Update to CDC's U.S. Medical Eligibility Criteria for Contraceptive Use, 2010: Revised Recommendations for the Use of Hormonal Contraception Among Women at High Risk for HIV Infection or Infected with HIV

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Prevention of unintended pregnancy among women at risk for human immunodeficiency virus (HIV) infection or infected with HIV is critically important. One strategy for preventing unintended pregnancies in this population is improving access to a broad range of effective contraceptive methods. In 2010, CDC published U.S. Medical Eligibility Criteria for Contraceptive Use, 2010 (US MEC), providing evidence-based guidance for the safe use of contraceptive methods among women with certain characteristics or medical conditions, including women who are at high risk for HIV infection or are HIV infected (1). Recently, CDC assessed the evidence regarding hormonal contraceptive use and the risk for HIV acquisition, transmission, and disease progression. This report summarizes that assessment and the resulting updated guidance. These updated recommendations affirm the previous guidance, which stated that 1) the use of hormonal contraceptives, including combined hormonal contraceptives, progestin-only pills, depot medroxyprogesterone acetate (DMPA), and implants, is safe for women at high risk for HIV infection or infected with HIV (US MEC category 1), and 2) all women who use contraceptive methods other than condoms should be counseled regarding the use of condoms and the risk for sexually transmitted infections (1). However, a clarification is added to the recommendation for women at high risk for HIV infection who use progestin-only injectables to acknowledge the inconclusive nature of the body of evidence regarding the association between progestin-only injectable use and HIV acquisition. The clarification also notes the importance of condom use and other HIV preventive measures, expansion of the variety of contraceptive methods available (i.e., contraceptive method mix), and the need for further research on these issues.

Background

Half of all pregnancies in the United States are unintended, and those pregnancies are at increased risk for adverse maternal and infant outcomes (2,3). Approximately 4 million women at risk for unintended pregnancy in the United States are not using contraception (4), demonstrating the need for increased contraceptive access and use. HIV infection also is a critical public health issue in the United States. In 2010, an estimated 10,000 new HIV infections occurred among U.S. women.* One in 139 women will be diagnosed with HIV during her lifetime.† Pregnancy itself carries risks, including morbidity, mortality, and a possible increased risk for HIV infection (5–7). Pregnancies among HIV-infected women confer additional risks including the risk for mother-to-child transmission of HIV; therefore, the need for contraceptive use to avoid unintended pregnancy in sexually active HIV-infected women is important.

Some recent studies have suggested that women using progestin-only injectables (primarily DMPA) or combined oral contraceptives might have an increased risk for HIV acquisition and transmission to noninfected partners, whereas others studies have not found these associations (8). Animal and laboratory studies have assessed potential mechanisms by which hormonal contraception might influence risk for HIV acquisition, transmission, and disease progression, including effects on the vaginal epithelium and other changes in the genital tract, as well as alteration of local and systemic immune responses (8). However, the clinical relevance of these mechanisms in humans remains unclear (8). Therefore, evaluation was needed of the published studies on hormonal contraception and HIV acquisition among women at high risk for HIV infection, as well as HIV disease progression and HIV transmission to noninfected male partners among women living with HIV.

Rationale and Methods

Published by CDC in 2010, US MEC was adapted from Medical Eligibility Criteria for Contraceptive Use,§ published by the World Health Organization (WHO), which has been publishing global evidence-based contraceptive guidance since 1996. Recommendations are provided using categories 1 to 4; 1 represents a method that is safe to use without restriction and 4 represents an unacceptable health risk (Table). CDC is committed to ensuring that these recommendations remain up-to-date and based on the best available scientific evidence. An update can be triggered either by identification of new evidence or by any evidence-based updates made to the WHO global guidance. In February 2012, based on new evidence, WHO affirmed its previous guidance on the safety of hormonal contraceptives among women at high risk for HIV infection and those living with HIV infection and clarified its recommendation on the use of progestin-only injectables by women at high risk for HIV infection (8). Because of this update, CDC initiated a process to assess whether its guidance should be updated similarly.

Three systematic reviews conducted for WHO have summarized published evidence regarding the use of hormonal contraception and the risk for HIV acquisition, transmission, and disease progression and were considered during CDC's review of the evidence and the WHO recommendations (8).¶ With regard to the question about hormonal contraceptive use and risk for HIV acquisition among HIV-negative women, 20 observational studies were identified (8). Among these studies, as well as a subset of higher-quality studies, most found no significant association between oral contraceptive use and HIV acquisition. Among studies that assessed use of injectables, including DMPA and norethisterone enanthate (NET-EN), evidence was equivocal, with some studies finding a statistically significant increase in risk for HIV acquisition, whereas others did not. All of the studies had limitations that affect the interpretation of these data, and concerns remain regarding the potential for residual confounding, especially around differential condom use, even in the subset of higher quality studies. Overall, the evidence does not suggest an association between oral contraceptive use and risk for HIV acquisition. Evidence on injectable use does not establish a causal association with HIV acquisition, nor does it definitively rule out the possibility of an effect (8).

With regard to hormonal contraceptive use among HIV-positive women and risk for female-to-male HIV transmission, one observational study provided direct evidence (8). The study showed a significant increased risk for transmission with use of injectables, but not oral contraceptives, as compared with no hormonal contraceptive use. This study also observed increased genital HIV-1 RNA among injectable users, but not oral contraceptive users. The systematic review noted several strengths of this study, including statistical adjustment for confounders, high retention rate and frequent follow-up visits, large study population, genetic linkage of HIV transmissions, and measurement of genital viral shedding. The study also discussed several limitations, such as the potential for residual confounding particularly with regard to condom use, uncertainty about whether the amount of genital shedding detected among the injectable users was consistent with the observed increase in transmission risk, and limited statistical power because of the small number of new HIV infections among men (8). Several studies that provided indirect evidence assessed outcomes among users of hormonal contraceptives such as changes in genital viral shedding or plasma viral load (8). The studies of genital viral shedding had mixed results, whereas studies assessing plasma viral load generally showed no adverse effects. Many of the studies had methodological weaknesses, and the implications for HIV infectivity are unclear. Given the limited direct data on this question, more evidence is needed (8).

None of the 10 observational studies that examined hormonal contraceptive use and risk for HIV disease progression (as measured by mortality, progression to acquired immunodeficiency syndrome [AIDS], increased viral load, or decreased CD4 count) observed statistically significant associations (8). One randomized controlled trial showed an increased risk for disease progression among women using hormonal contraceptives as compared with women using copper intrauterine devices; however, the study was subject to high rates of method switching and loss to follow-up (8). Overall, this evidence is reassuring and does not suggest an increased risk for HIV disease progression with hormonal contraceptive use (8).

CDC invited seven participants from outside the agency and two participants from inside the agency to serve as ad hoc reviewers of the evidence and the WHO revised recommendations. The reviewers were selected based on their expertise in HIV infection or family planning. The reviewers participated in a March 2012 teleconference with CDC during which they reviewed and discussed the scientific evidence base, as well as information on unintended pregnancy, contraceptive use, HIV infection, and maternal risk in the United States. Finally, the reviewers provided their individual perspectives regarding whether WHO's revised recommendations were suitable for use in the United States. The reviewers considered the evidence, the conclusions from the WHO consultation, and how the WHO recommendations might apply to the United States. Although acknowledging that the United States context differs from the global context in a number of ways (e.g., lower HIV incidence and prevalence; greater access to health-care services, including contraceptive methods, antiretroviral therapy, and HIV testing and counseling; and lower pregnancy-related risks), the individual reviewers strongly and consistently favored adopting the WHO revised recommendations.

Recommendations for the Use of Hormonal Contraceptives in Women at High Risk for HIV Infection or Infected with HIV

CDC affirmed the previous recommendations, which stated that 1) the use of hormonal contraceptives, including combined hormonal contraceptives, progestin-only pills, DMPA, and implants, is safe for women at high risk for HIV infection or infected with HIV (US MEC category 1) and 2) all women who use contraceptive methods other than condoms should be counseled about the use of condoms and the risk for sexually transmitted infections (1). However, consistent with WHO, CDC added a clarification for women at high risk for HIV infection using progestin-only injectables, which highlights the inconclusive nature of the evidence around hormonal contraceptive use and risk for HIV acquisition among women, and strongly encourages condom use and other measures to prevent HIV (Table).

In addition, the previous US MEC guidance included a clarification for the recommendations on hormonal contraceptive methods for women with AIDS regarding the potential for drug interactions between hormonal contraceptives and antiretroviral (ARV) drugs. However, current guidance from the U.S. Department of Health and Human Services recommends that many patients with HIV infection should also take ARV drugs, including any patient with a CD4 count ≤500 cells/mm3.** Therefore, CDC has added this clarification regarding potential drug interactions between hormonal contraception and ARV drugs to the recommendations for women with HIV (Table).

Contraception is critically important to prevent unintended pregnancy among women at risk for HIV infection or infected with HIV and such women can continue to use all hormonal contraceptive methods without restriction. However, HIV infection preventive measures, such as voluntary testing and counseling, access and adherence to ARV drugs, and correct and consistent use of condoms, should be strongly encouraged among all women at risk for HIV acquisition and women living with HIV infection. Additional information is available at http://www.cdc.gov/reproductivehealth/unintendedpregnancy/usmec.htm.

Reported by

Naomi K. Tepper, MD, Kathryn M. Curtis, PhD, Denise J. Jamieson, MD, Polly A. Marchbanks, PhD, Div of Reproductive Health, National Center for Chronic Disease Prevention and Health Promotion, CDC. Corresponding contributor: Naomi K. Tepper, ntepper@cdc.gov, 770-488-6506.

Acknowledgments

Systematic review leaders: Chelsea Polis, PhD, U.S. Agency for International Development, Washington DC. Sharon Phillips, MD, World Health Organization, Geneva, Switzerland.

Ad hoc reviewers: Jean Anderson, MD, Johns Hopkins Univ, Baltimore, Maryland. Paul Blumenthal, MD, Stanford Univ, Palo Alto, California. Willard Cates, Jr., MD, FHI 360, Research Triangle Park, North Carolina. Roxanne Jamshidi, MD, American College of Obstetricians and Gynecologists and Johns Hopkins Univ, Baltimore, Maryland. Amy Medley, PhD, Center for Global Health, CDC. Susan Moskosky, MS, U.S. Dept of Health and Human Services. Deborah Nucatola, MD, Planned Parenthood Federation of America, New York, New York. Herbert Peterson, MD, Univ of North Carolina, Chapel Hill, North Carolina. Madeline Sutton, MD, National Center for HIV/AIDS, Viral Hepatitis, STD, and TB Prevention, CDC.

References

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