World Health Organization | Viet Nam Country Office1 Enhancing Benefits of Early Antiretroviral Therapy Evidence, Implication and Preliminary Findings from an Implementation Research in Viet Nam Masaya Kato, WHO Viet Nam National Scientific Conference on HIV/AIDS November 2015, Hanoi, Viet Nam

World Health Organization | Viet Nam Country Office2 Early ART – Evidence of Therapeutic Benefits - Two large randomized controlled trials - TEMPERANOSTART Sample size CD4 inclusion criteria Immediate ART Deferred ART CD4<800 Immediate start CD4<250, 350, 500 CD4>500 Immediate start CD4<350 Primary outcomes Death or severe HIV- related illness Composite end point: Serious AIDS & non- AIDS events, deaths, TB, etc Hazard ratio of primary outcomes 0.56 ( )0.43 ( )

World Health Organization | Viet Nam Country Office3 Early ART – Evidence of Preventive Benefits - HPTN052 – RCT among serodiscordant partners - 3 Early ART (CD ) vs delayed ART (CD4<250) in index partners 93% decrease in linked infections Only 8 cases of transmission when index partner was on ART o 4 diagnosed shortly after ART start → Likely before viral suppression o 4 occurred while treatment failure No transmissions when viral load undetectable 93% reduction N = 1761

World Health Organization | Viet Nam Country Office4 WHO - When to Start in Adults: Evidence summary A systematic review comparing ART initiation at CD4 <500 CD4 vs ≥500 CD4 cells/µL 1 RCT* (TEMPRANO) and 17 cohorts or meta-analyses of cohorts Less severe HIV morbidity, HIV disease progression and HIV transmission, without increase in grade III/IV lab adverse events. WHO 2015 Early Release Guidelines ART should be initiated among all adults with HIV regardless of WHO clinical stage and at any CD4 cell count As a priority, ART should be initiated among all adults with severe or advanced HIV clinical disease (WHO clinical stage 3 or 4) and adults with CD4 count ≤350 cells/mm 3

World Health Organization | Viet Nam Country Office5 Viet Nam: Findings from Modelling Studies Three modelling studies on potential impact of early ART in Viet Nam:  VAAC, WHO, CDC, Can Tho data (JAIDS, (5): e142-9)  UNSW, PrevTool (Lancet Global Health, : e23-34)  VAAC, Asian Epidemic Model (VAAC) Early diagnosis and immediate ART → significant reduction in HIV transmission and AIDS deaths  Highly effective and cost-efficient if high coverage achieved in key populations  Initial investment needed, but will leads to high returns New HIV infection Asian Epidemic Model Baseline 80% CD4<350 + immediate ART for key populations

World Health Organization | Viet Nam Country Office6 Implication for Programme Need for Higher Coverage at Cascade Steps Sources: Estimation by Asian Epidemic Model (PLHIV); Case reporting system (Diagnosed); Routine reporting system Decision 28 (Enrolled in OPC, On ART); Estimated from the results of acquired HIV drug resistance survey (viral suppression) Viral suppression needed for full benefits of ART Diagnosis EnrolmentART Viral suppression Viet Nam HIV Care Cascade 2014

World Health Organization | Viet Nam Country Office7 Viet Nam: Care Cascade in Key Populations Cascade among PWID using Viet Nam IBBS 2013 data Earlier diagnosis and improved cascade in key populations critical to achieve benefits of early ART Large gap

World Health Organization | Viet Nam Country Office8 Translating Evidence into Programme - Operational Questions - Feasibility and acceptability in Viet Nam programme  Earlier diagnosis and immediate ART  Especially among key populations Adherence, retention and viral suppression  Among those starting ART with higher CD4 count Possible behavioral disinhibition (risk compensation) after ART initiation ARV toxicity especially among people with high CD4 count Hence, an implementation research study to inform implementation of early ART in Vietnam

World Health Organization | Viet Nam Country Office9 Implementation Research Viet Nam HIV Testing and Early ART (V-HEART) By VAAC, HMU, NIHE, WHO Objective  To assess the operational feasibility and acceptability of periodic voluntary HIV testing among PWID, and immediate ART irrespective of CD4 count among HIV+ PWID in Viet Nam’s programme. Outcome indicators (selected)  Viral suppression at 6 and 12 months after ART start  Retention across the care cascade  Self-reported risk behaviours  Qualitative analysis of feasibility and acceptability (not shown in this presentation) Study ongoing: Interim results shown in this presentation

World Health Organization | Viet Nam Country Office10 Methods Study setting and interventions Since April 2014, in Thai Nguyen and Thanh Hoa provinces: –HIV testing every 6 month recommended to PWID, and –Immediate ART (irrespective of CD4 count) offered to PWID diagnosed HIV+ –Counselling promoting concomitant use of other prevention methods –Following consent after informed on benefits and risks of immediate ART Participants PWID defined as an individual: –who self-reported injecting drugs within 30 days; or –who self-reported ever injecting drugs and had a visible injection site; or –on MMT Assessments & Procedures HIV viral load (VL) assessed before ART start (baseline), at months 6 and 12 Behaviours assessed at baseline, at months 3, 6, and 12.

World Health Organization | Viet Nam Country Office11 Participant Baseline Characteristics Interim analysis based on 251 individuals who started ART by December 2014 CD4 ≤ 350CD4 > 350Overall N = 163N = 88N = 251 Sex % Male 98.2%98.9%98.4% Age (Years) Median (IQR) 34 (30-39)36 (30-39)34 (30-39) Education % Secondary school and above 80.4%86.4%82.5% CD4 baseline Median (IQR) 97 (31-204)478 ( )208 (55-402) Viral load baseline (copies/ml) Median (IQR) 112,201 (43,651 – 257,039) 16,595 (5,754 – 47,863) 63,095 (15, ,824)

World Health Organization | Viet Nam Country Office12 Retention on ART (by baseline CD4 count) Retention high in the first 6 month of ART, especially those starting ART at CD4>350 Baseline CD4 count

World Health Organization | Viet Nam Country Office13 Viral suppression at Month 6 At month 6, >85% achieved viral suppression (<1000 copies/ml) irrespective of CD4 count N (CD4 ≤ 350) N (CD4 > 350)8872

World Health Organization | Viet Nam Country Office14 Self-reported Risk Behaviors No increase in risk behaviours observed in the first 6 months % Clean needle use in the last injection among those reporting injection drug use in the past 1 month % Consistent condom use in the past 3 months among those reporting ongoing sex partners

World Health Organization | Viet Nam Country Office15 Summary Strong evidence supporting benefits of early ART  Prevents morbidity, mortality and transmission  WHO recommends ART initiation at any CD4 cell count Programmatic Implications of early ART  Earlier diagnosis and improved cascade in key populations critical  Cost-effective, and investment likely leads to high return Implementation research interim analysis  In early phase of ART, high retention and viral suppression achieved among PWID starting ART at the higher CD4 count  Comprehensive analysis to inform programming of early ART

World Health Organization | Viet Nam Country Office16 Acknowledgement Viet Nam Authority for HIV/AIDS Control Nguyen Hoang Long Bui Duc Duong Nguyen Huu Hai Do Thi Nhan Hanoi Medical University Le Minh Giang Dinh Thi Thanh Thuy Nguyễn Minh Sang Truong Van Hai National Institute of Hygien and Epidemiology Pham Hong Thang Nguyen Le Hai Tran Hong Tram Thai Nguyen Provincial AIDS Center Le Ai Kim Anh Ho Thi Quynh Trang Thanh Hoa Provincial AIDS Center Nguyen Ba Can Vu Dinh Nam WHO Viet Nam Masaya Kato Nguyen Thi Thuy Van Vu Quoc Dat Amitabh Suthar WHO WPRO Ying-Ru Lo VAAC, MOH V-HEART study participants Health care workers at study sites Community collaborators, peer educators Donors: –MAC AIDS Foundation, –Global Fund –United Nations in Viet Nam Nathan Ford, Naoko Ishikawa V-HEART investigators