Ibis Reproductive Health

Methods for Improving Reproductive Health in Africa (MIRA) trial

Overview

Partners

Objectives

Sub-studies and ancillary projects

Policy and advocacy

Standard of care

Results

Publications

Overview:

Women are becoming infected with HIV at alarming rates in many countries, and now the majority of people newly infected worldwide are women. Women are not always able to negotiate condom use with their sexual partners, and thus need prevention methods that they themselves can control. The Methods for Improving Reproductive Health in Africa (MIRA) trial was a multi-site, randomized controlled trial that measured the effectiveness of the diaphragm and lubricant gel in preventing heterosexual acquisition of HIV infection among women. The study was powered to detect effectiveness (biological efficacy combined with adherence) of 33 percent. We enrolled sexually active, HIV-negative women in South Africa and Zimbabwe (N=5,045), and followed them for 12 to 24 months (median of 21 months). The study began enrollment in August 2003 and completed follow-up in December 2006. All trial participants received voluntary counseling and testing, safer-sex counseling, free male condoms, and diagnosis and treatment of curable sexually transmitted infections (STIs). Half of the participants were randomly selected to receive, in addition, an Ortho All-Flexâ latex diaphragm and a non-contraceptive lubricant (Replensâ gel). We evaluated the effect of providing the diaphragm, gel, and condoms (intervention) compared to condoms-alone (control) on HIV incidence in women. The trial also investigated the acceptability of the diaphragm in this study population.

Ibis staff led the data, clinical, and laboratory monitoring; the policy and advocacy activities; the Standard of Care Impact Evaluation; and the MIRA Social Science Study, which collected data on women’s experiences with the diaphragm, the diaphragm’s acceptability among women and male partners, use patterns, gender-based violence, and other important topics.

Partners:

MIRA was supported by a grant from the Bill and Melinda Gates Foundation. Dr. Nancy Padian of the Women’s Global Health Imperative at RTI International is the trial’s principal investigator. The collaborating institutions and co-investigators include:

Women’s Global Health Imperative (WGHI), RTI International (Dr. Nancy Padian, Dr. Ariane van der Straten) (Note: Most of the work for this study was conducted while Dr. Padian and Dr. van der Straten were at the Department of Obstetrics, Gynecology and Reproductive Sciences, University of California, San Francisco.)
Ibis Reproductive Health (Ms. Kelly Blanchard)
University of Zimbabwe-UCSF Collaborative Research Programme (Dr. Tsungai Chipato)
Medical Research Council of South Africa (Dr. Gita Ramjee)
Perinatal HIV Research Unit of South Africa (Dr. Guy De Bruyn)
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Objectives:
Primary objective:
To determine the effectiveness of the diaphragm with non-contraceptive, lubricant gel in preventing heterosexual HIV transmission in women.

Secondary objectives:

To determine the effectiveness of the diaphragm with lubricant gel in preventing cervical infections with Chlamydia trachomatis and Neisseria gonorrhoeae.
To assess the long-term acceptability of diaphragms with lubricant gel for use as an HIV prevention method.
To examine the effect of using the diaphragm and lubricant gel on Trichomonas vaginalis (TV) and herpes simplex virus type 2 (HSV-2) infection, and to evaluate Treponema pallidum, TV, and HSV-2 as potential effect modifiers of a diaphragm-HIV relationship.
To examine the feasibility of the diaphragm and lubricant gel as a sustainable HIV prevention strategy, including logistical factors such as: access to product in a timely fashion, hygiene and diaphragm washing and reuse, problems associated with use, ability to use the diaphragm covertly when so desired, and other related acceptability issues. (MIRA Social Science Study)
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Sub-studies and ancillary projects:
Several sub-studies and ancillary projects were also incorporated into the MIRA trial. The objectives were:

To evaluate the effect of Replensâ gel on cervical human papillomavirus (HPV) testing, urine PCR testing for chlamydia and gonorrhea, and cervical cytology quality. This pilot study was conducted at WGHI only.
To evaluate whether the diaphragm and Replensâ gel can decrease the incidence and persistence of HPV, and hence reduce the risk of cervical cancer; the study also evaluated whether HPV infection and high HPV viral load increase the risk of male-to-female vaginal HIV transmission. This sub-study was conducted in Zimbabwe only.
To evaluate whether the diaphragm and Replensâ gel can decrease the incidence and persistence of bacterial vaginosis. This sub-study was conducted in Zimbabwe only.
To determine the prevalence of HSV-2 in the study screening population. This sub-study was conducted in Durban, South Africa, only.
To determine whether women in the intervention arm have a reduced incidence of pelvic inflammatory disease.
To educate and train participants of clinical trials to become peer educators as a way to increase STI/HIV awareness and knowledge in the target communities. This project was conducted in Durban, South Africa, only.
To assess the effect of male involvement on women’s diaphragm, gel, and condom adherence and acceptability. This sub-study was conducted in Zimbabwe only.
To determine time requirements for diaphragm education and counseling, fitting, and practice at study visits.
To determine the prevalence of recent HSV-2 infection in a cohort of HIV-negative women as measured by avidity index score ≤40. This sub-study was conducted in Johannesburg, South Africa, only.
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Policy and advocacy:
The MIRA trial also undertook a number of policy and advocacy-focused activities to support the trial as follows:

Established partnerships in the family planning and STI/HIV/AIDS fields and served as a key resource on cervical barriers, including establishing the Cervical Barrier Advancement Society (CBAS).
Built awareness of cervical barriers and the MIRA trial among researchers, providers, and policy makers through presentations at meetings and conferences.
Investigated the legal and regulatory issues relevant to cervical barriers in the US, South Africa, and Zimbabwe.
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Standard of care:
The MIRA trial established relationships with community referral sites and facilitated treatment and care for HIV-positive trial participants through these sites. The MIRA team also elicited feedback regarding trial-referral site relationships and assessed the impact of the trial and its referral system on the community referral service providers. (MIRA Standard of Care Impact Evaluation)

MIRA trial results:

The trial found that in the context of a comprehensive HIV prevention package, including condom provision, there was no added protective benefit from the diaphragm and lubricant gel. The HIV infection rates observed in the trial were the same in both the control arm (where women received condoms only) and the intervention arm (condom plus diaphragm plus gel). All women received safer-sex counseling and treatment of curable STIs. Over the course of the study (2003-2006), 151 out of 2,476 women (annual incidence: 3.9%) became HIV infected in the group that received condoms only, and 158 out of 2,472 women (annual incidence: 4.1%) became HIV infected in the group that received the diaphragm, lubricant, and condoms.

The study could not evaluate whether using the diaphragm was better than using nothing because it was not designed to answer this question; furthermore, most women in both arms of the trial reported male condom use.

Publications:

Padian NS, van der Straten A, Ramjee G, Chipato T, de Bruyn G, Blanchard K, Shiboski S, Montgomery ET, Fancher H, Cheng H, Rosenblum M, van der Laan M, Jewell N, McIntyre J, the MIRA Team. Diaphragm and lubricant gel for prevention of HIV acquisition in southern African women: a randomized controlled trial. Lancet 2007;370(9583):251-61.

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