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Is There an Increased Risk of HIV Transmission with Use of Hormonal Contraception?
Abstract & Commentary
By Maureen Baldwin, MD, MPH, Instructor and Fellow in Family Planning, Department of Obstetrics & Gynecology, Oregon Health and Science University, Portland.
Alison Edelman, MD, MPH, Associate Professor, Co-Director of the Family Planning Fellowship, Department of Obstetrics & Gynecology, Oregon Health and Science University, Portland, is Associate Editor for OB/GYN Clinical Alert.
Dr. Baldwin reports no financial relationships relevant to this field of study.
Dr. Edelman reports that she is a subdermal implant trainer for Merck.
Synopsis: There may be an increased risk of HIV transmission among sero-discordant couples when the woman is using hormonal contraception, but this does not currently change the recommendations for contraceptive use in this population.
Source: Heffron R, et al. Use of hormonal contraceptives and risk of HIV-1 transmission: A prospective cohort study. Lancet Infect Dis 2012;12:19-26.
Heffron et al conducted a secondary analysis of two longitudinal studies (2004-2010) performed in Africa.1 The original purpose of these studies was to evaluate HIV-1 transmission in discordant couples when the HIV-positive (HIV+) partner was also infected with herpes simplex virus (HSV type 2) but taking acyclovir.2 Initial HIV status was documented and couples were followed for an average of 18 months. A total of 3790 couples were studied; at the start of the trial, the male partner was HIV+/HSV+ in 1314 couples and the female partner was HIV+/HSV+ in the remaining 2476 couples. The uninfected partner was tested every 3 months for HIV status.
The main objective of this secondary analysis was to evaluate if hormonal contraception affected HIV acquisition in the uninfected partner. Contraceptive status was self-reported every 3 months. The proportion of women using hormonal contraception was low: 15% of uninfected women and 17% of infected women. Overall, new HIV infections doubled among couples where the female partner was using hormonal contraception (risk to men: 19/727 vs 40/2647 sero-conversions per person-years, adjusted hazard ratio [HR] 1.97; 95% confidence interval [CI], 1.12-3.45; P = 0.02; risk to women: 13/197 vs 60/1586, adjusted HR 1.98; 95% CI, 1.06-3.68; P = 0.03). In HIV- women using hormonal contraception, 13 women sero-converted (injectables = 10, oral contraceptives = 3). In HIV- male partners of HIV+ women using hormonal contraception, 19 men became infected with the same genetically linked HIV-1 strain as their partner (15 = injectables, 4 = oral contraceptives). Less condom use was reported in couples where the woman was HIV+ and using hormonal contraception.
Once again, contraception was the focus of negative media attention, with headlines around the world reporting that hormonal contraception causes HIV. Here are several important points to understand about this study:
The concern regarding HIV and hormonal contraception is not new; more than 40 studies have previously examined this relationship.3-7 Unfortunately many of these studies suffered from significant flaws similar to this most recent study including:
Although researchers adjusted for the biggest confounders — unprotected sex, sexual frequency with HIV exposure, and pregnancy — these factors varied between the groups. With extremely small numbers of participants using hormonal contraception, adjusting for confounders is fraught with errors and can give the illusion of an effect when one does not exist. In other words, the HIV infections easily could have occurred from one of these other risk factors rather than due to the hormonal contraception.
Is there any biologic plausibility to the hypothesis that hormonal contraception increases the risk of HIV transmission? The thought is that perhaps there is increased viral shedding in HIV-infected women using hormonal contraception, thereby increasing the risk of HIV transmission to their male partners. Several studies have looked at the presence of HIV-1 RNA in cervicovaginal secretions of women, including Heffron's study.10,11 HIV-1 RNA was found to be higher in women using hormonal contraception, particularly injectable methods. Interestingly, the amount of RNA in the cervicovaginal secretions was not associated with plasma HIV-1 concentrations. However, no analysis was performed to correlate if high levels of viral shedding were related to actual HIV acquisition. The story of male to female transmission is much less clear. There is no known association of higher levels of HIV-1 RNA in semen or penile secretions of infected men with uninfected female partners using hormonal contraception.
At the end of the day, can we condense this information into a clinically relevant recommendation? Although there are limitations to these data, we do not want to ignore something as significant and life-altering as becoming infected with HIV. Summarizing the findings in a different way might help. If we take the study at face value, then being in a high-risk relationship confers a 2% risk of HIV infection over 18 months and the use of hormonal contraception may increase this risk to 4%. However, the risks of not using contraception include pregnancy. The chance of pregnancy in such a population is about 5% while using hormonal contraception and about 15% without using hormonal contraception. HIV transmission in pregnancy also is doubled. Maternal mortality rates vary depending on location, but specific to Sub-Saharan Africa, it is extremely high and even higher for an HIV+ woman. Plus there is the risk of transmission to the unborn child. Clearly, systemwide recommendations need to take into account the significant benefits of contraceptive methods.
Current guidelines are based on composite data and recommend the use of effective contraceptive methods, including hormonal contraception and barrier protection in women with HIV and who are exposed to HIV. Based on these most recent data, the World Health Organization will convene in February 2012 to discuss further recommendations and will issue a position statement at that time.