Hormonal Contraception and HIV: Implications for Contraceptive Guidance Michael Lowe, PhD, MSPH Division of Reproductive Health Centers for Disease Control and Prevention This presentation was created and previously presented by Naomi K. Tepper, MD, MPH, FACOG (CDC employee) May 13, 2013 National Center for Chronic Disease Prevention and Health Promotion Division of Reproductive Health

Disclosures No conflicts of interest

Objectives To discuss the evidence for hormonal contraception and HIV acquisition, transmission and progression To discuss competing risks for women at risk for HIV or infected with HIV/AIDS To discuss CDC’s updated guidance on use of hormonal contraceptives among women at risk for HIV or infected with HIV/AIDS

Effectiveness of Reversible Contraceptives More Effective Less IUD Implant Depo Pill Patch Ring Diaphragm Condoms Withdrawal Spermicide

Effectiveness of Reversible Contraceptives More Effective Less Less User Dependent More User IUD Implant Depo Pill Patch Ring Diaphragm Condoms Withdrawal Spermicide

WHO Global Contraceptive Guidance

WHO Global Contraceptive Guidance To base family planning practices on the best available evidence To address misconceptions regarding who can safely use contraception To reduce medical barriers To improve access and quality of care in family planning

WHO Medical Eligibility Criteria for Contraceptive Use (MEC) Purpose: who can use contraceptive methods WHO MEC, 4th edition, 2009, http://www.who.int/reproductivehealth/publications/family_planning/9789241563888/en/

MEC categories No restriction for use of the contraceptive method Advantages of using the method generally outweigh theoretical or proven risks Theoretical or proven risks usually outweigh advantages of using the method Unacceptable health risk if the contraceptive method is used

WHO MEC HIV/AIDS recommendations Condition CHC POP DMPA, NET-EN Implants High risk for HIV 1 HIV infection AIDS 1* * Clarification: Drug interactions may occur between hormonal contraceptives and ARV therapy; refer to the section on drug interactions. http://www.who.int/reproductivehealth/publications/family_planning/9789241563888/en/index.html

WHO Intent for MEC “The guidance in this document is intended for interpretation at country and programme levels in a manner that reflects the diversity of situations and settings in which contraceptives are provided.” WHO MEC, 4th edition, 2009, http://www.who.int/reproductivehealth/publications/family_planning/9789241563888/en/

Same recommendations as WHO for women at risk for HIV and with HIV/AIDS

Source: fhi360

Hormonal Contraception and HIV: Evidence

Hormonal Contraception and HIV Does hormonal contraceptive use increase risk for: HIV acquisition among non-infected women? HIV transmission to non-infected male partners? HIV disease progression? interaction with antiretroviral therapy?

Hormonal Contraception and HIV: Acquisition

Prospective, observational studies of OC pills & HIV acquisition (including studies that did not meet minimum quality criteria) Adjusted OR, IRR, or HR (log scale) and 95% CI * includes MSM and Cox estimates Source: Polis, USAID

Prospective, observational studies of injectables & HIV acquisition (including studies that did not meet minimum quality criteria) Adjusted OR, IRR, or HR (log scale) and 95% CI * includes MSM and Cox estimates Source: Polis, USAID

Biological mechanisms for acquisition HC may induce changes in vagina/cervix Cervical ectopy Thinning of vaginal epithelium Reduction of lactobacilli Immunologic changes Viral diversity or virulence Other STIs Animal studies

Hormonal Contraception and HIV: Transmission

HC and HIV transmission from women to men Hormonal contraceptive Hazard Ratio* (95% CI) Number of men infected Injectable 2.0 (1.1-3.6) 15 Oral 2.1 (0.8-5.8) 4 * Compared with no hormonal contraceptive use Heffron, Lancet Infect Dis 2012;12:19-26.

HC and HIV transmission: indirect evidence 16 studies Outcomes: genital viral shedding or plasma viral load Genital shedding evidence mixed Plasma viral load no effect Limitations Viral shedding is proxy No measurement consensus

Hormonal Contraception and HIV: Disease Progression

HC and HIV progression 12 studies Outcomes: mortality or progression to AIDS 7 observational studies no difference 1 RCT- increased risk with OC and injectables (high levels of switching and loss to follow up) Outcomes: change in CD4 count or viral load 5 observational studies No differences

Summary of evidence HIV acquisition HIV transmission OCs and Net-EN: no increased risk DMPA: data inconsistent, possibility of increased risk not ruled out HIV transmission Direct evidence: 1 study showed increased risk with DMPA Indirect evidence: mixed for changes in genital shedding, no effect on plasma viral load HIV disease progression Most studies showed no progression, 1 RCT showed increased risk

Limitations Objective of study Limited power Measurement of exposure, outcome and key variables Behavioral differences Comparison group Confounding Follow up

Putting Evidence into Context: Balancing Competing Health Risks

Competing risks HIV infection Unintended pregnancy Pregnancy and HIV transmission Maternal mortality and morbidity

Number of women with HIV/AIDS, 2009 16 million women HIV-infected globally 76% of HIV-infected women in sub-Saharan Africa http://www.globalhealthfacts.org/data/topic/map.aspx?ind=4

350,000 women die of pregnancy-related causes every year 1 in 30 in sub-Saharan Africa For every maternal mortality, 50-100 women suffer maternal morbidity http://www.who.int/making_pregnancy_safer/topics/maternal_mortality/en/

HIV diagnoses among females (N=10,168) U.S., 2010 CDC, HIV surveillance report 2010, http://www.cdc.gov/hiv/surveillance/resources/reports/2010report/pdf/2010_HIV_Surveillance_Report_vol_22.pdf

HIV diagnoses, women ages >13 U.S., 2009 CDC, NCHHSTP Atlas, http://www.cdc.gov/nchhstp/atlas/.

Unintended pregnancy U.S., 2006 Finer, Contraception, 2011;84:478.

Maternal mortality ratio, 2008 http://whqlibdoc.who.int/publications/2010/9789241500265_eng.pdf

Pregnancy-related mortality U.S., 1998-2005 Berg, Obstet Gynecol, 2010;116:1302.

Maternal mortality, by race/ethnicity U.S., 2007 NCHS, http://mchb.hrsa.gov/whusa10/hstat/mh/pages/237mm.html

Maternal morbidity U.S.,2001-2005 Type of morbidity 1993-1997 Percent Number 2001-2005 Obstetric complications 28.6 1,091,200 1,141,100 Preexisting medical conditions 4.1 155,300 4.9 194,100 Berg, Obstet Gynecol, 2009;113:1075.

CDC consultation March 2012 teleconference Reviewed evidence and WHO recommendation Discussed whether any changes needed to be made for US recommendations

CDC updated guidance CDC. MMWR 2012;61:449-452. http://www.cdc.gov/mmwr/preview/mmwrhtml/mm6124a4.htm?s_cid=mm6124a4_e%0d%0a

MEC HIV/AIDS recommendations Condition CHC POP DMPA Implants High risk for HIV 1 1† HIV infection 1* AIDS * Clarification: Drug interactions might exist between hormonal contraceptives and antiretroviral drugs; refer to the section on drug interactions. † Clarification: See next slide. CDC. MMWR 2012;61:449-452. http://www.cdc.gov/mmwr/preview/mmwrhtml/mm6124a4.htm?s_cid=mm6124a4_e%0d%0a

Clarification for progestin-only injectables among women at high risk of HIV Some studies suggest that women using progestin-only injectable contraception might be at increased risk for HIV acquisition; other studies do not show this association. CDC reviewed all available evidence and agreed that the data were not sufficiently conclusive to change current guidance. However, because of the inconclusive nature of the body of evidence on possible increased risk for HIV acquisition, women using progestin-only injectable contraception should be strongly advised to also always use condoms (male or female) and take other HIV preventive measures. Expansion of contraceptive method mix and further research on the relationship between hormonal contraception and HIV infection are essential. These recommendations will be continually reviewed in light of new evidence.

Conclusions Evidence mixed on hormonal contraceptives and HIV risk Consider health risks of HIV, unintended pregnancy and maternal mortality/morbidity Counseling about dual protection critical

http://www.cdc.gov/reproductivehealth/UnintendedPregnancy/USMEC.htm

Thank you flk4@cdc.gov For more information please contact Centers for Disease Control and Prevention 1600 Clifton Road NE, Atlanta, GA 30333 Telephone: 1-800-CDC-INFO (232-4636)/TTY: 1-888-232-6348 E-mail: cdcinfo@cdc.gov Web: http://www.cdc.gov The findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the Centers for Disease Control and Prevention. National Center for Chronic Disease Prevention and Health Promotion Division of Reproductive Health