Methods for Improving Reproductive Health in Africa (MIRA) trial
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. Half of the participants were randomly selected to receive, in addition, an Ortho All-Flex latex diaphragm and a non-contraceptive lubricant (Replens 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. We are continuing to work on manuscripts exploring different aspects of the data.
Overall HIV annual incidence in the trial was 4.0%. There was no statistical difference in the rate of new HIV infections in the two study groups: in the intervention group (those who received a diaphragm plus lubricant along with male condoms) 158 out of 2472 women became HIV infected (a 4.1% HIV incidence per 100 woman-years) whereas in the control group (those who received male condoms only) 151 out of 2476 women became HIV infected (a 3.9% HIV incidence per 100 woman-years). Therefore, the study findings do not support the addition of the diaphragm to current HIV prevention strategies.
While there was high condom uptake among all study participants, uptake was lower in the intervention group than in the control group. On average, the proportion of last sex acts where women reported using male condoms was 54% in the intervention group compared to 85% in the control group (p<0.0001). However, the lower reported condom use among women provided with diaphragms did not result in increased infection, a finding which merits further research.
Reporting of adverse events was similar between the two groups, confirming that the study products are safe. Rates of pregnancy were the same in both groups, with an overall annual incidence of first pregnancy of 13.1%.
There were 471 first Chlamydia trachomatis (CT) infections and 192 first Neisseria gonorrhoeae (GC) infections among the 4,968 participants who had at least one follow-up urine sample for CT/GC analysis; overall incidence of CT and GC in the trial was 6.2 and 2.4 per 100 woman-years, respectively. Intention-to-treat analysis found no statistical difference in the rate of new CT or GC infections in the two groups. However, in a separate analysis that examined the effect of the intervention among those who reported “always use” of the diaphragm since the last quarterly visit as compared to those who reported use less than always, there was a statistically significant reduction in the incidence of GC among women in the intervention group as compared to those in the control group (RH 0.61, 95% CI: 0.41-0.91). These findings do not support the addition of the diaphragm to current STI prevention strategies, though they do suggest that consistent use of the diaphragm may reduce GC acquisition.
Montgomery ET, Blanchard K, Cheng H, Chipato T, Bruyn G, Ramjee G, Padian N, van der Straten A. Diaphragm and lubricant gel acceptance, skills and patterns of use among women in an effectiveness trial in Southern Africa. The European Journal of Contraception & Reproductive Health Care. December 2009;14(6):410-419
Van der Straten A, Cheng H, Moore J, Kacanek D, Blanchard K, et al. The use of the diaphragm instead of condoms in a phase III diaphragm trial. AIDS Behavior. December 2008.
Ramjee G, van der Straten A, Chipato T, de Bruyn G, Blanchard K, et al. The diaphragm and lubricant gel for prevention of cervical sexually transmitted infections: Results of a randomized controlled trial. Plos One. October 2008; 3(10):e3488.
Padian NS, van der Straten A, Ramjee G, ChipatoT, 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 randomised controlled trial. Lancet. 21 July 2007; 370(9583):251-261.