Reproductive Health Care in HIV

1. Reproductive Health Care in HIV Joanne Hayes, MPH, PA-C Sinai Hospital of Baltimore September 8, 2006

2. Learning Objectives • Understand standards for reproductive health care for HIV-infected women. • Understand the biology of perinatal transmission and the efficacy of intervention strategies as it relates to reproductive choice counseling and the care of pregnant patients.

3. HIV Prevention in Reproductive Health Care • Primary prevention • assess risk (sexual practice, substance abuse, mental health disorder, domestic violence) • teach safer sex practices/negotiation skills • offer routine testing • post exposure prophylaxis • contraceptive method • risk reduction for HIV and other STIs

4. HIV Prevention • Male and female condoms proven to prevent HIV and STI • Microbicides • Post-exposure prophylaxis • Vaccines

5. Reproductive Health Care in HIV • Disease Prevention • Screening and management of HIV/STIs • PAP smear screening • Contraception: • Interaction of hormonal contraception methods with PIs may decrease the effectiveness of the contraception • Pregnancy • Reduction of perinatal transmission

6. Pre-Conception Counseling • Desire for pregnancy • Consequences of unintended pregnancy • Discordant couples • sperm washing • pre-exposure prophylaxis • Future child care • HAART based on family planning choices

7. Natural History of HIV Disease

8. Symptoms associated with CD4 Decline

9. Case Study 1: Ev • 22 year old • First pregnancy • PMH: seizure disorder, asthma • Acute illness 4 weeks prior to pre-natal visit with fever to 103, headache, myalgia ER rx vs. UTI • Social: single, lives with aunt; FOB unavailable No tobacco, ETOH, IDU; Clerical work.

10. National Recommendations for HIV Testing of Pregnant Women • CDC (USPHS) recommendations for HIV screening of pregnant women (4-22-03) • Prenatal: routine HIV screening for all pregnant women using the “opt out” approach • Labor and delivery: Routine rapid testing for women whose HIV status is unknown • Postnatal: Rapid testing for all infants whose mother’s status is unknown • Regulations vary from state to state

11. Ev-Continued Routine Testing/Screening • Ultrasound: twin gestation, 10 weeks • PAP: LGSIL colposcopy: LGSIL • Screening C&S Cervix: GC  ceftriaxone • HIV EIA: reactive • Western Blot: indeterminate: p24 reactive

12. HIV Serology • EIA: reactive • Western Blot is positive if there is reactivity to at least • gp41 and gp 120/160 or • p24 and gp120/160 • Reactive EIA and negative WB is not a “positive HIV test”.

13. HIV SeroconversionSchacker, T; Post Grad Med 104:4

14. HIV Western Blot Conversion

15. Symptoms of Seroconversion Illness • Fever 85% • Sore throat 70% • Orbital pain 70% • LAD 65% • Rash 50% • Myalgia 50% • Headache 40% • Diarrhea 30%

16. Ev: Additional labs • HIV RNA PCR: 724,000 copies/ml • CD4 count: 800 (20%) • HBVsAG: neg HBVsAB: neg HCVAB: neg • PPD: no induration

17. Ev: Additional labs • Repeat HIV serology • EIA: reactive • WB: p24, p51, gp120 gp160 • Serology now confirms infection • HIV-1 Genotype: no mutations

18. Perinatal HIV Transmission • Without antiretroviral (ARV) drugs during pregnancy, mother-to-child transmission (MTCT) has ranged from 16%–25% in North America and Europe • 21% transmission rate in the US in 1994 before the standard zidovudine (ZDV) recommendation during pregnancy • With the change in practice, transmission was 11% in 1995 • Today, risk of perinatal transmission can be <2% with • effective antiretroviral therapy (ART) • elective cesarean section (C/S) as appropriate • formula feeding

19. Pregnancy in HIV Disease Adverse Pregnancy Outcomes in Untreated HIV • Increased risk • stillbirth in developing countries • perinatal/infant mortality in developing countries • Possible increased risk • Spontaneous abortion • Intrauterine growth restriction • low birth weight in advanced disease • preterm delivery in advanced disease

20. Pregnancy in HIV Disease • Effect of pregnancy on maternal health • CD4 counts may decrease during pregnancy in both HIV+ and HIV- patients • no change in CD4 percentage • no effect on HIV RNA PCR during pregnancy in the absence of HAART • postpartum increase in viral load in the absence of HAART-transient and unexplained

21. Timing of Perinatal Transmission Of cases of documented MTCT: In utero 25-40% Intrapartum 60-70%

22. Additional MTCT Risk Breastfeeding 15% Seroconversion 29%

23. Risk Factors for MTCT Variable Adjusted OR • HIV RNA PCR 12.1 • CD4 count 2.01 • Premature delivery 1.83 • Mode of delivery 0.38 • HAART 0.13 European Collaborative Study CID 2005: 40:458-465

24. MTCT Reduction • 3 part ART intervention • Optimal therapy for the mother • IV AZT during the intra-partum period • Oral AZT for the neo-nate • Mode of delivery • based on response to HAART

25. Number of cases

26. Guidelines for HAART in Pregnancy • Use optimal ARVs for the woman’s health unless there is established adverse effects of therapy on the mother or fetus • Offer 3-part ZDV regimen for reducing perinatal transmission, alone or in combination with other antivirals • Discuss preventable risk factors for perinatal transmission • Support decision-making by the woman following discussion of known and unknown benefits and risks • Acceptance or refusal of antiviral therapy should not result in denial of care or punitive action

27. Clinical Category CD4 Count HIV RNA Recommendations Symptomatic Any value Any value Treat Asymptomatic, AIDS CD4+ T cells <200/mm3 Any value Treat Asymptomatic CD4+ T cells >200/mm3 but <350/mm3 Any value Treatment should generally be offered, though controversy exists* Asymptomatic CD4+ T cells >350/mm3 >100,000 (RT-PCR) Some experts would defer initiating therapy; some would defer and monitor CD4+ counts* Asymptomatic CD4+ T cells >350/mm3 <100,000 ( RT-PCR) Many experts would defer therapy & observe* Recommendations for the Initiation of HAART

28. Initiation of HAART in Pregnancy • Decision to initiate HAART in pregnancy is the same as in the non-pregnant woman • When possible, include AZT in the regimen • HAART to be utilized in the ante-natal, intra-partum and postpartum regimen to maximize reduction of MTCT • Monitor for toxicities related to HAART esp those that may mimic complications of pregnancy

29. Initiation of HAART in Pregnancy • AZT monotherapy is an option when: • Viral Load <1000 copies/ml and • CD4 is >350 cells/mm3 • AZT 300 mg BID • possible selection of AZT resistant HIV • PACTG 367 suggests improved MTCT prevention with combination therapy even with VL < 1000 copies

30. Preferred Antiretroviral Agents in Pregnancy • NRTI Class • Preferred: AZT/3TC • Alternates: ddI, FTC, d4T, ABC • Insufficient data: TDF • Not recommended: ddC • NNRTI Class • Preferred: NVP (if baseline CD4 is < 250/mm3) • Not recommended: EFV and DLV • Insufficient data: ENF

31. Preferred Antiretroviral Agents in Pregnancy • PI Class • Recommended: NFV (1250 mg bid), SQV/r (1000/100 mg bid) • Alternatives: IDV, LPV/r, RTV • Insufficient data: APV, FPV, ATV, TPV • Entry Inhibitor Class

32. Baseline Studies

33. Ev: Approach to Management • HAART indicated • Seroconversion, HIV RNA PCR >100K • Prevention of MTCT • Triple combination initiated at 11 week f/u AZT 300 mg/lamivudine 150mg (Combivir) BID + lopinavir/ritonavir (Kaletra) 400/100 BID • Prophylaxis vs. OI not indicated • Vaccinate: pneumococcal and HBV; dT was UTD • Method of delivery

34. Ev Case Summary • Seroconversion Illness during pregnancy • OB: twin gestation; method of delivery • Concomittant GYN conditions: • gonococcal cervicitis • abnormal PAP • Co-morbid medical conditions • seizure disorder and asthma • Social Issues • supportive counseling through adjustment process • access emergency medication coverage and MA • preparation for twins

35. Human Papilloma Virus • Most common STI • HPV linked to cancer of anus, penis, vagina, vulva and cervix • More common in HIV infection • associated with lower CD4 • >30 types • Visible warts:Usually types 6, 11 • Cervical dysplasia/neoplasia: Usually types 16, 18, 31, 33, 35 • Most are asymptomatic • Can be felt if external

36. Cervical Cancer and HIV • Invasive Cervical Cancer is an AIDS defining condition (1993) • Risk of Cervical CA in HIV infected woman may be as high as 9 fold greater • Not related to CD4 count: Ave CD4 at dx: 443 • Younger age at diagnosis • HIV+ women with invasive cervical cancer present at more advanced stages and have poorer response to standard therapy

37. PAP Smear Screening • Complete GYN evaluation including PAP and pelvic exam at initial evaluation • Pap smear x 2 during the first year after HIV dx; if normal, annual exam thereafter • Abnormal PAP evaluation based on histologic findings and ACOG recommendations of management (1993).

38. Case 2: Terri • 38 yo G1P1 with chronic HIV infection • AIDS defined by CD4 count, No OI • Sexually active; partner aware and accompanies Terri to all visits • Declines contraception • Never uses condoms • Desires another child

39. Case 2: Terri • PMH: negative • Surgical Hx: Prior C-section • Medication • zidovudine/lamivudine/lopinavir/ritonavir • Social History: homemaker, HS diploma no tobacco, ETOH or drugs • PE: unremarkable

40. Case 2: Terri Labs: • HIV RNA PCR < 50 copies/ml • Max HIV RNA PCR: 68,000copies/ml • CD4: 450 cells/mm3 • Nadir CD4 count: 198 cells/mm3

41. Case 2: Terri Laboratory Results • b HCG: reactive • Ultrasound: 8 weeks gestation • Counseling: desired pregnancy • HAART decision

42. Women Currently on ARV Therapy • Consider continuing or stopping current therapy during first trimester • If therapy is stopped, stop and restart all ARV simultaneously • Discuss benefits and potential risks of her regimen during pregnancy • Discuss benefits and potential risks of stopping and re-starting the regimen • Recommend intrapartum and neonatal AZT

43. Women Currently on ARV Therapy • Discontinue teratogenic drugs • Add or substitute ZDV after the 1st trimester if possible • Resistance testing for sub-optimal viral suppression

44. Adverse Effects of HAART on Pregnancy • Preterm delivery? Conflicting data • CNS Defects associated with efavirenz exposure in early pregnancy • Anemia associated with in utero AZT exposure • mild and resolves spontaneously • Amprenavir liquid is contra-indicated • Data on individual drugs available at www.aidsinfo.nih.gov

45. Maternal Adverse Effects of HAART • AZT related Anemia • GI toxicity • nausea and vomiting common side effect of HAART • may need to delay HAART until morning sickness has resolved • Hepatotoxicity • Increased transaminases • commonly associated with PI but also be associated with NRTI

46. Maternal Adverse Effects of HAART • Lactic Acidosis/Mitochondrial Toxicity • most commonly associated with the “d” drugs • elevated transaminases/steatosis • pancreatitis • peripheral neuropathy • death • Combination d4T+ddI in discouraged • d4T+ddI+Hydroxyurea is contra-indicated

47. Maternal Adverse Effects of HAART • Hypersensitivity Reaction with hepatonecrosis • associated with nevirapine administration in pregnant women with CD4 >250 cells/mm3 • elevated LFTs with rash • most common in 1st 6 weeks of therapy • can be fatal even with discontinuation of therapy

48. Terri: Management Decisions • Remain on current therapy (AZT/3TC/KLT) • zidovudine already part of regimen • No prophylaxis vs OI indicated • Vaccines : pneumococcal, HBV, dT influenza vaccine annually • Repeat PPD: no induration

49. Antepartum Follow Up Related to the Initiation of HAART • Evaluation and lab assessment monthly until full response to therapy, then, at least once, every trimester • Laboratory data • CBC, electrolytes, liver enzymes • CD4 count/% • HIV RNA PCR • HIV Genotype

50. Antepartum Follow Up related to the Initiation of HAART • Antepartum Fetal Surveillance according to ACOG recommendations