HIV, conception, pregnancy and contraception

1. HIV, conception, pregnancy and contraception Women for Positive Action is an educational program funded and initiated by Abbott Laboratories

2. Contents Introduction Un/planned pregnancy Vertical transmission (MTCT) Treatment and care during pregnancy and after childbirth Routine testing during pregnancy The need for further research Case studies

3. Introduction Women for Positive Action is an educational program funded and initiated by Abbott Laboratories

4. Women with HIV are an important but under recognised group • In 2009 an estimated 33.3 million people were living with HIV • 16.5 million of these were women • Over 3.28 million women with HIV give birth each year • Most of these are of childbearing potential • An estimated 370,000 children were infected with HIV in 2009 - most through vertical transmission UNAIDS, 2010

5. Prevalence of HIV among pregnant women in Europe and North America Higher pockets of HIV prevalence among pregnant women have been reported in several countries e.g. in parts of Ukraine and in and around London in the UK 1. Downs et al. IAS 2006; 2. Jayaraman et al. Can Med Assoc J 2003; 3. Remis et al. Can J Infect Dis 2003

6. Pregnancy – planned and unplanned Preparing for the possibility of pregnancy, whether planned or unplanned, is an important component of care With access to optimal management, giving birth to a healthy, HIV negative baby is possible for the vast majority of women of childbearing age

7. Planning for pregnancy: Considerations What happens if my baby is HIV+? When will I know? How do I get pregnant without infecting my partner? Will my healthcare workers treat me differently? What is the risk that I will infect my partner? ? What is the risk of my baby being infected? Will I survive to see my children grow up? Will the treatment harm me or my baby? Should I bottle-or breastfeed my baby? Will pregnancy make my HIV worse? Do I have to have a caesarean?

8. Un/planned pregnancy Women for Positive Action is an educational program funded and initiated by Abbott Laboratories

9. Unplanned pregnancy • Up to 85% of pregnancies in HIV+ women reported as ‘unplanned’1,2 • Risk factors for unplanned pregnancy similar to those for HIV3: • substance abuse (the woman or her partner) • mental illness • domestic violence • frequent unstable sexual relationships and unsafe sexual practices in adolescents 1. Loutfy et al. HIV Med 2012; 2. Sutton et al. CROI 2012; 3. Koenig et al. Am J Obstet Gynecol 2007

10. Planning for unplanned pregnancies Anticipate the possibility of pregnancy in all HIV+ women of childbearing potential Consult guidelines and consider effective ART regimens that need minimal modification if pregnancy occurs

11. Pregnancy intention and desire • Research has shown that people living with HIV face 3 key decisions – disclosure, adherence to ART and desire for parenthood1 • Factors positively influencing the desire and intention to have children include:2,3 • Younger age • Previous children and number of living children • Access to PMTCT and ART programs • Individual perception of current health status • Spousal, family’s and society’s expectations • Fear of stigmatisation • Ethnicity 1. Bravo et al. AIDS Rev 2010; 2. Nattabi et al. AIDS Behav 2009; 3. Loutfy et al. PLoS ONE 2009

12. Routine reproductive counselling for women with HIV is important • In a survey of 700 women with HIV, 22% became pregnant after HIV diagnosis • 58% of these never discussed pregnancy or treatment options before pregnancy • 42% had limited/no knowledge of ART options during early pregnancy • Among women considering pregnancy, or pregnant at the time of HIV diagnosis • 48% were never asked by a HCP if they had or were considering having children Squires et al. AIDS Patient Care & STDs 2011

13. Routine reproductive counselling for women with HIV is important • In a cross-sectional survey of 181 women living with HIV age (15-44 years) and receiving clinical care at two urban health clinics (USA) • 67% reported a general discussion about pregnancy and HIV1 • 31% reported a personalised discussion about future childbearing plans with their provider, of which 64% were patient initiated1 • Unmet reproductive counselling needs were higher for personalised discussions about future pregnancies (56%) than general discussions about HIV and pregnancy (23%)1 • Accurate knowledge of vertical transmission (MTCT) was low (15%)2 1. Finocchario-Kessler et al. AIDS Patient Care STDS. 2010; 2. Finocchario-Kessler et al. AIDS Behav 2010

14. What is reproductive counselling? Advice, education, and discussion on: • Effective contraception • Maternal reproductive health issues • Healthy pre-conception planning to reduce horizontal transmission • Safe conception • Reproductive options – risks, costs and success rates • Impact of HIV on pregnancy • Impact of pregnancy on HIV • Vertical transmission • Long-term health of mother and ability to care for children • Importance of early and intense antenatal care • Use of ARTs and other drugs in pregnancy • Stigma and fears • Mental health preparation • Psychosocial issues, postpartum impact on adherence and outpatient visits • Other STIs • Should involve a two way interaction to explore coping, decision-making, emotional reactions and to plan/prepare • Should involve partners and be culturally relevant

15. Pre-conception counselling: a risk reduction strategy • Optimise HIV management • Choice of ART • Screen for and treat sexually transmitted infections • Reproductive options – risks, costs and success rates • Sex only when woman is in fertile period of her cycle • Stop unprotected sex as soon as pregnant • Avoid genital tract irritant • Refer for assessment if unsuccessful after 3-12 months (earlier if >35 years) • Possibility of treatment failure and ability to care for child • Encourage sexual partners to receive HIV testing, counselling and care

16. The importance of the patient–HCP relationship Help women to cope with HIV-related challenges Empower women to be active partners in their own healthcare \ Support Positive relationshipbetween patient and HCP Trust Open, two-way, effective communication Compassion Respect

17. The role of a partner • Seroconversion in pregnant women due to transmission from HIV positive male partners remains a risk1 • In men diagnosed with HIV, the desire to have a family is high2,3 • Despite this, interventions aimed at involving males in family planning are often limited, with little planning and provision for male treatment and care2 • The support of a partner during pregnancy and in the postpartum period may improve health outcomes for mothers and children4 • However, this must be assessed on an individual basis • Dhairyawan et al. Sex Transm Infect 2012; • 2. Sherr & Croome J Int AIDS Soc 2012; 3. Sherr J Int AIDS Soc 2010;4. Maman et al. J Midwifery Womens Health 2011

18. Conception planning: Prevention of horizontal transmission • Different clinical scenarios • HIV+ man and HIV- woman (serodifferent) • HIV+ woman with HIV- man (serodifferent) or who is single or in same sex relationship • HIV+ man and HIV+ woman • Different scenarios have different risk and require different strategies to prevent horizontal transmission

19. Reproductive options HIV+ man & HIV- woman • IUI, IVF or ICSI following sperm washing • Natural conception (if effective viral suppression) • Insemination of donor sperm at ovulation • Pre-Exposure Prophylaxis (PrEP) • Adoption HIV+ woman & HIV- man • Insemination of partner’s sperm at ovulation (if not on ART / detectable viral load) • Natural conception (if effective viral suppression) • Assisted reproduction in case of fertility disorders • Adoption HIV+ man & woman • Insemination of donor sperm or sperm washing to prevent superinfection • Natural conception • Assisted reproduction in case of fertility disorders 19

20. Pre-Exposure Prophylaxis (PrEP) • Pre-exposure prophylaxis (PrEP) aims to prevent transmission of HIV through use of ART before potential exposure to HIV • Several clinical trials of topical1,2 and oral PrEP2-4 in serodiscordant couples (where the partner with HIV is not receiving ART) have been completed ,with other trials underway • PrEP may have the potential to contribute to effective and safe HIV prevention if it is: 1. Abdool-Karim et al. Science 2010; 2. VOICE, Available at: http://www.mtnstopshiv.org/news/studies/mtn003; 3. Baeten & Celum IAS 2011; 4. Thigpen et al. IAS 2011

21. Pre-Exposure Prophylaxis (PrEP) • A body of evidence suggests that fully suppressive HAART has virtually eliminated the risk of sexual transmission of HIV1 • No cases of transmission under stable HAART have been published2,3 • Despite this, serodiscordant couples often strongly overestimate the risk of transmission4 • Risk reduction using timed intercourse and PrEP have been shown to be effective in reducing the already very low residual risk of transmission4 1. Vernazza et al. Bull Med Suisses 2008; 2. Stürmer et al. Antivir Ther 2008; 3. Vernazza et al. Antivir Ther 2008; 4. Vernazza et al. AIDS 2011

22. HIV and fertility • Evidence that women with HIV have higher incidence of fertility disorders • Fertility assistance has important ethical and practical implications for patients and professionals • Fertility treatment options • IUI (+/- sperm washing) ~ IVF • Donor insemination ~ ICSI • Limited data on IVF/ICSI success • Pregnancy rate substantially lower in HIV+ women IUI=intra-uterine insemination; IVF=in vitro fertilisation; ICSI=intracytoplasmic sperm injection

23. Access to assisted reproduction options in HIV

24. The ideal contraceptive . . . . currently means it must involve condoms Reliable Safe Convenient Reversible Prevent transmission of HIV Not interfere with HAART Affordable

25. Contraception options in HIV 1. Mostad et al. Lancet 1997; 2. Trussell, Contraceptive Technology 2007; 3. Wang et al. AIDS 2004

26. Hormonal contraception and HIV acquisition It has been suggested that women using progesterone-only injectable contraception may be at increased risk of HIV acquisition WHO (2012) highlight that due to the inconclusive nature of these studies women should always use dual protection with a condom Further research is required in this area WHO, 2012

27. Vertical transmission (MTCT) Women for Positive Action is an educational program funded and initiated by Abbott Laboratories

28. Vertical transmission (MTCT) • HIV can be transmitted from mother to child at various stages of pregnancy and motherhood: During gestation1 During labour and delivery2-5 Breast-feeding6-9 • Connor et al. N Engl J Med 1994; 2. Kind et al. AIDS 1998; 3. Read et al. N Engl J Med 1999; 4. Parazzini et al. Lancet 1999; 5. Shapiro et al. CROI 2002; 6. Dunn et al. Lancet 1992; 7. Nduati et al. JAMA 2000; 8. Coutsoudis et al. JID 2004; 9. Coutsoudis et al. Lancet 1999

29. Minimising the risk of MTCT Without optimal therapy and prevention the risk of transmitting HIV from a mother to a baby ranges from about 12-45%, depending on the setting and individual circumstances The risk of vertical transmission drops to less than 1% with optimal intervention

30. Trends in reduction of vertical transmission 35 30 25 20 % mother-to-child-transmission 15 10 5 0 1993 1994 1995 1996 1997 1998 1999 2000 2001 2002 2003 2004 USA and Europe Thailand Africa McIntyre et al. CROI 2005

31. Factors influencing perinatal vertical transmission Obstetric factors Maternal factors • Lack of awareness of HIV status • HIV-1 RNA levels • Low CD4 lymphocyte count • Other infections e.g. hepatitis C, CMV, bacterial vaginosis • Maternal injection drug use • Lack of ART prophylaxis • Non-adherence to ART • Length of ruptured foetal membranes (ROM) • Chorio-amnionitis • Vaginal delivery • Invasive procedures • No or inadequate antenatal care Infant factors • Prematurity • Sex of infant? • Low birthweight

32. Reducing vertical transmission: Issues to address • HIV infection among women of childbearing potential • Unplanned pregnancy among women with HIV • Transmission during pregnancy, labour and delivery, and breastfeeding

33. Interventions to reduce vertical transmission Caesarean section Exclusive formula feeding Avoid procedures during delivery ARTs Antenatal care Reduced MTCT Antenatal HIV testing and counselling Infection prevention practices

34. The MmaBana Study: Background • The MmaBana study examined the efficacy of different HAART regimens for prevention of MTCT during pregnancy and breastfeeding • Study participants were randomised to one of two treatment groups: • Abacavir / zidovudine / lamivudine (NRTI group) • Lopinavir/ritonavir plus zidovudine/lamivudine (PI- group) • The control group received zidovudine/lamivudine plus nevirapine • Treatment lasted from 26 to 34 weeks’ gestation through to 6 months post partum Shapiro et al. N Engl J Med 2010

35. The MmaBana Study: Low rate of MTCT with HAART 1% overall transmission through 6 months • 95% CI for overall MTCT rate = 0.5% to 2.0% • All regimens of HAART from pregnancy through 6 months post partum resulted in high rates of virologic suppression • No significant difference in the likelihood of MTCT between treatments • The overall rate of MTCT was just 1.1% • *P = NS for difference in between randomised arms; §Result doesn’t include in an infant who died without a confirmed AIDS-defining cause after a positive PCR result at birth; Shapiro et al. N Engl J Med 2010

36. Treatment and care during pregnancy and childbirth Women for Positive Action is an educational program funded and initiated by Abbott Laboratories

37. Individualising care Socio-economic class Age Family issues Sexual issues Medical history HIV care should vary depending on the unique needs and personal circumstances of each woman . . . Pregnancy Support Stage of HIV journey Immigration Child-bearing potential Violence or sexual abuse Co-morbid problems (e.g. alcoholism, drug use, depression) Acceptance of diagnosis Culture or religion Language and understanding

38. Individualising care . . . and consider women in their social contexte.g. as a mother, a partner, a daughter, a caregiver

39. Antenatal care and HIV WHO, 1998

40. Tests in pregnancy

41. HIV drug resistance testing is recommended • HIV drug-resistance studies should be performed before starting or modifying ARV regimens in: • All pregnant women whose HIV RNA levels are above the threshold for resistance testing (that is >500–1,000 copies/mL) prior to initiation of ARVs • For those entering pregnancy with detectable HIV RNA levels while receiving ARV therapy, or who have suboptimal viral suppression after starting ARVs during pregnancy • In order to prevent perinatal transmission, and ensure maternal health, women who present late in pregnancy should initiate empiric ARV without waiting for the results of resistance testing and adjust as needed after test results are available DHHS, 2012

42. Goals of treatment in pregnancy Minimise risk to the infant Reduce the risk of vertical transmission Minimise maternal side-effects Optimal maternal health

43. What do the treatment guidelines recommend? • Summary of UK (BHIVA), WHO and USA (DHHS) guidelines for initiating therapy in women who wish to become pregnant: • Boosted protease inhibitorsare preferred • Nevirapineas an alternative • Efavirenznot preferred during preconception or for first 6 weeks of pregnancy

44. European (EACS) guidelines for ART-naïve individuals ART regimen used in pregnant women starting ART is the same as in non-pregnant women, except: Avoid EFV, ddI + d4T and triple NRTI combinations NVP not to be initiated (continuation possible if started before pregnancy) Use LPVr or SQV/r as preferred PI/r ZDV should be part of the regimen if possible Little data are available for RAL and DRV/r in pregnancy EACS, 2011

45. General guidelines: HIV treatment in pregnancy All cases of antiretroviral drug exposure during pregnancy should be reported to the Antiretroviral Pregnancy Registry (see details at http://www.APRegistry.com) 1. EACS, 2011; 2. DHHS, 2012

46. US guideline recommendation categories: Perinatal antiretroviral use 4 *Combination of Zidovudine and lamivudine is recommended as dual-NRTI backbone for pregnant women # Triple-NRTI regimens including abacavir have been less potent virologically compared with PI-based combination ARV drug regimens. Triple-NRTI regimens should be used only when an NNRTI- or PI-based combination regimen cannot be used, such as because of significant drug interactions † Should not be used with didanosine or zidovudine ‡ Preferred NRTI in combination with lamivudine or emtricitabine in women with chronic HBV infection. Monitor renal function § Avoid in first trimester. Use after first trimester can be considered if this is the best choice for specific women. Counsel re teratogenic potential ** Only use when preferred and alternative agents can’t be used. Must give as low-dose RTV boosted regimen + Consider in special circumstances for prophylaxis of transmission in whom therapy might not otherwise be indicated when alternative agents are not tolerated ª Safety and pharmacokinetic data in pregnancy are limited; can be considered for use in special circumstances when preferred and alternative agents cannot be used DHHS, 2012

47. BHIVA recommendations on mode of delivery • For women taking HAART, a decision regarding recommended mode of delivery should be made after review of plasma viral load results at 36 weeks • Decisions about mode of delivery should take into account : • actual viral load • trajectory of the viral load • length of time on treatment • adherence issues • obstetric factors • the woman’s views *Taking the factors above into account BHIVA, 2012

48. Post-exposure prophylaxis (PEP) for infants Monotherapy1 Dual therapy1 • For most infants: • ZDV monotherapy BID for 6 weeks (4 weeks in UK2) • or • Alternative suitable ART monotherapy if maternal therapy does not include ZDV • For infants born to: • untreated mothers • mothers with detectable viral RNA despite combination therapy • add • NVP - 3 doses over the first week of life OR 1. DHHS, 2012; 2. BHIVA, 2012

49. Hepatitis B Virus Coinfection • Screening for hepatitis B surface antigen • Interferon-based therapies and ribavirin are not recommended during pregnancy • Treatment should include tenofovir plus 3TC or emtricitabine (FTC) • Hepatic toxicity should be carefully monitored • Infants born to women with hepatitis B infection should receive hepatitis B immunoglobulin (HBIG) and the first dose of the HBV vaccine series within 12 hours of birth and the 2nd and 3rd doses of the HBV vaccine at 1 and 6 months DHHS, 2012

50. Vertical transmission of HIV when • Vertical transmission is possible, although extremely unlikely, when maternal viral load (VL) is <50 copies/ml • In a UK and Ireland study of 2,309 mothers with an undetectable VL at or near the time of delivery, three vertical transmissions were reported (transmission rate=0.1%)1 • In a French study of among 5,271 mothers who received ART during pregnancy, vertical transmission occurred in five cases, despite VL <50 copies/ml (transmission rate=0.4%)2 • In both cases the rate of vertical transmission was significantly higher in those mothers with detectable viral loads upon delivery, highlighting the importance of sustained viral suppression pre-delivery 1. Townsend et al. AIDS 2012; 2. Warszawski et al. AIDS 2008