8%). Analysis revealed that didanosine-based 2nd-line regimens have limitations for South African children, given the high frequency of mutations that confer cross-resistance to didanosine; especially after abacavir-exposure. This data has influenced South African paediatric treatment guidelines, which now recommend zidovudine-based 2nd-line regimens.

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.

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

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

PubMed

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

2009-01-01

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

'I was thinking too much': experiences of HIV-positive adults with common mental disorders and poor adherence to antiretroviral therapy in Zimbabwe.

PubMed

Kidia, Khameer; Machando, Debra; Bere, Tarisai; Macpherson, Kirsty; Nyamayaro, Primrose; Potter, Lucy; Makadzange, Tariro; Munjoma, Ronald; Marufu, Marshall; Araya, Ricardo; Safren, Steven; O'Cleirigh, Conall; Chibanda, Dixon; Abas, Melanie

2015-07-01

To document the lived experiences of people with both poor mental health and suboptimal adherence to antiretroviral therapy in high HIV prevalence settings. In-depth qualitative interviews were conducted with 47 (female = 31) HIV-positive adults who scored above the cut-point on a locally validated scale for common mental disorders (CMDs). Purposive sampling was used to recruit participants with evidence of poor adherence. Six additional key informant interviews (female = 6) were conducted with healthcare workers. Data were collected and analysed inductively by an interdisciplinary coding team. The major challenges faced by participants were stressors (poverty, stigma, marital problems) and symptoms of CMDs ('thinking too much', changes to appetite and sleep, 'burdened heart' and low energy levels). Thinking too much, which appears closely related to rumination, was the symptom with the greatest negative impact on adherence to antiretroviral therapy among HIV-positive adults with CMDs. In turn, thinking too much was commonly triggered by the stressors faced by people living with HIV/AIDS, especially poverty. Finally, participants desired private counselling, access to income-generating activities and family engagement in mental health care. Better understanding of the local expression of mental disorders and of underlying stressors can inform the development of culturally sensitive interventions to reduce CMDs and poor adherence to antiretroviral therapy. © 2015 John Wiley & Sons Ltd.

Antiretroviral Therapy and Central Nervous System HIV-1 Infection

PubMed Central

Price, Richard W.; Spudich, Serena

2008-01-01

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

US hospital care for patients with HIV infection and pneumonia: the role of public, private, and Veterans Affairs hospitals in the early highly active antiretroviral therapy era.

PubMed

Uphold, Constance R; Deloria-Knoll, Maria; Palella, Frank J; Parada, Jorge P; Chmiel, Joan S; Phan, Laura; Bennett, Charles L

2004-02-01

We evaluated differences in processes and outcomes of HIV-related pneumonia care among patients in Veterans Affairs (VA), public, and for-profit and not-for-profit private hospitals in the United States. We compared the results of our current study (1995 to 1997) with those of our previous study that included a sample of patients receiving care during the years 1987 to 1990 to determine how HIV-related pneumonia care had evolved over the last decade. The sample consisted of 1,231 patients with HIV infection who received care for Pneumocystis carinii pneumonia (PCP) and 750 patients with HIV infection who received care for community-acquired pneumonia (CAP) during the years 1995 to 1997. We conducted a retrospective medical record review and evaluated patient and hospital characteristics, HIV-related processes of care (timely use of anti-PCP medications, adjunctive corticosteroids), non-HIV-related processes of care (timely use of CAP treatment medications, diagnostic testing, ICU utilization, rates of endotracheal ventilation, placement on respiratory isolation), length of inpatient hospital stay, and inpatient mortality. Rates of timely use of antibiotics and adjunctive corticosteroids for treating PCP were high and improved dramatically from the prior decade. However, compliance with consensus guidelines that recommend < 8 h as the optimal time window for initiation of antibiotics to treat CAP was lower. For both PCP and CAP, variations in processes of care and lengths of in-hospital stays, but not mortality rates, were noted at VA, public, private not-for-profit hospitals, and for-profit hospitals. This study provides the first overview of HIV-related pneumonia care in the early highly active antiretroviral therapy era, and contrasts current findings with those of a similarly conducted study from a decade earlier. Quality of care for patients with PCP improved, but further efforts are needed to facilitate the appropriate management of CAP. In the third decade of

Marital sex among people living with HIV receiving antiretroviral treatment in northern Thailand.

PubMed

Le Coeur, Sophie; Bozon, Michel; Lelièvre, Eva; Sirijitraporn, Preecha; Pipustanawong, Narongdate; Cowatcharagul, Worawut; Pattanapornpun, Nopporn

2014-01-01

Before the advent of effective antiretroviral treatment (ART), the sexuality of people living with HIV was mostly discussed in terms of risk. To assess the extent to which ART allows people living with HIV to regain a regular sexual life, we surveyed all HIV-infected people treated in four hospitals in Northern Thailand and a control group from the general population matched by sex, age and residence. Data included socio-demographic and health characteristics, frequency of sexual intercourse in the last month and condom use. Our findings indicate that people living with HIV less often live in steady partnership (50% of the HIV-infected people versus 79% of the controls). After adjusting for factors known to influence sexuality, their probability of being sexually active was estimated to be about half that of the controls. When sexually active, men had a reduced sexual activity compared to controls (2.8 intercourse in the last month versus 4.0), while levels of reported sexual activity were similar among women (2.2 versus 2.8, respectively). Consistent condom use was high among people living with HIV (66% for women and 70% for men).

Responses to highly active antiretroviral therapy and clinical events in patients with a low CD4 cell count: late presenters vs. late starters.

PubMed

Waters, L; Fisher, M; Anderson, J; Wood, C; Delpech, V; Hill, T; Walsh, J; Orkin, C; Bansi, L; Gompels, M; Phillips, A; Johnson, M; Gilson, R; Easterbrook, P; Leen, C; Porter, K; Gazzard, B; Sabin, C

2011-05-01

We investigated whether adverse responses to highly active antiretroviral therapy (HAART) associated with late HIV presentation are secondary to low CD4 cell count per se or other confounding factors. A longitudinal analysis of the UK Collaborative HIV Cohort (CHIC) Study of individuals starting HAART in 1998-2007 was carried out, comparing late presenters (presenting/starting HAART at a CD4 count <200 cells/μL) with late starters (presenting at a CD4 count>350 cells/μL; starting HAART at a CD4 count<200 cells/μL), using 'ideal starters' (presenting at a CD4 count>350 cells/μL; starting HAART at a CD4 count of 200-350 cells/μL) as a comparator. Virological, immunological and clinical (new AIDS event/death) outcomes at 48 and 96 weeks were analysed, with the analysis being limited to those remaining on HAART for>3 months. A total of 4978 of 9095 individuals starting first-line HAART with HIV RNA>500 HIV-1 RNA copies/mL were included in the analysis: 2741 late presenters, 947 late starters and 1290 ideal starters. Late presenters were more commonly female, heterosexual and Black African. Most started nonnucleoside reverse transcriptase inhibitors (NNRTIs); 48-week virological suppression was similar in late presenters and starters (and marginally lower than in ideal starters); by week 96 differences were reduced and nonsignificant. The median CD4 cell count increase in late presenters was significantly lower than that in late starters (weeks 48 and 96). During year 1, new clinical events were more frequent for late presenters [odds ratio (OR) 2.04; 95% confidence interval (CI) 1.19-3.51; P=0.01]; by year 2, event rates were similar in all groups. Amongst patients who initiate, and remain on, HAART, late presentation is associated with lower rates of virological suppression, blunted CD4 cell count increases and more clinical events compared with late starters in year 1, but similar clinical and immunological outcomes by year 2 to those of both late and ideal

Antiretroviral therapy for human immunodeficiency virus infection in 1997.

PubMed Central

Katzenstein, D A

1997-01-01

It has become clear that the acquired immunodeficiency syndrome follows continuous replication of the human immunodeficiency virus (HIV) and a decrease in immune capability, most obviously a decline in the number of CD4 lymphocytes. An understanding of key elements in the infectious life cycle of HIV has led to the development of potent antiretroviral drugs selectively targeting unique reverse transcriptase and protease enzymes of the virus. Completed clinical trials have shown that antiretroviral therapy for HIV infection, begun early, reduces viral replication and reverses the decline in CD4 lymphocyte numbers. Recent studies of combination therapies have shown that decreases in plasma HIV viremia to low levels and sustained increases in CD4 cell numbers are associated with longer survival. Potent combination regimens including protease inhibitors and non-nucleoside reverse transcriptase inhibitors suppress detectable viral replication and have demonstrated clinical benefits in patients with advanced disease. Progress in antiretroviral therapy and methods to monitor responses to treatment are providing new hope in the treatment of HIV infection. PMID:9217434

Drug Interactions and Antiretroviral Drug Monitoring

PubMed Central

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

2014-01-01

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

CD4 cell responses to combination antiretroviral therapy in patients starting therapy at high CD4 cell counts.

PubMed

Wright, Stephen T; Carr, Andrew; Woolley, Ian; Giles, Michelle; Hoy, Jennifer; Cooper, David A; Law, Matthew G

2011-09-01

To examine CD4 cell responses to combination antiretroviral therapy (cART) in patients enrolled in the Australian HIV Observational Database who commenced cART at CD4 cell counts >350 cells per microliter. CD4 cell counts were modelled using random effects, repeated measurement models in 432 HIV-infected adults from Australian HIV Observational Database who commenced their first cART regimen and had a baseline CD4 count >350 cells per microliter. Using published AIDS and/or death incidence rates combined with the data summarized by time and predicted CD4 cell count, we calculated the expected reduction in risk of an event for different starting baseline CD4 strata. Mean CD4 counts increased above 500 cells per microliter in all baseline CD4 strata by 12 months (means of 596, 717, and 881 cells/μL in baseline CD4 strata 351-500, 501-650, and >650 cells/μL, respectively) and after 72 months since initiating cART, mean CD4 cell counts (by increasing baseline CD4 strata) were 689, 746, 742 cells per microliter. The expected reduction in risk of mortality for baseline CD4 counts >650 cells per microliter relative to 351-500 cells per microliter was approximately 8%, an absolute risk reduction 0.33 per 1000 treated patient-years. Patients starting cART at high CD4 cell counts (>650 cells/μL) tend to maintain this immunological level over 6 years of follow-up. Patients starting from 351 to 500 CD4 cells per microliter achieve levels of >650 cells per microliter after approximately 3 years of cART. Initiating cART with a baseline CD4 count 501-650 or >650 cells per microliter relative to 351-500 cells per microliter indicated a minimal reduction in risk of AIDS incidence and/or death.

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

PubMed

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

2014-07-01

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

Levels of HIV-1 persistence on antiretroviral therapy are not associated with markers of inflammation or activation

PubMed Central

Bosch, Ronald J.; Macatangay, Bernard J.; Rinaldo, Charles R.; Riddler, Sharon A.; Mellors, John W.

2017-01-01

Antiretroviral therapy (ART) reduces levels of HIV-1 and immune activation but both can persist despite clinically effective ART. The relationships among pre-ART and on-ART levels of HIV-1 and activation are incompletely understood, in part because prior studies have been small or cross-sectional. To address these limitations, we evaluated measures of HIV-1 persistence, inflammation, T cell activation and T cell cycling in a longitudinal cohort of 101 participants who initiated ART and had well-documented sustained suppression of plasma viremia for a median of 7 years. During the first 4 years following ART initiation, HIV-1 DNA declined by 15-fold (93%) whereas cell-associated HIV-1 RNA (CA-RNA) fell 525-fold (>99%). Thereafter, HIV-1 DNA levels continued to decline slowly (5% per year) with a half-life of 13 years. Participants who had higher HIV-1 DNA and CA-RNA before starting treatment had higher levels while on ART, despite suppression of plasma viremia for many years. Markers of inflammation and T cell activation were associated with plasma HIV-1 RNA levels before ART was initiated but there were no consistent associations between these markers and HIV-1 DNA or CA-RNA during long-term ART, suggesting that HIV-1 persistence is not driving or driven by inflammation or activation. Higher levels of inflammation, T cell activation and cycling before ART were associated with higher levels during ART, indicating that immunologic events that occurred well before ART initiation had long-lasting effects despite sustained virologic suppression. These findings should stimulate studies of viral and host factors that affect virologic, inflammatory and immunologic set points prior to ART initiation and should inform the design of strategies to reduce HIV-1 reservoirs and dampen immune activation that persists despite ART. PMID:28426825

The mixed lineage kinase-3 inhibitor URMC-099 improves therapeutic outcomes for long-acting antiretroviral therapy.

PubMed

Zhang, Gang; Guo, Dongwei; Dash, Prasanta K; Araínga, Mariluz; Wiederin, Jayme L; Haverland, Nicole A; Knibbe-Hollinger, Jaclyn; Martinez-Skinner, Andrea; Ciborowski, Pawel; Goodfellow, Val S; Wysocki, Tadeusz A; Wysocki, Beata J; Poluektova, Larisa Y; Liu, Xin-Ming; McMillan, JoEllyn M; Gorantla, Santhi; Gelbard, Harris A; Gendelman, Howard E

2016-01-01

During studies to extend the half-life of crystalline nanoformulated antiretroviral therapy (nanoART) the mixed lineage kinase-3 inhibitor URMC-099, developed as an adjunctive neuroprotective agent was shown to facilitate antiviral responses. Long-acting ritonavir-boosted atazanavir (nanoATV/r) nanoformulations co-administered with URMC-099 reduced viral load and the numbers of HIV-1 infected CD4+ T-cells in lymphoid tissues more than either drug alone in infected humanized NOD/SCID/IL2Rγc-/- mice. The drug effects were associated with sustained ART depots. Proteomics analyses demonstrated that the antiretroviral responses were linked to affected phagolysosomal storage pathways leading to sequestration of nanoATV/r in Rab-associated recycling and late endosomes; sites associated with viral maturation. URMC-099 administered with nanoATV induced a dose-dependent reduction in HIV-1p24 and reverse transcriptase activity. This drug combination offers a unique chemical marriage for cell-based viral clearance. From the Clinical Editor: Although successful in combating HIV-1 infection, the next improvement in antiretroviral therapy (nanoART) would be to devise long acting therapy, such as intra-cellular depots. In this report, the authors described the use of nanoformulated antiretroviral therapy given together with the mixed lineage kinase-3 inhibitor URMC-099, and showed that this combination not only prolonged drug half-life, but also had better efficacy. The findings are hoped to be translated into the clinical setting in the future. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

Pregnancy outcomes following exposure to efavirenz-based antiretroviral therapy in the Republic of Congo.

PubMed

Bisio, Francesca; Nicco, Elena; Calzi, Anna; Giacobbe, Daniele Roberto; Mesini, Alessio; Banguissa, Hubert; Vividila, Nicole Edith; Mahoungou, Pélagie; Boumba, Jean Denis; Mboungou, Franc Astyanax Mayinda; Bruzzone, Bianca; Ratto, Sandra; Icardi, Giancarlo; Viscoli, Claudio; Bruzzi, Paolo

2015-04-01

WHO recently recommended efavirenz (EFV) use for HIV infection through pregnancy, breastfeeding and childbearing age. However the use of EFV during pregnancy remains of concern and not all national guidelines reflect WHO advice. Few data are available concerning pregnancy outcomes. The objective of our study was to evaluate pregnancy outcomes in a cohort of women who conceived on EFV. A retrospective, multicenter cohort study was conducted in Pointe Noire, Republic of Congo (September 2005- June 2012). The following adverse pregnancy outcomes were considered: births defects, low birth weight, premature delivery, stillbirth and abortion, stratified by antiretroviral exposure at the time of conception. During the study period, 188 women conceived on antiretrovirals: 35 (18.6%) on EFV-based regimens and 153 (81.4%) on nevirapine-based regimens. Adverse pregnancy outcomes were observed in 17/35 (48.6%, 95% CI 33.0-64.4%) women in the EFV group and in 43/153 (28.1%, 95% CI 21.6-35.7%) in the non-EFV group (p=0.019). No birth defect was observed in either group. An increased incidence of adverse pregnancy outcomes was observed in the EFV group. As WHO is promoting a widespread use of EFV also for women in childbearing age, our study emphasizes the importance of launching large prospective cohort studies investigating pregnancy outcomes in exposed women.

HIV-1 Viral Escape in Cerebrospinal Fluid of Subjects on Suppressive Antiretroviral Treatment

PubMed Central

Edén, Arvid; Fuchs, Dietmar; Hagberg, Lars; Nilsson, Staffan; Spudich, Serena; Svennerholm, Bo; Price, Richard W.; Gisslén, Magnus

2010-01-01

Background. Occasional cases of viral escape in cerebrospinal fluid (CSF) despite suppression of plasma human immunodeficiency virus type 1 (HIV-1) RNA have been reported. We investigated CSF viral escape in subjects treated with commonly used antiretroviral therapy regimens in relation to intrathecal immune activation and central nervous system penetration effectiveness (CPE) rank. Methods. Sixty-nine neurologically asymptomatic subjects treated with antiretroviral therapy >6 months and plasma HIV-1 RNA <50 copies/mL were cross-sectionally included in the analysis. Antiretroviral therapy regimens included efavirenz, lopinavir/ritonavir or atazanavir/ritonavir combined with tenofovir, abacavir, or zidovudine and emtricitabine or lamivudine. HIV-1 RNA was analyzed with real-time polymerase chain reaction assays. Neopterin was analyzed by enzyme-linked immunosorbent assay. Results. Seven (10%) of the 69 subjects had detectable CSF HIV-1 RNA, in median 121 copies/mL (interquartile range, 54–213 copies/mL). Subjects with detectable CSF virus had significantly higher CSF neopterin and longer duration of treatment. Previous treatment interruptions were more common in subjects with CSF escape. Central nervous system penetration effectiveness rank was not a significant predictor of detectable CSF virus or CSF neopterin levels. Conclusions. Viral escape in CSF is more common than previously reported, suggesting that low-grade central nervous system infection may continue in treated patients. Although these findings need extension in longitudinal studies, they suggest the utility of monitoring CSF responses, as new treatment combinations and strategies modify clinical practice. PMID:21050119

HIV-1 viral escape in cerebrospinal fluid of subjects on suppressive antiretroviral treatment.

PubMed

Edén, Arvid; Fuchs, Dietmar; Hagberg, Lars; Nilsson, Staffan; Spudich, Serena; Svennerholm, Bo; Price, Richard W; Gisslén, Magnus

2010-12-15

Occasional cases of viral escape in cerebrospinal fluid (CSF) despite suppression of plasma human immunodeficiency virus type 1 (HIV-1) RNA have been reported. We investigated CSF viral escape in subjects treated with commonly used antiretroviral therapy regimens in relation to intrathecal immune activation and central nervous system penetration effectiveness (CPE) rank. Sixty-nine neurologically asymptomatic subjects treated with antiretroviral therapy >6 months and plasma HIV-1 RNA <50 copies/mL were cross-sectionally included in the analysis. Antiretroviral therapy regimens included efavirenz, lopinavir/ritonavir or atazanavir/ritonavir combined with tenofovir, abacavir, or zidovudine and emtricitabine or lamivudine. HIV-1 RNA was analyzed with real-time polymerase chain reaction assays. Neopterin was analyzed by enzyme-linked immunosorbent assay. Seven (10%) of the 69 subjects had detectable CSF HIV-1 RNA, in median 121 copies/mL (interquartile range, 54-213 copies/mL). Subjects with detectable CSF virus had significantly higher CSF neopterin and longer duration of treatment. Previous treatment interruptions were more common in subjects with CSF escape. Central nervous system penetration effectiveness rank was not a significant predictor of detectable CSF virus or CSF neopterin levels. Viral escape in CSF is more common than previously reported, suggesting that low-grade central nervous system infection may continue in treated patients. Although these findings need extension in longitudinal studies, they suggest the utility of monitoring CSF responses, as new treatment combinations and strategies modify clinical practice.

Impact of Stewardship Interventions on Antiretroviral Medication Errors in an Urban Medical Center: A 3-Year, Multiphase Study.

PubMed

Zucker, Jason; Mittal, Jaimie; Jen, Shin-Pung; Cheng, Lucy; Cennimo, David

2016-03-01

There is a high prevalence of HIV infection in Newark, New Jersey, with University Hospital admitting approximately 600 HIV-infected patients per year. Medication errors involving antiretroviral therapy (ART) could significantly affect treatment outcomes. The goal of this study was to evaluate the effectiveness of various stewardship interventions in reducing the prevalence of prescribing errors involving ART. This was a retrospective review of all inpatients receiving ART for HIV treatment during three distinct 6-month intervals over a 3-year period. During the first year, the baseline prevalence of medication errors was determined. During the second year, physician and pharmacist education was provided, and a computerized order entry system with drug information resources and prescribing recommendations was implemented. Prospective audit of ART orders with feedback was conducted in the third year. Analyses and comparisons were made across the three phases of this study. Of the 334 patients with HIV admitted in the first year, 45% had at least one antiretroviral medication error and 38% had uncorrected errors at the time of discharge. After education and computerized order entry, significant reductions in medication error rates were observed compared to baseline rates; 36% of 315 admissions had at least one error and 31% had uncorrected errors at discharge. While the prevalence of antiretroviral errors in year 3 was similar to that of year 2 (37% of 276 admissions), there was a significant decrease in the prevalence of uncorrected errors at discharge (12%) with the use of prospective review and intervention. Interventions, such as education and guideline development, can aid in reducing ART medication errors, but a committed stewardship program is necessary to elicit the greatest impact. © 2016 Pharmacotherapy Publications, Inc.

Wavenumber-4 structures observed in the low-latitude ionosphere during low and high solar activity periods using FORMOSAT/COSMIC observations

NASA Astrophysics Data System (ADS)

Onohara, Amelia Naomi; Staciarini Batista, Inez; Prado Batista, Paulo

2018-03-01

The main purpose of this study is to investigate the four-peak structure observed in the low-latitude equatorial ionosphere by the FORMOSAT/COSMIC satellites. Longitudinal distributions of NmF2 (the density of the F layer peak) and hmF2 (ionospheric F2-layer peak height) averages, obtained around September equinox periods from 2007 to 2015, were submitted to a bi-spectral Fourier analysis in order to obtain the amplitudes and phases of the main waves. The four-peak structure in the equatorial and low-latitude ionosphere was present in both low and high solar activity periods. This kind of structure possibly has tropospheric origins related to the tidal waves propagating from below that modulate the E-region dynamo, mainly the eastward non-migrating diurnal tide with wavenumber 3 (DE3, E for eastward). This wave when combined with the migrating diurnal tide (DW1, W for westward) presents a wavenumber-4 (wave-4) structure under a synoptic view. Electron densities observed during 2008 and 2013 September equinoxes revealed that the wave-4 structures became more prominent around or above the F-region altitude peak (˜ 300-350 km). The four-peak structure remains up to higher ionosphere altitudes (˜ 800 km). Spectral analysis showed DE3 and SPW4 (stationary planetary wave with wavenumber 4) signatures at these altitudes. We found that a combination of DE3 and SPW4 with migrating tides is able to reproduce the wave-4 pattern in most of the ionospheric parameters. For the first time a study using wave variations in ionospheric observations for different altitude intervals and solar cycle was done. The conclusion is that the wave-4 structure observed at high altitudes in ionosphere is related to effects of the E-region dynamo combined with transport effects in the F region.

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

PubMed Central

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

1995-01-01

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

Cognitive impairment and antiretroviral treatment in a Peruvian population of patients with human immunodeficiency virus.

PubMed

Guevara-Silva, E A

2014-05-01

HIV-associated cognitive impairment occurs even in the early stages of infection. Short-term memory, psychomotor speed, attention, and executive functioning are the main capacities affected. Controversy exists regarding whether highly active antiretroviral therapy (HAART) is helpful in combating this process. The objective of the present study is to determine the association between cognitive impairment and HAART in HIV-infected patients from Hospital Regional de Huacho. Prospective study of HIV patients meeting criteria to start HAART. Twenty-one HIV-positive patients were recruited between April and July 2011. Researchers administered a standardised neuropsychological test battery before and 4 weeks after onset of HAART. Psychomotor speed, executive function, short term memory (visual and verbal), attention, and visuospatial performance were evaluated. Nineteen patients completed the study (14 males and 5 females). In the pre-HAART evaluation, most patients scored below average on the executive function and psychomotor speed subtests. Psychomotor speed and immediate visual memory improved significantly after four months of treatment with HAART. Some degree of cognitive decline may present even in the early and asymptomatic stages of HIV infection. The benefits of antiretroviral treatment for cognitive performance can be detected after only a few weeks of follow-up. Copyright © 2013 Sociedad Española de Neurología. Published by Elsevier Espana. All rights reserved.

Neurocognitive performance enhanced by highly active antiretroviral therapy in HIV-infected women.

PubMed

Cohen, R A; Boland, R; Paul, R; Tashima, K T; Schoenbaum, E E; Celentano, D D; Schuman, P; Smith, D K; Carpenter, C C

2001-02-16

To determine whether highly active retroviral therapy (HAART) is associated with better neurocognitive outcome over time among HIV-infected women with severely impaired immune function. A semiannual neurocognitive examination on four tasks was administered: Color Trail Making, Controlled Oral Word Association, Grooved Pegboard and Four-Word Learning. This protocol was initiated in the HIV Epidemiological Research study (HERS) study when a woman's CD4 cell count fell to < 100 x 10(6) cells/l. Immune function (CD4), viral load status and depression severity (CESD) were also assessed semi-annually, along with an interview to determine medication intake and illicit drug use. HAART was not available to any participant at the time of enrollment (baseline), while 44% reported taking HAART at their most recent visit (mean duration of HAART 36.3 +/- 12.6 months). HAART-treated women had improved neurocognitive performance compared with those not treated with HAART. Women taking HAART for 18 months or more showed the strongest neurocognitive performance with improved verbal fluency, psychomotor and executive functions. These functions worsened among women not taking HAART. Substance abuse status, severity of depressive symptoms, age and educational level did not influence the HAART treatment effects on neurocognitive performance. Neurocognitive improvements were strongly associated with the magnitude of CD4 cell count increases. HAART appeared to produce beneficial effect on neurocognitive functioning in HIV-infected women with severely impaired immune systems. Benefits were greatest for women who reported receiving HAART for more than 18 months.

Relationship between medication synchronization and antiretroviral adherence.

PubMed

Ghassemi, Emily; Smith, Jennifer; Owens, Laura; Herring, Charles; Holland, Melissa

2018-06-12

To compare antiretroviral adherence (measured as the proportion of days covered [PDC]) and change in viral load in insured, HIV-infected, adult outpatients enrolled and not enrolled in a medication synchronization program. This was a multicenter, retrospective, pilot cohort study. Fifty-eight insured, HIV-infected, outpatients at least 18 years of age receiving antiretroviral therapy (ART) for at least 3 months as of August 2015 were included. PDC, viral load, PDC dichotomized into adherent or nonadherent, and viral load dichotomized into detectable or undetectable were collected for each patient. Study data were compared in those with (enrolled) and without (not enrolled or control) medication synchronization. The study end points were analyzed between the 2 groups retrospectively after 3 months. PDC in patients undergoing medication synchronization was significantly higher than in control patients: mean ± SD 96 ± 9% versus 71 ± 27%, respectively (P < 0.0001). The medication synchronization group was also more likely to be adherent to ART than the control group (odds ratio 10.67, 95% confidence interval 2.63-43.31). In the medication synchronization group, 75.9% of patients had an undetectable baseline viral load, and 83.3% had an undetectable viral load at study completion. In the control group, 62.1% and 64.7% had an undetectable viral load at baseline and completion, respectively. No statistically significant change in viral load was observed between groups (P = 0.34). In insured, HIV-infected, adult outpatients, implementation of a medication synchronization program was associated with improved ART adherence. Future studies are needed to better assess the impact of medication synchronization on clinical outcomes. Copyright © 2018 American Pharmacists Association®. All rights reserved.

Treatment of HIV in the CNS: effects of antiretroviral therapy and the promise of non-antiretroviral therapeutics.

PubMed

Peluso, Michael J; Spudich, Serena

2014-09-01

The growing recognition of the burden of neurologic disease associated with HIV infection in the last decade has led to renewed efforts to characterize the pathophysiology of the virus within the central nervous system (CNS). The concept of the AIDS-dementia complex is now better understood as a spectrum of HIV-associated neurocognitive disorders (HAND), which range from asymptomatic disease to severe impairment. Recent work has shown that even optimally treated patients can experience not only persistent HAND, but also the development of new neurologic abnormalities despite viral suppression. This has thrown into question what the impact of antiretroviral therapy has been on the incidence and prevalence of neurocognitive dysfunction. In this context, the last few years have seen a concentrated effort to identify the effects that antiretroviral therapy has on the neurologic manifestations of HIV and to develop therapeutic modalities that might specifically alter the trajectory of HIV within the CNS.

Antiretroviral therapy for adults infected with HIV: Guidelines for health care professionals from the Quebec HIV care committee

PubMed Central

Rouleau, Danielle; Fortin, Claude; Trottier, Benoît; Lalonde, Richard; Lapointe, Normand; Côté, Pierre; Routy, Jean-Pierre; Matte, Marie-France; Tsarevsky, Irina; Baril, Jean-Guy

2011-01-01

The appropriate use of antiretrovirals reduces morbidity and mortality caused by HIV infection. The present article provides health care professionals with a practical guide for the use of antiretrovirals. Therapy should be initiated based predominantly on clinical presentation and CD4 count, and should consist of three active drugs or at least two active drugs when this is not possible, as in cases of some treatment-experienced patients. This is the most effective way to achieve long-term suppression of viral replication. Selection of individual drugs in the regimen should consider the weight of the evidence supporting these choices, as well as their tolerability profiles and ease of use, the patients’ comorbidities and treatment history. Treatment interruption is not recommended, either in aviremic patients or in those who have experienced virological failure. Instead, the therapeutic regimen should be adjusted to minimize side effects, promote adherence and suppress viral replication. PMID:22654926

Antiretroviral therapy for adults infected with HIV: Guidelines for health care professionals from the Quebec HIV care committee.

PubMed

Rouleau, Danielle; Fortin, Claude; Trottier, Benoît; Lalonde, Richard; Lapointe, Normand; Côté, Pierre; Routy, Jean-Pierre; Matte, Marie-France; Tsarevsky, Irina; Baril, Jean-Guy

2011-01-01

The appropriate use of antiretrovirals reduces morbidity and mortality caused by HIV infection. The present article provides health care professionals with a practical guide for the use of antiretrovirals. Therapy should be initiated based predominantly on clinical presentation and CD4 count, and should consist of three active drugs or at least two active drugs when this is not possible, as in cases of some treatment-experienced patients. This is the most effective way to achieve long-term suppression of viral replication. Selection of individual drugs in the regimen should consider the weight of the evidence supporting these choices, as well as their tolerability profiles and ease of use, the patients' comorbidities and treatment history. Treatment interruption is not recommended, either in aviremic patients or in those who have experienced virological failure. Instead, the therapeutic regimen should be adjusted to minimize side effects, promote adherence and suppress viral replication.

Potential Implication of Residual Viremia in Patients on Effective Antiretroviral Therapy

PubMed Central

2015-01-01

Abstract The current antiretroviral therapy (ART) has suppressed viremia to below the limit of detection of clinical viral load assays; however, it cannot eliminate viremia completely in the body even after prolonged treatment. Plasma HIV-1 loads persist at extremely low levels below the clinical detection limit. This low-level viremia (termed “residual viremia”) cannot be abolished in most patients, even after the addition of a new class of drug, i.e., viral integrase inhibitor, to the combined antiretroviral regimens. Neither the cellular source nor the clinical significance of this residual viremia in patients on ART remains fully clear at present. Since residual plasma viruses generally do not evolve with time in the presence of effective ART, one prediction is that these viruses are persistently released at low levels from one or more stable but yet unknown HIV-1 reservoirs in the body during therapy. This review attempts to emphasize the source of residual viremia as another important reservoir (namely, “active reservoir”) distinct from the well-known latent HIV-1 reservoir in the body, and why its elimination should be a priority in the effort for HIV-1 eradication. PMID:25428885

Mutations Related to Antiretroviral Resistance Identified by Ultra-Deep Sequencing in HIV-1 Infected Children under Structured Interruptions of HAART

PubMed Central

Vazquez-Guillen, Jose Manuel; Palacios-Saucedo, Gerardo C.; Rivera-Morales, Lydia G.; Garcia-Campos, Jorge; Ortiz-Lopez, Rocio; Noguera-Julian, Marc; Paredes, Roger; Vielma-Ramirez, Herlinda J.; Ramirez, Teresa J.; Chavez-Garcia, Marcelino; Lopez-Guillen, Paulo; Briones-Lara, Evangelina; Sanchez-Sanchez, Luz M.; Vazquez-Martinez, Carlos A.; Rodriguez-Padilla, Cristina

2016-01-01

Although Structured Treatment Interruptions (STI) are currently not considered an alternative strategy for antiretroviral treatment, their true benefits and limitations have not been fully established. Some studies suggest the possibility of improving the quality of life of patients with this strategy; however, the information that has been obtained corresponds mostly to studies conducted in adults, with a lack of knowledge about its impact on children. Furthermore, mutations associated with antiretroviral resistance could be selected due to sub-therapeutic levels of HAART at each interruption period. Genotyping methods to determine the resistance profiles of the infecting viruses have become increasingly important for the management of patients under STI, thus low-abundance antiretroviral drug-resistant mutations (DRM’s) at levels under limit of detection of conventional genotyping (<20% of quasispecies) could increase the risk of virologic failure. In this work, we analyzed the protease and reverse transcriptase regions of the pol gene by ultra-deep sequencing in pediatric patients under STI with the aim of determining the presence of high- and low-abundance DRM’s in the viral rebounds generated by the STI. High-abundance mutations in protease and high- and low-abundance mutations in reverse transcriptase were detected but no one of these are directly associated with resistance to antiretroviral drugs. The results could suggest that the evaluated STI program is virologically safe, but strict and carefully planned studies, with greater numbers of patients and interruption/restart cycles, are still needed to evaluate the selection of DRM’s during STI. PMID:26807922

“I was thinking too much”: experiences of HIV-positive adults with common mental disorders and poor adherence to antiretroviral therapy in Zimbabwe

PubMed Central

Kidia, Khameer; Machando, Debra; Bere, Tarisai; Macpherson, Kirsty; Nyamayaro, Primrose; Potter, Lucy; Makadzange, Tariro; Munjoma, Ronald; Marufu, Marshall; Araya, Ricardo; Safren, Steven; O'Cleirgh, Conall; Chibanda, Dixon; Abas, Melanie

2015-01-01

Objective To document the lived experiences of people with both poor mental health and suboptimal adherence to antiretroviral therapy in high HIV prevalence settings. Methods In-depth qualitative interviews were conducted with 47 (female =31) HIV-positive adults who scored above the cut-point on a locally-validated scale for common mental disorders. Purposive sampling was used to recruit participants with evidence of poor adherence. Six additional key informant interviews (female = 6) were conducted with healthcare workers. Data were collected and analysed inductively by an interdisciplinary coding team. Results The major challenges faced by participants were stressors (poverty, stigma, marital problems) and symptoms of common mental disorders (“thinking too much”, changes to appetite and sleep, “burdened heart”, and low energy levels). Thinking too much, which appears closely related to rumination, was the symptom with the greatest negative impact on adherence to antiretroviral therapy among HIV-positive adults with common mental disorders. In turn, thinking too much was commonly triggered by the stressors faced by people living with HIV/AIDS, especially poverty. Finally, participants desired private counselling, access to income generating activities, and family engagement in mental health care. Conclusions Better understanding of the local expression of mental disorders and of underlying stressors can inform the development of culturally sensitive interventions to reduce common mental disorders and poor adherence to antiretroviral therapy. PMID:25754063

Taking Antiretroviral Therapy for HIV Infection

PubMed Central

Laws, M Barton; Wilson, Ira B; Bowser, Diana M; Kerr, Sarah E

2000-01-01

OBJECTIVE To describe how people with HIV understand and experience the problem of adhering to antiretroviral medication regimens. DESIGN We performed a qualitative study based on interviews with HIV-infected patients, including 46 clients of AIDS service organizations, who were sampled according to age, ethnicity, and injection drug use history, and a convenience sample of 15 patients. Interviews were conducted in English or Spanish and were audiotaped and transcribed. PARTICIPANTS Of 52 respondents who had prescriptions for antiretroviral therapy, 25 were randomly selected for in-depth analysis. Of these, 5 reported having an AIDS diagnosis, 15 reported symptoms they attributed to HIV, and 5 reported having no symptoms of HIV disease. MEASUREMENTS AND MAIN RESULTS Investigators prepared structured abstracts of interviews to extract adherence-related data. One investigator compared the abstracts with the original transcripts to confirm the interpretations, and used the abstracts to organize and classify the findings. Most subjects (84%) reported recent nonadherent behavior, including ceasing treatment, medication “holidays,” sleeping through doses, forgetting doses, skipping doses due to side effects, and following highly asymmetric schedules. Initially, most reported that they were not significantly nonadherent, and many did not consider their behavior nonadherent. Only a minority clearly understood the possible consequences of missing doses. Most said they had not discussed their nonadherence with their physicians. CONCLUSIONS Many people rationalize their difficulty in adhering to HIV treatment by deciding that the standard of adherence they can readily achieve is appropriate. Physicians should inquire about adherence-related behavior in specific detail, and ensure that patients understand the consequences of not meeting an appropriate standard. PMID:11119181

The importance of the patient-clinician relationship in adherence to antiretroviral medication.

PubMed

Molassiotis, Alex; Morris, Kate; Trueman, Ian

2007-12-01

The aim of the study was to assess dimensions of the patient-clinician relationship in relation to adherence with antiretroviral medication in a sample of HIV patients. This was a correlational evaluation, using a cross-sectional design. Thirty-eight HIV patients in two UK HIV units provided complete data. Analysis suggested that the elements of the patient-clinician relationship contributing to adherence with medication were the patient perception of being valued and respected by the clinician, the patients' ability to initiate discussions about the treatment, empowerment and level of trust placed in the nurse. The latter, and the time since starting antiretroviral treatment, were the only two variables that could predict adherence in a regression model, explaining 41% of the variance in adherence. Building trusted relationships with the patients and investing in educational and communication techniques to improve the therapeutic relationship could strongly contribute to HIV patients to maintaining high adherence rates.

The importance of the vaginal delivery route for antiretrovirals in HIV prevention

PubMed Central

Ferguson, Lindsay M; Rohan, Lisa Cencia

2012-01-01

The HIV/AIDS pandemic continues to be a global health priority, with high rates of new HIV-1 infections persisting in young women. One HIV prevention strategy is topical pre-exposure prophylactics or microbicides, which are applied vaginally or rectally to protect the user from HIV and possibly other sexually transmitted infections. Vaginal microbicide delivery will be the focus of this review. Multiple nonspecific and specific antiretroviral microbicide products have been clinically evaluated, and many are in preclinical development. The events of HIV mucosal transmission and dynamics of the cervicovaginal environment should be considered for successful vaginal microbicide delivery. Beyond conventional vaginal formulations, intravaginal rings, tablets and films are employed as platforms in the hope to increase the likelihood of microbicide use. Furthermore, combining multiple antiretrovirals within a given formulation, combining a microbicide product with a vaginal device and integrating novel drug-delivery strategies within a microbicide product are approaches to successful vaginal-microbicide delivery. PMID:22468220

Validation of an observation tool to assess physical activity-promoting physical education lessons in high schools: SOFIT.

PubMed

Fairclough, Stuart J; Weaver, R Glenn; Johnson, Siobhan; Rawlinson, Jack

2018-05-01

SOFIT+ is an observation tool to measure teacher practices related to moderate-to-vigorous physical activity (MVPA) promotion during physical education (PE). The objective of the study was to examine the validity of SOFIT+ during high school PE lessons. This cross-sectional, observational study tested the construct validity of SOFIT+ in boys' and girls' high school PE lessons. Twenty-one PE lessons were video-recorded and retrospectively coded using SOFIT+. Students wore hip-mounted accelerometers during lessons as an objective measure of MVPA. Multinomial logistic regression was used to estimate the likelihood of students engaging in MVPA during different teacher practices represented by observed individual codes and a combined SOFIT+ index-score. Fourteen individual SOFIT+ variables demonstrated a statistically significant relationship with girls' and boys' MVPA. Observed lesson segments identified as high MVPA-promoting were related to an increased likelihood of girls engaging in 5-10 (OR=2.86 [95% CI 2.41-3.40]), 15-25 (OR=7.41 [95% CI 6.05-9.06]), and 30-40 (OR=22.70 [95% CI 16.97-30.37])s of MVPA. For boys, observed high-MVPA promoting segments were related to an increased likelihood of engaging in 5-10 (OR=1.71 [95% CI 1.45-2.01]), 15-25 (OR=2.69 [95% CI 2.31-3.13]) and 30-40 (OR=4.26 [95% CI 3.44-5.29])s of MVPA. Teacher practices during high school PE lessons are significantly related to students' participation in MVPA. SOFIT+ is a valid and reliable tool to examine relationships between PE teacher practices and student MVPA during PE. Copyright © 2017 Sports Medicine Australia. Published by Elsevier Ltd. All rights reserved.

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

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.

Starting or changing therapy - a prospective study exploring antiretroviral decision-making.

PubMed

Fehr, J S; Nicca, D; Sendi, P; Wolf, E; Wagels, T; Kiss, A; Bregenzer, T; Vernazza, P; Jäger, H; Spirig, R; Battegay, M

2005-08-01

When to start or change antiretroviral treatment against HIV infection is of major importance. Patients' readiness is considered a major factor influencing such treatment decisions, in particular because no objective, absolute time point when to start antiretroviral therapy exists. We aimed at evaluating patients' readiness to start or change antiretroviral therapy (ART). HIV-infected patients starting or changing ART between July 2002 and February 2003, treating physicians and nurses participated in this prospective, observational multicenter study. We assessed shared decision-making including qualitative aspects, expected treatment decisions and treatment status after 3 months. 75 patients were included. Of 34 patients for whom starting ART was considered, 27 (79%) indicated that they were willing to start treatment. After 3 months, 21 of 27 (78%) actually started therapy, six did not. Patients with depression were less likely to be ready for ART (p < 0.05). Of 41 patients for whom changing ART was considered, 35 (85%) indicated that they were willing to change treatment. Of the latter 35 patients, 33 (94%) finally changed ART within 3 months. Physicians and nurses were too optimistic in predicting the start or change of ART. The main reason to start or change ART was the sole recommendation of the physician (52% in those starting, 61% in those changing ART). Patients mainly judged the decision as shared and were very satisfied (71%) with the process. Qualitative findings revealed the importance of a dialectic decisionmaking, described with two categories: "dealing with oneself and others"' and "understanding and being understood." Patients mainly shared the decision made during consultation. Although physicians have an essential role concerning ART, patients, physicians, and nurses all contribute to the decision. Qualitative findings indicate the importance for health-care providers to include patients' expertise and contributions.

The Effects of Opioid Substitution Treatment and Highly Active Antiretroviral Therapy on the Cause-Specific Risk of Mortality Among HIV-Positive People Who Inject Drugs.

PubMed

Nosyk, Bohdan; Min, Jeong E; Evans, Elizabeth; Li, Libo; Liu, Lei; Lima, Viviane D; Wood, Evan; Montaner, Julio S G

2015-10-01

Prior studies indicated opioid substitution treatment (OST) reduces mortality risk and improves the odds of accessing highly active antiretroviral therapy (HAART); however, the relative effects of these treatments for human immunodeficiency virus (HIV)-positive people who inject drugs (PWID) are unclear. We determine the independent and joint effects of OST and HAART on mortality, by cause, within a population of HIV-positive PWID initiating HAART. Using a linked population-level database for British Columbia, Canada, we used time-to-event analytic methods, including competing risks models, proportional hazards models with time-varying covariates, and marginal structural models, to identify the independent and joint effects of OST and HAART on all-cause as well as drug- and HIV-related mortality, controlling for covariates. Among 1727 HIV-positive PWID, 493 (28.5%) died during a median 5.1 years (interquartile range, 2.1-9.1) of follow-up: 18.7% due to drug-related causes, 55.8% due to HIV-related causes, and 25.6% due to other causes. Standardized mortality ratios were 12.2 (95% confidence interval [CI], 9.8, 15.0) during OST and 30.0 (27.1, 33.1) during periods out of OST. Both OST (adjusted hazard, 0.34; 95% CI, .23, .49) and HAART (0.39 [0.31, 0.48]) decreased the hazard of all-cause mortality; however, individuals were at lowest risk of death when these medications were used jointly (0.16 [0.10, 0.26]). Both OST and HAART independently protected against HIV-related death, drug-related death and death due to other causes. While both OST and HAART are life-saving treatments, joint administration is urgently needed to protect against both drug- and HIV-related mortality. © The Author 2015. 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.

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

Impact of antiretroviral therapy on serum lipoprotein levels and dyslipidemias: a systematic review and meta-analysis.

PubMed

Nduka, Chidozie; Sarki, Ahmed; Uthman, Olalekan; Stranges, Saverio

2015-11-15

Antiretroviral drugs increase biosynthesis and reduce hepatic clearance of serum cholesterol. It is thus important to evaluate the impact of antiretroviral treatment on serum lipoprotein levels and the risk of dyslipidemia. We searched EMBASE and PubMed for articles comparing lipid profiles between HIV-infected adult patients naïve and exposed to antiretroviral therapy (ART). Eligible studies were pooled by performing random-effects meta-analyses of mean serum lipoprotein levels and prevalence estimates of dyslipidemias. 51 observational studies comprising 37,110 patients were included in the meta-analyses. ART-exposed patients had significantly higher concentrations of total cholesterol (45 studies, mean difference [MD]=29.4mg/dL, 95% confidence interval [CI] 26.5 to 32.4, I(2)=82.2%), low density lipoprotein-cholesterol (37 studies, MD=14.9mg/dL, 95% CI 11.2 to 18.5, I(2)=86.1%), and triglycerides (43 studies, MD=46.8mg/dL, 95% CI 37.8 to 55.8, I(2)=97.1%), compared with ART-naïve patients. The risks of hypercholesterolemia (25 studies, pooled odds ratio [OR] 3.8, 95% CI 3.1 to 4.7, I(2)=60.0%) and hypertriglyceridemia (21 studies, OR 2.2, 95% CI 1.7 to 2.9, I(2)=81.7%) were also significantly higher among ART-exposed patients, compared with ART-naïve patients. Antiretroviral therapy is significantly associated with increase in serum lipid levels and increased risk of dyslipidemia. Whether or not these associations are causal should be investigated by future studies. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Utilization and costs of HIV antiretroviral drugs in Europe during the last ten years: Impact of generic antiretroviral drugs on cost reduction.