HIV/AIDS and Maternal and Child Health Programs in Resource-Limited Settings

1. HIV/AIDS and Maternal and Child Health Programs in Resource-Limited Settings Paula E. Brentlinger, MD, MPH Department of Global Health January 2012

2. Today’s Plan The epidemic in women and children Antiretroviral medications for treatment and prevention Treatment: Other considerations in women and children Real-world barriers to implementation Calls to action

3. HIV EpidemiologyinWomenandChildren: 1970s to present

4. Onset of AIDS Epidemic (US Data) “Since 1981, an outbreak of acquired immune dysfunction manifested by opportunistic infections and neoplastic disorders such as Kaposi’s sarcoma and malignant lymphomas has been reported in more than 1000 homosexual men.” Metroka CE et al. Generalized lymphadenopathy in homosexual men. Ann Int Med 1983;99:585-91.

5. Women, HIV, and Western Washington “Living in Olympia I felt alone, like I was the only woman in town with this disease [AIDS]. I got a lot of support from all of the wonderful gay men....I attended their support group every week, but felt I needed another woman to talk with, someone who could identify with having kids.” “Anna B.” Reflections on taking pills, being a mom, and living in a rural community. STEP Perspective, 1998;98(2):7. (STEP: Seattle Treatment Education Program)

6. HIV and Women in Africa “Antibody to human T-cell lymphotrophic virus type III (HTLV-III) was detected in the serum of 66% of prostitutes of low socioecononomic status............the relatively high female:male ratio of cases of AIDS in Africa (1:1 in Zaire, compared with 1:16 in the United States)...raises the possibility that perinatal transmission may result in high rates of the infection among infants and children...” Kreiss JK et al. AIDS virus infection in Nairobi prostitutes. N Engl J Med 1986;314:414-8.

7. Thecurrentnumbers: 34 millionlivingwith HIV in 2010 (WHO 2011)

8. HalfofAdultswith HIV areWomen (59% insub-SaharanAfrica) (WHO 2011)

9. Likelihood of MTCT (UNICEF: Children and AIDS: Fifth Stocktaking Report, 2010)

10. 3.4 MillionChildrenUnder 15 Livingwith HIV 2010 (90% inAfrica) (WHO 2011)

11. Distribution of new infections by mode of exposure in Ghana and Swaziland, 2008 100 No risk 80 Medical injections Blood transfusions Injecting drug use (IDU) Partners IDU 60 Sex workers % Clients Partners of Clients 40 Men who have sex with men (MSM) Female partners of MSM Engaged in casual sex (CS) 20 Partners of CS Low-risk heterosexual 0 Ghana Swaziland 1 Swaziland 2 Note: sensitivity analysis for Swaziland used different data sources. Sources: Bosu et al. (2009) and Mngadi et al. (2009). Figure 3

12. Distributionof HIV IncidencebyModeofExposure

13. DistributionofReported HIV InfectionsbyModeofExposure

14. 1990s & Onward: Antiretrovirals for TreatmentandPrevention!

15. ARV: Antiretroviral (medication) HAART: Highly active antiretroviral therapy (later called cART) PMTCT: Prevention of mother-to-child transmission

16. SurvivalandAntiretroviralTherapy (HAART) inAdultswithAIDS

17. Impact of HAART in South Africa Medecins sans Frontieres project in Khayelitsha: Of 1st 287 adult patients started on HAART, 86.3% still alive at 24 months Median CD4 count gain 288 at 24 months Viral load < 400 copies/ml in 69.7% of patients at 24 months Coetzee D, et al. AIDS 2004.

18. Mortality on HAART: developed vs. developing countries (from ART-LINC)

19. Special Considerations re ARV use in Women of Reproductive Age Some ARVs are probably teratogenic (based on animal studies) and should not be given in pregnancy or to women at risk of pregnancy. Some ARVs appear to have increased toxicity in pregnancy (e.g. DDI and D4T in combination). Some ARV side effects more common in women (e.g. nevirapine rash and hepatotoxicity). Drug-drug interactions involving contraception and ARVs (?) Drug resistance risk if starting/stopping with each pregnancy

20. Perinatal InfectionandSurvival (beforethe era oftreatment) Cohort of HIV-infected children born between 1979 and 1987, Florida: “The median survival time of all 172 children was 38 months from the time of diagnosis. Mortality was highest in the first year of life (17%).....children with perinatally acquired HIV-1 infection have a very poor prognosis.” Scott GB et al. Survival in children with perinatally acquired human immunodeficiency virus type-1 infection. N Engl J Med 1989;321:1791-6.

21. AIDS and Mortality in South African Children Cause-specific mortality in South Africa: Age group % deaths from AIDS 0-28 days 5.0% 29 days – 1 year 34.0% 1-4 years* 61.0% 5-9 years* 33.0% 10-14 years* 17.0% * Most common cause of death in this age group Garrib A et al, 2006.

22. SurvivalandHAARTinChildren:CHER(Violarietal, NEJM 2008)

23. CHER, cont’d

24. HIV, HAART, PediatricNeurodevelopmentalOutcomes(HeidariSet al., JofAIDS 2012;59:161-9)

25. SpecialConsiderationsreARTinChildren • HIV infectionprogressesveryrapidly (months to afewyears) to AIDS anddeathininfants; earlydiagnosisandtreatment are essential • Dosingisdifferentinchildrenbecauseofdifferencesinweightanddrugmetabolism; increase dose aschildgrows; gapsinPK data • LiquidformulationsofARVs for kids are harder to acquireandhandlethanpillformulations for adults • Importanceofneurodevelopmentaloutcomes • Importanceofcaregivers

26. Antiretrovirals and Prevention: PMTCT.The 1stPMTCT Trial (PACTG 076) Monotherapy with zidovudine (AZT) in late pregnancy reduced HIV transmission during pregnancy and childbirth by 67% (25.5% with placebo vs. 8.3% with zidovudine) in PACTG 076 trial. Connor E, N Engl J Med 1994.

27. sdNVP No ART HAART pre-preg HAART during preg AZT >4 wk +sdNVP AZT >4wk alone AZT <4 wk alone AZT <4 wk +sdNVP MTCT at Age 6 Weeks by ARV Regimen Botswana National Data Oct 2006-Nov 2007Tlale J et al. IAS Mexico City Aug 2008 (Abs ThAC04), quoted in Mofenson L 2008 Most Women Formula Feed Their Infants

28. 6 Month vs. 6 Week NVP (Coovadia HM et al, Lancet 2012;379:221-8)

29. Earlier vs. Later Maternal HAART (Chibwesha CA et al, J of AIDS 2011;58:224-8)

30. InfantMortality, Maternal HAART, Breast-feeding(Homsyetal, JAIDS Jan 2010)

31. WHOPolicy, 2009: The Radical Changes Mothersknown to beHIV-infectedshouldbeprovidedwithlifelongantiretroviraltherapyorantiretroviralprophylaxisinterventions to reduce HIV transmissionthroughbreastfeedingaccording to WHOrecommendations. Mothersknown to beHIV-infectedshouldexclusivelybreastfeedtheirinfants for thefirst 6 monthsoflife, introducingappropriatecomplementaryfoodsthereafter, and continue breast-feeding for thefirst 12 monthsoflife.

32. AntiretroviralsandPrevention: Sexual Transmission(Celum&Baeten, CurrOpinInfectDis 2012;25(51-7)

33. Prevention: Microbicides (2) - Tenofovir gel

34. PrEP: Aspects Specific to Women Vaginal vs. blood concentrations of drug Female-controlled (unlike condom use) Drug interactions involving oral PrEP and hormonal contraceptives (?????) In the pipeline: drug-eluting vaginal rings?

35. HIV Prevention: OtherConsiderationsinWomenand/orChildren

36. Other Considerations in PMTCT (1) Prevention of unwanted pregnancies is the first step in PMTCT!

37. OtherConsiderationsinPMTCT (2): ObstetricalInterventions Anincompletelistofobstetricalinterventionsorchoicesthatincreaselikelihoodof vertical transmission: • Choosingprolonged labor overcaesareandelivery (especiallywithprolongedruptureofmembranes) • Episiotomy • Placementofinternalmonitors • Artificial ruptureofmembranes • Forcepsdeliveries • Transfusionswithunscreened/infectedblood

38. OtherConsiderationsinPMTCT (3): Vertical HIV TransmissionandPlacentalMalaria(Brahmbhatt 2008)

39. Prevention: Male Circumcision Male circumcision prevents sexual transmission of HIV to uninfected men, but: In Uganda, serodiscordant (husband HIV+, wife HIV-) randomized to circumcision vs none: HIV transmission to wives13.8/100 py in circumcision group 9.6/100py in non-circumcision group Wawer et al, CROI abstract 33 LB, 2008

40. Prevention: Condoms work if used Some successful targeted condom programs: • Targeted condom promotion (condom distribution plus individual and group counseling) in female commercial sex workers in Kenya. Condom use associated with threefold reduction of risk of HIV seroconversion. • Condom use and HIV education in female sex workers in India led to decreased HIV incidence (by about 67%) in intervention group. • Targeted condom distribution and HIV education in male army conscripts in Thailand led to 50% reduction in HIV incidence. Merson M, et al. AIDS 2000.

41. Prevention: Voluntary Counseling & Testing for HIV (VCT) Some aftermath of VCT: For women who were HIV+ and disclosed their status to a partner: 14% reported break-up of marriage, 26% breakup of sexual relationship, 7% physical abuse, 3% neglected or disowned by family (vs. 1%, 14%, 4%, and 2% if HIV-negative and disclosed). Grinstead O, et al. AIDS 2001.

42. “Cheap Solutions Cut AIDS Toll for Poor Kenyan Youths”(NYT, 6 Aug 2006) “....when girls were given free school uniforms instead of having to pay $6 for them – the principal remaining economic barrier to education in Kenya – they were significantly less likely to drop out and become pregnant...” “...classroom debates and essay-writing contests on whether students should be taught about condoms to prevent HIV increased the use of condoms without increasing sexual activity...”

43. HIV/AIDS Treatment: Other Considerations in Women and Children

45. Growth and HIV exposure (Filteau et al)

46. Orphansandschoolattendance (from UNICEF, 2010)

47. Infantgrowth vs watersupply (Patelet al.)

48. Real-World Barriers to Coverage of Prevention and Treatment

49. ART Coverage

50. The PMTCT cascade (Braun et al)