Hormonal Contraception and Risk of HIV

Z Mike Chirenje MD FRCOG UZ-UCSF Collaborative Research Program 15 Phillips Ave, Belgravia Harare, Zimbabwe chirenje@uz-ucsf.co.zw

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