|
|
|
|
Cervicovaginal Shedding of HIV-1 Is Related to Genital Tract Inflammation Independent of Changes in Vaginal Microbiota
|
|
|
Reported by Jules Levin_CROI 2009 Feb 8-12 Montreal
Caroline Mitchell*1, J Hitti1, K Paul1, K Agnew1, R Gausman1, S Cohn2, A Luque2, and R Coombs1
1Univ of Washington, Seattle, US and 2Univ of Rochester, NY, US
Background: Genital tract inflammation from infection or other causes may increase genital shedding of HIV-1. We examined the relationship of pro-inflammatory vaginal cytokines and secretory leukocyte protease inhibitor (SLPI) with genital HIV-1 shedding after controlling for genital co-infections.
Methods: We enrolled 57 HIV-1-infected women in a prospective, observational study in Seattle, Washington (n = 38) and Rochester, New York (n = 19) and followed them every 3 to 4 months for a total of 391 visits (median visits per person, 6). At each visit, plasma and cervicovaginal lavage (CVL) were tested for HIV-1 RNA using an independently validated quantitative polymerase chain reaction (qPCR) assay. Vaginal swabs were tested for bacterial vaginosis/intermediate flora (Gram stain), yeast (culture), hydrogen peroxide-producing (H2O2+) Lactobacillus colonization (culture), Trichomonas vaginalis (In-Pouch), Neisseria gonorrhoeae, and Chlamydia trachomatis (Amplicor PCR). CVL was tested for interleukins (IL) -1b, -6, and -8 and SLPI using ELISA. We used linear regression with generalized estimating equations to examine effects of log10 cytokine concentrations on log10 CVL HIV-1 RNA, adjusted for log10 plasma HIV RNA, abnormal vaginal flora, H2O2+ Lactobacillus colonization, yeast and T. vaginalis.
Results: Of 391 visits, we obtained complete data for analysis for 348 (89%). Mean entry CD4 count was 456±285 cells/μL, and use of ART was reported at 54% of baseline visits. Log10 CVL IL-1b and IL-8 were significantly associated with log10 CVL HIV-1 RNA and this persisted after adjusting for log10 plasma HIV RNA. For each doubling of log10 IL-1b, the geometric mean log10 CVL HIV-1 concentration was increased 1.20-fold (p = 0.001); for a doubling of IL-8, it increased 1.24-fold (p <0.001). After adjusting for the presence of H2O2+ Lactobacillus (61% visits), bacterial vaginosis or intermediate vaginal flora (45%), yeast (20%), and T. vaginalis (5%), this relationship was attenuated but still significant (IL-1b, p = 0.031; IL-8, p <0.001.)
Conclusions: The pro-inflammatory cytokines IL-1b and IL-8 are associated with higher cervicovaginal HIV-1 RNA concentrations, an association which persists after controlling for plasma viral load and vaginal microbial co-factors. This association suggests that there may be additional, non-infectious causes of inflammation that increase cervicovaginal HIV-1 shedding.
|
|
|
|
|
|
|