Potential link found between hormonal contraception, HIV risk

WHO to hold technical consultation in early 2012

Results from an analysis presented at the recent 2011 International AIDS Society conference in Rome suggest that using certain methods of hormonal contraception — particularly injectable contraception – might double the risk of HIV acquisition in a previously uninfected woman and also might double the risk that an HIV- infected woman will transmit HIV to a previously uninfected male sexual partner.1

The researchers analyzed data from women and men in HIV discordant couples, prospectively following 3,790 heterosexual HIV-1 serodiscordant couples (in which one partner was HIV-1 seropositive and the other seronegative) from Kenya, Uganda, Rwanda, Botswana, Zambia, Tanzania, and South Africa for up to 24 months. The scientists looked at hormonal contraceptive users and nonusers, comparing rates of HIV-1 acquisition in women and HIV-1 transmission from women to men using multivariate Cox proportional hazards regression and marginal structural modeling. The information presented at the Rome conference has not yet been peer-reviewed or published; its findings are available only in slide and oral form.

Most of the couples for whom data were available were part of a randomized placebo-controlled trial, designed to assess the efficacy of acyclovir in preventing HIV infection associated with herpes simplex infection.2,3 Other data in the analysis came from a parallel observational study of immune correlates of HIV protection at two of the same study sites. All couples were provided comprehensive HIV-prevention services, including risk-reduction counseling for individuals and couples, free condoms, and treatment for sexually transmitted infections (STIs). Most couples reported using condoms.

Among 1,314 couples in which the HIV-1 seronegative partner was female, HIV-1 acquisition rates were 6.61 and 3.78 per 100 person-years in women using and not using hormonal contraception (adjusted hazard ratio [HR] 1.98, 95% confidence interval [CI] 1.06-3.68, p=0.03). Among 2,476 couples in which the HIV-1 seronegative partner was male, HIV-1 transmission rates from women to men were 2.61 and 1.51 per 100 person-years in those whose partners used versus did not use hormonal contraception (adjusted HR 1.97, 95% CI 1.12-3.45, p=0.02).]1

The U.S. Agency for International Development (USAID) in Washington, DC, plans to co-fund a technical consultation being organized by the World Health Organization (WHO) for late January in Geneva, Switzerland, says Chelsea Polis, PhD, USAID epidemiological advisor. The consultation is being called to assess whether current WHO recommendations on contraceptive use for women at risk of HIV infection, women with HIV infection or AIDS, or women taking antiretroviral therapy remain consistent with the current body of evidence, given the new research findings, states Mary Lyn Gaffield, MPH, PhD, a scientist at WHO's Department of Reproductive Health.

The consultation will include a multi-disciplinary group of experts who will evaluate the available scientific evidence on the use of hormonal contraceptives and HIV acquisition, progression, and infectivity/transmission. The consultation is designed to review implications for programs, service delivery, and future research, notes Gaffield.

More information needed

Both the USAID and the International Planned Parenthood Federation (IPPF) in London have issued separate statements regarding current practice with hormonal contraception in light of the new data. "USAID does not believe that a change in contraceptive policy or programming is appropriate or necessary at this time," reads an August 2011 field communication.4 "We do not yet have full information on this analysis or its implications."

In a response to the release of the study information, IPPF says it is consulting with partners in the family planning and HIV/AIDS communities to fully understand the implications of the study's findings and its potential affect on family planning clients and services.5 "Currently, IPPF considers that this study should not be used to draw conclusions on hormonal contraceptive use overall and its potential role in increasing users risk of HIV acquisition or transmission," states the IPPF response. "There were not enough women using oral contraceptives (OC) in this study to find statistically significant results on the links between use of OC and HIV."

Women using contraceptive implants or intrauterine devices containing hormonal contraception were not included in this study, the IPPF response notes. "The study's findings can therefore only really highlight important considerations for injectable contraceptives," the IPPF response notes. "Available information we have from the study thus far does not indicate which injectables were used (depot medroxyprogesterone acetate [DMPA] or northisterone enanthate), nor the duration of use — factors which could affect the level of risk."

Stay tuned for more

Safe and effective contraceptive choices are essential for women with and at risk for HIV-1 infection. The new data have highlighted concerns about the safety of hormonal contraceptives in settings with high HIV prevalence and incidence, and they require a thorough review of all data, the context, and alternative options available to women wishing to avoid unwanted pregnancy, says Gaffield.

More than 50 studies have looked at whether use of hormonal contraception is a risk factor for HIV-1 infection. Most were cross-sectional; 15 were prospective studies.6

In a 2007 study designed to measure the risk of HIV-1 infection associated with hormonal contraceptive use, neither OCs nor DMPA was associated with HIV-1 acquisition.7 However, among women who were negative for herpes simplex virus type 2 at study enrollment (48% of the study population), both methods increased risk of HIV-1 acquisition.

What should providers do until more definitive data is available? The IPPF directs clinicians to look to the WHO Medical Eligibility Criteria for Contraceptive Use.8 "Until conclusive findings are available, the World Health Organization (WHO) guidance is the best available guide for programmatic decisions that affect most women," the IPPF statement reads. "The WHO has addressed this issue in the context of Medical Eligibility Criteria for Contraceptive Use and concluded that hormonal contraception remains a safe option for women at high risk of and living with HIV."

U.S. medical eligibility criteria currently categorize use of combined hormonal methods, progestin-only pills, contraceptive injection, and implant as "1" — no restrictions on use — in women at high risk for HIV, HIV-infected, or AIDS diagnosed. Initiation and continuation of the levonorgestrel intrauterine system and the Copper T380A intrauterine device are categorized as "2" — advantages generally outweigh theoretical or proven risks- for women at high risk for HIV or HIV-infected. Initiation of both types of intrauterine contraception are classified as "3" — theoretical or proven risks usually outweigh the advantages — for women who are diagnosed with AIDS. Continuation of both devices is categorized as a "2" for women with AIDS.9

Dual protection against unintended pregnancy and STIs, including HIV, can be achieved by using condoms along with a highly effective method of contraception, advises USAID. Program managers should continue to promote condoms to prevent transmission of STIs, including HIV.4

References

  1. Heffron R, Donnell D, Rees H, et al. Hormonal contraceptive use and risk of HIV-1 transmission: a prospective cohort analysis. Presented at the sixth annual International AIDS Society Conference on HIV Pathogenesis, Treatment and Prevention. Rome, Italy; July 2011.
  2. Celum C, Wald A, Lingappa JR, et al. Acyclovir and transmission of HIV-1 from persons infected with HIV-1 and HSV-2. NEJM 2010; 362:427-439.
  3. Heffron R, Were E, Celum C, et al. A prospective study of contraceptive
  4. use among African women in HIV-1 serodiscordant partnerships. Sex Transm Dis 2010; 37:621-628.
  5. Radloff R. USAID communication to the field (Aug. 5, 2011): USAID response to new findings on hormonal contraception and HIV acquisition in uninfected women and HIV transmission from infected women to male partners. Accessed at http://www.usaid.gov/our_work/global_health/pop/techareas/docs/usaid_hc_hiv.pdf.
  6. International Planned Parenthood Federation. IPPF's response to "Hormonal contraceptive use increases women's risk of acquiring and transmitting HIV, 2011." Accessed at http://www.ippf.org/en/Resources/Statements.
  7. Baeten JM, Lavreys L, Overbaugh J. The influence of hormonal contraceptive use on HIV-1 transmission and disease progression. Clin Infect Dis 2007; 45:360-369.
  8. Morrison CS, Richardson BA, Mmiro F, et al. Hormonal contraception and the risk of HIV acquisition. AIDS 2007; 21:85-95.
  9. World Health Organization. Medical eligibility criteria for contraceptive use. Fourth ed. Geneva: WHO; 2009.
  10. Centers for Disease Control and Prevention (CDC). U S. medical eligibility criteria for contraceptive use, 2010. MMWR Recomm Rep 2010; 59(RR-4):1-86.