Download - 20th International AIDS Conference 2014
Feasibility and acceptability of an antiretroviral treatment
as prevention (TasP) intervention in rural South
AfricaResults from the ANRS 12249
TasP cluster-randomised trial
C. Iwuji, J. Orne-Gliemann, F. Tanser, R. Thiébaut, J. Larmarange, N. Okesola, ML. Newell, F. Dabis for the
ANRS 12249 TasP study
20th International AIDS Conference 2014
Background and objectives
Plasma HIV viral load: primary determinant of the risk of HIV transmission (Quinn NEJM 2000)
Good evidence that ART reduces sexual transmission of HIV (Cohen NEJM 2011, Tanser Science 2013)
What is the effectiveness of using ART as prevention (TasP) at the population level in an HIV hyper-endemic community in rural KwaZulu-Natal?
ART as prevention
Objectives of the ANRS TasP trial
Phase 1: March 2012-June 2014 To estimate the feasibility and acceptability of the TasP
intervention at community and health facility levels To validate and update the parameters of the model
used to estimate the impact of the intervention and sample size: uptake of HIV testing, HIV prevalence, linkage to care
upon HIV diagnosis, ART uptake and internal migration
Overall: March 2012-June 2016 To evaluate the effect of ART initiated immediately
after HIV diagnosis, irrespective of CD4 count criteria, on HIV incidence in the general population in the same setting Phase 1
20142012 2016
Phase 2
Design and methods(Registration number in http://clinicaltrials.gov/: NCT01509508)
Study design Cluster randomized trial protocol: (Iwuji C et al. Trials
2013)
Sample size calculations and assumptions 1,000 eligible participants/cluster; 22,000
participants in the 22 clusters implemented in full trial
80% power to show a 34% reduction in cumulative incidence
Home-based HIV-testingControl
Treat all HIV+ individuals according to South African guidelines
(<=350 CD4,WHO stage 3 or 4)
Intervention
Treat all HIV+ individuals regardless of CD4 count
and clinical stage
TasP trial area
Sub-district : HlabisaRegion : KwaZulu-Natal 1 430 Km2
228,000 Zulu speaking people HIV prevalence is 24%
10 clusters (4 then 6) in phase 1
An additional 12 clusters in phase 2
Trial procedures
Homestead identification
(GPS)
Trial procedures
Homestead identification
(GPS)
Homestead visit 1. Head of
household verbal consent
2. Registration of individualsInclusion criteria
• Resident member of a household
• 16 years or older• Able to give informed
consentExclusion criteria• Untreated psychiatric
disorder• Neurological impairment
Trial procedures
Homestead identification
(GPS)
Homestead procedures 1. Household assets
questionnaire2. Individual
questionnaire3. DBS sample, rapid HIV
testing4. TasP card
Homestead visit 1. Head of
household verbal consent
2. Registration of individuals
Trial procedures
Homestead identification
(GPS)
Homestead procedures 1. Household assets
questionnaire2. Individual questionnaire3. DBS sample, rapid HIV
testing4. TasP card
Homestead visit 1. Head of
household verbal consent
2. Registration of individuals
Referral to TasP clinics
Repeat HIV test 6 mths later
HIV +
HIV -TasP clinic
- One per cluster (45mn walk max)- HIV treatment and care- Study questionnaires
Results
Trial enrolment flowchart as of 22nd of May 2014
Trial enrolment flowchart as of 22nd of May 2014
95% of contacted individuals completed study questionnaire
Trial enrolment flowchart as of 22nd of May 2014
Trial enrolment flowchart as of 22nd of May 2014
Trial enrolment flowchart as of 22nd of May 2014
Trial enrolment flowchart as of 22nd of May 2014
Repeat HIV ascertainment
Ascertainment = rapid test performed (with a valid result)or if individual reported to the fieldworkers already knowing being HIV+
ART coverage at referral
(among all HIV+ referred)
ART coverage at referral: 39.7% (1,021 / 2,570)[95% CI: 37.4% - 42.1%]
Control clusters: 40.8% (583 / 1,430) [37.6 - 44.0]
Intervention clusters: 38.4% (438 / 1,140) [36.5 - 40.4]
ART initiation (among those not on ART at
referral, denominator includes those not in care)
ART initiation after referral: 33.9% (525 / 1,549)
ART initiation after referral (individuals observed at least one year): 48.0% (300 / 625) Control clusters: 38.9% (107 / 275) Intervention clusters: 55.1% (193 / 350)
ART initiation (among those not on ART at referral who are linked to
TasP clinics)
ART initiation after referral: 64.2% (386 / 601) Control clusters: 45.2% (142 / 314) Intervention clusters: 85.0% (244 / 287)
For those with CD4 > 350 cells/mm3: 80.1% (129 / 161)
Model parameters versus observed estimatesProtocol v2.0 Observation phase 1 (2012-14)
ParameterAssumption
s Indicator Values (%)
[95% CI]ART reduction in infectiousness
90% - -
Proportion with partners in opposite arm
10% - Not yet available
Protocol v2.0 Observation phase 1 (2012-14)
ParameterAssumption
s Indicator Values (%)
[95% CI]ART reduction in infectiousness
90% - -
Proportion with partners in opposite arm
10% - Not yet available
HIV test offer among those registered
90% Contact rate per calendar round (/CR)
67% [63-71]
Test acceptance among those offered
80% HIV ascertainment rate/CR
77% [74-80]
Model parameters versus observed estimates
Protocol v2.0 Observation phase 1 (2012-14)
ParameterAssumption
s Indicator Values (%)
[95% CI]ART reduction in infectiousness
90% - -
Proportion with partners in opposite arm
10% - Not yet available
HIV test offer among those registered
90% Contact rate per calendar round (/CR)
67% [63-71]
Test acceptance among those offered
80% HIV ascertainment rate/CR
77% [74-80]
Linkage to care upon diagnosis among those accepting the test
70% Entry into care within 6 months among individuals not in care
48%[44-52]
Proportion of all HIV+ on ART in end 2011
39% ART coverage at the beginning of the trial
39% [36-42]
Model parameters versus observed estimates
Protocol v2.0 Observation phase 1 (2012-14)
ParameterAssumption
s Indicator Values (%)
[95% CI]ART reduction in infectiousness
90% - -
Proportion with partners in opposite arm
10% - Not yet available
HIV test offer among those registered
90% Contact rate per calendar round (/CR)
67% [63-71]
Test acceptance among those offered
80% HIV ascertainment rate/CR
77% [74-80]
Linkage to care upon diagnosis among those accepting the test
70% Entry into care within 6 months among individuals not in care
48%[44-52]
Proportion of all HIV+ on ART in end 2011
39% ART coverage at the beginning of the trial
39% [36-42]
HIV prevalence in end-2011 (15 years +)
24% HIV prevalence (first DBS)
30%[29-31]
HIV incidence in end 2011 (15 years +)
2.4 / 100 PY Observed HIV incidence
2.35 / 100 PY[1.40-3.31]
Model parameters versus observed estimates
Conclusions High community acceptance of the trial with 95%
of contacted individuals participating High initial and repeat HIV ascertainment rates High initial ART coverage Linkage to care amongst newly diagnosed HIV +
takes time High ART uptake rates amongst those linked to
TasP clinics Interventions to improve linkage to care being
scaled-up Phase 2 started June 2014
Acknowledgements Trial participants Africa Centre staff Traditional Authority Department of Health, South Africa Merck/Gilead
ANRS 12249 Study Group: Till Bärnighausen, Sylvie Boyer, Alexandra Calmy, François Dabis (co-PI), Rosemary Dray-Spira, Ken Freedberg, John Imrie, Collins Iwuji (Coordinator South), Sophie Karcher, Joseph Larmarange, France Lert, Richard Lessells, Kevi Naidu, Colin Newell, Marie-Louise Newell (co-PI), Nonhlanhla Okesola, Tulio de Oliveira, Joanna Orne-Gliemann (Coordinator North), Deenan Pillay (co-PI), Bruno Spire, Frank Tanser, Rodolphe Thiébaut, Johannes Viljoen