Elimination of Mother-to-Child HIV Transmission: Knowledge to Practice Countdown to Zero Believe it. …………….. Do it. Rangsima Lolekha, MD Chief, eMTCT and Pediatrics Section Global AIDS Program Thailand/Asia Regional Office CDC Southeast Asia Regional Office

Outlines Global goals to elimination of MTCT and AIDS Free Generation Key summary of PMTCT interventions and new Thai PMTCT guidelines 2014 Situation of MTCT rate and early infant access to treatment and care in Thailand UNAIDS recommendations for Country Implementation Action: 10-Point Plan towards eMTCT

Global Goal: Towards EMTCT by 2015 Global Target #1: Reduce the number of new HIV infections among children by 90% Global Target #2: Reduce the number of AIDS-related maternal deaths by 50% Launched by UNAIDS and PEPFAR: calls for exceptional global and national efforts Reduce MTCT of HIV to <5% in breast-fed population <2% in non-breastfed population

Millennium Development Goals and EMTCT The EMTCT contributes directly towards achieving four of the MDGs MDG3: Promote gender equality and empower women MDG4: Reduce child mortality MDG5: Improve maternal health MDG6: Combat HIV/AIDS, malaria and other diseases

Key elements of prevention of HIV transmission to babies and keeping their mothers alive Key elements of eliminating new HIV infections among children and keeping their mothers alive 1. Preventing new HIV infections among women of reproductive age. 2. Helping women living with HIV avoid unintended pregnancies. 3. Ensuring that pregnant women have access to HIV testing and counselling; and that those who test positive have access to antiretroviral medicines to prevent transmission during pregnancy, delivery or breastfeeding. 4. Providing HIV care, treatment and support for women, children living with HIV and their families.

The Virtual Elimination of MTCT of HIV is Possible Estimated New HIV infections among children 0-14: Different scenarios for 25 countries with largest numbers of HIV+ pregnant women Data from 25 countries with the largest numbers of HIV+pregnant women were used to create different scenarios to evaluate different PMTCT interventions. A Spectrum model was used to estimate new child HIV infections as a measure of the impact of interventions. If 90% of women reached with services matching WHO GL, there will be 60% reduction in new HIV infections among children in 2015 If 90% of women reached with services matching WHO GL, and incidence of new infection reduced by 50% and eliminate unmet need for family planning, there will be 80% reduction in new HIV infected children If 90% of women reached with services matching WHO GL, and incidence of new infection reduced by 50% and eliminate unmet need for family planning and restricted BF to 12 mo, there will be 90% reduction in new HIV infected children by 2015. To achieve virtual elimination of new child infections, PMTCT program must achieve high coverage of more effective ARV interventions and safer infant feeding practices. In addition a comprehensive approach including meeting unmet family planning needs and reducing new HIV infections among reproductive age women is required. Source: Mahy M, Stover J, Kiragu K, et al. What will it take to achieve virtual elimination of mother-to-child transmission of HIV? An assessment of current progress and future needs. Sex Trans Infect (Suppl) 2010.

Monitoring Framework for 2015

Estimated Risk and Timing of Mother-To-Child (MTCT) HIV Transmission In utero During labor 4% 12% Post partum through breastfeeding 1% 0-14 wk 14-36 wk 36 wk -labor Delivery 8% 7% 0-6 month 6-24 month 3% Overall without breastfeeding 20-25 % Overall with breastfeeding till 6 months 25-30 % Overall with breast feeding till 18-24 months 30-35 % Trainers reviews the estimated risk by timing of delivery. Highlight on overall transmission rate without any intervention stratified by breastfeeding performance. Source: De Cock KM, et al. JAMA. 2000; 283 (9): 1175-82 Kourtis et al. JAMA 2001; DeCock et al. JAMA 2000 The risk of perinatal transmission can now be less than 2% (1 in 50) with: Highly effective ARV therapy (HAART), elective cesarean section as appropriate; formula feeding

PMTCT is the most effective intervention among prevention technologies reducing HIV transmission cART vs. no ARV (076 placebo) (0.8% vs. 25.5%) US/Europe 2006 97% Option A vs. no ARV S Africa (1.5% vs. 22%) Dihn 2011, IAS; Rundare 2012, CROI 93% Karim SSA et al. Lancet 2011;378:e23-25 Adapted from Mofenson L’s slide

Summary of peripartum transmission probabilities by ART regimen and maternal CD4 count (The UNAIDS reference group on estimates, modelling and projections) Incident peripartum infections with no ARV prophylaxis (range of reported transmission probabilities) = 30% (13-30%) The risk of perinatal transmission can now be less than 2% with HAART and formula feeding Incident infections occuring during pregnancy are estimated to be associated with a 30% probability of MTCT. Tx rate was high among women with CD4 count<200 compared with those with higher CD4 count. With WHO 2010 recommended regimens options A or B are estimated to be associated with a 2% peripartum transmission probability. Peripartum Tx rate was lowest for women who were taking ART before pregnancy (0.5%) Rollins N et al. STI 2012

Postnatal Transmission rate per month of any breastfeeding probabilities by ART and maternal CD4 count (The UNAIDS reference group on estimates, modelling and projections) Incident postnatal infections with no ARV prophylaxis (range of reported transmission probabilities) = 28% (14-56%) The risk of perinatal transmission can now be less than 5% with HAART and exclusive BF for 12 mo Incident infections occuring during breastfeeding are estimated to be associated with a 28% probability of postnatal MTCT. Tx rate was high among women with CD4 count<350 compared with those with higher CD4 count. With WHO 2010 recommended regimens are estimated to be associated with a 0.2% transmission probability per month. Postnatal MTCT rate was lowest for women who were taking ART before pregnancy (0.16%/month) in one report only 0.07%/mo. Rollins N et al. STI 2012

The Mississippi Baby: Functional Cure of HIV Persaud D, 2013 CROI, Abstract 48LB

Mimicking the Mississippi baby The Way Forward: Mimicking the Mississippi baby Early diagnosis of infected babies Nation-wide active enrollment Triple ART Including to high-risk Infants immediately after birth Immediate ART to minimize latently infected cells ART interruption in clinical trial Control HIV viremia

Thai GL 2014 สูตรยาต้านไวรัสและระยะเวลาในการให้ยาต้านไวรัสสำหรับหญิงตั้งครรภ์ที่ไม่เคยได้รับยาต้านไวรัสก่อนเริ่มตั้งครรภ์ สูตรที่แนะนำ การเริ่มยา (ไม่ต้องรอผล CD4 count) การหยุดยา ให้พิจารณาตามความสมัครใจ และความพร้อมในการกินยา   สูตรแรกที่แนะนำ TDF+3TC+EFV สูตรทางเลือก# TDF หรือ AZT+3TC+LPV/r เริ่มยาทันทีโดยเร็วที่สุด - ให้ยาต่อเนื่องหลังคลอด ในทุกรายที่สมัครใจ มีความพร้อมและสามารถกินยาได้ต่อเนื่อง สม่ำเสมอ โดยเฉพาะกรณีต่อไปนี้ CD4 count ก่อนเริ่มยา <500 cells/mm3 กรณีที่มีคู่ผลเลือดลบ หรือไม่ทราบผลเลือดของสามี มีการติดเชื้อวัณโรค หรือ HBV หรือ HCV ร่วมด้วย โดยให้ส่งต่อเพื่อรักษาต่อเนื่องกับแผนกอายุรศาสตร์และเปลี่ยนสูตรยาตามแนวทางการดูแลรักษาผู้ใหญ่ -ขนาดยา: AZT 200-300 mg q 12 ชม.; 3TC 150 mg q 12 ชม.; AZT + 3TC (300 + 150) q 12 ชม.; LPV/r (200/50) 2 เม็ด q 12 ชม.; EFV 600 mg q 24 ชม. # ในกรณีที่มีอย่างน้อย 1 ข้อต่อไปนี้: ไม่แน่ใจว่าหญิงตั้งครรภ์จะสมัครใจกินยาต่อหลังคลอดหรือไม่ CD4 >500 cells/mm3 มีประวัติสามีของหญิงตั้งครรภ์รับการรักษาด้วยยาต้านไวรัสและสงสัยการดื้อยา หญิงตั้งครรภ์เคยรับยาสูตร AZT+SD NVP มาก่อน

Thai HIV Treatment and Care Guidelines 2014: PMTCT Recommendations Thai HIV Rx and care guidelines toward eMTCT and ped cure 2013 categorized babies into 2 groups. Babies with standard-risk (mothers receive ANC or suppressed viral load) In this group during antenatal period, pregnatn women should receive LPV/r or EFV-based HAART, intrapartum AZT 300 mg oral q 3 hrs and infants receive AZT for 4 wks. Babies with high risk for MTCT include babies born to mothers with no ANC, receive ARV<4 wks or failing ART with high VL near time of delivery. This group, a baby should receive AZT/3TC/NVP for 6 wks. No BF. And obtain blood test for HIV DNA PCR at 1, 2, 4 mo, if + immediated LPV/r as soon as possible. This is similar to that in the Mississippi baby that might lead to functional cure in baby. Early HIV diagnosis and immediate lopinavir/r-ART in all HIV-infected infants. The triple-ARV prophylaxis regimen for children at high risk for HIV similar to that in the Mississippi baby. *Infants at high risk for HIV infection: those born to mothers with no ANC, <4 weeks of triple-ART or failing ART (VL>50 copies/mL)

สูตรยาต้านไวรัสเพื่อป้องกันการถ่ายทอดเชื้อเอชไอวีจากแม่สู่ลูกในไทย กรณีไม่ฝากครรภ์หรือเสี่ยงสูงต่อการที่ทารกจะติดเชื้อ 2014 เสี่ยงสูง: ART < 4 wk, poor adherence, VL>50 at 36 wk GA/delivery, recent exposure สถานการณ์ ก่อนคลอด ระหว่างคลอด หลังคลอด แม่ ทารก ไม่ได้ฝากครรภ์หรือเสี่ยงสูงต่อทารกติดเชื้อ CD4>500 cells/mm3 - AZT (300) ทุก 3 ชั่วโมง + SD NVP* ให้ยา HAART ต่อเนื่องหลังคลอดทุกราย ยกเว้นในรายที่ไม่สมัครใจกินยาต่อหลังคลอดให้AZT+3TC+LPV/r x 4 สัปดาห์แล้วจึงหยุดยา -AZT+3TC+NVP 6 สัปดาห์ หรือจนกว่าจะได้ผล PCR เป็นลบอย่างน้อย 1 ครั้ง CD4< 500 cells/mm3 ไม่ต้องให้ SD NVP ในหญิงตั้งครรภ์ที่คาดว่าจะคลอดภายใน 2 ชั่วโมง ถ้าแม่ไม่ได้ SD NVP ไม่จำเป็นต้องให้ tail: AZT+3TC+LPV/r แต่ให้ HAART ต่อตามแนวทางการรักษาในผู้ใหญ่

Timeline for EID and early HIV treatment and care for infants born to HIV+ mothers Standard risk AZT PCR 1 PCR 2 HIV antibody High risk PCR 1 PCR 2 PCR 3 HIV antibody AZT/3TC/NVP 0 1 mo 2 mo 4 mo ……........12-18 mo age PCR+ at 1 mo AZT+3TC+LPV/r PCR+ at 2 mo AZT+3TC+LPV/r PCR+ at 4 mo AZT+3TC+LPV/r *ให้เก็บเลือดทารกทุกรายที่คลอดจากแม่ติดเชื้อเอชไอวีใส่กระดาษกรองไว้ (dried blood spot) เหมือนตรวจคัดกรองไทรอยด์เมื่อแรกเกิด และส่งเลือดไปที่กรมวิทยาศาสตร์ทางการแพทย์พร้อมการส่งตรวจคัดกรองไทรอยด์ ในกรณีที่เด็กติดเชื้อเอชไอวีจากผล PCR ที่ 1-2 เดือน หากมีเลือดเก็บไว้ที่แรกเกิดทางกรมวิทยาศาสตร์ทางการแพทย์จะตรวจ DNA PCR เพิ่มเติมให้เพื่อวินิจฉัยว่าเป็นการติดเชื้อตั้งแต่ในครรภ์หรือระหว่างคลอด ซึ่งอาจมีผลต่อแผนการรักษาในอนาคต

MTCT Rates 2013: 1.7% (accessed to PCR only) Weighted Average: 2.3% AIDS Zero portal website

Cascade of ARV-PMTCT/ART among Mothers NAP-Plus Database, NHSO 2009-2012 (58.3%) * Under reported Receipt of ARV (%) by Women Giving Birth with HIV-Seropositive (2013-14) 79% for Rx 2012: N = 2,461 (65% report) 2013: N = 3,193 (79% report) Source: DOH as of 17/04/2014

Cascade from Early Infant Diagnosis to Antiretroviral Treatment 2008-2011 However, when we look at the cascade from idenfing HIV-exposed infants, making diagnosis, providing CD4 counting and initiating ART. we still found the substantial leakage in the cascade. This leads to the Active Case Management Program that I mentioned in the very beginning. EID program evaluation 2008-2011: Thai MOPH, CDC Thailand, UNICEF-Thailand

HIV Treatment Cascade in the Real World In a perfect world, all HIV infected individuals would follow the same pathway in the spectrum of engagement into care: HIV Infected HIV Diagnosed Linked to HIV Care Retained in HIV Care Need ART On ART Adherent/Suppressed In the real world, there is leakage between each of these steps and individuals are often lost-to-follow-up. Understanding the leakage points and their causes are essential to optimize the effectiveness of HIV treatment program. Comprehensively monitoring in standardized metrics is needed

Country Implementation Action: 10-Point Plan (1) Conduct a strategic assessment of key barriers to eMTCT Develop or revise nationally-owned plans towards eMTCT Assess the available resources for eMTCT and develop a strategy to address unmet needs Implement and create demand for a comprehensive, integrated package of HIV prevention and treatment interventions and services Strengthen synergies and integration fit to context between HIV prevention and treatment and related health services to improve maternal and child health outcomes UNAIDS: Global plan towards the elimination of new HIV infections among children by 2015 and keeping their mothers alive 2011-15

Country Implementation Action: 10-Point Plan (2) Enhance the supply and utilization of human resources for health Evaluate and improve access to essential medicines and diagnostics and strengthen supply chain operations Strengthen community involvement and communication Better coordinated technical support to enhance service delivery Improve outcomes assessment, data quality, and impact assessment UNAIDS: Global plan towards the elimination of new HIV infections among children by 2015 and keeping their mothers alive 2011-15