Elsevier

The Lancet

Volume 370, Issue 9583, 21–27 July 2007, Pages 251-261
The Lancet

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

https://doi.org/10.1016/S0140-6736(07)60950-7Get rights and content

Summary

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.

Introduction

An estimated 39·5 million people worldwide were living with HIV/AIDS at the end of 2006.1 Southern Africa is considered the epicentre of the pandemic, and about 20% of adults in Zimbabwe and South Africa are infected with HIV. In this region, women have up to twice the risk of HIV infection compared with men.2 Because of sociocultural constraints and power differentials in gender roles, these women are often unable to negotiate the use of male condoms, a key component of HIV prevention strategies.3, 4, 5, 6, 7 Simple low-cost prevention methods that women can initiate and control could have a substantial effect on the management of the HIV epidemic.

Although the development of new female-controlled methods is well underway, availability of an effective microbicide for prevention of HIV and other sexually transmitted infections (STIs) is still years away, and several trials of candidate gels have recently been stopped early with disappointing results.8, 9, 10, 11, 12, 13, 14 The diaphragm has the potential advantage of a long history of use, and has been approved and used globally as a contraceptive method. The device is worn internally, covers the cervix, and blocks semen from ascending to the upper genital tract. Although it is no longer a widely used contraceptive, observational studies in several developing countries have shown high acceptability of the diaphragm in the general population.15, 16, 17, 18, 19, 20 Diaphragms are simple, reusable, and stable under varying environmental conditions, posing no disposal problems and little difficulty with cleaning and storage. The device can be used covertly and does not necessitate cooperation or knowledge from the male partner.21, 22

Evidence suggests that physical barriers covering the cervix offer safe and effective protection against HIV and STIs that exacerbate risk of HIV infection. Neisseria gonorrhoeae, Chlamydia trachomatis, and human papillomavirus (HPV) preferentially infect the cervix and upper genital tract, and results of observational studies suggest that diaphragm users have a reduced risk of these cervical STIs, pelvic inflammatory disease, and HPV-associated cervical neoplasia.8, 23 Unlike the multilayered vaginal squamous epithelium, the cervix has only one layer of delicate columnar epithelial cells, making target cells more accessible to HIV. The transformation zone at the cervix (the area of demarcation between columnar and squamous epithelium) has been shown to have a greater concentration of HIV-receptor susceptible cells close to the mucosal surface—including CD4-positive T lymphocytes (CD4 cells), Langerhans cells, macrophages, and cells with CCR5, CXCR4s, and Fc-γ receptors23, 24, 25, 26, 27—compared with vaginal epithelium.

In the present Methods for Improving Reproductive Health in Africa (MIRA) trial, we did a multisite, randomised controlled open-label study to assess the effectiveness of the latex diaphragm with a lubricant gel in preventing heterosexual acquisition of HIV among women in southern Africa, compared with provision of condoms alone.

Section snippets

Study design and participants

Between September, 2003, and September, 2005, we recruited sexually active (an average of at least four sex acts per month) women aged 18–49 years to join the MIRA trial in Durban and Johannesburg, South Africa, and Harare, Zimbabwe. Participants who met protocol inclusion and exclusion criteria (see panel 1) were then randomised into one of two groups: the intervention group, who received a clinician-fitted diaphragm (All-Flex Arcing Spring diaphragm; Ortho-McNeil Pharmaceutical, Raritan, NJ,

Results

Figure 1 shows the trial profile. Rates of missed visits and discontinuation (due to early withdrawals or reaching scheduled closing visits), were similar between the groups throughout the follow-up period. The median duration of follow-up was 21 months (range 0–24). Of the 368 (7%) women who did not complete a closing visit as scheduled, 6% in the intervention group and 5% in the control group were classified as lost to follow-up, defined as participants who did not complete a closing visit

Discussion

Among women receiving a state-of-the-art HIV prevention package (including risk reduction counselling, voluntary counselling and testing, and diagnosis and treatment of STIs), we observed no added protective benefit of providing the diaphragm and lubricant gel in addition to provision of male condoms. Incidence of HIV in the intervention group was similar to that in the control group of the study. This result held true across all pre-specified subgroups assessed, although this population mainly

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