Understanding the Effects of Hormonal Contraception on HIV Transmission

What are the risks and benefits of using hormonal contraception in HIV prevention trials?

Because little or no human data exist regarding safety of HIV vaccine candidates during pregnancy, either for the woman or the fetus, investigators usually require women of reproductive age to use contraception when they decide to participate in AIDS vaccine trials. Pregnant or breast-feeding women are excluded from participating in HIV vaccine trials.

If women choose to volunteer for an HIV vaccine trial, the nurses and staff at clinical trial centers go to great lengths to deliver pregnancy prevention counseling before the study begins, and to provide women with different contraception options, such as male or female condoms, oral hormonal contraceptives that must be taken daily, or injectable hormonal contraceptives such as Depo-Provera, which lasts for three months.

Injectable hormonal contraception is the most popular among women in developing countries, where the burden of HIV/AIDS is highest and the need for an AIDS vaccine is greatest. In sub-Saharan Africa, for instance, about 12 million women use injectable contraceptives, 8 million use oral contraceptives, and another 11 million use condoms, according to the Alan Guttmacher Institute, a New York City-based non-profit that advances sexual and reproductive health research. About 140 million women worldwide use hormonal contraceptives. Injectable contraceptives have the clear advantage of lasting for three months. All of the other methods are behavior dependent. This makes injectable contraception a preferable method.

However, a number of studies have suggested that the use of hormonal contraception may increase a woman’s risk of HIV acquisition. The most recent and strongest findings appeared in the October 18 issue of the scientific journalLancet Infectious Diseases, in which researchers from the University of Washington reported a doubling of the risk of HIV infection among women and, for the first time, a doubling of the risk of HIV transmission from women to men.

While the study did not differentiate between oral or injectable hormonal contraceptives, the long-acting injectable hormonal contraceptives were the most commonly used by women in the study, involving 3,790 heterosexual serodiscordant couples—in which one partner is HIV infected and the other is not. The cohort of serodiscordant couples was enrolled in Botswana, Kenya, Rwanda, South Africa, Tanzania, Uganda, and Zambia, and is the largest group in which the effect of hormonal contraception on HIV transmission has been studied.


The mechanism 

Despite the recent data, the mechanism of how hormonal contraception increases the risk of HIV infection is not entirely clear. Hormonal contraceptives primarily work by suppressing the release of protein hormones that regulate reproductive development, which in turn prevents the ovary from releasing eggs and deprives sperm of their targets.

Some hormonal contraceptives, such as birth control pills, contain small amounts of synthetic reproductive hormones from both the estrogen and progestin families. Others, such as Depo-Provera, contain only progestin.

Hormonal contraceptives that contain just progestin also appear to be able to cause the cervical mucus to thicken, which blocks and prevents sperm from fertilizing an egg. And progestin-only hormonal contraception also thins the lining of the uterus, which in theory could prevent pregnancy by keeping a fertilized egg from attaching to the uterus.


An animal model 

Scientists have been studying the effects of hormonal contraception in nonhuman primates. The vaginal mucosa is a common portal of entry for both HIV and simian immunodeficiency virus (SIV), the monkey equivalent of HIV, and identifying the mechanisms that accelerate or block viral entry in this region is important both in the study of HIV pathogenesis and prevention.

By labeling HIV with a fluorescent protein that causes the pathogen to light up like a neon sign, scientists were able to track viral particles within the vaginal mucosa of monkeys, some of which had been given the hormonal contraceptive Depo-Provera. Scientists observed more T cells—the primary targets of HIV—close to the mucosal surfaces of monkeys treated with Depo-Provera. This might explain why the use of the hormonal contraceptive increases HIV transmission.

While researchers continue to study how reproductive hormones may or may not influence HIV transmission and infection, it is likely that women will still be offered multiple contraception options, including hormonal contraceptives, if they are enrolled in HIV vaccine and other prevention trials.

However, some caution may be warranted in the future. The World Health Organization is convening a meeting in January to consider whether the evidence suggesting hormonal contraception increases HIV infection and/or transmission risk is now strong enough for them to issue a warning. Still, researchers who conducted the most recent study expect hormonal contraception will continue to be offered in HIV prevention trials.