Contraceptive May Double HIV Transmission Risk
Use of hormonal contraceptives and risk of HIV-1 transmission: a prospective cohort study - (10/05/11)|
Hormonal contraception and HIV: an unanswered question EDITORIAL - (10/05/11)
Contraceptive Used in Africa May Double Risk of H.I.V.
NY Times Oct 3 2011
The most popular contraceptive for women in eastern and southern Africa, a hormone shot given every three months, appears to double the risk the women will become infected with H.I.V., according to a large study published Monday. And when it is used by H.I.V.-positive women, their male partners are twice as likely to become infected than if the women had used no contraception.
The findings potentially present an alarming quandary for women in Africa. Hundreds of thousands of them suffer injuries, bleeding, infections and even death in childbirth from unintended pregnancies. Finding affordable and convenient contraceptives is a pressing goal for international health authorities.
But many countries where pregnancy rates are highest are also ravaged by H.I.V., the virus that causes AIDS. So the evidence suggesting that the injectable contraceptive has biological properties that may make women and men more vulnerable to H.I.V. infection is particularly troubling.
Injectable hormones are very popular. About 12 million women between the ages of 15 and 49 in sub-Saharan Africa, roughly 6 percent of all women in that age group, use them. In the United States, it is 1.2 million, or 3 percent of women using contraception. While the study involved only African women, scientists said biological effects would probably be the same for all women. But they emphasized that concern was greatest in Africa because the risk of H.I.V.
transmission from heterosexual sex was so much higher there than elsewhere.
"The best contraception today is injectable hormonal contraception because you don't need a doctor, it's long-lasting, it enables women to control timing and spacing of birth without a lot of fuss and travel," said Isobel Coleman, director of the women and foreign policy program at the Council on Foreign Relations. "If it is now proven that these contraceptions are helping spread the AIDS epidemic, we have a major health crisis on our hands."
The study, which several experts said added significant heft to previous research while still having some limitations, has prompted the World Health Organization to convene a meeting in January to consider if evidence is now strong enough to advise women that the method may increase their risk of getting or transmitting H.I.V.
"We are going to be re-evaluating W.H.O.'s clinical recommendations on contraceptive use," said Mary Lyn Gaffield, an epidemiologist in the World Health Organization's department of reproductive health and research. Before the meeting, scientists will review research concerning hormonal contraceptives and women's risk of acquiring H.I.V., transmitting it to men, and the possibility (not examined in the new study) that hormonal contraceptives accelerate H.I.V.'s severity in infected women.
"We want to make sure that we warn when there is a real need to warn, but at the same time we don't want to come up with a hasty judgment that would have far-reaching severe consequences for the sexual and reproductive health of women," she said. "This is a very difficult dilemma."
The study, led by researchers at the University of Washington and published in The Lancet Infectious Diseases, involved 3,800 couples in Botswana, Kenya, Rwanda, South Africa, Tanzania, Uganda and Zambia. In each couple, either the man or the woman was already infected with H.I.V. Researchers followed most couples for two years, had them report their contraception methods, and tracked whether the uninfected partner contracted H.I.V. from the infected partner, said Dr. Jared Baeten, an author and an epidemiologist and infectious disease specialist.
The research was presented at an international AIDS conference this summer, but has now gained traction, scientists said, with publication in a major peer-reviewed journal.
The manufacturer of the branded version of the injectable, Depo-Provera, is Pfizer, which declined to comment on the study, saying officials had not yet read it. The study's authors said the injectables used by the African women were probably generic versions.
The study found that women using hormonal contraception became infected at a rate of 6.61 per 100 person-years, compared with 3.78 for those not using that method. Transmission of H.I.V. to men occurred at a rate of 2.61 per 100 person-years for women using hormonal contraception compared with 1.51 for those who did not.
While at least two other rigorous studies have found that injectable contraceptives increase the risk of women's acquiring H.I.V., the new research has some strengths over previous work, said Charles Morrison, senior director of clinical sciences at FHI 360, a nonprofit organization whose work includes researching the intersection of family planning and H.I.V.
Those strengths include the fact that researchers followed couples and were therefore able to track transmission of H.I.V. to both men and women. Dr. Morrison said only one other less rigorous study had looked at whether hormonal contraception increased the risk of infected women's transmitting the virus to men.
"This is a good study, and I think it does add some important evidence," said Dr. Morrison, who wrote a commentary accompanying the Lancet article.
Although the study has limitations, including its use of data not originally intended to determine the link between contraceptive use and H.I.V., "I think this does raise the suspicion" that injectable contraceptives could increase transmission risk, he said.
Why that would occur is unclear. The researchers recorded condom use, essentially excluding the possibility that increased infection occurred because couples using contraceptives were less likely to use condoms.
The progestin in injectable contraceptives appears to have a physiological effect, scientists said. Renee Heffron, an epidemiologist and co-author of the study, said research examining whether the hormone changes genital tissue or vaginal mucous had been inconclusive. Studies in macaques found that progestin thins vaginal tissue, she said, "but studies among women didn't show the same amount of thinning."
It could be that progestin causes "immunologic changes in the vagina and cervix" or could increase the H.I.V.'s "ability to replicate," Dr. Morrison said.
At one point, the researchers measured the concentration of H.I.V. in infected women's genital fluid, finding "there was more H.I.V. in the genital fluid of those using hormonal contraception than those who aren't," Dr. Baeten said, a possible reason men might have increased risk of infection from hormonal contraceptive users. Those women "don't have more H.I.V. in their blood," he said.
The researchers also found that oral contraceptives appeared to increase risk of H.I.V. infection and transmission, but the number of pill users in the study was too small to be considered statistically significant, the authors said.
Previous research on the pill has been more mixed than with injectables, which could have a greater impact because they involve a strong dose meant to last for three months, Dr. Baeten said.
In another troubling finding, results from the same study, published separately, showed that pregnancy also doubled the risk of women's contracting H.l.V. and of infected women's transmitting it to men. That may partly be due to increased unprotected sex, but could also relate to hormones, researchers said.
But there are no simple solutions, the authors acknowledge. Any warning against such a popular contraceptive method may not only increase complications from pregnancy but increase H.I.V. transmission, too, since pregnancy itself may raise a woman's risk of H.I.V. infection.
First, the researchers and others say, greater emphasis should be placed on condom use along with hormonal methods.
Some experts, like Dr. Morrison, favor a randomized controlled trial for more definitive proof, but others question how to "randomize women who may have strong preferences about their contraception," he added.
Dr. Ludo Lavreys, an epidemiologist who led one of the first studies to link injectable contraceptives to increased H.I.V. risk, said intrauterine devices, implants and other methods should be explored and expanded. "Before you stop" recommending injectables, he said, "you have to offer them something else."
The Faulty Birth-Control-HIV Link
Oct 6, 2011 12:21 PM EDT
A new study says that African women using birth-control shots have a higher risk of contracting and passing on HIV. Why the research may be wrong.
This week, The New York Times published a shocking front-page article on a study claiming that African women using injectable hormonal contraceptives like Depo-Provera have double the risk of contracting HIV from an infected partner, and nearly triple the risk of passing on the disease to uninfected men as well. The study has caused heated debate among those working in the fields of reproductive health and family planning. If the results of this study are to be believed, hundreds of thousands of women could face the impossible choice between preventing unwanted pregnancies-and all their associated risks-and avoiding the transmission of HIV. Damned if they use birth control, damned if they don't.
Problem is, the study is hardly a smoking gun that exposes a concrete link between birth-control use and HIV infection. Rather, it is methodologically flawed, and contrary to what the study suggests, the jury is still out about the real risk of using birth control-if there is any risk at all.
It's crucial to get this information right, because the lives of hundreds of thousands of women hang in the balance. Every year, nearly 500,000 women-mostly in the developing world-die from complications related to childbirth. That's the equivalent of three 747-airplane crashes each day. For many of these women, health-care facilities are often too far away, too expensive, and too short-staffed to help in the case of pregnancy-related emergencies. In rural Ethiopia, where our research group has spent years working to make pregnancy safer for local women, a mother has a 1-in-40 chance of dying from childbirth in her lifetime. In the United States, that chance would be 1 in 2,000.
Administering birth control in the Musha Health Center in Rwanda, Shannon Jensen, AFP / Getty Images
That's why injectable contraceptives like Depo-Provera are so important to the more than 6 million women in sub-Saharan Africa who use them as a crucial tool for pregnancy prevention. By simply getting a shot once every three months, women who live far from health-care facilities have a reliable way to prevent unwanted pregnancies. Also, for women who feel they cannot or do not want to let their male partners know they are on birth control, Depo-Provera is a discreet and appealing option.
It's crucial to get this information right, because the lives of hundreds of thousands of women hang in the balance.
Clearly, injectable contraceptives are a critical tool for health providers in sub-Saharan Africa. Then again, no doctor would recommend that a woman place herself at grave danger of contracting HIV. That's why, as scientists, we are so concerned by the obvious limitations of the new study. Perhaps the most significant drawback to the study is the fact that it wasn't originally designed to look at the link between HIV and birth control. Rather, it was a randomized controlled trial to see whether herpes medication could help prevent HIV transmission. The trial was carefully designed to balance two groups-couples receiving herpes treatment and those not receiving it-and make sure they were as similar as possible. Whether a woman did or did not use contraceptives was not part of the researchers' original concern when creating the groups.
Because the study was not designed to answer their question, the researchers could not account for all the factors that might be different about women who use contraception and those who do not. In the absence of randomization, trying to compare those two groups of people is notoriously difficult, especially when there may be crucial differences in things like sexual behavior and, say, condom use-which is known to prevent the spread of HIV. Without complete information about such factors, it would be impossible to conclude that injectable contraceptives, rather than inconsistent condom use, are to blame for the increase in HIV transmission rates. And while the researchers did try to adjust for condom use to eliminate this problem, they relied on participants' own reports of contraceptive use-which is always unreliable-and never took any objective measures to assess how accurate these reports were.
What's more, the authors focused on the relative risk of contracting HIV for women on birth control, which simply tells us whether injectable contraceptives and HIV transmission are correlated-a measure that is arguably less relevant than the attributable risk, which could tell us whether injectable contraceptives actually cause higher HIV transmission rates. The authors don't report the attributable risks, but they're easy to calculate and actually quite small. For example, if we observed 100 women on injectable birth control like Depo-Provera, and 100 who didn't use injectables, for one year, we'd see three extra cases of HIV in the women using injectables. That's a very different thing from "double the risk" and could be within the realm of statistical error. In any case, it's far less alarming than the study's original conclusion.
There are other issues that skew the study's results, too. Overall contraceptive use was very low in the population it examined-as was the total number of new HIV infections. That means there may be some locations that never saw any new HIV infections. But it's impossible to examine the separate, and potentially important, results from each study site, since the researchers aggregated all their data.
To be fair, some previous studies have suggested a tentative link between hormonal birth control-especially in injectable form like Depo-Provera-and a higher susceptibility to HIV transmission. The current study suggests that this is a link worth investigating-but in a thorough, careful, and rigorous manner. As of now, there's still no consensus on the matter. And in the world of global public health, where our research has real-life implications for the world's most vulnerable populations, we must be especially careful not to conflate flawed data with fact.