Antiretroviral (ARV) drug resistance in the developing world.
ABSTRACT To describe the overall prevalence of ARV resistance in the developing world, focusing on: (1) treatment naïve populations, (2) the resistance consequences of prevention of mother to child transmission (pMTCT) drug regimens, and (3) the relationship of medication adherence to resistance.
We searched PubMed(R), EMBASE, the Cochrane Controlled Clinical Trials Register Database, and the Cochrane Database of Reviews of Effectiveness (DARE). Additional sources of evidence included the Stanford University HIV Drug Resistance Database; reports of WATCH: Worldwide Analysis of Resistance Transmission over Time of Chronically and Acute Infected HIV-1 infected persons; a recent unpublished pMTCT overview; and various conference proceedings. Studies that did not report original research, that reported data already reported in another article, and case studies of fewer than 20 individuals were excluded. Of 1,122 titles identified, 117 journal articles and presentations were included.
We abstracted data on geographic region, number of participants, subject demographics, HIV viral clade, medications taken (if any), years of data collection, how people were selected for resistance testing, and how and when resistance was assessed. Because of study heterogeneity, pooling was not possible; thus, the data are summarized qualitatively. Differences by region, population group, and HIV viral clade are described.
The patterns of ARV resistance among treatment naïve populations worldwide appear to reflect geographic trends in use of ARV medications. A worldwide surveillance program (WATCH) found the rate of resistance (to any drug) among treatment naïve individuals was 5.5 percent in Africa, 7.4 percent in East Asia, 5.7 percent in Southeast Asia, and 6.4 percent in Latin America, lower than in North America (11.4 percent) and Europe (10.6 percent). Resistance data on HIV clades other than A, B, C, and D were too scarce to permit reliable conclusions. We also identified very few studies designed to assess the effect of health services delivery factors or medication adherence on the development of resistance in patients in developing countries. Evidence provided by longitudinal analyses suggests that, among women taking intrapartum single dose nevirapine (SD-NVP) to prevent mother-to-child transmission of HIV, both the overall prevalence of NNRTI resistance as well as the frequency of mutant virus in the overall viral population decreases with time since SD-NVP prophylaxis was received.
In future resistance studies, rare HIV clades should be over-sampled in order to provide statistically meaningful data. Resistance surveillance programs should be maintained throughout the developing world, and data should be reported and analyzed in a consistent and timely manner. Where resources permit, studies of adherence in developing regions should conduct resistance testing.
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ABSTRACT: HIV-infected patients receiving antiretroviral (ARV) therapy (ART) in India are not all adequately virally suppressed. We analyzed ARV drug resistance in adults receiving ART in three private clinics in Mumbai, India. HIV viral load was measured in 200 patients with the Roche AMPLICOR HIV-1 Monitor Test, v1.5. HIV genotyping was performed with the ViroSeq HIV-1 Genotyping System for 61 participants who had HIV-1 RNA >1000 copies/ml. Genotyping results were obtained for 51 samples. The participants with resistance results were on ART for a median of 24 months and were on their current regimen for a median of 12 months (median CD4 cell count: 217 cells/mm(3); median HIV viral load: 28,200 copies/ml). ARV regimens included nonnucleoside reverse transcriptase inhibitor (NNRTI)-based regimens (n = 27), dual nucleoside reverse transcriptase inhibitors (NRTIs, n = 19), protease inhibitor (PI)-based regimens (n = 3), and other regimens (n = 2). Twenty-six participants (51.0%) were on their first ARV regimen and 24 (47%) reported >95% adherence. Forty-nine participants (96.1%) had resistance to at least one ARV drug; 47 (92.2%) had NRTI resistance, 32 (62.7%) had NNRTI resistance, and four (7.8%) had PI resistance. Thirty (58.8%) had two-class resistance and three (5.9%) had three-class resistance. Four (8%) had three or more resistance mutations associated with etravirine resistance and two (4%) had two mutations associated with reduced darunavir susceptibility. Almost all patients with HIV-1 RNA >1000 copies/ml had NRTI resistance and nearly two-thirds had NNRTI resistance; PI resistance was uncommon. Nearly 60% and 6% had two- and three-class resistance, respectively. This emphasizes the need for greater viral load and resistance monitoring, use of optimal ART combinations, and increased availability of second- and third-line agents for patients with ARV resistance.AIDS research and human retroviruses 01/2010; 26(1):25-31. · 2.18 Impact Factor
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ABSTRACT: To assess the impact of long-term combined antiretroviral therapy (cART) on HIV-RNA and HIV-DNA levels in cervicovaginal secretions of HIV-1-infected women with sustained undetectable plasma RNA viral load (PVL); to explore factors predictive of residual viral shedding; and to evaluate the risk of heterosexual transmission. Women with undetectable PVL (<50 copies/mL) for >6 months were included in this cross-sectional study. HIV-RNA and HIV-DNA were measured in blood and cervicovaginal lavage fluid (CVL). Women were systematically tested for genital infections. The risk of transmission to male partners during unprotected intercourse was estimated. Eighty-one women composed the study population: all had HIV-RNA <40 copies/mL in CVL. HIV-DNA was detectable in CVL of 29/78 patients (37%). There was a weak positive correlation between HIV-DNA levels in PBMCs and CVL (r = 0.20; p = 0.08). In multivariate analysis, two factors were associated with HIV-DNA detection in CVL: previous AIDS-defining illnesses (OR = 11; 95%CI = 2-61) and current residual viremia (20<PVL<50 cp/mL) (OR = 3.4; 95%CI = 1.1-10.9). Neither the classes of cART regimen nor the presence of genital bacterial or fungal colonization were associated with HIV-DNA detection in CVL. Twenty-eight percent of the women had unprotected intercourse with their regular HIV-seronegative male partner, for between 8 and 158 months. None of their male partners became infected, after a total of 14 000 exposures. In our experience, HIV-RNA was undetectable in the genital tract of women with sustained control of PVL on cART. HIV-DNA shedding persisted in about one third of cases, with no substantial evidence of residual infectiousness.PLoS ONE 01/2013; 8(8):e69686. · 3.53 Impact Factor
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ABSTRACT: Over 2 million children are thought to be living with HIV/AIDS worldwide, of whom over 80% live in sub-Saharan Africa. Without antiretroviral treatment, the risk of HIV transmission from infected mothers to their children is 15% to 30% during gestation or labour, with an additional transmission risk of 10% to 20% associated with prolonged breastfeeding. HIV-1 infection accounts for most infections; HIV-2 is rarely transmitted from mother to child. Transmission is more likely in mothers with high viral loads, advanced disease, or both, in the presence of other sexually transmitted diseases, and with increased exposure to maternal blood. Mixed feeding practices (breast milk plus other liquids or solids) and prolonged breastfeeding are also associated with increased risk of mother-to-child transmission of HIV. METHODS AND OUTCOMES: We conducted a systematic review and aimed to answer the following clinical question: What are the effects of measures to reduce mother-to-child transmission of HIV? We searched: Medline, Embase, The Cochrane Library, and other important databases up to October 2009 (Clinical Evidence reviews are updated periodically, please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA). We performed a GRADE evaluation of the quality of evidence for interventions. We found 53 systematic reviews, RCTs, or observational studies that met our inclusion criteria. In this systematic review we present information relating to the effectiveness and safety of the following interventions: antiretroviral drugs, different methods of infant feeding, elective caesarean section, immunotherapy, micronutrient supplements, vaginal microbicides, and vitamin supplements.Clinical evidence 01/2011; 2011.