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Selection analyses of paired HIV-1 gag and gp41 sequences obtained before and after antiretroviral therapy.

ABSTRACT: Most HIV-1-infected individuals with virological failure on a pharmacologically-boosted protease inhibitor (PI) regimen do not develop PI-resistance protease mutations. One proposed explanation is that HIV-1 gag or gp41 cytoplasmic domain mutations might also reduce PI susceptibility. In a recent study of paired gag and gp41 sequences from individuals with virological failure on a PI regimen, we did not identify PI-selected mutations and concluded that if such mutations existed, larger numbers of paired sequences from multiple studies would be needed for their identification. In this study, we generated site-specific amino acid profiles using gag and gp41 published sequences from 5,338 and 4,242 ART-naïve individuals, respectively, to assist researchers identify unusual mutations arising during therapy and to provide scripts for performing established and novel maximal likelihood estimates of dN/dS substitution rates in paired sequences. The pipelines used to generate the curated sequences, amino acid profiles, and dN/dS analyses will facilitate the application of consistent methods to paired gag and gp41 sequence datasets and expedite the identification of potential sites under PI-selection pressure.

SUBMITTER: Tzou PL

PROVIDER: S-EPMC6057438 | biostudies-literature | 2018 Jul

REPOSITORIES: biostudies-literature

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Selection analyses of paired HIV-1 gag and gp41 sequences obtained before and after antiretroviral therapy.

Tzou Philip L PL Rhee Soo-Yon SY Pond Sergei L Kosakovsky SLK Manasa Justen J Shafer Robert W RW

Scientific data 20180724

Most HIV-1-infected individuals with virological failure on a pharmacologically-boosted protease inhibitor (PI) regimen do not develop PI-resistance protease mutations. One proposed explanation is that HIV-1 gag or gp41 cytoplasmic domain mutations might also reduce PI susceptibility. In a recent study of paired gag and gp41 sequences from individuals with virological failure on a PI regimen, we did not identify PI-selected mutations and concluded that if such mutations existed, larger numbers o ...[more]

PMID: 30040081

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Project description:IntroductionInfants born to women living with HIV initiating combination antiretroviral therapy (cART) late in pregnancy are at high risk of intrapartum infection. Mother/infant perinatal antiretroviral intensification may substantially reduce this risk.MethodsIn this single-arm Bayesian trial, pregnant women with HIV receiving standard of care antiretroviral prophylaxis in Thailand (maternal antenatal lopinavir-based cART; nonbreastfed infants 4 weeks' postnatal zidovudine) were offered "antiretroviral intensification" (labor single-dose nevirapine plus infant zidovudine-lamivudine-nevirapine for 2 weeks followed by zidovudine-lamivudine for 2 weeks) if their antenatal cART was initiated ≤8 weeks before delivery. A negative birth HIV-DNA polymerase chain reaction (PCR) followed by a confirmed positive PCR defined intrapartum transmission. Before study initiation, we modeled intrapartum transmission probabilities using data from 3738 mother/infant pairs enrolled in our previous trials in Thailand using a logistic model, with perinatal maternal/infant antiretroviral regimen and predicted viral load at delivery as main covariates. Using the characteristics of the women enrolled who received intensification, prior intrapartum transmission probabilities (credibility intervals) with/without intensification were estimated. After including the transmission data observed in the current study, the corresponding Bayesian posterior transmission probability was derived.ResultsNo intrapartum transmission of HIV was observed among the 88 mother/infant pairs receiving intensification. The estimated intrapartum transmission probability was 2·2% (95% credibility interval 0·5-6·1) without intensification versus 0·3% (0·0-1·6) with intensification. The probability of superiority of intensification over standard of care was 94·4%. Antiretroviral intensification appeared safe.ConclusionMother/infant antiretroviral intensification was effective in preventing intrapartum transmission of HIV in pregnant women receiving ≤8 weeks antepartum cART.

Dataset Information

Selection analyses of paired HIV-1 gag and gp41 sequences obtained before and after antiretroviral therapy.

Publications

Selection analyses of paired HIV-1 gag and gp41 sequences obtained before and after antiretroviral therapy.

Similar Datasets

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