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

HIV/AIDS and Maternal and Child Health Programs in Resource-Constrained Settings. Paula E. Brentlinger, MD, MPH Department of Global Health; International Training and Education Center on HIV (I-TECH) February 2010. Today’s Plan. HIV epidemiology in women and children: Historical notes

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

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  1. HIV/AIDS and Maternal and Child Health Programs in Resource-Constrained Settings Paula E. Brentlinger, MD, MPH Department of Global Health; International Training and Education Center on HIV (I-TECH) February 2010

  2. Today’s Plan HIV epidemiology in women and children: Historical notes Prevention and treatment: Historical notes Misconceptions (historic and recent) re HIV in women and children, and evidence to refute them New WHO guidelines for PMTCT and infant feeding (2009) Some operational issues

  3. HIV epidemiologyinwomenandchildren: Theearliest data (1970s-80s)

  4. FirstYearsofAIDSEpidemic (US Data): WomenandChildrenAbsent! “Since 1981, anoutbreakofacquiredimmunedysfunctionmanifestedbyopportunisticinfectionsandneoplasticdisorderssuch as Kaposi’s sarcoma andmalignantlymphomashasbeenreportedin more than 1000 homosexualmen.” Metroka CE et al. Generalizedlymphadenopathyinhomosexualmen. AnnIntMed 1983;99:585-91.

  5. SlightlyLater: AIDSEpidemic (US Data): InfectioninWomenOccursbutIsRare: MostInfections Are AssociatedwithStigmatizedBehavior CohortofAIDSpatients, New Haven, Connecticut, 1981-7: 76% male. Meansof HIV acquisition (mayoverlap): Bloodtransfusion: 6% Heterosexualsex: 15% IVDU: 48% MSM: 45% Justice ACet al. A newprognosticstagingsystem for theacquiredimmunodeficiencysyndrome. NEngJMed 1989;320:1388-93.

  6. Estimated new HIV infections by transmission category, extended back calculation model, 50 US states and the District of Columbia, 1977–2006 80 000 70 000 60 000 MSM / IDU Heterosexual 50 000 Infections 40 000 30 000 20 000 10 000 0 1977- 1979 1980- 1981 1982- 1983 1984- 1985 1986- 1987 1988- 1990 1991- 1993 1994- 1996 1997- 1999 2000- 2002 2003- 2006 Period Men who have sex with men (MSM) Injecting drug use (IDU) Tick marks denote the beginning and end of a year. The model specified periods within which the number of HIV infections was assumed to be approximately constant. Source: Hall et al. (2008a). Figure 23

  7. Women, HIV, and King County “LivinginOlympiaIfeltalone, likeIwastheonlywomanintownwiththisdisease [AIDS]. Igot a lotofsupportfromallofthewonderful gay men....Iattendedtheirsupportgroupeveryweek, butfeltIneededanotherwoman to talkwith, someonewhocouldidentifywithhavingkids.” “AnnaB.” Reflectionsontakingpills, being a mom, andlivingin a ruralcommunity. STEP Perspective, 1998;98(2):7.

  8. NotOnlyCanWomenBeInfected: BabiesCanBeInfectedVertically Cowan MJ et al. Maternal transmission of acquired immune deficiency syndrome. Pediatrics 1984;73:382-6. Lapointe N et al. Transplacental transmission of HTLV-III virus. N Engl J Med 1985;312:1325-6.

  9. Perinatal Infection is Doom CohortofHIV-infectedchildrenbornbetween 1979 and 1987, Florida: “Themediansurvivaltimeofall 172 childrenwas 38 monthsfromthetimeofdiagnosis. Mortalitywashighestinthefirstyearoflife (17%).....childrenwithperinatallyacquiredHIV-1infectionhave a verypoorprognosis.” Scott GBet al. Survivalinchildrenwithperinatallyacquiredhumanimmunodeficiencyvirustype-1infection. NEnglJMed 1989;321:1791-6.

  10. PatternofInfectionDifferentinWomeninAfrica “Antibody to humanT-celllymphotrophicvirustypeIII (HTLV-III) wasdetectedintheserumof 66% ofprostitutesoflowsocioecononomic status............therelativelyhighfemale:male ratio of cases ofAIDSinAfrica (1:1 in Zaire, comparedwith 1:16 intheUnitedStates)...raisesthepossibilitythat perinatal transmissionmayresultinhigh rates oftheinfectionamonginfantsandchildren...” KreissJKet al. AIDSvirusinfectionin Nairobi prostitutes. NEnglJMed 1986;314:414-8.

  11. 1990s: Somethingcanbedone! (for somepeople)

  12. HAART: Highly active antiretroviral therapy PMTCT: Prevention of mother-to-child transmission

  13. Impact of HAART in Developed Countries: % survival 10 years after HIV infection in US, Canada, and Europe, by patient age Source: CASCADE Collaboration (Porter K), 2003

  14. The 1st PMTCT 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.

  15. Courseof HIV EpidemicWorldwideafterInventionofHAARTandPMTCT: WomenandChildren

  16. HIV prevalence (%) among pregnant women attending antenatal clinics in sub-Saharan Africa, 1997–2007 Southern Africa Botswana 50 Burkina Faso Lesotho 40 Mozambique 30 Namibia NOTE: Analysis restricted to consistent surveillance sites for all countries except South Africa (by province) and Swaziland (by region) Median HIV prevalence (%) 20 South Africa Ghana Swaziland 10 Zimbabwe 0 1997– 1998 1997– 1998 1997– 1998 1999– 2000 1999– 2000 1999– 2000 2001 2001 2001 2002 2002 2002 2003 2003 2003 2004 2004 2004 2005 2005 2005 2006 2006 2006 2007 2007 2007 Eastern Africa West Africa 20 20 15 15 Ethiopia 10 10 Median HIV prevalence (%) Median HIV prevalence (%) Côte d'Ivoire 5 5 Kenya Senegal 0 0 2.9 Source: National surveillance reports and UNAIDS/WHO/UNICEF, Epidemiological Fact Sheets on HIV and AIDS.  July 2008.

  17. 2.5 Millions 2.0 1.5 1.0 0.5 0 1990 1991 1992 1993 1994 1995 1996 1997 1998 1999 2000 2001 2002 2003 2004 2005 2006 2007 Year This bar indicates the range around the estimate Children living with HIV globally, 1990–2007 2.5

  18. Global SummaryoftheAIDSEpidemic, 2008 (WHO) AIDS related deaths in 2008: Total: 2.0 million Adults: 1.7 million Children (under 15 years): 280,000

  19. Estimated number of Life-years added due to antiretroviral therapy, by region, 1996–2008 8 7.2 million 7 6 5 (millions) 4 3 2.3 million 2 1.4 million 1 590 000 73 000 40 000 49 000 7500 0 Western Europe and North America Sub- Saharan Africa Latin America Asia Eastern Europe and Central Asia Caribbean Oceania Middle East and North Africa Figure VII

  20. Misconceptions (historic and recent) re HIV in women and children, and evidence to refute them HIV preventioninwomenissimple. HIV+ pregnantwomen are usuallyinstageI Short-courseperipartumARVswill do thejob Vertical HIVtransmissionistheonlyoutcomeofinterest Breast-feedingisbadifthemotheris HIV+ AIDStreatmentisimpossibleinAfrica (and similar settings) HIV-infectedchildren are justlikelittlerHIV-infectedadults

  21. Misconception 1: HIVpreventioninwomenissimple (“justsay no”)

  22. 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

  23. HIV transmission within marriage HIV incidencein Uganda, 2004-5: Ofnew HIV infections (withinpreceding 155 days): 65% inmarriedpersons 26% divorcedorwidowed 9% nevermarried FromHladiketal, CROI abstract 123, Feb 2008

  24. Prevention of sexual transmission to women (1): Condoms work if used: In female sex workers in Nigeria and Benin (15% IDU), increased condom use associated with reductions in: HIV acquisition (none vs 3/100 py) Syphilis acquisition (5% vs 10%) Gonorrhea acquisition (7% vs 11%) Busari et al, CROI abstract 30, 2008

  25. Condoms (2) Other 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.

  26. Condoms (3) • In one study in Nicaragua, provision of free condoms to users of rent-by-the hour motels only led to condom use in 62.1% of (presumed) commercial sexual encounters and 24.5% of non-commercial sexual encounters. Addition of educational materials actually decreased condom use slightly – odds ratio for condom use (commercial sex) when health education was also provided was 0.89 (95% CI 0.84 – 0.94). • One review of interventions to promote condom use: Effect range (“reduction in non-use of condoms”) ranged from 1% to 57%, depending on strategy and target. Egger M et al. Lancet 2000. Stover J et al, Lancet 2002.

  27. Preventionof sexual transmission to women (2) Male circumcision does not seem to work (for women): 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

  28. Preventionof sexual transmission to women (3) “More than 6000 women at three sites in South Africa participated in the $40 million, placebo-controlled trial [of Carraguard, a candidate microbicide with in vitro activity against HIV]… "Carraguard was shown to be safe but not effective against HIV," said principal investigator Khatija Ahmed, [who] reported a statistically insignificant difference in infection rates: 151 women in the placebo group versus 134 who received Carraguard. Women said they used the gel only 44.1% of the time, and just 10% said they always used it before sex.” Science, 22 Feb 2008 (Cohen J)

  29. Preventionof sexual transmission to women (4) Controlling herpes in women (and MSM) also does not seem to work to prevent HIV acquisition: HIV acquisition with herpes suppressive therapy: 3.9/100 py HIV acquisition without: 3.3/100 py Celum C et al, CROI abstract 32LB, 2008

  30. Preventionof sexual transmission to women (5) If a woman’s seropositive male partner successfully reduces HIV viral load with HAART, sexual transmission is reduced:

  31. Riskof sexual transmissionof HIV andpartner viral load HIV+ partner VL Transmission/100py <400 c/mL 0 400-3500 4.8 3500-50,000 14.0 >50,000 23.0 FromBartlett, 2007

  32. Preventionof sexual transmission to women (7) Voluntary counseling and testing (VCT) • Random assignment of individual or couple participants to VCT vs. health education alone in Kenya, Tanzania, and Trinidad. Outcome was reduction of unprotected intercourse with non-primary sexual partners (not reduction of HIV transmission). In men, 35% reduction with VCT vs. 13% with health education alone; in women 39% vs. 17%. Counseling visits were unlimited before and after HIV testing. Subsequent seroconversion of HIV-negative not reported. The Voluntary HIV-1 Counseling and Testing Efficacy Study Group. Lancet 2000;356:103-112.

  33. VCT (2) 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.

  34. VCT (3) Study of effect of VCT on sexual risk behavior and HIV acquisition in Rakai, Uganda, concluded: “In this rural cohort where VCT services are free and accessible, there is self-selection of individuals accepting VCT, and no impact of VCT on subsequent sexual risk factors or HIV incidence.” Matovu J et al, AIDS 2005.

  35. HIV vaccines: STEPtrial(Buchbinderetal, Lancet 2008)

  36. “CheapSolutionsCutAIDSToll for PoorKenyanYouths” (NYT, 6 Aug 2006) “....whengirlsweregivenfreeschooluniformsinsteadofhaving to pay $6 forthem – the principal remainingeconomicbarrier to educationinKenya – theyweresignificantlylesslikely to dropoutandbecomepregnant...” “...classroom debates andessay-writingcontestsonwhetherstudentsshouldbetaughtaboutcondoms to prevent HIV increasedthe use ofcondomswithoutincreasing sexual activity...”

  37. Best HIV preventionadvice for women: Stayinschool Delay sexual debut (stayinschool) Avoidunsafesexandunsafepartners Post-exposureprophylaxisinselectedsituations (rape) Ifpartneris positive, getpartneron antiretrovirals (reduce viral load); usecondoms Hope for aneffective HIV vaccineormicrobicide...

  38. Misconception 2: HIV+ pregnantwomen are usuallystillinstage 1 (soweonlyreallyneed to worryaboutthebaby’shealth) InitialPMTCTstrategyindevelopingcountries: Single-dose nevirapine tomotherandinfantatbirth (laterupdated to othershort-course2-drugARVcombinations). NO HAART for HIV-infectedmothers. [Avoidbreast-feedingifbetteroptionsavailable.]

  39. MTCT+ data: Health Status ofPregnant HIV+ WomenonEnrollment (Tonwe-Goldetal.2007)

  40. Causes of Maternal DeathinMozambique (Ordietal 2009)

  41. Maternal MortalityinMozambique (2)

  42. Hazard ratio forpost-partummortalityof HIV+ vsHIV-mothersin Zimbabwe

  43. Maternal mortality, Africa, from Khan

  44. Developed-country data (Fiorietal 2004)

  45. Misconception 3: Short-courseperipartumARVswill do thejob (for bothmotherandinfant)

  46. 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

  47. Increased Risk OI/Death/non-AIDS Morbidity with STISMART Study Group. NEJM 2006;355:2283-96 (from Mofenson L 2008) Death from any Cause OI or Death from any Cause Hazard ratio 2.6 (1.9-3.7) Hazard ratio 1.8 (1.2-2.9) Major CV, Renal, Hepatic Disease Grade 4 Adverse Event Hazard ratio 1.2 (1.0-1.5) Hazard ratio 1.7 (1.1-2.5) Interrupt Interrupt Continue Continue Interrupt Continue Interrupt Interrupt Continue

  48. Viral loadreboundandCD4 decline inmothersafterdiscontinuationofPMTCTregimens Viral loadreboundpost-partum: 84.7% ofwomenwhotookshort-coursePMTCTregimensthenstopped 15.3% ofwomenwhocontinuedART VLreboundassociatedwithCD4 decline 34% ofwomenwithVLrebound 2% ofwomenwith no VLrebound Cavalloet al. AbstractTUPECO46 IAS 2009

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