Transmitted drug-resistant HIV-1 in primary HIV-1 infection; incidence, evolution and impact on response to antiretroviral therapy

Objectives The aim of the study was to determine the incidence and persistence of transmitted drug-resistant HIV-1 in an incident cohort between 2000 and 2004, and to investigate the impact of transmitted drug-resistant HIV-1 on the response to antiretroviral therapy (ART). Methods A prospective, nonrandomized study was carried out on 140 individuals identified with primary HIV-1 infection (PHI). PHI was defined as an HIV-positive antibody test with an HIV antibody-negative result in the prior 6 months (n=69); positive HIV DNA in the absence of antibody (n=30); an evolving titre positive HIV antibody test (n=23), or an incident 'detuned' assay (B clade viruses only) (n=18). Genotypic resistance testing was performed at baseline, following ART and annually over a 4-year period. Results The prevalence of transmitted drug-resistant HIV-1 infection between January 2000 and June 2004 was nine in 140 (6.0%) and the annual incidence was stable. Seven of these nine patients had a single point mutation conferring single-class drug resistance and the other two patients had multiple mutations conferring multiclass drug resistance (MDR). In eight of the nine cases, mutations conferring drug resistance persisted for more than 12 months off therapy. In contrast to transmitted MDR HIV-1, the virological response to initial ART and CD4 decline were comparable in those with wild-type virus, virus with 'polymorphisms' (secondary mutations) and virus with single drug-resistance mutations. Conclusions The incidence of transmitted drug-resistant HIV remained stable and low over a 4-year period. Although MDR remains rare, its presence significantly affects the response to first-line ART, predisposes towards the accumulation of new resistance mutations and is associated with a more rapid CD4 decline.