Safer Conception for Sero-Discordant Couples Judy Levison, MD, MPH Associate Professor, Departments of Obstetrics and Gynecology and Family and Community Medicine Baylor College of Medicine Houston, Texas jlevison@bcm.edu

This teleconference is made possible by the Cooperative Agreement #5U65PS000815-03 from the Centers for Disease Control and Prevention Special thanks to AETC, Title X and CDC EMCT partners The views expressed by the speakers and moderators do not necessarily reflect the official polices of the Dept. of Health and Human Services nor does mention of trade names or organizations imply endorsement by the U.S. Government.

Objectives Describe two methods of conception for an HIV+ woman and an HIV- man List three methods of conception for an HIV+ man and an HIV- woman

The Serodiscordant Couple

HIV discordance in couples Population based sample of HIV infected persons in care 58% of men and 70% of women had a primary partner 50% of couples were in serodiscordant relationships 20% were in relationships with partners whose HIV status was unknown Family Planning Perspectives, 33 (4); 144-52, 2001 Estimated 140,000 serodiscordant heterosexual couples in the U.S., about half of whom want children Am Journal of Obst and Gyn, 204(6), 488e1-8, 2011 Although recent data are not available, a study of a population based sample of HIV-infected persons in care in 1996 found that 58% of men and 70% of women had a primary partner or spouse; approximately 50% of couples were in serodiscordant relationships and almost 20% were in relationships with partners whose HIV status was unknown. J. L. Chen, K. A. Philips, D. E. Kanouse et al., Fertility desires and intentions of HIV-positive men and women, Family Planning Perspectives, vol. 33, no. 4, pp. 144-52, 165, 2001. Extrapolating from this information and incorporating 2006 data about number and demographics of heterosexual adults living with HIV in the U.S., it has been estimated there are an approximately 140,000 HIV-heterosexual serodiscordant couples in the US, about half of whom want more children. This has significant implications in providing accurate information on achieving safe conception in the presence of HIV discordance. M. A. Lampe, D. K. Smith, G. J. Anderson et al., Achieving safe conception in HIV-discordant couples: the potential role of oral pre-exposure prophylaxis (PrEP) in the United States, American Journal of Obstetrics and Gynecology, vol. 204, no. 6, pp. 488 e1-8, 2011. A number of studies have suggested that HIV has an adverse effect on fertility in both symptomatic and asymptomatic women. This includes increased risk of infertility and pregnancy loss and higher viral loads are associated with decreased fertility. R. H. Gray, M. J. Wawer, D. Serwadda et al., Population-based study of fertility in women with HIV-1 infection in Uganda, Lancet, vol. 351, no. 9096, pp. 98-103, 1998. L. M. Lee, P. M. Wortley, P. L. Fleming et al., Duration of human immunodeficiency virus infection and likelihood of giving birth in a Medicaid population in Maryland, American Journal of Epidemiology, vol. 151, no. 10, pp. 1020-8, 2000. R. H. Nguyen, S. J. Gange, F. Wabwire-Mangen et al., Reduced fertility among HIV-infected women associated with viral load in Rakai district, Uganda, International Journal of STD & AIDS, vol. 17, no. 12, pp. 842-6, 2006 However, recent data suggest that effective ARV therapy may restore or improve fertility. As women receive effective treatment, they may become at increased risk for unintended pregnancy. F. E. Makumbi, G. Nakigozi, S. J. Reynolds et al., Associations between HIV Antiretroviral Therapy and the Prevalence and Incidence of Pregnancy in Rakai, Uganda, AIDS Research and Treatment, vol. 2011, pp. 519492, 2011. L. Myer, R. J. Carter, M. Katyal et al., Impact of antiretroviral therapy on incidence of pregnancy among HIV-infected women in Sub-Saharan Africa: a cohort study, PLoS Med, vol. 7, no. 2, pp. e1000229, 2010.

The first two responses may have been appropriate before we saw the successes of the HAART era But in 2012: Perinatal transmission is <1-2% Men and women with HIV can expect to live to see their children grow into adulthood

Preconception counseling If a woman is not on ARVs, consider starting them prior to attempting conception If a woman is on ARVs and is considering pregnancy Substitute other ARVs for efavirenz (Sustiva) because of possible risk of neural tube defects (NTDs) Recommend folate or prenatal vitamins preconceptionally to reduce chance of NTDs

Serodiscordant couples If the woman is HIV+ and the man is HIV-, discuss the options of: Ovulation predictor kits Home insemination (“turkey baster method”)

Ovulation predictor kits These test kits replace the old basal body temperature charts

When the time is right, the choices are: Home insemination with partner’s semen The “turkey baster” method *A needle-less syringe works fine

Home insemination During the 24 hours after the LH surge has occurred as documented by the ovulation predictor kit, ejaculate into a cup or into a condom without a spermicide Suction semen into a syringe Place syringe in vagina and deposit semen Remain lying down for 20 minutes Return to having protected sex with condoms

Alternatives Insemination in a doctor’s office with partner’s semen Penile/vaginal intercourse only during the 24 hours after the LH surge and using condoms the rest of the month. Placing the woman on ARVs prior to attempted conception will further protect her partner Post or pre-exposure prophylaxis for male (PEP or PrEP)? If yes, how many doses? Baeten, J. and Celum, C. (2011) The Partners PrEP Study. Int. AIDS Society, Rome

And one more word about condoms… If we do not broaden our discussions around reproductive health (leaving it at "use condoms“), many individuals will do what they will do at home in order to achieve pregnancy It’s much better that they conceive with support and knowledge of safe options. We don’t want clients to feel they have to hide their desire to have children.

Serodiscordance If the man is HIV+ and the woman is HIV-, consider: Maximal viral suppression of the male Ovulation predictor kit/ timed insemination with washed sperm Intracytoplasmic sperm injection (ICSI) Ovulation predictor kit/timed intercourse Post-exposure prophylaxis (PEP) or pre-exposure prophylaxis (PrEP) for female Donor insemination

Sperm washing Cost is in the $1500 range Not widely available http://aids.about.com/cs/womensresources/a/washing.htm http://www.thebody.com/content/art911.html

Has the time come for natural conception in the context of full viral suppression? Barreiro 62 serodiscordant couples HIV+ partner on ART and VL < 500 No transmission of HIV HPTN 052 96% reduction in transmission of HIV among serodiscordant couples (ARVs started if CD4 350-500) Barreiro et al. (2007) Human Reproduction, 22 (9), 2353 Cohen, M. et al. (2011). NEJM 365: 493-505.

What if both partners are HIV-positive? When a couple is not attempting conception, we recommend condoms to avoid superinfection and sharing of antiretroviral resistant virus If pregnancy desired: Ovulation predictor kit, maintaining an undetectable viral load, and once monthly unprotected sex is a reasonable approach

Preconception counseling is not being addressed Data suggests that reproductive counseling does not often occur until after conception Recent study of 181 women: Only 31% reported a personalized discussion with their provider specific to their childbearing plans. Of those who had a personalized discussion, most were initiated by the client rather than the provider. Women living with HIV express the desire to talk about reproductive plans with their healthcare providers; however, data suggests that such counseling does not often occur until after conception [22, 34, 35]. K. E. Squires, S. L. Hodder, J. Feinberg et al., AIDS Patient Care and STDS, vol. 25, no. 5, pp. 279-85, 2011. L. S. Massad, C. T. Evans, T. E. Wilson et al., Journal of Women's Health (Larchmt), vol. 16, no. 5, pp. 657-66, 2007. M. A. Lampe, D. K. Smith, G. J. Anderson et al. American Journal of Obstetrics and Gynecology, vol. 204, no. 6, pp. 488 e1-8, 2011. In a recent study of 181 women, 67% reported having a general discussion about pregnancy with their HIV health provider, but only 31% of women reported a discussion that was personalized and specific to their future childbearing plans. Of those who had a personalized discussion, most were initiated by the patient rather than the provider. S. Finocchario-Kessler, J. K. Dariotis, M. D. Sweat et al., AIDS Patient Care and STDS, vol. 24, no. 5, pp. 317-23, 2010. S. Finocchario-Kessler, et al., AIDS Patient Care and STDS, 24(5), 317-23, 2010

Support Tools: EPIC Template Are you interested in having a child? When do you wish to conceive? Currently 6 mos-1yr, 1-2 years; >2years Are you currently using condoms? Are you currently using contraceptive other than condoms? If yes, what method: If no, are you seeking pregnancy: Would you like information on planning a safe pregnancy that may reduce the risk of HIV transmission to your partner and your baby?

Support Tools: EPIC Template Do you know and understand your CD4 count and viral load? Do you understand the importance of being in optimal health before becoming pregnant? Counseling elements when definitely considering pregnancy: Antiretroviral medications that are not recommended in pregnancy (e.g. EFV) Options for discordant couples: Referral to Women’s Service: Preconception Counseling

Final notes on preconception counseling… Contraception and pregnancy desires change over time. Just because someone did not desire pregnancy in 2011 does not tell you what he or she wants in 2013. Don’t forget to ask the men if they and their partners are planning a pregnancy. Let them know that there are preconception counseling services available.

Thank you! Contact the FXB Center with questions or comments, or for a copy of the slide set: Mary Jo Hoyt hoyt@umdnj.edu