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.


METHODS
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.


CONCLUSIONS
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.
Kelley
Colleen F
CF
Emory University Department of Medicine, Atlanta, Georgia, USA. cfkelle@emory.edu <cfkelle@emory.edu>
Sullivan
Sharon T
ST
Lennox
Jeffrey L
JL
Evans-Strickfaden
Tammy
T
Hart
Clyde E
CE
D000293:Adolescent; D000328:Adult; D024882:Drug Resistance, Viral / Q000187:drug effects / Q000235:genetics*; D005260:Female; D015751:Genes, pol / Q000235:genetics*; D015658:HIV Infections / Q000097:blood / Q000188:drug therapy / Q000235:genetics* / Q000821:virology; D016333:HIV Protease / Q000235:genetics; D054303:HIV Reverse Transcriptase / Q000235:genetics; D015497:HIV-1 / Q000187:drug effects / Q000235:genetics*; D006801:Humans; D008137:Longitudinal Studies; D008875:Middle Aged; D009154:Mutation; D012367:RNA, Viral; D014621:Vagina / Q000821:virology*; D019562:Viral Load; D055815:Young Adult
D012367:RNA, Viral; D054303:HIV Reverse Transcriptase; D016333:HIV Protease