No increase in cervicovaginal proinflammatory cytokines after Carraguard use in a placebo-controlled randomized clinical trial.

BACKGROUND: Assessment of cervicovaginal cytokine levels may be helpful to evaluate subclinical epithelial inflammation during safety evaluations of candidate microbicides. METHODS: Fifty-five HIV-seronegative Thai women were enrolled in a safety trial of the candidate microbicide Carraguard and were randomized to use Carraguard or placebo gel before vaginal sex. Cervicovaginal lavages were collected at baseline and after 1 month of gel use; levels of interleukin (IL)-1beta, IL-6, IL-8, and secretory leukocyte protease inhibitor (SLPI) were measured using microwell plate-based enzyme immunoassays. Median levels were compared between the baseline and 1-month follow-up visits using paired t tests; the median change between groups was compared using Wilcoxon rank sum tests. Women were examined for the presence of genital findings; the association between genital findings and cytokine levels was studied. RESULTS: No increase in levels of proinflammatory cytokines after use of Carraguard gel or placebo gel was observed during the study. The median change from the baseline to 1 month of follow-up was not significantly different between Carraguard and placebo groups (IL-1beta: -0.3 pg/mL vs. -3.93 pg/mL; P = 0.4, IL-6: -0.3 pg/mL vs. 0 pg/mL; P = 0.3, IL-8: -40.1 pg/mL vs. -53.2 pg/mL; P = 0.8, and SLPI: -26.5 pg/mL vs. 12.6 pg/mL; P = 0.07). Genital findings with intact epithelium were found in 16 (29%) women; these women tended to have somewhat higher IL-6 levels than those with normal epithelium (14.9 pg/mL vs. 8.8 pg/mL; P = 0.08). CONCLUSION: We found no increase in proinflammatory cytokines after Carraguard and placebo gel use, suggesting that neither gel causes inflammation. Further studies to assess the role of cytokines in microbicide safety studies are warranted.

Palmtop-assisted self-interviewing for the collection of sensitive behavioral data: randomized trial with drug use urine testing.

Palmtop-assisted self-interviewing (PASI) may provide a cheaper and more mobile alternative to audio-computer-assisted self-interviewing (ACASI) for collecting sensitive behavioral data. To evaluate PASI, in late 2002 the authors enrolled 1,283 Thai students aged 15-21 years in a randomized trial. Data collection used PASI, ACASI, self-administered questionnaire, and face-to-face interview in combination with drug-use urine testing. By use of reported levels of behaviors and agreement between self-reports of smoking and urine test results, PASI and ACASI (alpha = 0.05) were compared for noninferiority, and PASI and interview were compared for superiority (alpha = 0.05). Noninferiority of PASI was demonstrated by use of self-reports of the most sensitive areas of sexual behavior (e.g., oral sex, sexual intercourse, commercial sex, history of genital ulcers, pregnancy), as well as self-reports of less sensitive behaviors (e.g., alcohol use, dietary behaviors, symptoms of depression). Data generally showed noninferiority of PASI, ACASI, and self-administered questionnaires when compared with each other and superiority of PASI, ACASI, and self-administered questionnaires when compared with interviews. PASI agreements between self-reports of tobacco smoking and presence of nicotine metabolites in urine were noninferior to ACASI and superior to interviews. The establishment of PASI noninferiority and superiority using behavioral and biologic measures suggests that PASI is a scientifically acceptable alternative for collecting sensitive behavioral data.