PMTCT 2010 Max Kroon Mowbray Maternity Hospital Division of Neonatal Medicine School of Child and Adolescent Health University of Cape Town
Prevention of Mother-To-Child Transmission of HIV or Prevention of Vertical Transmission of HIV.
Talk Outline Timing and determinants of MTCT HIV Prevalence globally and in South Africa Importance of PMTCT in Context of MDGs History of PMTCT research History of Guidelines in RSA and WC The New Guidelines 1. Mother 2. Infant Summary Future?
Timing of Vertical Transmission 5-10% antenatal. 10 20% during labour and delivery. 10 20% during breast feeding. Most during birth process and breast feeding. As PMTCT reduces antenatal and perinatal transmission, BF transmission becomes relatively more important.
Determinants of transmission High maternal viral load (sero-conversion in pregnancy/lactation and advanced disease) Mode of delivery (Elective < Emergency C/S; C/S < NVD) - Avoidance of labour Duration of ROM > 4hrs; chorioamnionitis. Invasive procedures Feeding Mode (solids + BF > BF + FF > EBF, No transmission with FF ) Duration of breast feeding Maternal ARVs or infant NVP
HIV Prevalence Globally and in South Africa
Annual national antenatal HIV and syphilis seroprevalence survey
National Trends
Regression Analysis of 2008 Data Classification tree regression. <22 years had HIV prevalence of 16.8% compared to the 34.8% HIV prevalence among women 22 years and older. Race: African subgroup (37.6%) is identified versus the rest (6.8%) of White, Asian and Coloured African women >22 years grade 12 or more have lower HIV prevalence than less educated subgroup
Prevalence by age group: National
Interpretation Prevalence in the 52 health districts: 4 above 40% 18 between 30% and 40% 19 between 20% and 30% 9 between 10% and 20% 2 below 10 %. The least populated areas of South Africa and those most rural have recorded lower prevalence.
Prevalence: National vs WC National 29.1%:Western Cape 15.1%
HIV prevalence by area in WC
HIV prevalence by area in WC
HIV in communities Prevalence variation within districts and areas is poorly shown by the survey. E.g. Metropole s Southern sub-district average prevalence is 12,5% but in Imizamo Yethu (Hout Bay) and Masiphumelele (Noordhoek) prevalence is close to that in Khayelitsha.
In-depth Analysis of the 2008 Data for the Western Cape Distribution of participants: Africans 50.8% (1896) Coloured 48.6% (1817) Whites 0.6% (21) Asian 0% (1). HIV infection: Africans 29.4% Coloureds only 3.0%
PMTCT in context of HIV in RSA The HIV prevalence amongst adults >15 yrs was estimated at 15,5 18,4% in 2008. Disease burden greatest in sexually active adults (4,2-5, 3 million). Women (2,8 3,6 million) > men. HIV infected children (230-450 000) are relatively few and contribute little to spread. Pregnant women with HIV (110-280 000 p.a.) are a fraction of total cases. PMTCT targets only a small part of the overall burden.
So why is PMTCT so important? Up to 60% of inpatient paediatric deaths in RSA are HIV associated. MTCT is by far most significant cause of HIV infection in children <15 years. Good evidence that MTCT of HIV is preventable. Cost effective intervention. (Paediatric HIV is expensive to treat and is overburdening limited child health resources.) In State Health Service PMTCT was the foot in the door for ART services. Opportunity for infrastructure creation Opportunity for testing and education.
Paediatric Mortality in South Most common reason children died: HIV, Malnutrition and poverty Africa Saving Children 2009
Saving Mother s Report Triennium 2005-2007 there has been a 20.1% increase in the number of deaths compared to 2002-2004 Major cause of death: AIDS (43.7%), HT (15%), Haemorrhage (12.4%) Pregnancy related sepsis (9%), Preexisting disease (6%) 4 th Report on Confidential Enquiries into Maternal Death in South Africa; 2009
Mortality among HIV-positive postpartum women Zimbabwe Mortality within 2 yrs after delivery was 54 times higher among HIV infected women with a CD4 < 200 vs. HIV negative women Of concern, the increased mortality among HIV infected women persists even with high CD4 cell counts (>500), although to a lesser degree. No ART use among these women Hargrove JW. AIDS 2010
Benefits of ART during pregnancy 3,148 HIV+ mothers infants followed at DREAM centers in Malawi and Mozambique from 7/2005 to 12/2008 ART from 14 weeks if CD4 <350 cells/mm 3 ART from 25 weeks until weaning. Marazzi MC IAS Cape Town 2009
HIV transmission and/ or deaths between 1 to 6 months according to pre-delivery length of ART n= 2,161 infants p = <0.001 p = 0.011
DREAM cohort Maternal mortality increased with shorter duration of ART, especially with CD4 count < 200 cells/mm 3 Overall, 3.2% vs. 0.7% if CD4 < 200, p<0.001 No. of days of prenatal ART none 0-30 31-90 > 90 p-value Maternal mortality 7.4 2.7 1.2 0.7 p<0.001 Marazzi MC et al. 5 th IAS, Cape Town 2009
2004 HIV Prevalence & Infant Mortality HIV Prevalence National 29.5% Western Cape 15.4% HIV prevalence in Sub-districts: Khayelitsha 33.0% Gugulethu/Nyanga 29.1% Helderberg 18.8% Stellenbosch 17.8% Knysna/Plettenberg 17.4% Infant Mortality/1000 live births National 59 Western Cape 30 Infant Mortality in Sub-districts: Khayelitsha 44 Gugulethu/Nyanga 40 Helderberg Stellenbosch Knysna/Plettenberg
http://www.childsurvivalcountdown.com/
Millenium Development Goals MDG 4: Reduce U5MR by two thirds. MDG 5: Reduce maternal mortality by 75%. MDG 6: Reduce MTCT of HIV to less than 5%.
History of PMTCT research 1980 s- MTCT documented. 1994-67% reduction in VT with antenatal, intrapartum and infant AZT and formula feeding (PACTG 076 NEJM). 1999- HIVNET 012 (sdnvp) and Thai AZT Study (both Lancet) each showed about 50% reduction with simpler regimens. 2003- sdnvp added to Thai Regimen dramatic reduction in transmission to only 1-2%. HAART in developed world eliminates VT.
History of PMTCT research Replacement feeding in developing world incurs significant morbidity and mortality. Focus of research now on reducing transmission during breastfeeding to make it safer. Exclusive breastfeeding reduces risk of VT. (Coutsoudis & Coovadia, 1999) 2004 (Ross &Piwoz): if IMR > 40 mortality from not breastfeeding exceeds mortality from VT. Breastfeeding with maternal ART or infant NVP (BAN, PEPI, SVEN, Kesho Bora, Mma Bara). New evidence shifts IMR for safe FF even lower.
Now that PMTCT is so Effective, The Most Important Determinant of Vertical Transmission of HIV is Failed PMTCT.
National 1999-18 sentinel sites (1 urban and 1 rural in each province) AZT Thai protocol 2004 National treatment guidelines stage 4 and CD4<200 2006- ALP forces national PMTCT roll-out (NVP monotherapy and targetted HAART) MTCT ~ 15% (6 wks) PMTCT in South Africa WC 1999- Khayalitsha MSF: AZT Thai protocol 2000- NVP PMTCT monotherapy roll-out level 1-2-3. Formula feeding. 2004- Dual therapy from 34 wks and targeted HAART from early. No HAART if booked after 34wks. 14 wk PCR. FF. 2006- unilateral change to 28 wks initially from UCT linked PMNS. Changes supported by WC DOH circular MTCT ~ 5% (6 wks)
National PMTCT in South Africa WC Feb 2008- Dual therapy and targetted HAART (CD4 <250) Roll out 3-2-1 2009- WC PMTCT revision (AZT from 28 weeks/6wk PCR/more emphasis on EBF.) (MTCT~3.5%) April 2010- New National PMTCT guidelines 2010- WC PMTCT revision
Transmission rates on South African PMTCT programs 2006 NVP monotherapy: 14% at 6 weeks, 20% at 6 months if EBF. Dual therapy (WC): 4 8% at 14 wks. (? At 6 months.) HIV free survival uncertain in WC.
Presidential announcement World AIDS Day 2009
HAART if. Pregnant and CD4<350 or stage 3 and 4 TB/HIV co-infection HIV infected infant (<1yr) regardless of CD4 or clinical stage AND AZT Prophylaxis for HIV + pregnant women to commence at 14 weeks if don t meet HAART criteria. IMPLEMENTATION DATE ON 1 APRIL 2010!!!!!
Main Aim KEEPING WOMEN AND CHILDREN HEALTHY.. AND IMPROVING THEIR QUALITY OF LIFE.. AND REDUCING MORTALITY.
New Emphasis Public health approach -harmonised with Adult and Paediatric Treatment Guidelines Promote health and survival of mother and infant, not just reduce vertical transmission Decentralised, nurse driven, nurse initiation, increased accessibility Opt out testing Promotes the integration of PMTCT with maternal, newborn and child health (IMCI/EPI/nutrition), ART, CCMT, family planning, STI and TB services. Aims to make breast feeding safer
MOTHER: 2010 PMTCT Guidelines Stage 3 and 4 or CD4 < 350: HAART (now TDF, 3TC, NVP) Fast track to HAART if stage 4 or CD4 < 100 Intra-partum: nil extra if on HAART Stage 1 and 2 and CD4 > 350: AZT from as soon as 14 wks Intra-partum: stat NVP/intra-partum AZT every 3 hours. TDF/FTC post delivery to reduce NVP resistance.
INFANT: 2010 PMTCT Guidelines Daily NVP x 6 wk from soon after delivery for all. Continue daily NVP beyond 6 weeks for duration of BF if mum not on HAART. Emphasis on EBF but individual choice and free formula still available. 6 wk PCR fast track to HAART if positive.
New National Guidelines HAART stage 3 and 4 or CD4 < 350 Fast track to HAART if stage 4 or CD4 < 100 (now TDF Nil extra intra-partum CD4 > 350 AZT from 14 wks; stat NVP/intrapartum AZT. TDF/FTC post delivery. Infant daily NVP x 6 wk from soon after delivery. Daily NVP for duration of BF if mum not on HAART. Emphasis on EBF but individual choice and free formula still available. 6 wk PCR fast track to HAART if pos.
VEXED FEEDING CHOICE Breastfeeding promotes infant health and survival especially in less resourced settings. Most vertical transmission is now post-natal (assuming high uptake of antenatal care). In developed world, HIV infected woman who breastfeeds may be prosecuted!!! Promoting unsafe feeding practice may undo the gains of effective PVT in pregnancy, labor and neonatal period.
BF Survival Benefit 2000 WHO: odds of infant death due to not breast-feeding rapidly declines with age (pooled data from 6 developing countries): < 2 mnths: 5.8 [95% CI: 3.4 9.8] 4 5 mnths: 2.6 (95% CI: 1.6 3.9) 6 8 mnths: 1.8 (95% CI: 1.2 2.8) 9 11 mnths: 1.4 (95% CI: 0.8 2.6)
Breastfeeding Saves Lives Relative risk of infectious disease mortality from not breastfeeding Source: WHO, 2000 67
Estimated probability of being HIV positive BAN: Probability HIV positive by week 28 visit in infants uninfected at birth 0.00 0.02 0.04 0.06 0.08 Control vs Maternal HAART: p= 0.0032 Control vs Infant NVP: p <0.0001 Maternal HAART vs Infant NVP: p= 0.1203 Control Maternal HAART Infant NVP 1 4 8 12 16 20 24 28 Age (weeks) 6.4% 3.0% 1.8%
Estimated probability HIV positive or death 0.00 0.02 0.04 0.06 0.08 BAN: Probability HIV positive or death by week 28 visit in infants uninfected at birth Control vs Maternal HAART: p= 0.0310 Control vs Infant NVP: p <0.0001 Maternal HAART vs Infant NVP: p= 0.0698 1 4 8 12 16 20 24 28 Age (weeks) Control Maternal HAART Infant NVP 7.6% 4.7% 2.9%
Nevirapine Resistance NVP Tail cover reduces resistance to about 12%. Maternal sdnvp unnecessary if >1mnth antenatal AZT. (MASHI) Breastmilk may have NVP resistant virus. Infants on dnvpp! Maternal 1 st line regimen still contains NVP Infant 1 st line doesn t contain NVP.
Preterm dnvpp No evidence on pks or efficacy Study underway Interim guideline for PVT in preterms
Conclusion: PMTCT is underpinned by Prevention of new HIV infections in the fertile. Helping HIV infected people have babies safely and avoid unintended pregnancies. Early (1st trimester) pregnancy test and early booking to ensure high uptake of PMTCT. and Breastfeeding is much safer on ARV s. and I think risk:benefit and cost:benefit of feeding strategy lies in promoting EBF on dnvpp in WC.
The Future HAART for all pregnant women living with HIV and during breast feeding???
References CLINICAL GUIDELINES: PMTCT (Prevention of Mother-to- Child Transmission) 2010 National Department of Health, South Africa; South African National AIDS Council ANTIRETROVIRAL DRUGS FOR TREATING PREGNANT WOMEN AND PREVENTING HIV INFECTION IN INFANTS Recommendations for a public health approach 2010 version. WHO. Guidelines on HIV and infant feeding 2010 Principles and recommendations for infant feeding in the context of HIV and a summary of evidence. WHO.