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Background:  HIV-1 populations in different body compartments may present unique viral dynamics. We compared the response of vaginal and plasma HIV-1 to anti-retrovirals by identifying drug-resistance mutations.  Cell tropism and phylogenetic relationship between plasma and vaginal HIV-1 was determined by C2-V3 sequences to assess the role of vaginal tract as viral reservoir.

Methods:  We collected 45 paired blood and vaginal samples from HIV-1-infected females. Viral loads were assessed using Amplicor HIV Monitor. Paired HIV-1 samples were analyzed for drug resistance mutations using TruGene Genotyping Kit. Envelope C2-V3 region was amplified, cloned and sequenced.

Results:  Detectable RNA in both plasma and vaginal samples was found in 16 of 45 (35.5%) cases and sequences were obtained for 15. Concordant drug resistance mutation patterns between plasma and vaginal HIV-1 were observed in 26.6% (4/15) cases. Discordant mutation patterns between plasma and vaginal HIV-1 were observed in 73.3% (11/15) of cases. Two cases (18.2%) appeared to show delayed emergence of drug resistance in vaginal HIV-1 while 3 cases (27.3%) appeared to show delayed clearance of drug resistance from vaginal HIV-1. Treatment history of "discordant" cases showed about 18% of cases presented delayed emergence of resistance in vaginal HIV-1 while about 27% showed delayed clearance of resistant mutants from vaginal virus even 2 to 4 years after stopping use of the drug. Sequence homology was lower (91.7 to 97.5%) in cases with discordant patterns compared to those with concordant patterns (98.9% to 99.9%). In most cases, we observed higher variability in plasma C2-V3 and 10-66.7% of clones were T-tropic. In all cases, vaginal HIV-1 was M tropic despite presence of T-tropic viruses in plasma and regardless of concordance or discordance of resistance mutations. C2-V3 phylogenetic analysis showed plasma and vaginal sequences tended to cluster separately, suggesting they represent independent viral lineages.

Conclusions:  Our data suggests the vaginal HIV-1 lineage may be evolving under particular population dynamics and local selective forces independently from plasma HIV-1. The presence of delayed emergence/clearance of drug resistance mutations suggests differences in viral turnover rates and other local differences that may include pharmacological factors. These observations suggest the vaginal tract may serve as reservoir for M-tropic drug resistant strains.

Keywords: vaginal; resistance; discordance