1. HIV, CONTRACEPTION AND ASSISTED REPRODUCTIVE TECHNOLOGY PERSEPECTIVES FROM A DEVELOPING COUNTRY (KENYA) Elizabeth Bukusi

2. OVERVIEW Contraceptive use among HIV positive women in a cohort in Nairobi Hormonal contraceptive use and their effects among a sex worker cohort in Mombasa Assisted reproduction technology- a needs perspective from Kenya

3. Kenyan Research Sites

4. Characteristics of a cohort of HIV infected women on steroid and non-steroid hormone contraception Mwachari C 1, Omondi C 1, Kariuki J 1, Thiongo L 1, Cohen CR 2* 1. Kenya Medical Research Institute, Nairobi 2. University of Washington, Seattle,* Current affiliation University of San Francisco, California

5. BACKGROUND Dec 2002 UNAIDS/WHO estimated 19.2M women were infected with HIV worldwide The majority of these women in the reproductive age hence need for reliable contraception Many women use steroid hormones for contraception Steroid hormones may interact with HIV virus or alter the immune function through various mechanisms

6. CONT…BACKGROUND Identified a need to study the effects of hormonal contraception on HIV progression

7. METHODS Study sites: Nairobi, Kenya and Harare, Zimbabwe, Chula, Thailand. Study Design: Prospective non-randomized cohort study Subjects assigned to contraceptive group (current contraceptive method of their choice at least 3 months prior to enrollment)

8. METHODS (cont..) Subject population: 18-35 years documented HIV infection CD4 count ≥ 500 cells/ul At least 3 months of contraception Nairobi resident Follow up every 3 months for 4 years

9. CLINICAL PROCEDURES Obtain study and HIV consent Medical, behavioral, contraception history Medical examination

10. Laboratory Procedures At Enrollment- FBC, RPR, plasma viral load, CD4/CD8 - pap smear - CVL Every 6 months- FBC, CD4/CD8, plasma viral load Every 12 months- pap smear - CVL - RPR

11. RESULTS 5,188 WOMEN SCREENED 25.8% HIV SEROPREVALENCE 227(4.5%) HIV-1 INFECTED WOMEN ENROLLED 175 (77%) ON STEROID HORMONE CONTRACEPTIVES AND 52 (23%) ON NON-STEROID HORMONE CONTRACEPTIVES 75% FOLLOW-UP AFTER ONE YEAR

12. Steroid hormone contraceptives

13. Table 1: Socio-demographic profile of cohort CHARACTERISTICHORMONAL N=175 NON- HORMONAL N=52 P- VALUE AGE <30 YRS162 (92.6%)32 (61.5%)P<0.01 MARRIED WIDOWED SINGLE 160 (91.4%) 12 (6.9%) 3 (1.7%) 34 (65.4%) 14 (26.9%) 4 (7.7%) P<0.01 SES LOW SES HIGH 138 (78.9%) 37 (21.1%) 31(59.6%) 21 (40.4%) P<0.01 Ever Alcohol Use YES33 (18.9%)25 (51.9%)P<0.01 Ever Smoked YES6 (3.4%)6 (11.6%)P=0.05 Breastfeeding YES81 (46.8%)7 (13.5%)p<0.01

14. Cont…Table 1: Socio-demographic profile of cohort CHARACTERISTIC HORMONAL USERS N=149 NON HORMONAL USERS N=30 SIGNIFANCE CONDOM USE IN LAST ONE MONTH Never/less than half the time More than half the time Always 136 (91.3%) 6 (4.0%) 7 (4.7%) 13 (43.3%) 3 (10.0%) 14 (46.7%)P <0.01 n=174n=52 NUMBER OF SEXUAL PARTNERS EVER HAD 1 partner 2-3 partners 4+ partners 26 (14.9%) 97 (55.7%) 51(29.3%) 6 (11.5%) 21 (40.4%) 25 (49.1%)P<0.03

16. SUMMARY HIV + women using steroid hormone contraceptives tended to be younger, married, lower SES, and likely to be breastfeeding at one year. There was significantly lower condom use among hormonal contraceptive users than that of non- hormonal contraceptive users.

17. SUMMARY In this cohort steroid hormonal users tended to have higher median CD4 counts, lower at one year. Median rate of CD4 decline over one year was not significant between steroid hormonal users Vs non-steroid hormonal users

18. Acknowledgements Dr. Craig Cohen, Dr. Abuaba, Kariuki J, Lucy S, Lilian M, Jabuya E, Miheso B, Lawrence T, Jane M, Scola M, Jarmen K, Henry K Study participants KEMRI

19. Hormonal contraception and sexually transmitted infections / HIV-1 infection in women Ludo Lavreys University of Washington, Seattle, USA University of Nairobi, Nairobi, Kenya Annual Review Meeting UoN STD/AIDS Collaborative Group Holiday Inn Mayfair Hotel, Nairobi, 2 February 2005

20. Contraceptive use in Mombasa Cohort and in Kenya Cohort a Kenya – 2003 a,b Oral contraceptive pills Depot medroxyprogesterone acetate (DMPA - Depo) Norplant Condoms IUD Female sterilization Diaphragm 12.3% 22.2% 1.9% 10.6% 1.9% 2.4% 0.0% 7.2% 13.8% 1.6% 1.2% 2.4% 4.3% ? a % married: cohort: 1.5%; National survey: 100% b Kenya Demographic and Health Survey 2003 Preliminary Report

21. Hormonal contraception and sexually transmitted infections Does the use of hormonal contraception increase a woman’s risk for cervical sexually transmitted infections?

22. HCC use and cervical STIs among HIV-1 negative sex workers in Mombasa Baeten J, et al. Am J Obstet Gynecol 2001; 185:380-385. OCPDMPA HR (95% CI)P P C. trachomatis1.8 (1.1-2.9).031.6 (1.1-2.4).02 N. gonorrhoeae1.4 (0.9-2.1).11.1 (0.8-1.6).5 Cervicitis1.8 (1.5-2.2)<.0011.5 (1.2-1.9).001 Adjusted for age, yrs of education, yrs of prostitution, parity, workplace, number of sexual partners per week, numbers of sex encounters per week, and condom use

23. Hormonal contraceptive use and cervical STIs among HIV-1 positive sex workers in Mombasa Incidence per 100 PY of FU (N cases) OCPDMPA HR (95% CI)P P C. trachomatis7.7(26)2.2 (0.7-7.3).23.1 (1.0-9.4).05 N. gonorrhoeae 14.9(119)0.6 (0.3-1.3).21.0 (0.6-1.7).9 Cervicitis24.2(193)2.3 (1.4-3.8).0011.6 (1.0-2.3).03 Adjusted for age, yrs of education, yrs of prostitution, parity, workplace, number of sexual partners per week, and condom use Lavreys L, et al. AIDS 2004;18:2179-84.

24. Summary (1) The use of hormonal contraception is associated with increased risk for:  Cervical infections in HIV-1 negative and positive women, suggesting increased HIV-1 susceptibility and infectiousness

25. Hormonal contraception and HIV-1 acquisition Does the use of hormonal contraception increase a woman’s risk for HIV-1 acquisition?

26. Hormonal contraception and risk of HIV-1 acquisition Period 1993-1997 1 (N=779) HR95% CI p None/Tubal ligation 1.0 DMPA2.01.3-.1.003 Oral contraceptive s 1.30.8- 2.2.3 Adjusting for sexual behavior, condom use, and sexually transmitted infections 1 Martin HM, et al. J Infect Dis 1998;178:1053-1059.

27. Hormonal contraception and risk of HIV-1 acquisition Period 1993-1997 1 (N=779) Period 1993-2003 2 (N=1272) HR95% CI pHR95% CI p None/Tubal ligation 1.0 DMPA2.01.3- 3.1.0031.81.4-2.4<.00 1 Oral contraceptives 1.30.8- 2.2.31.51.0-2.1.04 Adjusting for sexual behavior, condom use, and sexually transmitted infections 1 Martin HM, et al. J Infect Dis 1998;178:1053-1059. 2 Lavreys L, et al. AIDS 2004;18:695-697.

28. Summary (2) The use of hormonal contraception is associated with increased risk for:  Cervical infections in HIV-1 negative and positive women, suggesting increased HIV-1 susceptibility and infectiousness  HIV-1 acquisition

29. Hormonal contraception and natural history of HIV-1 Does the use of hormonal contraception affect the natural history of HIV-1 infection?

30. DMPA NO DMPA DMPA Lavreys L, et al. J Infect Dis 2004;189:303-311.

31. Viral diversity and use of DMPA Multiple viral variants detected in 89/156 women (57%) HIV-1 viral diversity during primary infection was associated with use of DMPA at the time of HIV-1 acquisition (OR 3.0, 95% CI 1.3-6.9, p=0.005) Sagar M, et al. AIDS 2004;18:615-619.

32. Summary (3) The use of hormonal contraception is associated with increased risk for:  Cervical infections in HIV-1 negative and positive women, suggesting increased HIV-1 susceptibility and infectiousness  HIV-1 acquisition  Higher viral load at set point, which might lead to faster disease progression  Acquisition of a more complex viral population, leading to a higher plasma viral load, and faster decline in CD4 count

33. Hormonal contraception and HIV-1 infectiousness Does the use of hormonal contraception affect shedding of HIV-1 in the female genital tract, and hence the risk of transmitting HIV-1 infection?

34. Hormonal contraception and HIV-1 infectiousness Mostad, et al. Lancet 1997;350:922-927 Adjusted odds ratio Cross-sectional N=308

35. Hormonal contraception and HIV-1 infectiousness Wang et al. AIDS 2004;18:205-209 Adjusted odds ratio Cervical HIV-1 DNA prevalence (n=211) Cross-sectionalProspective Before HCAfter HCOR (95% CI)P 42%52%1.62 (1.03-2.63)0.03 N=308 Mostad, et al. Lancet 1997;350:922-927

36. Summary (4) The use of hormonal contraception is associated with increased risk for:  Cervical infections in HIV-1 negative and positive women, suggesting increased HIV-1 susceptibility and infectiousness  HIV-1 acquisition  Higher viral load at set point, which might lead to faster disease progression  Acquisition of a more complex viral population, leading to a higher plasma viral load, and faster decline in CD4 count  Shedding of virus in the genital tract of HIV-1 infected women, which might lead to increased infectiousness

37. Recommendations? Ref: Network Vol 23, number 3, 2004. Family Health International

38. Recommendations? Ref: Network Vol 23, number 3, 2004. Family Health International

39. Our Collaborators Mombasa: Bhavna Chohan ** Varsha Chohan Wisal Hassan Christine Katingima Kishor Mandaliya Scott McClelland Clinic and lab staff All patients Nairobi (UoN) : Walter Jaoko Jeckoniah Ndinya-Achola Seattle (UW and FHCRC): Jared Baeten* Julie Overbaugh Dana Panteleeff Barbra Richardson Manish Sagar IARTP staff *Current affiliation: Massachusetts General Hospital, Boston * *Current affiliation: Fred Hutchinson Cancer Research Center, Seattle

40. High Acceptability Of Hiv-1 Testing Among Infertile Couples Attending A Refferal Infertility Clinic In Nairobi, Kenya Bukusi E 1,2, Sinei S 2, Cohen C 2,3 1 Kenya Medical Research Institute 2 University of Nairobi, 3 University of Washington

41. Women and Men combined 36/40 (90%) Couples17/20(85%) Women only19/20(95%) Men only17/20(85%) ACCEPTANCE OF HIV TESTING AMONG INFERTILE COUPLES

42. HIV-1 concordant negative couples 13/17 (76%) HIV-1 concordant positive couples 1/17(6%) HIV-1 discordant couples 3/17 (18%) Discordant couple male HIV-1 positive 1/3 (33%) Discordant couple female HIV -1 positive 2/3(66%) HIV-1 serostatus among Infertile couples

43. Phase III Randomized Placebo-Controlled Trial of HSV-2 Suppression to Prevent HIV Transmission among HIV-Discordant Couples Dr. Craig Cohen 1, Dr. Elizabeth Bukusi 2, Dr. Videlis Nduba 2, Dr. Anjali Sharma 2, Dr. Kawango Agot 3 1 University of California, San Francisco, 2 Kenya Medical Research Institute, 3 University of Nairobi, University of Manitoba and University of Illinois

44. Kisumu CIS Discordant couple data* Positive PartnerNumber Total 101 Female71 Male30 *Jan 2005, VCT sites