1. Washington D.C., USA, 22-27 July 2012www.aids2012.org Pregnancy and HIV Acquisition Nelly Mugo Kenyatta National Hospital/ University of Washington Hormonal Contraception: the Role of Fertility Choice in HIV Prevention AIDS 2012, Global Village, Session Room 1 Thursday 26 th July

2. Washington D.C., USA, 22-27 July 2012www.aids2012.org Outline Fertility rates Association of pregnancy & HIV »Biological plausibility HIV Incidence in pregnancy & breast feeding

3. Washington D.C., USA, 22-27 July 2012www.aids2012.org Back ground  More than 50% of women with HIV- 1infection worldwide are women (UNAIDS 2010 Report)  In sub-Saharan Africa, fertility rates are high Majority (42%) of new HIV infections occur within reproductive years age 15- 24 years United Nation's Millennium Development Goals 4 and 5 aim to reduce child deaths and improve maternal health.

4. Washington D.C., USA, 22-27 July 2012www.aids2012.org Swaziland Malawi Peak HIV prevalence among women age: 24-34 years

5. Washington D.C., USA, 22-27 July 2012www.aids2012.org High Fertility Rates in Sub Saharan Africa WHO Report

6. Washington D.C., USA, 22-27 July 2012www.aids2012.org Does Pregnancy Increase HIV-1 Risk?  Physiological changes of pregnancy  High levels of progesterone could induce systemic and immunologic changes  Unprotected sex in efforts to conceive and continued during pregnancy make pregnant women vulnerable to HIV-1 infection Sheffield JS., Reprod Sci. 2009

7. Washington D.C., USA, 22-27 July 2012www.aids2012.org Male-to-female HIV-1 transmission (increased susceptibility of HIV neg pregnant woman) HIV-1 Female-to-male HIV-1 transmission (increased infectiousness of HIV-pos pregnant woman) HIV-neg male HIV-pos pregnant female HIV-neg pregnant female HIV-pos male HIV-1 Does Pregnancy Increase HIV-1 Risk?

8. Washington D.C., USA, 22-27 July 2012www.aids2012.org HIV incidence during pregnancy /and or breastfeeding Author, yearLocationPopulationHIV Incidence/100 per years Keating MA, PloSOne 2012 MalawiANC4.0 Mugo, NR, AIDS 2011 East & South AfricaSerodiscordant couples 7.4 Moodley JID 2011Kwa Zulu Natal, South Africa ANC2.5 Humprey JH, BMJ 2010 ZimbabweANC3.5 Kinuthia J, Curr HIV Res 2010 KenyaANC 6.8 Morrison C, AIDS 2007 Uganda ZimbabweFamily Planning clinics 1.6 Gray RH, Lancet 2005 UgandaSero-discordant couples 2.2 Mbidzo MT, Centr Afri J Med 2001 ZimbabweANC4.8

9. Washington D.C., USA, 22-27 July 2012www.aids2012.org Pregnancy and HIV-1 Risk: Summary Male-to-female HIV-1 Transmission  Observational studies demonstrate increased HIV incidence in pregnancy and early post partum (2.6 - 4.4%)*  Only 3 prospective studies have examined in detail the effect of pregnancy on women’s HIV risk with contradictory findings:  Uganda: IRR 2.16  Uganda/ Zimbabwe: HR 0.6  East/South Africa: 2.3 Female-to-male HIV-1 Transmission  The effect of pregnancy on HIV transmission risk is only hypothesized through indirect studies of HIV infectiousness e.g., increased genital HIV-1 shedding (Clemetson D, JAMA1993)  One study has explored pregnancy as a direct risk factor for F-to-M HIV transmission

10. Washington D.C., USA, 22-27 July 2012www.aids2012.org Risk of Neonatal Infection Acute HIV infection increases risk for mother to child transmission –26% (95% CI 22-30%) A proportion of 15,000 of 57,000 neonatal infections Johnson LF, J Acquir Immun Defic Syndr. 2012

11. Washington D.C., USA, 22-27 July 2012www.aids2012.org SUMMARY: Pregnancy Incidence, HSV/HIV Transmission Study

12. Washington D.C., USA, 22-27 July 2012www.aids2012.org 14 Sites for Partners in Prevention HSV/HIV Transmission Study Nairobi, Thika Eldoret, Kisumu Kenya (4) Kampala, Uganda Moshi, Tanzania Soweto, Orange Farm, Cape Town (Gugulethu) South Africa (3) Gaborone, Botswana Lusaka, Kitwe, Ndola, Zambia (3) Kigali, Rwanda

13. Washington D.C., USA, 22-27 July 2012www.aids2012.org Study Population & HIV-1 Incidence 58 *linked* HIV-1 seroconversion events HIV-1 incidence: 1.7 per 100 person-years 61 HIV-1 seroconversion events HIV-1 incidence: 3.6 per 100 person-years 1085 (33%) male HIV-pos female HIV-neg 3321 eligible couples 2236 (67%) female HIV-pos male HIV-neg Male-to-female transmission Female-to-male transmission

14. Washington D.C., USA, 22-27 July 2012www.aids2012.org Increased risk for HIV-1 transmission risk in pregnancy HIV-1 events HIV-1 incidence¹ Un-adjusted HR (95% CI) ²Adjusted HR (95% CI) Male-female All seroconversions613.6 Not during pregnancy443.01.0 During pregnancy177.4 2.3 (1.3-4) p=0.009 1.6 (0.9-2.9) p=0.12 Linked female-male All seroconversion581.7 Not during pregnancy461.61.0 During pregnancy123.5 2.2 (1.2-4.1) p=0.02 2.3 (1.2-4.4)³ p=0.02 ¹per 100 person-years ²Adjusted for age, unprotected sex and contraceptive use; ³male circumcision, plasma HIV VL, CD4 cell count, outside partners, ART use, sex acts did not confound this risk estimate Mugo et al AIDS 2011

15. Washington D.C., USA, 22-27 July 2012www.aids2012.org Increased Risk for HIV Transmission and Acquisition in Pregnancy Approximately 2-fold increased HIV-1 risk during pregnancy for both HIV-1 uninfected pregnant woman & HIV-1 uninfected male partners of HIV-1 infected pregnant woman  male-to-female unadjusted HR 2.3  95% CI (1.3 - 4) p=0.009  female-to-male HIV transmission unadjusted HR 2.2  95% CI (1.1 - 4.1) p= 0.02 Mugo et al AIDS 2011

16. Washington D.C., USA, 22-27 July 2012www.aids2012.org Pregnancy and Male-to-Female HIV-1 Transmission  The effect of pregnancy on male-to-female appeared to be largely explained by behavioural factors, becoming attenuated and not statistically significant in adjusted analysis  unadjusted HR 2.3, 95% CI 1.3-4.0, p=0.009  adjusted HR: 1.6, 95% CI 0.9-2.9, p=0.12  Pregnancy & HIV-1 infection both require unprotected sex  Socio-cultural pressure & desire for pregnancy may outweigh motivation to prevent HIV-1 infection among couples

17. Washington D.C., USA, 22-27 July 2012www.aids2012.org Pregnancy and Female-to-Male HIV-1 Transmission  In contrast, female-to-male increased transmission risk is not fully attributable to confounding factors –Unadjusted HR 2.2, 95% CI 1.2-4.4, p=0.02 –Adjusted HR 2.3, 95% CI 1.2-4.4, p=0.02  May be due to increased HIV-1 genital shedding ( surrogate for infectiousness ) in pregnancy (Clemetson et al JAMA 1993) This has been the first study to demonstrate an increase in female-to-male HIV-1 risk with pregnancy.

18. Washington D.C., USA, 22-27 July 2012www.aids2012.org Discussion  Women spend a substantial number of years pregnant in sub- Saharan Africa (fertility @ 4 pregnancies per lifetime)  Pregnancy exposure is an important risk factor for HIV infection (mother, baby, partner)  Calls for repeat HIV testing in 3 rd Trimester and possibly post partum where it is not yet routine  Male partner prevention is often not factored into perinatal HIV-1 strategies  Opportunity for couples counseling and reduction both perinatal and sexual transmission of HIV

19. Washington D.C., USA, 22-27 July 2012www.aids2012.org Acknowledgement FHI 360 IAS conference organizers HSV/HIV Transmission study teams All of you All pregnant women-lets work towards improving maternal and neonatal health

20. Washington D.C., USA, 22-27 July 2012www.aids2012.org Thank you Asante Sana