1. Welcome to I-TECH HIV/AIDS Clinical Seminar Series 3 rd June 2010 Contraception in the Setting of HIV R. Scott McClelland, MD, MPH

2. Outline Brief ‘world view’ of contraception and HIV What are the benefits of contraception? Contraception in the setting of HIV Clinical case studies in contraception –Safety –Efficacy –Side effects –Management in different clinical scenarios

3. Learning Objectives Be able to provide HIV-positive women with a clear explanation of the potential benefits and risks of different contraceptive choices Feel comfortable with basic clinical decision making for initiation and continuation of contraception in HIV-positive women

4. Global Use of Contraception ~800 million women use modern methods of contraception –~150 million use hormonal contraceptives –Others use intra-uterine contraceptive devices, barriers, and tubal ligation

5. Unmet Contraceptive Need Ref: Network Vol 23, number 3, 2004. Family Health International

6. Benefits of Contraception in the Setting of HIV Contraception reduces pregnancy and may provide additional health, social, and economic benefits. –Groups should discuss briefly, then rank top three benefits of contraception. Consider both general benefits and specific advantages of contraception in the setting of HIV.

7. Benefits of Contraception Avoid unplanned pregnancies –Potential for obstetrical complications –Spacing pregnancies benefits the health of women, infants, and children Family planning empowers women, reducing gender inequality HIV-positive women may wish to reduce risk of vertical transmission by preventing further pregnancies

8. Case 1 24 y.o. HIV+ woman presents for 6 week post- partum visit. She initiated ART during pregnancy with CD4=226. She would like to avoid another pregnancy. –Can she be offered hormonal contraception?

9. Many Women Living with HIV Remain Sexually Active Abstinence eliminates sexual transmission risk, but often not possible or desired by women or partners Dual protection minimizes HIV/STI transmission risk and lowers risk of pregnancy

10. Case 1 24 y.o. HIV+ woman presents for 6 week post- partum visit. She initiated ART during pregnancy with CD4=226. She would like to avoid another pregnancy. –Will contraception influence the risk of HIV progression?

11. Hormonal Contraception and HIV Progression Secondary analysis from 1 RCT suggests increased disease progression with HC compared to intrauterine device (IUD) 1 7 prospective cohort studies suggest HC in chronic HIV doesn’t significantly change CD4, plasma viral load, or mortality 2,3 1.Stringer et al. AIDS 2009; 23: 1377-82 2.Curtis et al. AIDS 2009; 23 Supplement 1:S55-S67 3.Polis et al. CROI 2010, San Francisco, Feb 2010, abstract 152

12. Hormonal Contraception vs. IUD in HIV+ Women 599 postpartum women in Lusaka, Zambia RCT IUD vs. hormonal contraception Followed for at least 2 years Primary endpoint: Safety and efficacy of intrauterine device vs. hormonal contraception Secondary endpoints: –Time to CD4<200 –Time to death –Combined endpoint including either time to CD4<200 or death Stringer AJOG 2007:197:144.e1-144.e8

13. Hormonal Contraception vs. IUD in HIV+ Women Only one episode of PID in IUD arm Higher rate of discontinuation in IUD arm Pregnancy higher in HC vs. IUD –HR 2.2 (95% CI 1.2-2.4) Mortality did not differ significantly –HR 1.4 (95% CI 0.7-3.0) Faster progression to CD4<200 with hormonal contraception compared to IUD –HR 1.6 (95% CI 1.04-2.03)

14. Hormonal Contraception vs. IUD in HIV+ Women CD4 decline Death

15. Hormonal Contraception vs. IUD in HIV+ Women CD4 decline Death Time to CD4<200 or death faster in HC vs. IUD HR 1.6 (95% CI 1.1-2.3) CD4 decline or death

16. Study Summary: Hormonal Contraception vs. IUD in HIV+ Women IUD appeared safe and was more effective than HC at preventing pregnancy No difference in mortality Time to CD4<200 longer with IUD vs. HC Limitations –~30% withdrew or lost to follow-up –~30% discontinued allocated method –Postnatal population; can we generalize to other women?

17. Hormonal Contraception in HIV+ Women 319 post-partum women in Nairobi 1 –No effect on CD4 or plasma VL to 24 months in Depo-Provera or OCP compared to no HC US Women’s Interagency HIV Study 2 –Plasma VL not influenced by HC –Small increase in CD4 over long-term follow-up 213 women initiating HC in Mombasa 3 –No increase in plasma VL over 2 months 1.Richardson AIDS 2007; 21:749-53 2.Cejtin AIDS 2003;17:1702-4 3.Wang AIDS 2004;18:205-9

18. Hormonal Contraception and Time to AIDS or Death: Rakai, Uganda 625 women followed from HIV acquisition Use of HC associated with lower risk of AIDS/death aHR (0.70, 95%CI 0.50-0.97) –Effect appeared to be present only after median time to AIDS/death (4.4 years) –Compared to women using non-hormonal contraception, HC users had similar risk of progression Polis et al. CROI 2010, San Francisco, Feb 2010, Abstract 152

19. Hormonal Contraception and HIV Progression Majority of evidence (from cohort studies) suggests that initiating HC in HIV+ women does not increase disease progression –One RCT suggested increased progression, but with several important limitations

20. Case 2 27 y.o. woman reports sex work and has been screened periodically for HIV with multiple prior negative tests. Uses Depo-Provera to prevent pregnancy. She now has a positive HIV test. –Will Depo-Provera use at the time of HIV acquisition influence the natural history of her HIV infection? http://www.street-papers.org/eastern-asia/

21. Hormonal Contraception and HIV Progression Effect may differ depending on the timing of hormonal contraception in relation to HIV-1 acquisition –Hormonal contraception initiation during chronic HIV infection (e.g. Case 1) –Hormonal contraception at the time of HIV acquisition (e.g. Case 2)

22. Depo-Provera at Time of HIV Acquisition Indirect evidence from surrogate endpoints –Women using DMPA at the time of HIV acquisition have Higher set-point plasma viral load Greater viral diversity at infection Viral diversity is associated with more rapid CD4 decline Sagar et al. J Virol 2003; 77:12921-12926 Sagar M et al. AIDS 2004;18:615-619.

23. Hormonal Contraception and HIV Progression Majority of evidence (from cohort studies) suggests that initiating HC in HIV+ women does not increase disease progression –One RCT suggested increased progression, but with several important limitations HC at time of infection may influence diversity of the infecting viral population, set point VL, and rate of CD4 decline –Unknown effect on morbidity and mortality

24. Case 3 30 y.o. HIV+ woman with CD4=440 desires oral contraceptive pills (OCPs) to prevent pregnancy. Which of the following does WHO recommend prior to initiating OCPs? –A) Medical History and blood pressure –B) Pap Smear –C) Breast examination –D) STI screening –E) All of the above

25. Case 3 30 y.o. HIV+ woman with CD4=440 desires oral contraceptive pills (OCPs) to prevent pregnancy. Which of the following does WHO recommend prior to initiating OCPs? –A) Medical History and blood pressure –B) Pap Smear –C) Breast examination –D) STI screening –E) All of the above

26. Screening prior to Hormonal Contraceptive Initiation Careful medical history and BP are recommended. –Other elements of health screening advisable, but not required for initiation of hormonal contraception

27. Screening prior to Hormonal Contraceptive Initiation Which element of medical history and exam would be a contraindication to OCPs? –A) Smokes regularly, ~20 cigarettes/day –B) History of leg blood clot after long bus ride –C) Current blood pressure 138/88 –D) History of hypertension during pregnancy with normal blood pressure on present exam –E) All of the above would be contraindications to OCPs in this patient

28. Screening prior to Hormonal Contraceptive Initiation Which element of medical history and exam would be a contraindication to OCPs? –A) Smokes regularly, ~20 cigarettes/day –B) History of leg blood clot after long bus ride –C) Current blood pressure 138/88 –D) History of hypertension during pregnancy with normal blood pressure on present exam –E) All of the above would be contraindications to OCPs in this patient

29. Contraindications to OCPs Pregnancy Prior thromboembolic event or stroke History of estrogen-dependent tumor Active liver disease Undiagnosed abnormal uterine bleeding Hypertriglyceridemia Age >35 AND smoking >15 cigarettes daily Age >35 with migraine Migraine with aura (any age) Poorly controlled hypertension

30. Case 3 30 y.o. HIV+ woman with CD4=440 starts OCPs on the first Sunday after her menses. What is the annual risk of pregnancy with typical use? –A) 0.1% –B) 1.0% –C) 4% –D) 8% –E) 12%

31. Case 3 30 y.o. HIV+ woman with CD4=440 starts OCPs on the first Sunday after her menses. What is the annual risk of pregnancy with typical use? –A) 0.1% –B) 1.0% –C) 4% –D) 8% –E) 12%

32. Pregnancy Rates in First Year Typical UseCorrect Use Male Condom15%2% Depo-Provera3%<1% IUD<1% OCP (E/P)8%<1% Contraceptive Technology, 19 th Ed. 2007

33. Case 3 30 y.o. HIV+ woman with CD4=440 starting OCPs (E/P with 30 mcg ethinyl estradiol). She should be advised to use backup contraception: –A) Until next menses if she misses a single dose –B) For 7 days if she misses a single dose –C) For 1 month after missing 3 consecutive doses –D) For 7 days if she misses 3 consecutive doses –E) None of the above

34. Case 3 30 y.o. HIV+ woman with CD4=440 starting OCPs (E/P with 30 mcg ethinyl estradiol). She should be advised to use backup contraception: –A) Until next menses if she misses a single dose –B) For 7 days if she misses a single dose –C) For 1 month after missing 3 consecutive doses –D) For 7 days if she misses 3 consecutive doses –E) None of the above

35. Missed Doses WHO. Family Planning Handbook

36. Case 4 32 y.o. HIV+ woman was diagnosed with HIV/TB co- infection and CD4=236. Now on AZT, 3TC, NVP (month 5) and in her 5 th month of TB treatment (continuation phase with INH+Rifampicin). Also taking daily Septrin. She asks about family planning. WHO. Family Planning Handbook

37. Case 4 What medications may interact with hormonal contraceptives? –A) Rifampicin –B) Isoniazid –C) Nevirapine –D) All of the above –E) A and C

38. Case 4 What medications may interact with hormonal contraceptives? –A) Rifampicin –B) Isoniazid –C) Nevirapine –D) All of the above –E) A and C

39. Drug Interactions Metabolism of steroid hormones increased –Rifampicin –NNRTIs –Some anticonvulsants Metabolism of steroid hormones decreased –Lopinavir boosted with ritonavir (Kaletra/Aluvia)

40. Case 4 Based on potential drug interactions in this patient taking AZT, 3TC, NVP, INH, Rif, and Septrin, which contraceptive regimen may be expected to have benefits generally outweighing risks: –A) Progesterone-only pills –B) Combined oral contraceptive pills –C) Depot Medroxyprogesterone acetate (Depo-Provera) –D) None of the above, she should use a non-hormonal method for contraception

41. Case 4 Based on potential drug interactions in this patient taking AZT, 3TC, NVP, INH, Rif, and Septrin, which contraceptive regimen may be expected to have benefits generally outweighing risks: –A) Progesterone-only pills –B) Combined oral contraceptive pills –C) Depot Medroxyprogesterone acetate (Depo-Provera) –D) None of the above, she should use a non-hormonal method for contraception

42. Drug Interactions There are generally fewer clinically significant interactions with Depo Provera Contraceptive efficacy remains high despite theoretical interactions WHO. Family Planning Handbook

43. Case 4 32 y.o. HIV+ woman was with HIV/TB co-infection and CD4=236. On AZT, 3TC, NVP, INH, Rif, and Septrin. Initiated Depo-Provera within 5 days of menses. She was given a follow-up visit for 12 weeks later, but arrived 10 days late for the scheduled visit. The WHO recommends: –A) Give her next injection now without pregnancy test –B) Pregnancy test now; if negative give next injection –C) Use condoms until next menses, then re-initiate hormonal contraception

44. Case 4 32 y.o. HIV+ woman was with HIV/TB co-infection and CD4=236. On AZT, 3TC, NVP, INH, Rif, and Septrin. Initiated Depo-Provera within 5 days of menses. She was given a follow-up visit for 12 weeks later, but arrived 10 days late for the scheduled visit. The WHO recommends: –A) Give her next injection now without pregnancy test –B) Pregnancy test now; if negative give next injection –C) Use condoms until next menses, then re-initiate hormonal contraception

45. Late for Depo-Provera? WHO 2008 update allows a grace period of up to 4 weeks without need for pregnancy testing Based on Steiner et. al. Contraception 2008 –On time 0.6 (95%CI 0.33-0.92) pregnancy/100 p-y –2 weeks 0.0 (95%CI 0.00-1.88) pregnancy/100 p-y –4 weeks 0.4 (95%CI 0.01-2.29) pregnancy/100 p-y

46. Case 4 32 y.o. HIV+ woman on ART, TB treatment, and Depo-Provera. Side effects of DMPA include: –A) Increased risk of endometrial cancer –B) Reduced bone mineral density –C) Increased risk of deep venous thrombosis –D) A and C –E) All of the above

47. Case 4 32 y.o. HIV+ woman on ART, TB treatment, and Depo-Provera. Side effects of DMPA include: –A) Increased risk of endometrial cancer –B) Reduced bone mineral density –C) Increased risk of deep venous thrombosis –D) A and C –E) All of the above

48. Depo-Provera Side Effects Menstrual changes Weight changes Decreased bone mineral density –BMD decreased by 0.5-3.5% after one year and by 5.7-7.5% after two years –Most important in young women who have not attained peak bone mass and in peri- menopausal women ACOG Committee. Obstet Gynecol 2008; 112:727.

49. Depo-Provera Non-Contraceptive Benefits Depo-Provera associated with 80% lower risk of endometrial cancer 1 No increase in risk for ovarian, cervical, hepatic malignancy In contrast to combined OCPs: –No increased production of coagulation factors –No increase in DVT, stroke, or MI –No adverse effects on blood pressure

50. Case 5 37 year old woman presents to clinic for initial evaluation for HIV. CD4=177. No history of significant illness. She had a Copper T IUD inserted 3 years ago. What is recommended for her contraception? –A) Leave the IUD in place –B) Remove IUD and recommend Depo-Provera –C) Remove IUD and recommend barrier method until she is on ART at least 6 months

51. Case 5 37 year old woman presents to clinic for initial evaluation for HIV. CD4=177. No history of significant illness. She had a Copper T IUD inserted 3 years ago. What is recommended for her contraception? –A) Leave the IUD in place –B) Remove IUD and recommend Depo-Provera –C) Remove IUD and recommend barrier method until she is on ART at least 6 months

52. IUD for Women with HIV Women with HIV or with AIDS but on ART and clinically well can have IUD inserted Women with AIDS, not on ART or not clinically well should not have IUD inserted If a woman develops AIDS and has IUD in place, it does not have to be removed

53. Summary Contraceptive services important for comprehensive HIV care Initiating contraception does not increase HIV progression Contraception similar in HIV+ and HIV- women –Encourage dual method use including a barrier method –Consider drug interactions

54. Thank you! Next session: June 17th Nina Kim, OIs Email: DLinfo@u.washington.edu