It has long been known that women are at increased risk of becoming infected with HIV at approximately the time of pregnancy. Part of the reason is behavioral — a relaxing of safer sex practices in an attempt to conceive. Another part is because the woman's immune system regulates in intensity to accommodate the partially foreign fetus. However, no one had really looked at men before, said lead author Nelly Mugo, MD, of the University of Nairobi and the Kenyatta National Hospital, Kenya.

The researchers observed 3321 serodiscordant couples for as long as 2 years at 14 sites in 7 countries in southern and eastern Africa. The serodiscordant coupes consisted of 1085 in which the man was infected and 2236 in which the woman was infected. The couples knew their serostatus and were regularly counseled on safer sex behavior.

Pregnancies were observed in 320 couples in which the man tested positive for HIV-1 and 503 couples in which the woman tested positive for HIV-1.

Among the women who became infected with HIV-1, 17 (26.6%) of 64 became infected during pregnancy. Among men, 12 (21.1%) of 57 became infected while their partner was pregnant. Genotypic analysis of virus from both partners confirmed the source of the infection.

The male-to-female rate of transmission was 3 per 100 person-years when not pregnant vs. 7.4 per 100 person-years during pregnancy. "However when we adjusted the analysis, this was no longer significant," Dr. Mugo stated.

The incidence of transmission from women to men was 1.6 outside of pregnancy and 3.5 during pregnancy, "an unadjusted hazards ration of 2.2, which was significant," Dr. Mugo reported. Even after adjusting for age, unprotected sex, and contraceptive use, this finding remained statistically significant, she said.

Dr. Mugo also said that social pressure to have children likely overcame the need to protect against HIV infection and resulted in reduced safer sex practices in an effort to conceive a child. That a slightly greater portion of persons became infected at approximately the time of conception than later on in the pregnancy suggests this might be the case.

Previous studies have shown that viral load and vaginal shedding of HIV often increase during the course of pregnancy, as the mother's immune system becomes attenuated to accommodate the growing fetus, thus putting the man at greater risk for exposure.

HIV-positive women who became pregnant during the trial were referred for prevention of mother-to-child transmission, which was administered according to local standards. Those standards varied from site to site and, at the time of the study, seldom included administration of antiretroviral drugs for the mother. Therefore, data were not collected or analyzed.

"We need to rethink our strategies," said Dr. Mugo. "We need to think about more than the baby but also about the mums and the dads. We need to have men more involved with prenatal care, 'for their own good.'"

This study points to the need to include male partners as part of perinatal HIV prevention activities. "Whether the increased risk that we have demonstrated is behavioral or biological, it presents a real opportunity for HIV prevention interventions through couples HIV testing in antenatal clinics," she said.

Ward Cates, MD, MPH, with Family Health International, which is headquartered in Research Triangle Park, North Carolina, said, "This could be among the more important presentations at this conference. It provides an additional justification for treatment of the infected woman during pregnancy. You are preventing both horizontal and vertical transmission by giving treatment at pregnancy."

Pilot Study of 1% Tenofovir Gel

At the same session of the meeting, Richard Beigi, MD, presented a pilot safety study of 1% tenofovir gel applied to the vagina of volunteers (n = 16) approximately 4 hours before cesarean delivery at the University of Pittsburgh Medical Center.

Tenofovir has proven to be safe and effective when used as an antiretroviral. The purpose of this study was to ascertain pharmacokinetics when used topically during pregnancy. There was maternal absorption but at a level of approximately 1% of a standard oral dose, and the absorption rates were lower still in the infant.

Dr. Beigi presented data that showed that a "single application of tenofovir 1% vaginal gel in term pregnancy produces low overall serum levels consistent with levels reported in nonpregnant women. Although tenofovir does appear to cross the placenta, absolute fetal exposure after vaginal dosing is low with a similar cord:maternal ratio noted after oral dosing."

The University of Pittsburgh team said that the findings "support the ongoing investigation of tenofovir 1% vaginal gel in pregnant women."

One future study will extend the topical dosing during pregnancy, and another will enroll lactating women to better define the safety profile of this candidate microbicide.

The African study was conducted with the support of the Bill and Melinda Gates Foundation, and the Pittsburgh study was conducted with the support of multiple nonprofit and government sources. The speakers of both presentations have disclosed no relevant financial relationships.

2010 International Microbicides Conference (M2010): Abstracts 8 and 9. Presented May 23, 2010.

www.medscape.com/viewarticle/722295