ABSTRACT
OBJECTIVE: While transmission of drug-resistant HIV-1 has been reported, estimates of prevalence of resistance in drug-naïve populations are incomplete. We investigated the prevalence of genotypic mutations and phenotypic antiretroviral resistance in a cohort of HIV-1 infected U.S. military personnel prior to the institution of antiretroviral therapy. DESIGN: Cross-sectional cohort study. METHODS: Plasma was obtained from 114 recently HIV-1 infected subjects enrolled in an epidemiological study. Genotypic resistance was determined by consensus sequencing of a PCR product from the HIV-1 pol gene. Sequences were interpreted by a phenotypic-genotypic correlative database. Resistance phenotypes were determined by a recombinant virus cell culture assay. RESULTS: Genotypic mutations and phenotypic resistance were found at a higher than expected frequency. Resistance to non-nucleoside reverse transcriptase inhibitors was most common, with a prevalence of 15% of 95 subjects by genotype and 26% of 91 subjects by phenotype. Genotypic and phenotypic resistance respectively were found in 4% and 8% of subjects for nucleoside reverse transcriptase inhibitors and in 10% and 1% for protease inhibitors. One subject harbored virus with resistance to all three drug classes. CONCLUSIONS: A substantial frequency of resistance to antiretroviral drugs was identified in a therapy-naïve U.S. cohort. In most cases, the genotypic and phenotypic assays yielded similar results, although the genotypic assay could detect some protease inhibitor resistance-associated mutations in the absence of phenotypic resistance. These data suggest the need for optimization of treatment guidelines based on current estimates of the prevalence of drug resistance in HIV-1 seroconverters.
Subject(s)
Anti-HIV Agents/pharmacology , HIV Infections/virology , HIV-1/drug effects , Military Personnel , Reverse Transcriptase Inhibitors/pharmacology , Adult , Cohort Studies , Cross-Sectional Studies , Drug Resistance, Microbial/genetics , Drug Resistance, Multiple/genetics , Female , Genes, pol , Genotype , HIV Infections/drug therapy , HIV Infections/epidemiology , HIV-1/classification , HIV-1/genetics , Humans , Male , Microbial Sensitivity Tests/methods , Middle Aged , Mutation , Phenotype , RNA, Viral/analysis , Recombination, Genetic , United StatesABSTRACT
BACKGROUND: Regular testing of military personnel identifies early HIV infection; this identification provides a sentinel cohort in which to describe the evolving molecular epidemiology of HIV-1 transmission. OBJECTIVE: To describe the prevalence and epidemiologic correlates associated with the acquisition of non-subtype B and drug-resistant HIV infections. DESIGN: Cross-sectional study. SETTING: Military referral hospital. PATIENTS: 95 military personnel with HIV-1 seroconversion. MEASUREMENTS: Self-reported questionnaire, CD4 cell counts, plasma HIV-1 RNA levels, and nucleic acid sequence analysis for drug-resistant mutations and HIV-1 genetic subtype. RESULTS: 95 patients were enrolled between February 1997 and February 1998. The likely geographic location of HIV-1 acquisition was overseas in 8% of patients, the United States in 68%, and either overseas or the United States in 24%. Seven patients (7.4%) had subtype E infection; the remainder had subtype B infection. Eight of 31 (26%) treatment-naive patients had mutations in the reverse transcriptase or protease gene associated with drug resistance. CONCLUSIONS: The percentage of HIV-1 non-subtype B infection and antiretroviral drug-resistant mutations was relatively high in U.S. military personnel with recently acquired HIV-1 infection.
