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Hormonal Contraception and Risk of HIV
Z Mike Chirenje MD FRCOG UZ-UCSF Collaborative Research Program 15 Phillips Ave, Belgravia Harare, Zimbabwe [email protected]
HC and HIV Risk • Safe and effective contraceptive methods have been
cornerstone for reduction in unintended pregnancies and improved maternal health worldwide (since 1960’s)
• Yearly there are 100 million users (OCP), 41 million (injectable )
• Unintended pregnancy and acquisition of STI’s including HIV remain most important health risks faced by many women worldwide particularly in SSA countries that have 60% women living with HIV/AIDS
• Women in HIV endemic countries require effective contraception that does not increase acquisition of STI’s/HIV
0%
10%
20%
30%
40%
50%
60%
70%
80%
90%
100%
Provide, prescribe, or
counsel on temp. FP methods
Provide methods with estrogen
Provide injectables
Provide IUDs Provide implants
Among all facilities surveyed in a Service Provision Assessment, percentage that:
Kenya 2010 Namibia 2009 Uganda 2007 Tanzania 2006
What evidence is available to explain association of HC and HIV acquisition?
• During past 2 decades there has been inconsistent data from epidemiological studies on effect of HC use and risk of acquiring HIV
• Out of 16 published prospective studies on OCP, only 2 reported a significant increase in HIV acquisition risk
• Among 12 prospective observational studies that assessed DMPA(depot), only 4 reported increased HIV acquisition risk
Studies of COCs and HIV Acquisition Plummer 1991 Sinei 1996* Kilmarx 1998 Plourde 1994 Heffron 2011 Feldblum 2010 Baeten 2007 Morrison 2010 Kiddugavu 2003 Kapiga 1998
Saracco 1993 Reid 2010 Laga 1993 Myer 2007 De Vincenzi 1994 Ungchusak 1996
Studies of Injectables & HIV Acquisition
Kumwenda 2008
Ungchusak 1996
Feldblum 2010
Heffron 2011
Bulterys 1994
Baeten 2007
Watson-Jones 2009
Kilmarx 1998
Morrison 2010
Myer 2007
Reid 2010
Kiddugavu 2003
Kleinschmidt 2007
Kapiga 1998
HC study (Morrison C et al AIDS 2007
Inclusion • 18 to 35 years of age • HIV seronegative • Low dose COCs for > 3 months
- DMPA for > 3 months - or non-hormonal method or no method
Exclusion • Pregnant (intending to become pregnant) • Used an IUD in last month • Used any HC besides COC or DMPA within 3
months
Study Retention
• 24-month retention rates were high:
– 92% African participants (96% UG; 88% ZM)
– Contraceptive groups (91% COC; 93% DMPA; 91% NH)
• Mean follow-up: 21.9 months
• Median time between visits: 11.5 weeks
Incident HIV Infections by Country and Contraceptive Group
COC N/wy (incidence rate per 100 wy)
DMPA N/wy (incidence rate per 100 wy)
NH N/wy (incidence rate per 100 wy)
Total N/wy (incidence rate
per 100 wy)
Uganda 20/1271 (1.57) 26/1384 (1.88) 17/1433 (1.19) 63/4075* (1.55)
Zimbabwe 51/1475 (3.46) 61/1413 (4.32) 41/841 (4.87) 150#/3683* (4.07)
Thailand 0/878 (0) 3/992 (0.30) 1/883 (0.11) 4/2732* (0.15)
Total 71/3625 (1.96) 90/3789 (2.38) 59/3157 (1.87) 217#/10490* (2.07)
Total Africa only 71/2747 (2.59) 87/2797 (3.11) 58/2274 (2.55) 213#/7758* (2.75)
* Total woman-years is less than sum of contraceptive method woman-years because some women used multiple methods within same segment
# 3 women used multiple methods in segment where seroconversion occurred
Biological effect of hormones on susceptibility to HIV
! Observational studies can not truly isolate biological effects
! Biological effect assessment in none hormonal users after primate studies
! Behavioral changes are variable over time, often influenced by male partner(mediator/confounding effect)
Method of hormonal contraception (e.g., DMPA)
Risk of HIV acquisition Behavioral changes that
influence risk of HIV acquisition (e.g., less
condom use)
12
Is the risk true biological effect?
Hormones and HIV Possible Mechanisms
• Vaginal and cervical epithelium (ectopy, etc.)
• Cervical mucus • Menstrual patterns • Vaginal and cervical immunology • Viral (HIV) replication • Acquisition of other STI
Shattock and Moore 2003
Mucosal Transmission of HIV Infection
Limitations of HC/HIV Observational Studies
• Potential for unmeasured selection bias
• Potential for confounding
• Non-hormonal comparison group with greater condom use
• Hormonal contraceptive use not adequately documented
WHO Consultation- The Solution
• Recommendation – MEC Category 1 (no restrictions)
• 1* Clarification – “women using progestogen-only injectable strongly advised to also always use condoms”
WHO Consultation – Programmatic Recommendations
• Withdrawal of hormonal contraception from FP programs is not warranted
• Contraceptive method mix needs to be expanded, especially for women at risk of HIV
• Condoms must be strongly emphasized
• FP and HIV programs should be integrated
WHO Consultation – Research Recommendations
• Higher quality clinical studies are need to improve the HC/HIV acquisition evidence
• Developing new multipurpose technologies to prevent both HIV and unintended pregnancy – a high level priority
• Understanding the biology of HC/HIV interactions essential
In Conclusion and Way Forward
! Robust evidence of HC and effect on HIV acquisition is lacking
! A study (ECHO= Evidence for Contraceptive Options and HIV outcome) is in advanced planning
! Randomized Trial into ? 4 ( DMPA, Net-EN, Implant, IUCD) or 3 arms or 2 arms
! How feasible in randomization in a contraceptive trial?
! How do we limit method switch during enrollment period?
! WHO advocating for contraceptive mix in the mean time