P.S. Reichelderfer, PhD Harwood, Maryland

1. P.S. Reichelderfer, PhDHarwood, Maryland WHIN Meeting, 2005 Fertility Regulation Update

2. Fertility Regulation UpdateHistorical Perspective • January 2003 Meeting “Fertility Regulation and Systemic Hormones in HIV-infected and At-risk Women” • Contraceptive choices for HIV-infected and at-risk women • Hormonal influences on HIV acquisition • Hormonal influence on HIV disease and co-morbidities • Hormonal influence on treatment and the effect of treatments on contraceptive methods • Hormonal influence on changes in genital tract virological/immunological parameters and implications for transmission • What is the role of artificial insemination in HIV-discordant couples? • What is the role of hormonal menopausal therapy in HIV-infected and at-risk women?

3. Contraceptive Choices • Developing world • Depo-Provera is the most commonly used • Stigma associated with birth control of any type is the major issue • Developed world • Oral Contraceptives • Interaction with HIV therapeutic drugs is the major issue

4. Hormonal Influences on HIV Acquisition • Multivariate and ongoing analysis suggest contraceptive use both inject able and oral increase HIV acquisition • “HCARAT” a prospective trial of HIV acquisition and hormonal use suggests ? (check the Lancet website at the end of the month).

5. Hormonal Influence on Treatment and the Effect of Treatment on Hormonal Methods • There appears to be more rapid disease progression with women on contraceptives primarily due to selection of more “virulent/multiple strains” of virus during acute infection • Treatment with drugs that are metabolized through the same cytochrome system as the contraceptive is contraindicated

6. Hormonal Influences on Genital Tract Parameters • Shedding of virus in the genital tract (when it occurs) appears to be hormonally regulated • Cytokines in the genital tract appear to be hormonally regulated • Chemokine receptors (R5) appear to be up regulated by exogenous hormones

7. Artificial Insemination in Discordant Couples • The major issue in the developing world is the stigma associated with a women who does not have children • There is no incentive for male cooperation in volunteer counseling and testing for HIV • In the developed world, the major issue is prejudice on the part of society in general and health care providers specifically

8. Role of Menopausal Therapy • The major issue is that in applying the results of the large study on “normal” menopausal women we may overlook the impact on HIV-infected women, but doing the trials will be problematic from an IRB standpoint

9. Here and Now • Update from the AIDS Clinical Trials Group on what they have been doing in the area of fertility regulation • Discussion on assisted reproductive technology – leading to protocols/RO1s/RFAs/RFCs? • On with the show!

10. Future Research Directions 03 • Conduct epidemiological studies on contraceptive use and needs in HIV-infected and at-risk women nationally, internationally, married and single and throughout the life cycle. • Promote multidisciplinary studies integrating family planning and infectious disease expertise (training grants).

11. Future Research Directions 03 cont. • Analyze ongoing studies on hormonal contraceptive disease acquisition and progression, and define future research based on these studies. • Integrate studies on gender and ethnicity in clinical trials to elucidate the role of hormones versus genetics on therapy and disease course.

12. Future Research Directions 03 cont. • Increase measurement studies of virological and immunological parameters in the genital tract in all clinical studies. • Define potential studies to address the feasibility of assisted reproductive technology in serodiscordant couples, and the potential risk/benefit of hormonal therapy in HIV-infected women.