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