Kelly Blanchard

Diaphragm and lubricant gel for prevention of HIV acquisition in southern African women: a randomised controlled trial.

BACKGROUND Female-controlled methods of HIV prevention are urgently needed. We assessed the effect of provision of latex diaphragm, lubricant gel, and condoms (intervention), compared with condoms alone (control) on HIV seroincidence in women in South Africa and Zimbabwe. METHODS We did an open-label, randomised controlled trial in HIV-negative, sexually active women recruited from clinics and community-based organisations, who were followed up quarterly for 12-24 months (median 21 months). All participants received an HIV prevention package consisting of pre-test and post-test counselling about HIV and sexually transmitted infections, testing, treatment of curable sexually transmitted infections, and intensive risk-reduction counselling. The primary outcome was incident HIV infection. This study is registered with ClinicalTrials.gov, number NCT00121459. FINDINGS Overall HIV incidence was 4.0% per 100 woman-years: 4.1% in the intervention group (n=2472) and 3.9% in the control group (n=2476), corresponding to a relative hazard of 1.05 (95% CI 0.84-1.32, intention-to-treat analysis). The proportion of women using condoms was significantly lower in the intervention than in the control group (54%vs 85% of visits, p<0.0001). The proportions of participants who reported adverse events (60% [1523] vs 61% [1529]) and serious adverse events (5% [130] vs 4% [101]) were similar between the two groups. INTERPRETATION We observed no added protective benefit against HIV infection when the diaphragm and lubricant gel were provided in addition to condoms and a comprehensive HIV prevention package. Our observation that lower condom use in women provided with diaphragms did not result in increased infection merits further research. Although the intervention seemed safe, our findings do not support addition of the diaphragm to current HIV prevention strategies.

Emergency contraception: randomized comparison of advance provision and information only.

OBJECTIVE To determine whether multiple courses of emergency contraceptive therapy supplied in advance of need would tempt women using barrier methods to take risks with their more effective ongoing contraceptive methods. METHODS We randomly assigned 411 condom users attending an urban family planning clinic in Pune, India, to receive either information about emergency contraception along with three courses of therapy to keep in case of need, or to receive only information, including that about the locations where they could obtain emergency contraception if needed. For up to 1 year, women returned quarterly for follow‐up, answering questions about unprotected intercourse, emergency contraceptive use, pregnancies, sexually transmitted infections, and acceptability. RESULTS Women given advance supplies reported unprotected intercourse at rates nearly identical to those among women given only information (0.012 versus 0.016 acts per month). Among those who did have unprotected intercourse, however, supply recipients were nearly twice as likely (79% versus 44%) to have taken emergency contraception, although numbers were too small to permit statistically significant inferences. No women used emergency contraception more than once during the study, even though everyone in the advance‐supplies group had extra doses available. All women found knowing about emergency contraception useful, and all those receiving only information wished they had received supplies as well. CONCLUSION Multiple emergency contraception doses supplied in advance did not tempt condom users to risk unprotected intercourse. After unprotected intercourse, however, those with pills on hand used them more often. Women found advance provision useful.

Emergency contraception: a review of the programmatic and social science literature

Many biomedical aspects of emergency contraception have been investigated and documented for >30 years now. A large number of social science questions, however, remain to be answered. In this article, we review the rapidly growing but geographically lopsided literature on this topic. Using computer database searches supplemented by reference reviews and professional correspondence with those active in the field, we gathered literature on the social science and service delivery aspects of emergency contraception published in English up through December 1998, as well as a few unpublished papers from the same time and slightly later, representing regions where published material is practically nonexistent. Methodologically acceptable papers are summarized in our tables and text, and form the basis for suggested improvements in existing emergency contraceptive services. The review also offers ideas for designing new emergency contraception services where they do not yet exist. We conclude by proposing an agenda for further social science research in this area.

Misoprostol for women's health: a review.

OBJECTIVE To review published literature on misoprostol for womens health indications to provide a synthesis of available information and highlight areas in need of additional research. DATA SOURCES: Studies were identified through searches of medical literature databases including MEDLINE, Cochrane Database, and Popline, in addition to a review of references from identified articles. STUDY SELECTION: We included all studies reported in English and published before March 31, 2001, which evaluated the efficacy of misoprostol alone for labor and delivery, evacuation of the uterus after pregnancy failure and induced abortion. Studies were not excluded based on quality or sample size. TABULATION, INTEGRATION, AND RESULTS: Misoprostol shows promise for all of the womens health indications addressed. Currently available data, though, are often hard to interpret because of variations in regimen, dose, and outcome measures. The low cost, ease of administration and storage, and widespread availability of misoprostol make it particularly appealing for developing countries. Because many of the womens health problems for which misoprostol could be prescribed currently cause significant mortality and morbidity, increased access to and information on use of misoprostol could help improve womens health especially where these problems are most severe. CONCLUSION Further research is needed to identify optimal regimens for misoprostol for obstetric and gynecologic health indications. Registering misoprostol with national drug regulatory authorities for any of several womens health indications could help increase access to and safe use of this drug. Provider training would be a logical subsequent step.

Safety and acceptability of the candidate microbicide Carraguard in Thai Women: findings from a Phase II Clinical Trial

Objective:To determine the safety and acceptability of vaginal application of Carraguard, a carrageenan-derived candidate microbicide gel. Design:A randomized, placebo-controlled, triple-blinded clinical trial was conducted in Chiang Rai, northern Thailand. Methods:Women were asked to insert one applicator of study gel vaginally at least three times per week (with or without sex) and to use gel with condoms every time they had sex. Safety was assessed by visual inspection of the vagina and cervix, changes in vaginal flora and self-reported symptoms at day 14, month 1 and then monthly for up to 1 year. Acceptability was assessed through reported use of the gel, return of used and unused applicators, and quarterly interviews. Results:One hundred sixty-five women were randomized: 83 to Carraguard and 82 to the placebo (methylcellulose gel) group. Study gel use was similarly high in both groups throughout the trial with an average of four applicators per week. Carraguard use was not associated with abnormal genital clinical findings, abnormal vaginal flora, Pap smear abnormalities or other abnormal clinical signs or symptoms. Adverse events were mostly mild, not attributed to gel use, and similarly distributed between groups. Participants in both groups reported high acceptability. Conclusions:Carraguard can safely be used an average of four times per week with or without sex and is acceptable to Thai women. A Phase III efficacy trial of Carraguard is warranted and is currently ongoing in South Africa.

Epidemiological synergy of Trichomonas vaginalis and HIV in Zimbabwean and South African women.

Background: Trichomonas vaginalis (T. vaginalis) is the most common nonviral sexually transmitted infection in the world. Despite the coexisting global epidemics of T. vaginalis and HIV, little attention has focused on the emerging evidence that T. vaginalis increases susceptibility to, and potentially transmission of, HIV. Methods: We evaluated T. vaginalis infection in the context of a multisite, randomized controlled trial amongst women in South Africa and Zimbabwe, to determine first, if risk of HIV acquisition was increased among women recently infected with T. vaginalis, and second, if risk of T. vaginalis acquisition was increased among women infected with HIV. Results: After controlling for potential confounders, participants infected with T. vaginalis were more likely to test positive for HIV at their following visit, compared to participants uninfected with T. vaginalis (adjusted hazard ratio = 2.05; 95% CI, 1.05–4.02). Similarly, HIV-positive participants were twice as likely to have acquired T. vaginalis infection at the following visit, compared to HIV-negative participants (adjusted hazard ratio = 2.12; 95% CI, 1.35–3.32). Conclusions: We found an increased risk of both HIV acquisition associated with T. vaginalis infection and risk of T. vaginalis acquisition associated with HIV infection. This bidirectional relationship represents a potentially important factor in sustaining the HIV epidemic in populations where T. vaginalis is endemic.

Acceptability and feasibility of Micralax® applicators and of methyl cellulose gel placebo for large-scale clinical trials of vaginal microbicides

Objective(s)To evaluate the feasibility and acceptability of the Micralax® applicator and of methyl cellulose placebo gel for use in vaginal microbicide clinical trials. DesignA two-centre prospective study following women for 2 months. SettingTwo primary health care clinics in South Africa. Patients, participantsFemale volunteers (n = 28) 18 years or older who were HIV negative and had no clinically detectable genital tract abnormalities or reproductive tract infections. InterventionsParticipants used pre-filled Micralax® applicators to apply methyl cellulose gel every other day, as well as up to 1 h before to every episode of vaginal sex. Main outcome measure(s)Consistency in the weight of gel dispensed per application; side-effects attributed to applicator or gel use; and acceptability of the applicator and of the gel. ResultsOver a 2 month follow-up period the 22 women completing the study reported no adverse events related to gel or applicator use. The Micralax® applicator proved acceptable. The gel was not too messy and did not reduce sexual frequency or pleasure. On average, the applicator dispensed 4.7 ml per use (close to the 4 ml planned). ConclusionsThe Micralax® applicator performs well as a delivery system for potential vaginal microbicides; and methyl cellulose is an appropriate placebo for future microbicide trials.

Many vaginal microbicide trial participants acknowledged they had misreported sensitive sexual behavior in face-to-face interviews.

OBJECTIVE We investigated whether participants in a phase II randomized clinical trial of a candidate vaginal microbicide ever intentionally misled interviewers. STUDY DESIGN AND SETTING We used audio computer-assisted self-interviews (ACASI) to ask the South African women (n=132) participating in the trial about the accuracy of self-reported data collected during face-to-face interviews. The trial protocol recommended that women use their assigned gel (active microbicide or placebo) with condoms during each vaginal sex act. RESULTS Nearly four-fifths of participants (n=104, 79%) reported that they had misinformed trial interviewers at least once. Motivations included politeness (n=45, 34% of ACASI participants) to avoid criticism or seek praise (n=32, 24%), and embarrassment (n=24, 18%). Participants acknowledged misreporting eligibility characteristics to enroll (11%) and, during follow-up, exaggerating their enthusiasm for the study gel (13%), applicator (13%), and the effect of the gel on sexual pleasure (13%). In general, women who were untruthful had actually used the gel with condoms less and used the gel alone more than they had reported during the trial. Women overwhelmingly found the computer survey easy. CONCLUSION Researchers cannot assume that participants always tell the truth about sensitive behaviors in face-to-face interviews. ACASI was efficient and acceptable in this population.

Misoprostol used alone for the termination of early pregnancy. A review of the evidence.

Increased access to medical methods of abortion could significantly reduce maternal mortality, especially in developing countries. In light of the political and commercial difficulties in distributing the abortifacient mifepristone, the widely studied mifepristone-misoprostol regimen may not be sufficiently available in the near future. Thus, researchers have begun to look for alternative regimens, including regimens using misoprostol alone. This article reviews the current available evidence on the potential of a misoprostol-alone regimen for medical abortion. Although the data are varied and difficult to compare, recent studies indicate that a misoprostol-alone regimen could be safe and effective as a method of medical abortion. Misoprostol is widely marketed around the world for its other indications and is inexpensive, stable in tropical climates, easy to transport, and simple to administer. A misoprostol-alone regimen of medical abortion could thus greatly improve the access to safe medical abortion services by women in developing countries.

Advance provision of emergency contraception for pregnancy prevention: a meta-analysis.

OBJECTIVE: Advance provision of emergency contraception can circumvent some obstacles to timely use. We performed a meta-analysis to summarize randomized controlled trials evaluating advance provision of emergency contraception to explore effects on pregnancy rates, sexually transmitted infections, and sexual and contraceptive behaviors. DATA SOURCES: In August 2006, we searched CENTRAL, EMBASE, POPLINE, MEDLINE, a specialized emergency contraception article database, and contacted experts to identify published or unpublished trials. METHODS OF STUDY SELECTION: We included randomized controlled trials comparing advance provision to standard access, defined as any of the following: counseling (with or without information about emergency contraception) or provision of emergency contraception on request at a clinic or pharmacy. TABULATION, INTEGRATION AND RESULTS: Two reviewers independently assessed study quality. We performed a meta-analysis using Review Manager software. Eight randomized controlled trials met inclusion criteria, representing 6,389 patients in the United States, China, and India. Advance provision did not decrease pregnancy rates, despite increased use (single use, odds ratio [OR] 2.52, 95% confidence interval [CI] 1.72–3.70; multiple use: OR 4.13, 95% CI 1.77–9.63) and faster use (weighted mean difference –14.6 hours, 95% CI –16.77 to –12.4 hours). Advance provision did not increase rates of sexually transmitted infections (OR 0.99, 95% CI 0.73–1.34), unprotected intercourse, or changes in contraceptive methods. Women who received emergency contraception in advance were as likely to use condoms as other women. CONCLUSION: Advance provision of emergency contraception did not reduce pregnancy rates and did not negatively affect sexual and reproductive health behaviors and outcomes compared with conventional provision. LEVEL OF EVIDENCE: III