Prevention of mother-to-child HIV transmission (PMTCT) in Africa: time for a new approach

Transcription

1 Prevention of mother-to-child HIV transmission (PMTCT) in Africa: time for a new approach Elaine J Abrams, MD October 9, 2009 Prevention of Mother-to-Child HIV Transmission in Sub-Saharan Africa Scope of the pediatric HIV epidemic 4 Prongs of PMTCT 5 points: current approach and limitations New findings, new interest Moving forward: shifting the paradigm 1

2 Global Summary of the AIDS Epidemic, December 2007 Number of people living with HIV in 2007 Total Adults Women Children under 15 years 33 million [30 36 million] 30.8 million [ million] 15.5 million [ million] 2.0 million [ million] People newly infected with HIV in 2007 Total 2.7 million [ million] Adults 2.3 million [ million] Children under 15 years [ ] AIDS deaths in 2007 Total 2.0 million [ million] Adults 1.8 million [ million] Children under 15 years [ ] Over 7400 new HIV infections a day in 2007 More than 96% are in low and middle income countries About 6300 are in adults aged 15 years and older of whom: almost 50% are among women about 45% are among young people (15-24) About 1000 are in children under 15 years of age ->90% of pediatric infections are acquired through mother-to-child transmission (MTCT) 2

3 Number of children with HIV infection has escalated over the last decade Millions Year 2.5 This bar indicates the range around the estimate Vast majority of children with HIV infection live in the poorest countries of the world North America 1.2 million [ million] Caribbean [ ] Latin America 1.7 million [ million] Western & Central Europe Middle East & North Africa [ ] Sub-Saharan Africa 22.0 million [ million] Eastern Europe & Central Asia 1.5 million [ million] [ million] East Asia [ million] South & South-East Asia 4.2 million [ million] Oceania [ ] 3

4 Consequences of two decades of unsuccessful HIV prevention in Africa Reversed hard earned improvements in health outcomes Escalating rates of maternal and child mortality 56% of under-5 deaths attributed to HIV/AIDS in Lesotho Maternal death rate six times higher among HIV+ compared with HIV-women, , South Africa Staggering numbers of orphans Large numbers of children living with HIV infection At high risk for early death With increasingly availability of antiretroviral treatment (ART), living and coping with a stigmatized, complex, fatal chronic disease Why do so many children continue to acquire HIV infection? 1. High rates of HIV infection in women of reproductive age Disproportionately high rates in female youth HIV prevalence increased from 4.1% in 16yr old girls to 31.2% in 21 yr old women, South Africa (Pettifor, AIDS 2005) High incidence of seroconversion during pregnancy and postpartum period Incidence of seroconversion during pregnancy reported at 10.7% ( ) per 100 pregnant patient years, South Africa (Moodley et al, AIDS 2009) 4

5 Why do so many children continue to acquire HIV infection? 2. Unmet need for family planning High rates of unintended pregnancies & poorly planned pregnancies Multi-country surveys report rates of 50-90% of unintended pregnancies among HIV positive women in care High rates of pregnancy among women initiating ART 3. Failure to implement proven biomedical interventions (HIV testing, ART, infant feeding) to reduce the risk of MTCT Low HIV testing rates during pregnancy in Sub-Saharan Saharan Africa Percentage of women receiving an HIV test during pregnancy by year Towards Universal Access Scaling up priority HIV/AIDS interventions in the health sector. WHO/UNAIDS/UNICEF, June

6 Low rates of antiretroviral use for PMTCT in Sub-Saharan Saharan Africa Percentage of pregnant women living with HIV receiving antiretrovirals for PMTCT Percentage of HIV exposed infants receiving antiretrovirals for prophylaxis Towards Universal Access Scaling up priority HIV/AIDS interventions in the health sector. WHO/UNAIDS/UNICEF, Percentage distribution of ART regimens for pregnant women Towards Universal Access Scaling up priority HIV/AIDS interventions in the health sector. WHO/UNAIDS/UNICEF,

7 PMTCT prophylaxis and ART regimens among HIV+ women at ANC, ICAP, Jul 07 Jun 09 14,000 12,000 10,000 8,000 6,000 4,000 2,000 0 Cote d'ivoire Ethiopia Lesotho Mozambique Nigeria Rwanda South Africa Tanzania Sd-NVP Complex regimens HAART No prophylaxis Proportion of HIV+ pregnant women with CD4 test results among 224 PMTCT sites, ICAP, April June % 80% 60% 40% 20% 0% Cote d'ivoire Ethiopia Lesotho Mozambique Nigeria Rwanda South Africa Mean Apr-Jun 09 Mean: average proportion of HIV+ pregnant women with documented CD4 result from April 2008-March 2009 vs. latest reporting, Apr-Jun

8 United Nations comprehensive PMTCT strategy: four prongs 1. Primary prevention of HIV infection among women of childbearing age 2. Prevention of unintended pregnancies among women living with HIV 3. Preventing transmission of HIV from women living with HIV to their infants HIV testing, ART, infant feeding 4. Treatment, care and support for women and children living with HIV I. PMTCT has been conceptualized as a simple intervention Historically, posited that ART therapy during pregnancy was too complex and costly for low resource settings HIVNET 012 determined that single-dose nevirapine (sd- NVP) to the laboring mother and newborn baby could reduce MTCT risk by 42% Availability of rapid HIV tests and sd-nvp propelled efforts to implement PMTCT programs Simple intervention accomplished during one antenatal visit Relatively high rates of ANC attendance, at least one visit, in many but not all poor countries Early introduction of sub-optimal PMTCT regimen and singlevisit approach Failed to build systems to support optimal, more complex PMTCT regimens & approaches 8

9 SD-NVP to mom & baby for PMTCT Transmission Rate (%) AZT 6-8 weeks 42% reduction NVP Guay et al, Lancet 1999 HAART became the mainstay for PMTCT in well resourced settings Transmission Rate (%) none ZDV mono dual therapy HAART Attention was focused on finding easier regimens in Africa Cooper ER et al, JAIDS % Efficacy 100% 80% 60% 40% 20% short course ART regimens: AZT, AZT+3TC, +/-NVP 62% 63%68% 50% 50% 28% 33%37% 40% 42%42% 18% 0% 9

10 II. PMTCT has failed to address the health needs of pregnant women living with HIV ART intervention intended to reduce MTCT transmission risk Funded and supported as prevention rather than treatment programs Maternal health not routinely assessed or addressed 20-25% of HIV+ pregnant women have CD4<200 cells/mm % will have CD4<350 cells/mm 3 Systematic failure in most early trials/studies to identify and treat women eligible for ART for their own health HIV testing in the ANC has not been routinely linked to reflex CD4 cell count testing, unlike other HIV testing programs High MTCT risk associated with low maternal CD4+ cell count > CD4 Count < % 10% 20% 30% 40% 50% Percent Transmission In Utero Intrapartum-Early Postpartum Postpartum CD4 < 200: 55% of maternal deaths, 47% of postnatal infections Kuhn, ZEBS 10

11 III. No definitive ART interventions for PMTCT during breast feeding Early studies examined the safety and feasibility of replacement feeding, early weaning, exclusive breast feeding International guidance has been confusing and difficult to implement Most HIV+ women breast feed their infants for prolonged periods of time New findings from a number of clinical trials suggest that ART to mom or baby during breast feeding can reduce the risk of MTCT HAART during pregnancy and throughout breast feeding reduces MTCT: Mma Bana Infections among live-born infants, by maternal arm Arm A (TZV) N=283 Arm B (KAL/CBV) N=270 Obs Arm (NVP/CBV) N=156 In utero 3 (1.1%)* 1 (0.4%) 1 (0.6%) Intrapartum Breastfeeding 2 (0.7%) 0 0 Total at 6 months 5 (1.8%)* 1 (0.4%) 1 (0.6%) Overall Transmission 1% (95% CI, %) Through Age 6 Months Shapiro RL, et al, IAS, 2009, Abs. WeLBB101 11

12 Probability of HIV Infection or Death by Week 28 in Infants Uninfected at Birth: BAN study Estimated probability HIV positive or death Control vs Maternal HAART: p= Control vs Infant NVP: p < Maternal HAART vs Infant NVP: p= Control Sd-NVP Maternal HAART AZT+3TC+ LPV/r Infant daily NVP Age (weeks) 7.6% 4.7% 2.9% Chasela, et al, IAS 2009 IV. Limited attention to postnatal interventions and infant follow-up PMTCT effectively ends at delivery Poor linkage between maternal and child services Low utilization rates of PMTCT services including newborn ART prophylaxis, early infant diagnostic testing, cotrimoxazole prophylaxis Guidance to support optimal infant feeding has been confusing and difficult to implement 12

13 Pilot program for early infant diagnosis using DNA PCR, Lake Region, Tanzania Number of children ICAP Tanzania 2008 V. Layered PMTCT services onto Maternal Children Health programs Weak, overburdened systems accustomed to providing the most basic services to healthy women and children Fragile infrastructure with limited capacity, human and structural resources Predominantly lower level facilities Few physicians, limited access to laboratories Health systems in low resource settings are ill equipped for chronic disease management Accustomed to acute, episodic disease management Retooled for the ART roll-out but not PMTCT 13

14 Re-conceptualize PMTCT Not a simple prevention program HIV care and treatment program for pregnant women, children and families Inclusive of multiple interventions for mother and child, over and extended time period Built on the notion that ART is critical throughout the duration of exposure Apply approaches and lessons learned in the ART rollout Develop systems to effectively provide PMTCT in the context of maternal-child health services Access to CD4 testing, HAART for eligible women Integration of reproductive health services as an integral part of HIV care and treatment services Right moment in time for PMTCT Renewed interest in PMTCT by international bodies and national governments New monies targeted to six high burden countries for PMTCT through PEPFAR 15 years of accumulated scientific findings New WHO guidelines for PMTCT and infant feeding imminent Impatience, interest and excitement in the field 14

15 Special thanks to Lynne Mofenson, Rosalind Carter, Suzue Saito, Louise Kuhn, ICAP PMTCT team and Investigators, women and children participating in PMTCT studies 15