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Weighing 17 years of evidence: Does hormonal contraception increase HIV acquisition risk among Zambian
women in discordant couples?
Kristin M. Wall, [email protected]
Department of EpidemiologyRwanda Zambia HIV Research Group
Emory University, Atlanta, GA, USA
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Conflict of Interest Disclosure
The authors have no conflicts of interest due to financial or personal relationships that might be perceived to cause bias.
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BackgroundHormonal contraception• Prevents unintended pregnancy1
– Prong 2 PMTCT for HIV+ women1
• Is widely used in high HIV prevalence areas2
Use among married women in Zambia3:11% OCP 9% Injectable 0.4% Implant
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BackgroundExtant evidence is conflicting1
2012 World Health Organization technical meeting• Medical Eligibility Criteria (MEC) Category 1• Emphasized dual method use for high-risk women using
progestogen-only injectables1
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Study population
M+F- serodiscordant couples• Identified from couples’ voluntary HIV counseling and
testing services in Lusaka from 1994-2012• >16 years of age• Male partner was not on ART• Followed 3-monthly at the research site
– Contraception methods provided– HIV testing of negative partners
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Contraceptive exposures
Hormonal methods: – Implant (Norplant, Jadelle) – Injectable (150 mg IM DMPA)– Combined oral contraceptive pills (OCPs)
Non-hormonal control: – No method – Condoms– Copper intrauterine device (IUD)– Permanent methods
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HIV infection outcomes
• Time to any HIV infection – Genetically linked or unlinked to the study
partner
• Time to linked HIV infections
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AnalysesMultivariate Cox models• Potential effect-measure modifiers:
– Genital ulceration, inflammation, VL, fertility intentions, age
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AnalysesMultivariate Cox models• Potential effect-measure modifiers:
– Genital ulceration, inflammation, VL, fertility intentions, age
Sensitivity analyses explored effects of:• Method exposure/control categorizations• Cumulative exposure• Misclassification of unprotected sex• Time-dependent confounding
– Marginal structural models
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Non-seroconverting
couples (N = 1141)
Seroconverting couples
(N=207 linked & 45 unlinked)
Total (N = 1393 M+F- couples) 82% 18%
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Non-seroconverting
couples (N = 1141)
Seroconverting couples
(N=207 linked & 45 unlinked)
Total (N = 1393 M+F- couples) 82% 18%Baseline contraceptive method
None/condoms alone 72% 74% OCPs 11% 12% Injectables 10% 10% Implant 3% 3% IUD 2% 1% Permanent method 1% 0%
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Seroconversion rates among HIV-women in discordant relationships by method of contraception
METHOD#
infections CY Incidence /100 CY 95%CI p-value
(2-tail)
None/condoms 150 1796 8.4 7.1 9.8 ref
OCPs 49 425 11.5 8.6 15.1 0.06
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Seroconversion rates among HIV-women in discordant relationships by method of contraception
METHOD#
infections CY Incidence /100 CY 95%CI p-value
(2-tail)
None/condoms 150 1796 8.4 7.1 9.8 ref
OCPs 49 425 11.5 8.6 15.1 0.06
Injectables 42 392 10.7 7.8 14.3 0.16
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Seroconversion rates among HIV-women in discordant relationships by method of contraception
METHOD#
infections CY Incidence /100 CY 95%CI p-value
(2-tail)
None/condoms 150 1796 8.4 7.1 9.8 ref
OCPs 49 425 11.5 8.6 15.1 0.06
Injectables 42 392 10.7 7.8 14.3 0.16
Implant 9 124 7.3 3.6 13.4 0.72
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Multivariate models of time to ANY HIV seroconversion
METHOD aHR* 95%CI p-value (2-tail)
Non-hormonal ref
Implant 0.9 0.4 2.0 0.86
Injectables 1.2 0.8 1.8 0.32
OCPs 1.3 0.9 1.9 0.14
*Controlling for: • Woman's age (per year increase)• Woman's literacy in Nyanja• Sperm present on a wet prep during interval• Genital ulceration of woman in past 3 months• Genital inflammation of woman in the past 3 months
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Multivariate models of time to ANY HIV seroconversion
METHOD aHR* 95%CI p-value (2-tail)
Non-hormonal ref
Implant 0.9 0.4 2.0 0.86
Injectables 1.2 0.8 1.8 0.32
OCPs 1.3 0.9 1.9 0.14
*Controlling for: • Woman's age (per year increase)• Woman's literacy in Nyanja• Sperm present on a wet prep during interval• Genital ulceration of woman in past 3 months• Genital inflammation of woman in the past 3 months
Findings remained the same when controlling for pregnancy
and/or fertility intentions
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ResultsSimilarly, the results of:
• Multivariate models of linked infections only– Additionally controlling for baseline pregnancy, couples’
unprotected sex in past 3 months, genital ulceration and inflammation of male partner in past 3 months, and VL
• All sensitivity analyses
• Marginal structural models
did not indicate any significant increase in HIV risk for hormonal contraception users.
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Measures of unprotected sex by method of contraception
3-monthly measure of:
Non-hormonal
%OCPs
%p-value
(2-tailed)*
Incident pregnancy 3% 5% ^
Unprotected sex 29% 37% ^
Sperm on wet prep 6% 8% ^
^p-value <0.05 OCP vs. non-HC #p-value <0.001 injectables vs. non-HC&p-value <0.001 non-HC vs. implant
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Measures of unprotected sex by method of contraception
3-monthly measure of:
Non-hormonal
%OCPs
%Injectable
%p-value
(2-tailed)*
Incident pregnancy 3% 5% 1% #
Unprotected sex 29% 37% 34% #
Sperm on wet prep 6% 8% 6%
^p-value <0.05 OCP vs. non-HC #p-value <0.001 injectables vs. non-HC&p-value <0.001 non-HC vs. implant
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Measures of unprotected sex by method of contraception
3-monthly measure of:
Non-hormonal
%OCPs
%Injectable
%Implant
%p-value
(2-tailed)*
Incident pregnancy 3% 5% 1% 0% &
Unprotected sex 29% 37% 34% 18% &
Sperm on wet prep 6% 8% 6% 2% &
^p-value <0.05 OCP vs. non-HC #p-value <0.001 injectables vs. non-HC&p-value <0.001 non-HC vs. implant
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Measures of unprotected sex by pregnancy status
3-monthly measure of:
Not pregnant
%Pregnant
%
p-value
(2-tailed)*No. times unprotected sex (mean) 2 6 ^Any unprotected sex 28% 54% ^Sperm on wet prep 6% 10% ^
^p-value <0.001 pregnant vs. not pregnant
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Conclusions & RecommendationsWe found no association between hormonal
contraception and HIV acquisition risk in women
Reinforced condom counseling is needed during:• Oral contraceptive pill use• Injectable use • Pregnancy
These findings:• Add to a controversial literature • Are important when evaluating MEC Categories
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AcknowledgementsRwanda Zambia HIV Research Group (RZHRG) Contributors
William KilembeHtee Khu NawIlene BrillBellington VwalikaElwyn ChombaBrent JohnsonLisa HaddadAmanda TichacekSusan Allen
Zambian Ministry of Health & District Health Management Team
Study Participants & Clinic Staff
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FundingNational Institutes of Child Health and Development (NICHD RO1 HD40125)National Institute of Mental Health (NIMH R01 66,767)AIDS International Training and Research Program Fogarty International Center (D43 TW001042)Emory Center for AIDS Research (P30 AI050409)National Institute of Allergy and Infectious Diseases (NIAID R01 AI51231; NIAID R01 AI040951; NIAID R01 AI023980; NIAID R01 AI64060; NIAID R37 AI51231)US Centers for Disease Control and Prevention (5U2GPS000758)International AIDS Vaccine InitiativeThis study was made possible by the generous support of the American people through the United States Agency for International Development (USAID). The contents are the responsibility of the International AIDS Vaccine Initiative and do not necessarily reflect the views of USAID or the United States Government. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
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Seroconversion rates among HIV-negative women in discordant relationships by method of contraception
METHOD#
infections CY Incidence /100 CY 95%CI p-value
(2-tail)
Total 252 2839 8.9 7.8 10.0None/condoms 150 1796 8.4 7.1 9.8 refOCPs 49 425 11.5 8.6 15.1 0.06Injectables 42 392 10.7 7.8 14.3 0.16IUD 1 58 1.7 0.1 8.5 0.06Implant 9 124 7.3 3.6 13.4 0.72Permanent 1 43 2.3 0.1 11.4 0.15
