Background:  HIV vaccine efficacy trials recruit individuals at risk for HIV infection and follow them for incident infection. Viruses from the seroconvertors in these studies can provide an estimate of the prevalence of HIV-1 drug resistance in the study population. We performed protease (PR) and reverse transcriptase (RT) genotypic testing of the HIV isolates from subjects who seroconverted during the first large scale HIV-1 vaccine efficacy trial.

Methods:  From June 1998 through October 1999, 5095 HIV-seronegative non-monogamous men who had anal sex with men (MSM) and 308 women at high risk for HIV were enrolled into a 36-month, randomized, double-blind, placebo-controlled recombinant HIV-1 gp-120 vaccine efficacy trial. The study population was recruited at 61 clinical trial sites in 50 cities and 28 states in the United States, 3 cities in Canada, and 1 in the Netherlands. The study population was 83% white with median age of 36.  Subjects were vaccinated at baseline and months 1, 6, 12, 18, 24, and 30. Demographics, behavioral data, and HIV status were assessed at baseline and at 6-month intervals. The PR and RT genes from the HIV isolates obtained at the time of seroconversion were sequenced. The analysis considered amino acid substitutions as indicative of decreased drug susceptibility if they were included on the World Health Organization mutation list for surveillance of transmitted HIV drug resistance.

Results:  As previously reported, the vaccine proved ineffective and over the course of the trial, there were 362 infections in men and 6 infections in women. We sequenced 286 of the isolates. Among the isolates sequenced, there were 46 (16%) with ≥1 drug-resistance mutations:  28 isolates (10%) with nucleoside, 22 (8%) with non-nucleoside reverse transcriptase inhibitor (NNRTI), and 21 (7%) with protease inhibitor (PI) resistance mutations. We saw 2 drug class resistance mutations in 14 (5%), and 3 drug class resistance mutations in 6 (2%) of subjects.

Conclusions:  HIV vaccine efficacy trials offer the opportunity to study acute HIV infection and the prevalence of HIV resistance. The wide geographic distribution of the participants in this study suggests that the prevalence of circulating drug resistance mutations in newly infected, predominantly MSM in the United States is more geographically diverse than previously reported.