[show abstract][hide abstract] ABSTRACT: Nevirapine (NVP) is widely used in antiretroviral treatment (ART) of HIV-1 globally. The primary objective of the AA5208/OCTANE trial was to compare the efficacy of NVP-based versus lopinavir/ritonavir (LPV/r)-based initial ART.
In seven African countries (Botswana, Kenya, Malawi, South Africa, Uganda, Zambia, and Zimbabwe), 500 antiretroviral-naïve HIV-infected women with CD4<200 cells/mm(3) were enrolled into a two-arm randomized trial to initiate open-label ART with tenofovir (TDF)/emtricitabine (FTC) once/day plus either NVP (n = 249) or LPV/r (n = 251) twice/day, and followed for ≥48 weeks. The primary endpoint was time from randomization to death or confirmed virologic failure ([VF]) (plasma HIV RNA<1 log(10) below baseline 12 weeks after treatment initiation, or ≥400 copies/ml at or after 24 weeks), with comparison between treatments based on hazard ratios (HRs) in intention-to-treat analysis. Equivalence of randomized treatments was defined as finding the 95% CI for HR for virological failure or death in the range 0.5 to 2.0. Baseline characteristics were (median): age = 34 years, CD4 = 121 cells/mm(3), HIV RNA = 5.2 log(10)copies/ml. Median follow-up = 118 weeks; 29 (6%) women were lost to follow-up. 42 women (37 VFs, five deaths; 17%) in the NVP and 50 (43 VFs, seven deaths; 20%) in the LPV/r arm reached the primary endpoint (HR 0.85, 95% CI 0.56-1.29). During initial assigned treatment, 14% and 16% of women receiving NVP and LPV/r experienced grade 3/4 signs/symptoms and 26% and 22% experienced grade 3/4 laboratory abnormalities. However, 35 (14%) women discontinued NVP because of adverse events, most in the first 8 weeks, versus none for LPV/r (p<0.001). VF, death, or permanent treatment discontinuation occurred in 80 (32%) of NVP and 54 (22%) of LPV/r arms (HR = 1.7, 95% CI 1.2-2.4), with the difference primarily due to more treatment discontinuation in the NVP arm. 13 (45%) of 29 women tested in the NVP versus six (15%) of 40 in the LPV/r arm had any drug resistance mutation at time of VF.
Initial ART with NVP+TDF/FTC demonstrated equivalent virologic efficacy but higher rates of treatment discontinuation and new drug resistance compared with LPV/r+TDF/FTC in antiretroviral-naïve women with CD4<200 cells/mm(3).
PLoS Medicine 06/2012; 9(6):e1001236. · 15.25 Impact Factor
[show abstract][hide abstract] ABSTRACT: AIDS Clinical Trials Group (ACTG) A5199 compared the neurological and neuropsychological (NP) effects of 3 antiretroviral regimens in participants infected with human immunodeficiency virus type 1 (HIV-1) in resource-limited settings.
Participants from Brazil, India, Malawi, Peru, South Africa, Thailand, and Zimbabwe were randomized to 3 antiretroviral treatment arms: A (lamivudine-zidovudine plus efavirenz, n = 289), B (atazanavir, emtricitabine, and didanosine-EC, n = 293), and C (emtricitabine-tenofovir-disoproxil fumarate plus efavirenz, n = 278) as part of the ACTG PEARLS study (A5175). Standardized neurological and neuropsychological (NP) screening examinations (grooved pegboard, timed gait, semantic verbal fluency, and finger tapping) were administered every 24 weeks from February 2006 to May 2010. Associations with neurological and neuropsychological function were estimated from linear and logistic regression models using generalized estimating equations.
The median weeks on study was 168 (Q1 = 96, Q3 = 192) for the 860 participants. NP test scores improved (P < .05) with the exception of semantic verbal fluency. No differences in neurological and neuropsychological functioning between treatment regimens were detected (P > .10). Significant country effects were noted on all NP tests and neurological outcomes (P < .01).
The study detected no significant differences in neuropsychological and neurological outcomes between randomized ART regimens. Significant improvement occurred in neurocognitive and neurological functioning over time after initiation of ARTs. The etiology of these improvements is likely multifactorial, reflecting reduced central nervous system HIV infection, better general health, and practice effects. This study suggests that treatment with either of the World Health Organization -recommended first-line antiretroviral regimens in resource-limited settings will improve neuropsychological functioning and reduce neurological dysfunction.
[show abstract][hide abstract] ABSTRACT: Little is known about how the prevalence and incidence of neurological disease in HIV-infected patients in resource-limited settings. We present an analysis of neurological and neurocognitive function in antiretroviral naïve individuals in multinational resource-limited settings. This prospective multinational cohort study, a substudy of a large international randomized antiretroviral treatment trial, was conducted in seven low- and middle-income countries in sub-Saharan Africa, South America, and Asia. Subjects were HIV-infected and met regional criteria to initiate antiretroviral therapy. Standardized neurological examination and a brief motor-based neuropsychological examination were administered. A total of 860 subjects were studied. Overall 249 (29%) had one or more abnormalities on neurological examinations, but there was a low prevalence of HIV-associated dementia (HAD) and minor neurocognitive disorder (MND). Twenty percent of subjects had evidence of peripheral neuropathy. There were significant differences across countries (p < 0.001) in neuropsychological test performance. In this first multinational study of neurological function in antiretroviral naïve individuals in resource-limited settings, there was a substantial prevalence of peripheral neuropathy and low prevalence of dementia and other CNS diseases. There was significant variation in neurocognitive test performance and neurological examination findings across countries. These may reflect cultural differences, differences in HIV-related and unrelated diseases, and variations in test administration across sites. Longitudinal follow-up after antiretroviral treatment initiation may help to define more broadly the role of HIV in these differences as well as the impact of treatment on performance.
Journal of NeuroVirology 07/2011; 17(5):438-47. · 2.85 Impact Factor
[show abstract][hide abstract] ABSTRACT: In July of 2006, the National Institute of Mental Health (NIMH) Center for Mental Health Research on AIDS (CMHRA) sponsored the second conference on the Assessment of NeuroAIDS in Africa, which was held in Arusha, Tanzania. The conference mission was to address the regional variations in epidemiology of HIV-related neurological disorders as well as the assessment and diagnosis of these disorders. Participants discussed and presented data regarding the relevance and translation of neuroAIDS assessment measures developed in resource intensive settings and the challenges of neuro-assessment in Africa, including the applicability of current tools, higher prevalence of confounding diseases, and the complexity of diverse cultural settings. The conference presentations summarized here highlight the need for further research on neuroAIDS in Africa and methods for assessing HIV-related neurological disorders.
Journal of NeuroVirology 05/2008; 14(2):87-101. · 2.85 Impact Factor
[show abstract][hide abstract] ABSTRACT: Tuberculosis (TB) and cryptococcosis are common infectious complications in HIV in resource-limited settings and contribute substantial morbidity and mortality. The increasing access to highly active antiretroviral treatment (HAART) has invited numerous challenges such as timing of HAART, cotreatment (drug dosages and interaction), immune reconstitution syndromes, and withdrawal of chemoprophylaxis. Numerous small studies propose the feasibility of concomitant TB/HIV treatment that needs to be confirmed in large, randomized trials. Treatment of acute cryptococcocal meningo-encephalitis with amphoterecin B is fraught with logistic problems in resource-limited settings. An effective safe dose of fluconazole as monotherapy needs to be determined in phase II studies. Current management guidelines extrapolated from developed countries may not necessarily apply and need validation in resource-limited settings.
[show abstract][hide abstract] ABSTRACT: A 67-year male presented with relapse 14 days after treatment with vancomycin for a MRSA ventriculitis. CSF samples taken at the time of relapse grew MRSA with a MIC for vancomycin of 4 mg/L by E-test and therapy with linezolid (600 mg bd) and intraventricular vancomycin (20 mg od) was initiated. Using the macrodilution E-test, the isolate was found to have sub-populations with a MIC for vancomycin of 8 mg/L and teicoplanin of 12 mg/L and a population analysis profile almost identical to the hVISA strain MU3, indicative of a hVISA strain. Concentrations of vancomycin in the CSF over the period of therapy ranged from 25.6-192.5 mg/L after intraventricular administration and those of linezolid ranged from 3.4-6.7 mg/L after intravenous administration, exceeding the MICs for this isolate. The patient made a successful recovery, with no further episodes of ventriculitis at 1-year follow-up. We report the first case of ventriculitis due to hVISA. It was successfully treated with intrathecal vancomycin and intravenous linezolid. We also believe this to be the first documented case of clinical infection due to hVISA in South Africa.
Journal of Infection 05/2005; 50(3):252-7. · 4.07 Impact Factor