Improving maternal and child health in the context of HIV James McIntyre Anova Health Institute, Johannesburg, South Africa 1

HIV / AIDS Chasing MDG 4 & 5 also means chasing MDG 6 GOAL 4: REDUCE CHILD MORTALITY HIV / AIDS Target 1: Reduce by two thirds, between 1990 and 2015, the under-five mortality rate GOAL 5: IMPROVE MATERNAL HEALTH Target 1: Reduce by three quarters the maternal mortality ratio Target 2: Achieve universal access to reproductive health GOAL 6: COMBAT HIV/AIDS, MALARIA & OTHER DISEASES Target 1: Have halted by 2015 and begun to reverse the spread of HIV/AIDS Target 2: Achieve, by 2010, universal access to treatment for HIV/AIDS for all those who need it

The scale of the problems HIV/AIDS: 33.4 million people live with HIV/AIDS globally; 2 million people died of HIV/AIDS, nearly 3 million were newly infected in 2008 • Child Mortality: Nearly 9 million children die in the developing world every year; approximately 2/3 of these deaths are from preventable causes. • Maternal mortality: 530,000 mothers die in the developing world each year; every minute, a woman dies from complications related to pregnancy or childbirth and 20 more suffer injury, infection or disease.

Global prevalence Infant mortality World population Maternal mortality HIV (15 – 49 years) www.worldmapper.com

PMTCT: WHO’s four-pronged strategy Primary prevention of HIV in parents-to-be Prevention of unwanted pregnancies Prevention of transmission from HIV-infected mother to infant Providing appropriate treatment and care

Number and percentage of HIV-positive pregnant women receiving antiretroviral prophylaxis, 2004–2008 700 000 Number of HIV-positive pregnant women receiving antiretrovirals In 25 African countries, median PMTCT coverage rose from 31% in 2007 to 40% in June 2008 In Eastern and Southern Africa – where regional HIV prevalence is the highest in the world – PMTCT coverage averaged 58% in 2008 45 600 000 40 % of HIV-positive pregnant women receiving antiretrovirals 35 500 000 30 400 000 25 300 000 20 15 200 000 10 100 000 5 2004 2005 2006 2007 2008 Year Source: UNAIDS, UNICEF & WHO, 2008; data provided by countries. 4.13

Number of people receiving antiretroviral therapy in low- and middle-income countries, by region, 2002–2008 WHO: Towards universal access: scaling up priority HIV/AIDS interventions in the health sector : progress report 2009

“We have effective drugs. There is no reason why any mother should die of AIDS. There is no cause for any child to be born with HIV If we work hard enough we can virtually eliminate mother-to-child transmission.” Ban Ki Moon NY, September 2009

HIV and maternal health

Appropriate treatment and care PMTCT services should be gateways to treatment Women who need ongoing antiretroviral treatment should start as soon as possible in pregnancy HIV is an underestimated cause of maternal mortality, especially where HIV testing rates in pregnancy are low

Global maternal mortality, 1980 – 2008, and effect of HIV Source: Hogan et al, Lancet 2010, (375), 1609-23

The Reports on the Confidential Enquiry into Maternal Deaths (CEMD) in South Africa – 2002 - 2007 Non-pregnancy related infections were the most common cause of death: 37.8% of deaths in 2002 – 2004, 46% of deaths 2004 - 2007. AIDS was the single biggest cause of death at 20% - 22% of all deaths, higher than any direct obstetric cause. 2005 - 2007 institutional MMR: HIV-negative 34/100000 live births, HIV-Positive 328/100000 live births Unknown HIV: 275/100000 live births 2002 – 2004

HIV and TB in pregnancy TB and HIV are independent risk factors for maternal mortality TB more common in young women in high prevalence HIV settings in Africa than in older men or women A South African study showed a 10 fold higher TB incidence in HIV infected vs. HIV uninfected mothers (72.9/100,000 vs. 774.5/100,000) Maternal mortality in this study was 121.7/1000 with HIV and TB co-infection, compared with 38.5/1000 with TB alone. Khan et al, AIDS 2001

“Reducing maternal mortality in women with HIV will also require improvements in antenatal care and obstetric services, as well as specific attention to the management of conditions that are aggravated by the underlying HIV infection.” Lancet, 2010

The need for treatment vs The need for treatment vs. the need for prophylaxis in HIV+ve pregnant women

Based on 1025 women in trial in Zambia with follow up to 24 months Estimating eligibility for ART in pregnant women (Zambia) Based on 1025 women in trial in Zambia with follow up to 24 months CD4 count <350 New WHO eligibility criteria (CD4 <350 or Stage III/IV) Kuhn et al, AIDS 2010

Estimating proportion of transmission and maternal mortality Eligible for ART Not eligible for ART Proportion of Transmission by 6 weeks 87.5% 12.5% Proportion of Transmission after 6 weeks Maternal mortality 24 months after delivery 92% 8% New WHO eligibility criteria (CD4 <350 or Stage III/IV) Kuhn et al, AIDS 2010

First principles: Between 30% and 60% of pregnant HIV positive women will not be eligible for ongoing ART and will need prophylaxis These women who do not yet require ART should receive the best possible prophylactic regimen Single dose nevirapine, with breastfeeding unprotected by antiretroviral prophylaxis, is not an appropriate PMTCT strategy, other than in emergency settings

Stringer, E.M., JAMA. 2010 Jul 21;304(3):293-302. PEARL Study on PMTCT effectiveness 3,244 HIV positive pregnant women at health centres offering PMTCT services in Cameroon, Côte d’Ivoire, South Africa and Zambia Stringer, E.M., JAMA. 2010 Jul 21;304(3):293-302.

Remaining research questions: PROMISE BF will provide answers on the comparison between maternal triple ART and extended infant NVP – study to date have not been sufficiently powered to answer this head-to-head comparison PROMISE will provide answers on the risks and benefits of stopping maternal antiretrovirals after MTCT prophylaxis

HIV and child health

HIV and child health HIV is closely linked to the failure of many countries to be on track to meet MDG 4 Child health outcomes are affected by the health of the mother and family Maternal illness or death worsen child outcomes and increase child mortality HIV is increasing orphanhood in high prevalence areas Slow progress in improving access to ART for children

HIV is a major cause of death in children in high prevalence settings: Half of all deaths of children under five occur in Sub-Saharan Africa Africa accounts for: 90% of HIV infections in children 90% of HIV related deaths in children HIV underlying cause of one third of deaths in children under 5 in most affected countries in Sub-Saharan Africa.

Source: U.S. Bureau of the Census Estimated impact of AIDS on under 5 child mortality rates: Selected African Countries 2010 250 200 150 100 50 Deaths per 1000 live births with AIDS Botswana Kenya Malawi Tanzania Zambia Zimbabwe without AIDS US Bureau of the Census Source: U.S. Bureau of the Census

Child mortality in South Africa: contribution of HIV: Every Death Counts: Saving the lives of mothers, babies and children in South Africa, 2008

Early diagnosis and treatment saves children’s lives: Children with HIV Early Antiretroviral Therapy (CHER) Study ART initiated before 12 weeks reduces early mortality in young HIV-infected infants by 75% in first year HIV-infected children <12 weeks with CD4 >25% randomised to start ART immediately (n=125) or following standard CD4 and clinical criteria during follow up (n = 250) Survival in first year: Immediate treatment : 96% Deferred treatment: 84% Violari et al, NEJM, 2008

Early diagnosis and treatment saves children’s lives: Worldwide access to treatment for children with HIV: Reached 355 000 at the end of 2009, Up from 276 000 at the end of 2008 Many more children’s lives could be saved if more infants are started on medication earlier, following new WHO recommendations Very few children under the age of one year have been started on HIV treatment, partly because the testing needed for this group is available in many settings WHO, 2010

Early diagnosis and treatment saves children’s lives: Expanding the availability of early infant diagnostic testing is a critical need WHO is calling for greater access to infant diagnosis starting at four to six weeks after birth. Without diagnosis followed by prompt initiation of treatment, an estimated one-third of HIV-infected infants will die before their first birthday, and about half will die before reaching two years of age WHO, 2010

Treating mothers saves babies: At the Africa Centre in Kwazulu Natal, South Africa: The incidence of death by five years of age in children of untreated mothers was 9%, compared to 5.7% in children of mothers who received antiretroviral therapy. After adjustment for other risk factors – antiretroviral therapy was found to reduce the risk of child death by 75%. Ndirangu J et al. Impact of maternal HIV treatment on under-five child mortality in rural, high HIV prevalence South Africa. 18th International AIDS Conference, abstract MOAE0104, Vienna, 2010

The Implementation Challenge What can we do now to reach the MDG’s?

Coverage and linkages PMTCT Programme effectiveness is related more to coverage and the losses at each part of the PMTCT cascade than to the efficacy of the PMTCT regimen. HIV-infected women need to be identified during (or prior to) pregnancy, in order to provide appropriate PMTCT interventions. PMTCT interventions must reach and be accepted by the woman. Interventions to prevent breastmilk transmission are critical to success of PMTCT programmes .

Prevention of mother-to-child-transmission efforts may fail if they focus narrowly on women and their biological role in passing along the illness. Reaching MDGs 4, 5 and 6 requires a broader view and much increased coverage of strategies known to be effective.

Measuring progress across PMTCT combination interventions Indicators such as: Have the most effective multiple drug combinations for preventing HIV transmission (according to the latest guidelines), rather than the use of just one drug (such as nevirapine), been utilized? Were mothers evaluated for initiation of full, ongoing antiretroviral treatment? Have other sexual and reproductive health services been provided (e.g. congenital syphilis screening and treatment)? Joint Action for Results: UNAIDS Outcome Framework 2009–2011

Measuring progress across PMTCT combination interventions Were other members of the family provided services, with siblings and spouses being tested, counselled and started on therapy as needed? Has counselling taken place on infant feeding and on the future use of contraception? Has there been an exploration of the possible social support services that may be necessary, such as for nutrition and education? Joint Action for Results: UNAIDS Outcome Framework 2009–2011

Antiretroviral therapy PMTCT Program linkages Prevention of new infections in women Prevention of transmission to sexual partners Prevention of transmission to infants Family planning & reproductive health services Pre-ART care Antiretroviral therapy Infant diagnosis and care Men’s health care Circumcision PMTCT services Nutrition Support services

Absolute number of people on ART per country: MSF 2010 PMTCT in the context of other programmes PMTCT policies do not exist in a vacuum Resources for treatment are under threat 9 million people worldwide still lack access to ART - two thirds of them in sub-Saharan Africa alone Public health decisions on PMTCT regimens need to be made as part of broader country HIV programming Absolute number of people on ART per country: MSF 2010

Elimination of MTCT by 2015? From talking to action....... “We can prevent mothers dying and babies becoming infected with HIV. That is why I am calling for the virtual elimination of mother-to-child transmission of HIV by 2015” Michel Sidibe, UNAIDS December 2009

Towards elimination of paediatric HIV . Virtually eliminating HIV among babies will cost a little over USD 610 million each year in low- and middle-income countries. But the return on the investment is high. If programmes go to scale according to plan, the world could avert about 2.1 million child infections cumulatively between 2009 and 2015 UNAIDS Outlook 2010 Photo©IAS/Steve Forrest/Workers' Photos

Acknowledgements…… With thanks to: Lynne Mofenson Louise Kuhn Elaine Abrams Coceka Mnyani WHO Guideline committee