1. INA-RESPOND Test and Treat Study
Dr. M. Karyana, MPH
Pusat Teknologi Terapan Kesehatan dan Epidemiologi Klinik,
Badan Litbang Kesehatan – Kementerian Kesehatan RI
Jakarta, 28 October 2014

2. Global AIDS response – first 25 years
First cases of unusual immune deficiency are identified among gay men in the USA June 1981
First regimen to reduce MTCT of HIV
Global Fund to fight AIDS, TB and Malaria
Acquired Immune Deficiency Syndrome (AIDS) defined
WHO and UNAIDS launch the "3 x 5" initiative
Millions
HAART launched 50 45 40 35 30 25 20 15 10 5
A heterosexual AIDS epidemic is revealed in Africa
Brazil becomes the first developing country to provide ART
HIV identified as cause of AIDS May 1983
The first HIV antibody test becomes available
Global Network of People living with HIV/AIDS (GNP+)
The WHO launches the Global Programme on AIDS
President Bush announces PEPFAR
The first therapy for AIDS - zidovudine/ AZT - is approved for use in the USA
The UN General Assembly Special Session on HIV/AIDS
UNAIDS created
2010 International AIDS Conference in Durban
People living with HIV
1980
‘81
‘82
‘83
‘84
‘85
‘86
‘87
‘88
‘89
‘90
‘91
‘92
‘93
‘94
‘95
‘96
‘97
‘98
‘99
‘00
‘01
‘02
‘03
‘04
‘05
The chronology above summarizes the ‘BIG Picture’ of AIDS – from the UNAIDS website
Source: UNAIDS 2008 2

3. Source: UNAIDS Global Report 2014
Global number of people living with HIV & HIV-related deaths: Changes post-2005
Source: UNAIDS Global Report 2014

4. Top 20 countries: People living with HIV
Zambia
South Africa
Nigeria
India
Kenya
Mozambique
14.7 million = 42%
Uganda
Tanzania
Zimbabwe
USA
Zambia
21.5 million = 61%
Malawi
China
Ethiopia
Russia
Brazil
25.6 million = 73%
Indonesia
Cameroon
D.R.Congo
Thailand
Cote d’Ivoire
28 million = 80%
Source: UNAIDS Global Report 2014

5. ARV prophylaxis HIV PREVENTION Male circumcision Treatment of STIs
Auvert B, PloS Med 2005
Gray R, Lancet 2007
Bailey R, Lancet 2007
Treatment of STIs
Grosskurth H, Lancet 2000
Microbicides
for women
Abdool Karim Q, Science 2010
Female Condoms
Male Condoms
HIV
PREVENTION
Grant R, NEJM 2010 (MSM)
Baeten J , NEJM 2012 (Couples)
Paxton L, NEJM 2012 (Heterosexuals)
Choopanya K, Lancet 2013 (IDU)
Oral pre-exposure prophylaxis
HIV Counselling and Testing
Coates T, Lancet 2000
Sweat M, Lancet 2011
Post Exposure
prophylaxis (PEP)
Scheckter M, 2002
Treatment for prevention
Cohen M, NEJM, 2011
Donnell D, Lancet 2010
Tanser, Science 2013
Behavioural Intervention
Note: PMTCT, Screening transfusions, Harm reduction, Universal precautions, etc. have not been included – this is on sexual transmission

6. Clinical trial evidence for preventing HIV transmission – July 2013
Effect size
(95%CI)
Prevention
in IDUs
Bangkok Tenofovir Study - Daily oral PrEP for IDUs
49% (10; 72)
HPTN ART for prevention
96% (73; 99)
PartnersPrEP - Daily PrEP for discordant couples
73% (49; 85)
TDF2 - Daily PrEP for heterosexual men and women
62% (22; 84)
Medical male circumcision
54% (38; 66)
Sexual transmission prevention
iPrEX - Daily PrEP for MSM
44% (15; 63)
Mwanza - STD treatment
42% (21; 58)
CAPRISA Coital microbicide for women
39% (6; 60)
RV144 - HIV vaccine
31% (1; 51)
MTN Daily microbicide for women
15% (-21; 40)
FEM-PrEP - Daily oral PrEP for women
6% (-52; 41)
-60
-20 20 40 60 80
100
Effectiveness (%)
Source: adapted from Abdool Karim SS. Lancet 2013

7. Audience with the Minister of Health

8. Study Title
Indonesia Prevention of HIV and AIDS Transmission by Increasing Testing and Prompt Treatment

9. Research Question
“Does a strategy of combination HIV prevention including universal HIV testing and treatment reduce HIV transmission (incidence) at community level?”

10. Hypothesis
Universal voluntary HIV testing with appropriate combination prevention offered to all those testing HIV negative - in addition to immediate ART for all those testing HIV positive - will have a substantial impact on HIV incidence at population level

11. Lancet : 48-57

12. Why is a Study Needed?
Not known whether a UTT intervention can be delivered with high acceptability
Many uncertainties in model parameters
Population-level impact of intervention package is not known
A rigorously designed study can measure the costs and benefits of this strategy and provide reliable evidence on cost-effectiveness for health policy makers

13. Design Issues What should the combination prevention package contain?
HCT- universal uptake
Linkage to care and provision of ART
Sexual risk reduction
PMTCT
STI TB
What scenarios would be useful to policy makers?
Universal test and treat Vs current
Costs of each
Delivery under routine programmatic conditions as far as possible

14. Study Design

15. Study Coverage

16. Measuring HIV Incidence
HIV incidence will be estimated by assessing HIV seroconversion in a longitudinal cohort
Advantages
Gold standard approach for HIV incidence estimation
Uses routine HIV test methods
Provides interim and cumulative incidence estimates
Cohort allows for measurement of other indicators
Disadvantages
Requires longitudinal cohort follow-up
Impacted by loss-to-follow up, including differential loss to follow-up
Complex sampling is needed to ensure that the cohort reflects the population as a whole

17. Intervention Package Health centre
Universal testing: annual door-to-door HCT
Follow-up
on referral
Support for:
Retention in care
Adherence
to treatment
CHiPs: Community HIV-care Providers
PMTCT: Prevention of Mother to Child Transmission
TB: Tuberculosis
STI: Sexually Transmitted Infections
Service promotion and referral for
- HIV care for HIV +ve
including PMTCT
- TB
- STI
Universal treatment for
HIV +ve
irrespective of CD4 count
Facilitated
by CHiPs

18. What is the influence of process parameters?
efficacy of ART in
blocking transmission
treatment
drop-out/failure
Relative reduction in 3-year HIV incidence in arms A and B
Linear model
uptake of testing,
ART
Effect of counselling
on infectivity
% sex acts with partners
from other communities
Delays in linkage to care

19. Conclusions
This study will use a cohort measure of HIV incidence to assess the effectiveness of a package of combination HIV prevention including a “universal test and treat” approach
Adoption of new consolidated WHO guidelines should only moderately affect ability to detect differences between arms in the study
Primary outcome mostly depends on
Community-level changes in behaviours
Efficacy of ART in blocking transmission (adherence)
Uptake of HIV testing and treatment

20. Acknowledgement Supported by:
The National Institute of Allergy and Infectious Diseases (NIAID), the U.S. National Institutes of Health (NIH)
National Institutes of Health Research and Development (NIHRD), the Indonesia Ministry of Health

21. THANK YOU
TERIMA KASIH
MATUR SUKSMA
MATUR SUWUN
HATUR NUHUN