Background: The frequency of transmitted drug resistant HIV-1 has varied in recent years. In addition, the degree to which these viruses are related has remained unexplored.

Methods: Baseline samples from 85 newly HIV-1 infected individuals (NI) identified in 2001–2002 were analyzed by sequencing (TruGene) and by drug susceptibility testing (PhenoSense). Phylogenetic analyses were performed to infer linkages between sequences of protease (PR) and reverse transcriptase (RT) regions of 219 NI recruited at a single clinical site between 1995–2002.

Results: Eighty-five (85) genotypes and 80 phenotypes were available for analysis (C: 2001–2002 n = 85) and were compared to the findings of previous observation periods (A: 1995–1998 n = 76; B: 1999–2000 n = 71). The prevalence of genotypic resistance decreased in the last 2 yrs (A: 13.2%, B: 19.7%, C: 14.1%). The frequency of variants with reduced susceptibility to any drug (> 5-fold) varied to a lesser extent over the years (A: 7.9%, B: 9.9%, C: 8.2%). The pattern of drug resistance, however, changed in 2001–2002; we noted a sharp drop of resistance to NRTI, while genotypic and phenotypic resistance to PI and NNRTI increased. There were 7 known transmission events during acute infection, 5 of which occurred in 2001–2002. Therefore, we tested the entire dataset for unrecognized linkages. Fourteen (14) additional links (13 pairs and a cluster of 6) within the cohort were seen (bootstrap: > 75%). In contrast to the 7 known pairs that displayed minimal intra-sample distances (median: 0, range 0–0.0012), the 13 phylogenetically linked sequence pairs were characterized by significantly larger pairwise distances (median: 0.018, range: 0.004–0.035). However, these distances remained distinctively smaller than those between unlinked samples (median 0.051). The group of 6 sequences consisted of a subset of 5 samples from 2000–2002 (range: 0–0.012) that clustered with a sample from 1997 (bootstrap: 100%). Three (3) of the 21 pairs/cluster involved drug resistant strains (16% of all documented resistant variants 1995–2002).

Conclusions: While there was an increase in resistance to PI and NNRTI, the overall prevalence of transmitted drug resistance has decreased during the last 2 yrs. It seems that the spread of viruses, as mapped in this homogenous cohort over the past 7 yrs, is mainly due to independent events. However, phylogenetic analyses based on PR and RT sequences confirmed linkage in 7 cases and identified 14 previously unrecognized links.