# Treatment as Prevention (TasP) studies: the challenge of CD4 count treatment eligibility changes in Africa. Perspectives from the TasP ANRS 12249 trial

Joseph Larmarange

► To cite this version:

Joseph Larmarange. Treatment as Prevention (TasP) studies: the challenge of CD4 count treatment eligibility changes in Africa. Perspectives from the TasP ANRS 12249 trial. 9th INTEREST Workshop, May 2015, Harare, Zimbabwe. ird-04112528

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Submitted on 31 May 2023

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Distributed under a Creative Commons Attribution 4.0 International License
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TasP

Antiretroviral Treatment as Prevention • ANRS 12249
Ukuphila kwami, ukuphila kwethu (my health for our health)

<figure><img src="image_3.png" /></figure>

AFRICA CENTRE
FOR HEALTH AND POPULATION STUDIES

Bordeaux school of public health
ISPED
Institut de Santé Publique d'Épidémiologie et de Développement

# Treatment as Prevention (TasP) studies: the challenge of CD4 count treatment eligibility changes in Africa. Perspectives from the TasP ANRS 12249 trial

Joseph LARMARANGE

Ceped (UMR 196 - Paris Descartes - IRD), IRD, France
hosted by Africa Centre, UKZN, South Africa

anRS
France
REcherche
Nord & sud
Santé
Hépatites

INTEREST Workshop – Harare – 7th May 2015
Main hypothesis (formulated in 2010)

HIV testing of all adult members of a community,
followed by immediate ART initiation
of all, or nearly all, HIV-infected participants
regardless of immunological or clinical staging
i.e. **Universal Test and Treat**

will prevent onward transmission
and **reduce HIV incidence** in this population
<figure><img src="image_4.png" /></figure>

# TasP trial area

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Sub-district : Hlabisa

Region : KwaZulu-Natal

- Zulu speaking people

- HIV prevalence is ~30%

- Unemployment is ~80%

- 3 DoH clinics located in the trial area

<figure><img src="image_6.png" /></figure>

4 clusters opened in 2012

6 clusters opened in 2013

12 clusters opened in 2014
<figure><img src="image_7.png" /></figure>

# TasP trial design

* TasP is a cluster randomized trial.

* Each cluster has a population of approx. 1250 adults (16+ years).

* The **TasP intervention** has 2 components:

"universal" repeat testing (all clusters) + early treatment (intervention cluster)

* In each cluster, rounds of **home-based HIV testing** repeated every ~ 6 months

* All HIV+ identified participants are referred to local TasP clinics (at least one clinic per cluster)

<table><thead><tr><td>Control clusters</td><td>Intervention clusters</td></tr></thead><tbody><tr><td>ARV treatment according to national guidelines (&lt;350 CD4 or WHO stage 3 or 4) (since Jan. 2015, &lt;500 CD4)</td><td>ARV treatment regardless of CD4 or clinical staging</td></tr></tbody></table>
<figure><img src="image_8.png" /></figure>

# Current package of interventions

## From March 2012

* Home-based HIV testing

* Clinic-based HIV testing for individuals not wanted to test at home

* Clinic-based ART

* ART counselling

## In June 2013, added:

* Phone call / Home visit if not linked to TasP clinics within 3 months

* Phone call by nurse in case of a missed appointment in TasP clinic

* A 'tracking team' for patients not reached by the nurse or requiring additional support
<figure><img src="image_9.png" /></figure>

Model parameters versus observed estimates

<table><thead><tr><th colspan="2">Protocol v2.0</th><th colspan="2">Observation phase 1 (2012-14)</th></tr><tr><th>Parameter</th><th>Assumptions</th><th>Indicator</th><th>Values (%) [95% CI]</th></tr></thead><tbody><tr><td>HIV test offer among those registered</td><td>90%</td><td>Contact rate per calendar round (/CR)</td><td>67% [63-71]</td></tr><tr><td>Test acceptance among those offered</td><td>80%</td><td>HIV ascertainment rate/CR</td><td>77% [74-80]</td></tr><tr><td>Linkage to care upon diagnosis among those accepting the test</td><td>70%</td><td>Entry into care within 6 months among individuals not in care</td><td>48% [44-52]</td></tr><tr><td>Proportion of all HIV+ on ART in end 2011</td><td>39%</td><td>ART coverage at the beginning of the trial</td><td>39% [36-42]</td></tr><tr><td>HIV prevalence in end-2011 (15 years +)</td><td>24%</td><td>HIV prevalence (first DBS)</td><td>30% [29-31]</td></tr><tr><td>HIV incidence in end 2011 (15 years +)</td><td>2.4 / 100 PY</td><td>Observed HIV incidence</td><td>2.35 / 100 PY [1.40-3.31]</td></tr></tbody></table>
Estimated Cascade of HIV care at the end of phase 1

<figure><img src="image_10.png" /></figure>

Preliminary
results

- As of
  31st May 2014

- 10 clusters

- Taking into account
  both TasP and DoH
  clinics

- Including
  non-observed HIV+
  living in the area
# The 90-90-90 target

## TasP trial area (end of phase 1)

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<figure><img src="image_12.png" /></figure>

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38.1%
(27.5%
without TasP)

## UNAIDS' target

<figure><img src="image_14.png" /></figure>

<figure><img src="image_15.png" /></figure>

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72.9%

diagnosed

on treatment

virally suppressed

Overall
# Implementation the 500 CD4 guideline

* Started in January 2015 (as in DoH clinics)

* Affects mainly the clusters opened in 2014

* Conditional power estimates done in November 2014 testing several scenarios (taking into account the new guideline):

* power to detect an impact on incidence range from 40 to 95% (depends mainly on the baseline incidence in the 12 clusters opened in 2014)

* DSMB concluded that there is no reason to stop this study for futility at this point

* Recommendation of implementing new interventions to improve the cascade of HIV care and treatment

* May 2015:

* Interim analysis among the ten first clusters

* DSMB will look at it next week
<figure><img src="image_17.png" /></figure>

Ongoing discussion

■ Implementation of a new interventions package?

- Community level: improving community engagement and mobilization package

- HIV testing: combination of repeat home-based testing, mobile testing and clinic testing

- Linkage to care: SMS reminders, counselling and motivational support (phone calls, face-to-face visits), escort to clinics, health navigators, clinical assessment at home, option between home-based or clinic-based ART initiation

- Retention in care: SMS reminders, phone calls and home visits in case of missed appointment, simplified ART care for stable patients, additional health services in clinics
Ongoing discussion

■ How to implement this new interventions package?

- Contingent upon May 12 DSMB conclusions

□ Starting during the 2nd semester of 2015?

- Extending follow-up until mid-2018?
<figure><img src="image_18.png" /></figure>

Conclusions

■ Real world is complex

■ Impact of interventions on the cascade, and therefore on HIV incidence takes time

■ Can we reach 90-90-90 at population level in real world?

■ Which services/tools to propose in a comprehensive HIV interventions package?

■ What would be the impact on HIV incidence?

■ At what cost?
<figure><img src="image_19.png" /></figure>

Primary objective remains

to demonstate that
a UTT approach
reduces HIV incidence
at population level

Target date to close the trial:
June 2016
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# Acknowledgements

* Trial participants

* Africa Centre staff

* Traditional Authority

* Department of Health, South Africa

* Merck/Gilead

wellcome trust

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UNIVERSITY OF
KWAZULU-NATAL

anRS

France
REcherche
Nord & suc
Sida-hiv
Hépatites

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giz

3
ie

**ANRS 12249 Study Group:** François Dabis (co-PI), Marie-Louise Newell (co-PI), Deenan Pillay (co-PI), Collins Iwuji (South coordinator), Joanna Orne-Gliemann (North coordinator), Till Bärnighausen, Eric Balestre, Sylvie Boyer, Alexandra Calmy, Vincent Calvez, Marie-Laure Chaix, Rosemary Dray-Spira, Kamal El Farouki, Kenneth Freedberg, Kobus Herbst, John Imrie, Sophie Karcher, Joseph Larmarange, France Lert, Richard Lessells, Thembisa Makowa, Anne-Geneviève Marcelin, Laura March, Nuala McGrath, Kevi Naidu, Colin Newell, Nonhlanhla Okesola, Tulio de Oliveira, Melanie Plazy, Tamsen Rochat, Bruno Spire, Frank Tanser, Rodolphe Thiébaut, Johannes Viljoen, Thembelile Zuma.

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Inserm

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University
of Southampton

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# Registered Individuals (as of 4th May 2014)
## PRELIMINARY RESULTS

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