Background

Recent studies have indicated a relatively high prevalence of drug resistance mutations in patients newly infected with HIV in North America and Europe, reflecting the transmission of resistant virus.

It has been unclear to what degree transmitted resistance mutations persist in the absence of antiretroviral therapy, as they would appear to confer no replicative advantage to the virus in the absence of antiretroviral therapy.

Persistence of Transmitted Drug-resistant Virus among Subjects with Primary HIV Infection Deferring Antiretroviral Therapy

Abstract: Little S, Koelsch K, Ignacio C, et al. Persistence of Transmitted Drug-resistant Virus among Subjects with Primary HIV Infection Deferring Antiretroviral Therapy. 11th CROI, Abstract 36LB.

Description: To evaluate this question, this study followed 12 subjects with primary HIV infection (mean time from estimated date of exposure, 56 days) who had at least one major drug resistance mutation at presentation and who elected to defer antiretroviral therapy. Subjects were evaluated by repeated sampling for a median of 310 days.

Results: By nucleotide sequence analysis of the reverse transctiptase gene (pol) 10 subjects had NNRTI resistance mutations at baseline, 4 had PI mutations, and 5 had NRTI mutations. In subjects with NNRTI resistance mutations, the mean time to detection of a wild type/resistant virus mixture (indicating partial reversion to wild type) was 375 days. In only one subject did NNRTI resistance revert fully (within the sensitivity of the assay) to wild type, at day 1019. In subjects with NRTI mutations (all of whom also had PI and/or NNRTI mutations), the mean time to detection of wild type/resistant mixture was 362 days; none reverted fully to wild type. In those with PI resistance mutations, none showed reversion to wild type in up to 689 days of follow up.

Unlike resistant viruses in ARV-experienced patients, these transmitted resistant viruses, with one exception, were not associated with reduced replication capacity.

Comment: Transmitted drug resistance mutations involving the three major antiretroviral drug classes appear to persist for months, even years, after infection. Reversion to wild type may occur incompletely, resulting in mixtures of wild type and resistant virus.

These finding have implications for treatment of recently and chronically infected individuals and lend support to recommendations favoring the use of resistance assays prior to initial treatment.