A total of 57 women enrolled in the study, 38 in Seattle and 19 in Rochester, and completed a total of 391 visits (median visits per person 6, range 1–15). In total, 312 of 391 visits (80%) had complete data for analysis. Participants ranged in age from 23 to 52 years, with a mean of 38
6 years. At enrollment, the mean plasma viral load was 26,218
c/ml, the CD4 count was 456
285 cells/ml, and the use of antiretroviral therapy was reported by 31/57 (54%). The cohort was primarily white 33/57 (58%), with 13/57 (23%) reporting African-American race and 11/57 (19%) reporting another ethnicity. Just over half, 38/57(55%), had a high school education or less, 10/57(17%) reported some college or technical school, and 9/57 (16%) reported college education or masters degree. Mean gravidity was 6
8 and mean parity was 3
The majority of samples (72%) were collected during the luteal phase of the menstrual cycle. At over half of the visits (52%) women had been sexually active in the past 30 days, and at a third of the visits (30%) women had been sexually active in the past week, but the median time since last intercourse was 13 days (IQR 5, 16). The majority of women (71%) reported sex in the past year with only male partners, while 5 (9%) reported only female partners and 6 (11%) reported both genders. Of 53 women who answered the question at the enrollment visit, 9 (17%) reported never using condoms (4 of whom reported sex only with women in the past year), while 24 (45%) reported always using condoms.
Genital shedding of HIV-1 RNA was detected in CVL at 56/312 (18%) of the visits. The most common genital infection was BV, diagnosed at 89 (29%) of 312 visits, followed by yeast, which was present at 64/312 visits (21%). Trichomoniasis was diagnosed at a small number of visits (15/312, 5%), as were N. gonorrhea and C. trachomatis (4/312, 1%). Although 38/45 (84%) of participants had positive serology for HSV-2, genital shedding of HSV-2 was detected at only 7/312 (2%) of visits. CMV shedding was detected at 10/312 (3%) of visits. H2O2-producing lactobacilli were detected at the majority of visits (193/312; 62%). At 46/312 (15%) visits women had intermediate Nugent scores (4–6). Nonspecific cervicitis, diagnosed by the presence of more than 30 white blood cells per high-powered microscopy field in a cervical swab, was present at 123/312 (39%) of visits.
IL-1β was detectable at 278/312 (90%) visits, IL-6 at 161 (52%), IL-8 at 308 (99%), and SLPI at 232 (74%). In univariate analysis, the presence of abnormal vaginal flora, trichomoniasis, and HSV-2 shedding () were associated with higher levels of IL-1β, while the presence of H2O2-producing lactobacilli was associated with lower levels. Yeast vaginitis and HSV-2 shedding were associated with higher levels of IL-8, while the presence of an abnormal Nugent score was associated with lower quantities of SLPI.
Results of Univariate Regression Analysis for Association Between Cytokines Measured in Cervicovaginal Lavage and Presence of Genital Infections at 391 Visits from 57 HIV-1-Infected Womena
Values of IL-1β and IL-8 were significantly different between visits with and without HIV-1 genital shedding detected (). In regression analysis CVL IL-1β and IL-8 were significantly associated with concentration of CVL HIV-1 RNA and this persisted after adjusting for plasma HIV RNA (). After adjusting for the presence of H2O2+ Lactobacillus, abnormal Nugent score, yeast, Trichomonas, and CMV or HSV-2 genital shedding, this relationship was attenuated for IL-1β but was still significant for IL-8. Adjusting for sexual activity in the past month, time since sex, time since menses, antiretroviral use, or HSV-2 serology did not change the results of the analysis (data not shown).
Multivariate Analysis of Association Between Cervicovaginal Lavage Cytokines and HIV-1 Genital Sheddinga