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
24-25 November 2015, Hanoi, Viet Nam
World Health Organization | Viet Nam Country Office
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Early ART – Evidence of Therapeutic Benefits
- Two large randomized controlled trials Sample size
TEMPERANO
START
2056
4651
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 HIVrelated illness
• Composite end point:
Serious AIDS & nonAIDS events, deaths,
TB, etc
Hazard ratio of primary
outcomes
World Health Organization | Viet Nam Country Office
0.56 (0.41-0.76)
0.43 (0.30-0.62)
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Early ART – Evidence of Preventive Benefits
- HPTN052 – RCT among serodiscordant partners Linked transmission
50
40
30
43
93%
reduction
•
•
•
20
10
3
0
Delayed ART Early ART
•
Early ART (CD4 350-550) 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
N = 1761
3
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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/mm3
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Viet Nam: Findings from Modelling Studies
New HIV infection 2013-30
Asian Epidemic Model
•
Baseline
80% CD4<350
80% CD4<350
+ immediate ART for key populations
Three modelling studies on potential
impact of early ART in Viet Nam:
 VAAC, WHO, CDC, Can Tho data (JAIDS,
2013. 63(5): e142-9)
 UNSW, PrevTool (Lancet Global Health,
2014. 2: 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
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Implication for Programme
Need for Higher Coverage at Cascade Steps
Diagnosis
Enrolment
Viral
suppression
ART
Viet Nam HIV Care Cascade 2014
Number of PLHIV
300,000
250,000
250,060
100%
Viral suppression
needed for full
benefits of ART
171,000
68%
200,000
150,000
100,000
94,693
38%
93,298
37%
86,674
35%
Enrolled in
OPC
On ART
Virally
suppressed
50,000
0
PLHIV
Diagnosed
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)
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Viet Nam: Care Cascade in Key Populations
Cascade among PWID using Viet Nam IBBS 2013 data
Number of PWID
1000
800
Large gap
600
400
200
0
HIV+
Diagnosed
Enrolled in
care
ART started
Still on ART
Earlier diagnosis and improved cascade in key populations
critical to achieve benefits of early ART
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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
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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
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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.
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Participant Baseline Characteristics
Interim analysis based on 251 individuals who started ART by December
2014
CD4 ≤ 350
CD4 > 350
Overall
N = 163
N = 88
N = 251
98.2%
98.9%
98.4%
34 (30-39)
36 (30-39)
34 (30-39)
80.4%
86.4%
82.5%
97 (31-204)
478 (402-632)
208 (55-402)
112,201
(43,651 – 257,039)
16,595
(5,754 – 47,863)
63,095
(15,848-169,824)
Sex
% Male
Age (Years)
Median (IQR)
Education
% Secondary school and above
CD4 baseline
Median (IQR)
Viral load baseline
(copies/ml)
Median (IQR)
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Retention on ART (by baseline CD4 count)
Baseline CD4 count
Retention high in the first 6 month of ART, especially those starting
ART at CD4>350
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Viral suppression at Month 6
%VL< 1000 copies/ml
100%
80%
89%
CD4 ≤ 350
CD4 > 350
86%
60%
40%
20%
0%
14%
4%
Month 0 (ART start)
Month 6
N (CD4 ≤ 350)
168
120
N (CD4 > 350)
88
72
At month 6, >85% achieved viral suppression (<1000 copies/ml)
irrespective of CD4 count
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Self-reported Risk Behaviors
% 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
100%
% Consistent condom use
% Clean needle use
90%
80%
70%
60%
50%
40%
30%
20%
10%
0%
Month 0
Month 3
Month 6
100%
90%
80%
70%
60%
50%
40%
30%
20%
10%
0%
Month 0
Month 3
Month 6
No increase in risk behaviours observed in the first 6 months
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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
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Acknowledgement
•
•
V-HEART study participants
•
Health care workers at study
sites
•
•
Community collaborators, peer
educators
Donors:
–
–
–
•
V-HEART investigators
VAAC, MOH
MAC AIDS Foundation,
Global Fund
United Nations in Viet Nam
Nathan Ford, Naoko Ishikawa
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
World Health Organization | Viet Nam Country Office
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
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