Global Phase IIb/III Microbicide Clinical Trials

<div><p><b>Red circle:</b> Carraguard. Sponsored by Population Council. Phase III study of the efficacy and safety of the microbicide Carraguard in preventing HIV seroconversion in women.</p> <p><b>Blue cross: 2% and 0.5% PRO2000.</b> Sponsored by Microbicide Development Programme. A phase III, multi-centre, randomised, double-blind, placebo-controlled trial to evaluate the effectiveness and safety of 0.5% PRO2000 and 2% PRO2000 gels for the prevention of vaginally acquired HIV infection.</p> <p><b>Yellow cross: BufferGel and 0.5% PRO2000.</b> Sponsored by US National Institutes of Health. HPTN 035: Phase II/IIb safety and effectiveness study of the vaginal microbicides BufferGel and 0.5% PRO 2000 gel (P) for the prevention of HIV infection in women.</p> <p><b>Green star: Cellulose sulphate—East and Southern Africa.</b> Sponsored by CONRAD. Randomised controlled trial of 6% cellulose sulphate gel and the effect on vaginal HIV transmission.</p> <p><b>Green star: Cellulose sulphate—Nigeria.</b> Sponsored by Family Health International. Phase III trial of cellulose sulphate for HIV prevention. <b>Pink box: C31G (SAVVY).</b> Sponsored by Family Health International. Phase III trial of SAVVY in Ghana and Nigeria.</p></div

Crude incidence rates for HIV seroconversion.

<p>Crude incidence rates for HIV seroconversion.</p

Safety of a silicone elastomer vaginal ring as potential microbicide delivery method in African women: A Phase 1 randomized trial

<div><p>Background</p><p>Women in sub-Saharan Africa are in urgent need of female-initiated human immunodeficiency virus (HIV) preventative methods. Vaginal rings are one dosage form in development for delivery of HIV microbicides. However, African women have limited experience with vaginal rings.</p><p>Objectives</p><p>This Phase I, randomized, crossover trial assessed and compared the safety, acceptability and adherence of a silicone elastomer placebo vaginal ring, intended as a microbicide delivery method, inserted for a 12-week period in healthy, HIV-negative, sexually active women in South Africa and Tanzania.</p><p>Methods</p><p>170 women, aged 18 to 35 years were enrolled with 88 women randomized to Group A, using a placebo vaginal ring for 12 weeks followed by a 12-week safety observation period. 82 women were randomized to Group B and observed for safety first, followed by a placebo vaginal ring for 12 weeks. Safety was assessed by clinical laboratory assessments, pelvic/colposcopy examinations and adverse events. Possible carry-over effect was addressed by ensuring no signs or symptoms of genital irritation at crossover.</p><p>Results</p><p>No safety concerns were identified for any safety variables assessed during the trial. No serious adverse events were reported considered related to the placebo vaginal ring. Vaginal candidiasis was the most common adverse event occurring in 11% of participants during each trial period. Vaginal discharge (2%), vaginal odour (2%), and bacterial vaginitis (2%) were assessed as possibly or probably related to the vaginal ring. Thirty-four percent of participants had sexually transmitted infections (STIs) at screening, compared to 12% of participants who tested positive for STIs at crossover and the final trial visit. Three participants (2%) tested HIV positive during the trial.</p><p>Conclusions</p><p>The silicone elastomer vaginal ring had no safety concerns, demonstrating a profile favorable for further development for topical release of antiretroviral-based microbicides.</p></div

Demographic and other baseline characteristics.

<p>Demographic and other baseline characteristics.</p

Incidence of adverse events that occurred in at least 5% of participants, regardless of causality.

<p>Incidence of adverse events that occurred in at least 5% of participants, regardless of causality.</p

Incidence of adverse events assessed by the investigator as possibly or probably related to the vaginal ring during the intervention phase.

<p>Incidence of adverse events assessed by the investigator as possibly or probably related to the vaginal ring during the intervention phase.</p

Trial design and overview of safety assessments.

<p>Group A: Participants in this group participated in a placebo vaginal ring regimen for the first 12 weeks of the trial where after they crossed over to a 12-week observational period without a ring. Group B: Participants in this group participated in an observational period for the first 12 weeks of the trial where after they crossed over to a 12-week placebo vaginal ring period. A = Group A; B = Group B, Colpo = colposcopic examination; HCG = human chorionic gonadotropin; HIV = human immunodeficiency virus; Pelvic = pelvic examination; Quest = questionnaire; Scrn = screening; STI = sexually transmitted infection; TEAE = treatment emergent adverse event.</p

Demographic Factors for All Evaluable Participants and the Subset that was HIV Positive and Tested for Drug Resistance in MTN-009.

<p>Notes: SD = Standard Deviation.</p

CD4+ T Cell Counts and HIV-1 RNA Levels of HIV-1 Positive Participants.

<p>Histogram showing frequency of HIV positive participants (n = 400) that have (A) CD4+ T cell counts <200 cells/mm³ indicating risk for AIDS, 200–349 cells/mm³ indicating treatment eligibility, and >350 cells/mm³; and (B) varying levels of HIV-1 RNA (copies/ml).</p

Consort Diagram.

<p>Consort Diagram.</p