Dr Tin Tin Sint Department of HIV/AIDS World Health Organization WHO guidelines on use of antiretroviral drugs for the prevention of mother-to-child transmission of HIV Dr Tin Tin Sint Department of HIV/AIDS World Health Organization

Mother-to-child transmission of HIV Without any intervention 15%-45% of infants born to mothers living with HIV will become infected Virtual elimination of MTCT have been achieved in developed countries (<2%) A comprehensive package is needed: Primary prevention in parents-to-be Prevention of unintended pregnancies among HIV-infected women Prevention of HIV transmission from women living with HIV to their infants Provision of appropriate treatment, care and support to all those infected and affected Women account for approximately half of all adults living with HIV/AIDS – 15.4 out of 33.2 million 90% of all HIV-infected pregnant women in low- and middle-income countries live in 20 high burden countries, all but on of these are in sub-Saharan Africa (list of the 20 countries) Every day around 1200 children under the age of 15 years get newly infected with HIV and MTCT is the cause in more than 90% of cases Without any intervention 15-45% of infants will acquire the virus from the infected mother depending on the duration of breastfeeding (5-10% during pregnancy, 10-20% during labour and delivery, and 5-20% through breastfeeding) However, the transmission rate has been reduced to around 2% in developed countries using specific interventions, and equally around 5% in resource-limited setting where breastfeeding is the norm WHO and other UN agencies recommend a four element comprehensive approach to maximize the reduction in number of women living with HIV and infants being infected through MTCT We will in this session focus on intervention related to preventing HIV transmission from infected mothers, with a focus on antiretroviral durgs

The evolution of interventions and national programmes Research on use of ARV for PMTCT started in the '90s with reported efficacy of various regimen in the late '90s (Shaffer et al.; Wiktor et al.; Guay et al.) Several regimens using mono-, dual-, or combination prophylaxis found to be efficacious Pilot projects to define implementation feasibility carried out in resource-limited settings Recent scale up of pilot projects to national programmes (88 out of 109 reporting countries)

Current WHO 2006 recommendations: HIV testing and counselling All pregnant women should be offered HIV testing and counselling as part of routine ANC First step in providing targeted interventions including PMTCT Using provider-initiated testing and counselling should be the norm and greatly increases access to the services Rapid testing with same day result should enable more clients to be aware of their own serostatus and therefore increases uptake of services Only, about 18% of total estimated number of pregnant women in low- and middle-income countries received an HIV test (2007)

Percentage of pregnant women in low- and middle-income countries receiving an HIV test (2004-2007) Source: Universal Access Report, 2007

Current WHO 2006 recommendations: screening for ART eligibility When a pregnant woman is identified with HIV eligibility for ART must be assessed using clinical staging and/or CD4 cell count, and ART provided as necessary High viral load and low CD4 means high transmission Women with low CD4 are those who needs ART Providing ART to pregnant women in need will address the health issue of the mother and in addition significantly reduce MTCT Only 12% of pregnant women identified as HIV-positive during ANC were assessed for eligibility (2007)

Eligibility criteria 1 2 3 4 WHO clinical stage CD4 testing not available CD4 testing available 1 Do not treat (A-III) Treat if CD4 <200 cells/mm3 2 3 Treat Treat if CD4 <350 cells/mm3 4 Treat irrespective of CD4 cell count (A-III)

AZT + 3TC + NVP twice daily Recommended regimens for treating pregnant women and prophylactic regimen for infants For women, including pregnant women, who need ART for their own health: Mother Antepartum AZT + 3TC + NVP twice daily Intrapartum Postpartum Infant AZT x 7 days* * If the mother receives < 4 wks of ART during pregnancy, give 4 wks of infant AZT

Combination ARVs are more effective and reduces resistance Current WHO 2006 recommendations: more efficacious regimens for prophylaxis If not eligible for therapy, use more efficacious prophylactic regimens Combination ARVs are more effective and reduces resistance Risk of transmission at 18 months 20% with no ARV (WITS)* 10.4% with AZT monotherapy (WITS)* 3.8% with dual-ARV (WITS)* 1.2% with triple-ARV (WITS)* 15.7% with single-dose nevirapine vs. 25.8% with AZT (HIVNET 012)** *Cooper E et al. JAIDS 2002 **Jackson JB et al. Lancet 2003

The recommended prophylactic regimen is: Recommended regimens for treating pregnant women and prophylactic regimen for infants Women who do not need ART should be offered ARV prophylaxis for MTCT prevention: The recommended prophylactic regimen is: Mother Antepartum AZT starting at 28 wks of pregnancy or as soon as thereafter Intrapartum Sd-NVP + AZT/3TC Postpartum AZT/3TC for 7 days Infant Single dose NVP plus one week AZT* * If the mother receives < 4 wks of ART during pregnancy, give 4 wks of infant AZT

More efficacious regimens Combination prophylaxis regimen lowers transmission rate AZT given for a longer period during pregnancy is more efficacious Nevirapine is important in preventing early postnatal transmission through breastfeeding due to its long half-life Addition of 3TC is to prevent resistance to nevirapine (for future treatment options)

Time of administration Different approaches for using ARV prophylaxis to prevent HIV infection in infants Ranking Time of administration Pregnancy Labour Postpartum Maternal Infant Recommended AZT (>28 wks gestation) Sd-NVP + AZT/3TC AZT/3TC x 7 days Sd NVP + AZT x 7 days Alternative Minimum -- + AZT/3TC Sd NVP

Distribution of ARV regimens for PMTCT (2007) Source: Universal Access Report, 2007

Time of administration ARV prophylaxis for PMTCT among pregnant women who have not received antenatal ART or prophylaxis Ranking Time of administration Labour Postpartum Maternal Infant Recommended Sd-NVP + AZT/3TC AZT/3TC x 7 days Sd NVP + AZT x 4 wks Alternative AZT + 3TC AZT/3TC x 7 days Minimum Sd NVP Sd-NVP

Time of administration ARV prophylaxis for infants born to HIV-positive women who have not received ART or ARV prophylaxis Ranking Time of administration Infant Postpartum Recommended Sd-NVP + AZT x 4 weeks1 Alternative Sd-NVP + AZT x 1 week Minimum Sd NVP 1 NVP administered immediately after birth, if possible within 12 hours after delivery, is likely to result in a larger reduction in transmission than later initiation. Data on added efficacy of 4 weeks of infant AZT in this situation limited

Setting priorities The health of the mother is the first priority Identify most effective interventions that can be provided to a maximum number of women Quality of services should not be neglected while scaling up Improved child survival should be the outcome

Review of evidence WHO systematically reviews available evidence and programme performance, and will convene an expert consultation in late 2008 Department of HIV/AIDS Department of Child and Adolescent Health and Development Department of Reproductive Health and Research