Declining trend in transmission of drug-resistant HIV-1 in Amsterdam

Abstract

Objective: Symptomatic primary HIV infections are over-represented in the mainly hospital-based studies on transmission of resistant HIV-1. We examined a more general population for the prevalence of resistant HIV-1 strains among primary infections.

Design: From 1994 to 2002 primary infections were identified within the Amsterdam Cohort Studies (ACS) among homosexual men and drug users, and at the Academic Medical Center (AMC). Whereas primary HIV-1-infected AMC patients, often presented with symptoms of acute retroviral syndrome, ACS participants largely seroconverted during follow-up and thus brought also asymptomatic primary infections to our study.

Methods: Reverse transcriptase (RT) and protease sequences were obtained by population-based nucleotide sequence analysis of the first HIV RNA-positive sample available. Subtypes were identified by phylogenetic analysis. Mutations were identified based on the IAS-USA resistance table.

Results: A total of 100 primary HIV-1 infections were identified (32 AMC and 68 ACS). Transmission of drug-resistant strains decreased over calendar time, with 20% [95% confidence interval (CI), 10-34%] of infections bearing drug-resistant mutations before 1998 versus only 6% (95% CI, 1-17%) after 1998. No multi-drug resistance pattern was observed. The median plasma HIV-1 RNA level of the first RNA positive sample was significantly lower for the individuals infected with a resistant strain versus those infected with wild-type, suggesting a fitness-cost to resistance. Four of seven non-B subtypes corresponded with the prevalent subtype in the presumed country of infection, and none showed resistance mutations.

Conclusions: The transmission of drug-resistant HIV-1 strains in Amsterdam has decreased over time. Monitoring should be continued as this trend might change.