Dataset Information

Antiretroviral drug susceptibility among drug-naive adults with recent HIV infection in Rakai, Uganda.

ABSTRACT: OBJECTIVE:To analyze antiretroviral drug susceptibility in HIV from recently infected adults in Rakai, Uganda, prior to the availability of antiretroviral drug treatment. METHODS:Samples obtained at the time of HIV seroconversion (1998-2003) were analyzed using the GeneSeq HIV and PhenoSense HIV assays (Monogram Biosciences, Inc., South San Francisco, California, USA). RESULTS:Test results were obtained for 104 samples (subtypes: 26A, 1C, 66D, 9A/D, 1C/D, 1 intersubtype recombinant). Mutations used for genotypic surveillance of transmitted antiretroviral drug resistance were identified in six samples: three had nucleoside reverse transcriptase inhibitor (NRTI) surveillance mutations (two had M41L, one had K219R), and three had protease inhibitor surveillance mutations (I47V, F53L, N88D); none had nonnucleoside reverse transcriptase inhibitor (NNRTI) surveillance mutations. Other resistance-associated mutations were identified in some samples. However, none of the samples had a sufficient number of mutations to predict reduced antiretroviral drug susceptibility. Ten (9.6%) of the samples had reduced phenotypic susceptibility to at least one drug (one had partial susceptibility to didanosine, one had nevirapine resistance, and eight had resistance or partial susceptibility to at least one protease inhibitor). Fifty-three (51%) of the samples had hypersusceptibility to at least one drug (seven had zidovudine hypersusceptibility, 28 had NNRTI hypersusceptibility, 34 had protease inhibitor hypersusceptibility). Delavirdine hypersusceptibility was more frequent in subtype A than D. In subtype D, efavirenz hypersusceptibility was associated with substitutions at codon 11 in HIV-reverse transcriptase. CONCLUSION:Phenotyping detected reduced antiretroviral drug susceptibility and hypersusceptibility in HIV from some antiretroviral-naive Ugandan adults that was not predicted by genotyping. Phenotyping may complement genotyping for analysis of antiretroviral drug susceptibility in populations with nonsubtype B HIV infection.

SUBMITTER: Eshleman SH

PROVIDER: S-EPMC2676205 | biostudies-literature | 2009 Apr

REPOSITORIES: biostudies-literature

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Antiretroviral drug susceptibility among drug-naive adults with recent HIV infection in Rakai, Uganda.

Eshleman Susan H SH Laeyendecker Oliver O Parkin Neil N Huang Wei W Chappey Colombe C Paquet Agnes C AC Serwadda David D Reynolds Steven J SJ Kiwanuka Noah N Quinn Thomas C TC Gray Ronald R Wawer Maria M

AIDS (London, England) 20090401 7

<h4>Objective</h4>To analyze antiretroviral drug susceptibility in HIV from recently infected adults in Rakai, Uganda, prior to the availability of antiretroviral drug treatment.<h4>Methods</h4>Samples obtained at the time of HIV seroconversion (1998-2003) were analyzed using the GeneSeq HIV and PhenoSense HIV assays (Monogram Biosciences, Inc., South San Francisco, California, USA).<h4>Results</h4>Test results were obtained for 104 samples (subtypes: 26A, 1C, 66D, 9A/D, 1C/D, 1 intersubtype rec ...[more]

PMID: 19276794

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Project description:ImportanceMedical male circumcision (MMC) and antiretroviral therapy (ART) are proven HIV prevention interventions, but there are limited data on the population-level effect of scale-up of these interventions in sub-Saharan Africa. Such evaluation is important for planning and resource allocation.ObjectiveTo examine whether increasing community MMC and ART coverage was associated with reduced community HIV incidence in Rakai District, Uganda.Design, setting, and participantsUsing person-level data from population-based surveys conducted from 1999 through 2013 in 45 rural Rakai communities, community-level ART and MMC coverage, sociodemographics, sexual behaviors, and HIV prevalence and incidence were estimated in 3 periods: prior to the availability of ART and MMC (1999-2004), during early availability of ART and MMC (2004-2007), and during mature program scale-up (2007-2013).ExposuresCommunity MMC coverage in males and ART coverage in HIV-positive persons of the opposite sex based on self-reported MMC status and ART use.Main outcomes and measuresAdjusted incidence rate ratios (IRRs) for sex-specific community HIV incidence estimated using multivariable Poisson regression with generalized estimating equations.ResultsFrom 1999 through 2013, 44,688 persons participated in 1 or more surveys (mean age at the first survey, 24.6 years [range, 15-49]; female, 56.5%; mean survey participation rate, 92.6% [95% CI, 92.4%-92.7%]). Median community MMC coverage increased from 19% to 39%, and median community ART coverage rose from 0% to 21% in males and from 0% to 26% in females. Median community HIV incidence declined from 1.25 to 0.84 per 100 person-years in males, and from 1.25 to 0.99 per 100 person-years in females. Among males, each 10% increase in community MMC coverage was associated with an adjusted IRR of 0.87 (95% CI, 0.82-0.93). Comparing communities with MMC coverage more than 40% (mean male community incidence, 1.03 per 100 person-years) with communities with coverage of 10% or less (mean male incidence, 1.69 per 100 person-years), the adjusted IRR was 0.61 (95% CI, 0.43-0.88). For each 10% increase in female self-reported ART coverage, there was no significant reduction in male HIV incidence (adjusted IRR, 0.95 [95% CI, 0.81-1.13]). Comparing communities with female ART coverage more than 20% (mean male incidence, 0.87 per 100 person-years) to communities with female ART coverage of 20% or less (mean male incidence, 1.17 per 100 person-years), the adjusted IRR was 0.77 (95% CI, 0.61-0.98). Neither MMC nor male ART coverage was associated with lower female community HIV incidence.Conclusions and relevanceIn Rakai, Uganda, increasing community MMC and female ART coverage was associated with lower community HIV incidence in males. If similar associations are found elsewhere, this would support further scale-up of MMC and ART for HIV prevention in sub-Saharan Africa.

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Antiretroviral drug susceptibility among drug-naive adults with recent HIV infection in Rakai, Uganda.

Publications

Antiretroviral drug susceptibility among drug-naive adults with recent HIV infection in Rakai, Uganda.

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