One even larger trial yielded negative results that resonated through both conferences (Padian et al., Lancet July 2007 and IAS 2007 abstracts TUAC101 [Govender et al.], TUAC102 [van der Straten et al.], TUAC104 [Watadzaushe et al.], TUAC105 [Montgomery et al.], WEPEC046 [Milford et al.], WESS304 [Padian], and WEPL103 [Padian]). That trial enrolled 5,000 southern African HIV negative women to test the protective effect of a standard contraceptive barrier device, cervical diaphragms. The relatively thin cervical lining is considered a potentially sensitive area for HIV infection in women. Half the trial participants received the diaphragms plus a neutral lubricating gel to ease insertion. Everyone received randomized repeated safe sex counseling with free condoms. They also were treated at study entry for curable (i.e. bacterial) STDs. Notably, 59% of enrollees tested positive for HSV-2 at enrollment.
After 24 months, the rate of HIV acquisition was virtually the same, about 4%, in the diaphragm and control groups. The incidence rates were also the same in each arm for women with baseline positive tests for bacterial STDs or herpes. (But the HSV-2-positive women as a whole acquired HIV at a rate of almost 5%, compared with 3% for the HSV-2-negative women.) Reproductive tract infections were also equal in the diaphragm and non-diaphragm arms, as was the pregnancy rate.
Diaphragm use left something to be desired: Over the course of the study, women in the diaphragm arm reported using diaphragms at 73% of their most recent sexual activity. In any case, the high-adherence population did not show a reduced risk for HIV. One important difference between the diaphragm and control groups was condom use: After entry into the trial, women in both groups greatly increased their use of condoms during sex, but the non-diaphragm arm increased its rate still more. Yet, the groups' HIV rates were equal. There might be some protective effect after all.
But one suspects that participants' reports of their condom use were inaccurate: in the regular clinical surveys, 85% of the control group members reported that they had used condoms during their most recent sexual act, yet 6% of them acquired HIV. It doesn't add up. And here's another aspect that doesn't make sense: The yearly pregnancy rate in both arms was 13%. You might well conclude from this trial that diaphragms are not protective against pregnancy as well as HIV.
This trial wasn't designed to compare diaphragms to no condoms, and didn't have the size and statistical power to look only at high condom adherers, either. A trial that focuses on the sizable number of women who are unable to use condoms due to lack of partner cooperation might provide some valuable insights.
When diaphragms are used for contraception, a spermicidal cream or gel is added. The cream was not used in this study for fear that it would prove irritating and, hence, promote HIV transmission. For HIV protection, it might be necessary to add an antiretroviral microbicide. An initial safety and acceptability trial of that combination recently took place in Madagascar with 192 women (Behets et al. ISSTDR 2007 abstract O-021 and Norris Turner et al. abstract P-493). That trial used the AcidForm microbicide, which keeps the cervicovaginal environment mildly acidic and hostile to HIV. An agent that directly kills HIV might be used instead. One example is tenofovir gel, now the subject of a 1,000-woman South African trial testing its value as a standalone microbicide.
Back to September 2007 issue of HHS Watch