5th Conference on Retroviruses and Opportunistic Infections Chicago, IL - February 1-5, 1998

Conf Retroviruses Opportunistic Infect 1998 Feb 1-5; 5th:81 (abstract no. 13)

Lennox JL, Ellerbrock TV, Schinazi RF, Clancy K, Pratt-Palmore M, Bush T, Hough L, Schnell C, Hart C; Emory University, Atlanta, GA.

OBJECTIVE: To compare HIV-1 genotypes, RNA quasispecies, drug resistance mutations, and the quantity of HIV and HCV in plasma and vaginal secretions.

METHODS: Plasma and vaginal ravage samples were obtained from women enrolled in a prospective study, a subset of whom were receiving antiretroviral therapy. The C2-V(3) region of gp120 was examined using direct cycle sequencing of HIV-1 DNA amplified from reverse-transcribed RNA. Drug resistance mutations in the reverse transcriptase region of pol were detected using sequencing and a Line Probe Assay. For quasispecies analysis, amplified DNA was cloned and sequenced. HCV and HIV RNA were quantified using the respective Roche RT-PCR assays.

RESULTS: The major C2-V(3) genotypes expressed in plasma and vaginal ravage were determined for 7 women. The predicted amino acid differences between plasma and vaginal virus for 5 of the 7 women were 0%, 0.9%, 3.5%, 7%, and 9.6%. For the 2 older women, the major vaginal species had an insertion or deletion, not found in the major plasma species, that would result in a truncated gp120 protein. In one woman, phylogenetic analysis showed a distinct segregation of most vaginal and plasma quasispecies with only 3 minor plasma clones grouping with the 10 vaginal clones. Of 8 women tested repeatedly, 4 had drug resistance mutations in plasma. None of these 4 developed a simultaneous resistance mutation in the vagina. For each of 5 women, the HCV viral load was greater than the HIV viral load in plasma. In the vaginal lavages of these women, HIV viral loads ranged from 7,000-122,000 copies/ ravage, while HCV RNA was undetectable. None of the lavages inhibited the quantification of the HCV internal standard.

CONCLUSIONS: The differences in gp120 genotypes, RNA quasispecies, drug resistance mutations, and comparative amounts of HIV and HCV suggest that selected HIV-1 variants are actively produced in the female genital tract.

1998-02-01
13

Copyright © 1998 - Foundation for Retrovirology and Human Health (IAS). Reproduction of this abstract (other than one copy for personal reference) must be cleared through the Foundation for Retrovirology and Human Health. Licensed from National Library of Medicine.