Differential virus evolution in blood and genital tract of HIV-infected females: evidence for the involvement of drug and non-drug resistance-associated mutations.
There is increasing evidence that male or female genital tract represent a distinct replication compartment for human immunodeficiency virus type 1 (HIV-1) and that such compartments may serve as a virus reservoir. Forty-four paired plasma and vaginal samples from HIV-infected females undergoing HAART were collected to examine the viral responses to antiretroviral therapy and to assess the possible role of the vaginal tract as a reservoir for drug-resistant variants. Twenty-one females had detectable viral RNA both in plasma and vaginal fluid, whereas 14 females had detectable virus only in plasma. Twelve paired samples were used to analyze HIV-1 pol sequences for the presence of drug resistance-associated mutations. Nine of the twelve paired samples exhibited discordant drug resistance mutation patterns. The other three females showed identical drug resistance-associated mutations. However, further examination of protease and RT showed numerous non-drug-associated mutations that corresponded to predefined CTL epitopes. These non-drug-associated mutations were different between plasma and vaginal viruses, suggesting that evolution of HIV-1 was independent in these two compartments.
Tirado
Grissell
G
Laboratory of Viral Immunology, Ponce School of Medicine, Ponce 00732, Puerto Rico.
Jove
Gloria
G
Kumar
Rakesh
R
Noel
Richard J
RJ
Reyes
Evelyn
E
Sepulveda
Gladys
G
Yamamura
Y
Y
Kumar
Anil
A
D000328:Adult; D000595:Amino Acid Sequence; D019380:Anti-HIV Agents / Q000494:pharmacology*; D023241:Antiretroviral Therapy, Highly Active; D018562:Disease Transmission, Infectious; D024882:Drug Resistance, Viral / Q000235:genetics*; D005260:Female; D015751:Genes, pol / Q000235:genetics; D015658:HIV Infections / Q000097:blood / Q000635:transmission / Q000821:virology*; D016333:HIV Protease / Q000235:genetics; D054303:HIV Reverse Transcriptase / Q000235:genetics; D015497:HIV-1 / Q000187:drug effects / Q000235:genetics*; D006801:Humans; D018445:Infectious Disease Transmission, Vertical; D008969:Molecular Sequence Data; D009154:Mutation; D012367:RNA, Viral / Q000032:analysis / Q000097:blood; D016415:Sequence Alignment; D014621:Vagina / Q000821:virology
D019380:Anti-HIV Agents; D012367:RNA, Viral; D054303:HIV Reverse Transcriptase; D016333:HIV Protease