Longitudinal Assessment of Systemic and Genital Tract Inflammatory Markers and Endogenous Genital Tract E. coli Inhibitory Activity in HIV-Infected and Uninfected Women.

PROBLEM: Stability over time of systemic and mucosal immunity and their associations with bacterial vaginosis (BV) and HIV-specific parameters were assessed. METHOD OF STUDY: Immune mediators and HIV viral load in plasma and cervicovaginal lavage (CVL), E. coli inhibition, and Nugent score were measured at three semiannual visits among 94 participants in the Women's Interagency HIV Study. Mixed models identified the factors associated with immune mediators. RESULTS: There was higher E. coli inhibition and lower inflammation over time in the genital tract and systemically. BV was consistently associated with higher CVL inflammatory mediators and lower CVL E. coli inhibition. HIV-infected women with higher CD4 counts had lower systemic and genital inflammatory mediators, and genital HIV shedding was associated with higher CVL inflammatory mediators. Use of antiretroviral therapy (ART) was associated with lower plasma and CVL mediators, but higher E. coli inhibition. CONCLUSION: HIV and BV are linked to inflammation, and ART may be associated with improved vaginal health.

Evaluation of 3 approaches for assessing adherence to vaginal gel application in clinical trials.

BACKGROUND: Accurate measurement of adherence to product use is an ongoing challenge in microbicide trials. METHODS: We compared adherence estimates using 2 applicator tests (a dye stain assay [DSA] and an ultraviolet light assay [UVA]), the Wisebag (an applicator container that electronically tracks container openings), and self-reported adherence (ability, frequency, and percent missed doses). Healthy, HIV-negative, nonpregnant US women aged 23 to 45 years received a Wisebag and 32 applicators filled with placebo gel were instructed to insert 1 applicator daily for 30 days, returned the Wisebag and all applicators, and completed an exit interview. Emptied applicators were tested by UVA and then DSA, and scored by 2 blinded readers. Positive and negative controls were randomly included in applicator batches. RESULTS: Among 42 women enrolled, 39 completed the study. Both DSA and UVA yielded similar sensitivity (97% and 95%) and specificity (79% and 79%). Two participants had fully inoperable Wisebags, and 9 had partially inoperable Wisebags. The proportion of participants considered to have high adherence (≥80%) varied: 43% (Wisebag), 46% (UVA), 49% (DSA), and 62% to 82% (self-reports). For estimating high adherence, Wisebag had a sensitivity of 76% (95% confidence interval, 50%-93%) and a specificity of 85% (95% confidence interval, 62%-97%) compared with DSA. Although 28% of participants reported forgetting to open the Wisebag daily, 59% said that it helped them remember gel use. CONCLUSIONS: Dye stain assay and UVA performed similarly. Compared with these tests, self-reports overestimated and Wisebag underestimated adherence. Although Wisebag may encourage gel use, the applicator tests currently seem more useful for measuring use in clinical trials.

Assessment of adherence to product dosing in a pilot microbicide study.

OBJECTIVES: To determine whether applicator staining could be incorporated into a microbicide study as a marker of adherence. GOAL: To test whether observers could identify intravaginally inserted applicators and compare the observers' ratings to subjects' self reports. STUDY DESIGN: Subjects participating in a 14-day microbicide trial to assess the safety of 0.5% PRO 2000 or matched placebo gel returned used and unused applicators. Each applicator was individually dyed or batched and immersed in a 0.4% trypan blue waterbath. Masked observers rated the applicators as intravaginally inserted or not; results were compared to subjects' self-reports. To determine if the dye would allow observers to differentiate whether applicators had been filled before intravaginal insertion, staff either filled applicators and discarded gel ex vivo or asked volunteers to intravaginally insert applicators without gel and mixed these with a random sampling of used and unused study samples. RESULTS: 358 of 360 applicators were returned; 306 were reported to have been vaginally inserted and 52 unused. Observers agreed with the participant's self reports in 98-99% of cases. No differences were observed between applicators stained individually or in batches. The ability to distinguish between applicators that were presumed to have been used properly, intravaginally inserted without gel, filled with gel and emptied ex vivo, or unused ranged from 76 to 87%. CONCLUSIONS: Staining of applicators is accurate, inexpensive, and correlated well with self-report in a study of short duration. This method could prove useful in assessing adherence to product dosing in future microbicide trials.

Male sexual dysfunction associated with antiretroviral therapy.

To determine whether treatment with protease inhibitors (PIs) is associated with male sexual dysfunction, we conducted a retrospective, cohort study of 254 adult male PI recipients who received care from the staff-model division of a large managed care organization in New England between 1993 and 1998. After a median of 5.0 years of observation, 80 incident cases of sexual dysfunction were observed. Relative to unexposed individuals, the rate of sexual dysfunction adjusted for confounding was most elevated with use of ritonavir (hazard ratio [HR], 2.83; 95% confidence interval [CI], 1.34-5.97; p =.006) followed by indinavir (HR, 1.69; 95% CI, 0.84-3.37; p =.14), nelfinavir (HR, 1.53; 95% CI, 0.66-3.54; p =.32) and saquinavir (HR, 1.25; 95% CI, 0.53-2.96; p =.60). We conclude that PIs, especially ritonavir, appear to increase the risk of sexual dysfunction.