Lack of effect of compartmentalized drug resistance mutations on HIV-1 pol divergence in antiretroviral-experienced women

Objective: To examine the persistence of compartmentalized HIV drug resistance mutations (DRM) over time in the female genital tract and its effect on pol gene divergence compared to that in blood. Design: Longitudinal cohort of 22 antiretroviral-experienced women in the Emory Vaginal Ecology study. Methods: Blood and vaginal secretions were collected at serial clinic visits. DRM in the HIV reverse transcriptase and protease regions of pol were determined using population based sequencing. Kimura-2 pairwise DNA distances were calculated to measure blood and vaginal secretions divergence in the intervals between clinic visits. Results: Only eight (36%) women had compartmentalized DRM detected at 14 (31%) of their 45 clinic visits. This compartmentalized resistance was transient; 13 of 14 mutations in blood and all 12 mutations in vaginal secretions were compartmentalized for only one clinic visit. Over time, divergence of both reverse transcriptase and protease were greater in vaginal secretions than in blood. However, divergence in blood, but not in vaginal secretions, increased significantly in the presence of drug resistance or compartmentalized drug resistance. Conclusion: Compartmentalized DRM between the blood and vaginal secretions are transient in nature, and the presence of DRM does not affect pol gene divergence in the vaginal secretions. Our results provide new evidence that the genital mucosa does not support an independently evolving subpopulation of HIV-1 genomes. (C) 2010 Wolters Kluwer Health | Lippincott Williams & Wilkins