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Universal Test and Treat and the HIV epidemic in rural South Africa: a phase 4, open-label, community cluster randomised trial

Universal Test and Treat and the HIV epidemic in rural South Africa: a phase 4, open-label, community cluster randomised trial
Universal Test and Treat and the HIV epidemic in rural South Africa: a phase 4, open-label, community cluster randomised trial

Background

Universal antiretroviral therapy (ART), as per the 2015 WHO recommendations, might reduce population HIV incidence. We investigated the effect of universal test and treat on HIV acquisition at population level in a high prevalence rural region of South Africa.

Methods

We did a phase 4, open-label, cluster randomised trial of 22 communities in rural KwaZulu-Natal, South Africa. We included individuals residing in the communities who were aged 16 years or older. The clusters were composed of aggregated local areas (neighbourhoods) that had been identified in a previous study in the Hlabisa subdistrict. The study statisticians randomly assigned clusters (1:1) with MapInfo Pro (version 11.0) to either the control or intervention communities, stratified on the basis of antenatal HIV prevalence. We offered residents repeated rapid HIV testing during home-based visits every 6 months for about 4 years in four clusters, 3 years in six clusters, and 2 years in 12 clusters (58 cluster-years) and referred HIV-positive participants to trial clinics for ART (fixed-dose combination of tenofovir, emtricitabine, and efavirenz) regardless of CD4 cell count (intervention) or according to national guidelines (initially ≤350 cells per μL and <500 cells per μL from January, 2015; control). Participants and investigators were not masked to treatment allocation. We used dried blood spots once every 6 months provided by participants who were HIV negative at baseline to estimate the primary outcome of HIV incidence with cluster-adjusted Poisson generalised estimated equations in the intention-to-treat population after 58 cluster-years of follow-up. This study is registered with ClinicalTrials.gov, number NCT01509508, and the South African National Clinical Trials Register, number DOH-27-0512-3974.

Findings

Between March 9, 2012, and June 30, 2016, we contacted 26 518 (93%) of 28 419 eligible individuals. Of 17 808 (67%) individuals with a first negative dried blood spot test, 14 223 (80%) had subsequent dried blood spot tests, of whom 503 seroconverted after follow-up of 22 891 person-years. Estimated HIV incidence was 2·11 per 100 person-years (95% CI 1·84–2·39) in the intervention group and 2·27 per 100 person-years (2·00–2·54) in the control group (adjusted hazard ratio 1·01, 95% CI 0·87–1·17; p=0·89). We documented one case of suicidal attempt in a woman following HIV seroconversion. 128 patients on ART had 189 life-threatening or grade 4 clinical events: 69 (4%) of 1652 in the control group and 59 (4%) of 1367 in the intervention group (p=0·83).

Interpretation

The absence of a lowering of HIV incidence in universal test and treat clusters most likely resulted from poor linkage to care. Policy change to HIV universal test and treat without innovation to improve health access is unlikely to reduce HIV incidence.

Funding

ANRS, GiZ, and 3ie.

2352-3018
116-125
Iwuji, Collins C
9172710f-6d53-4fc4-8948-2db34293c7ed
Orne-Gliemann, Joanna
2124c323-6911-49d3-9e50-bddb35f521f8
Larmarange, Joseph
8dc0592c-788f-4521-a3cb-4ff6c6aa06a3
Balestre, Eric
bd61dc3d-50e0-4457-8054-ae6229124d1e
Thiebaut, Rodolphe
3c607631-820e-4b01-b61b-74300e1a5ddd
Tanser, Frank
a7112c48-809b-4f7c-8662-eaef445891f4
Okesola, Nonhlanhla
0a55eb44-591c-4c9f-85a1-bd9268d845fc
Makowa, Thembisa
2609e3c2-face-480d-8856-934df629e7d5
Dreyer, Jaco
66cdb4a4-0837-4f68-bcc0-c903f1e10b9b
Herbst, Kobus
fab67269-11ef-4c52-91bc-635b00065504
Mcgrath, Nuala
b75c0232-24ec-443f-93a9-69e9e12dc961
Bärnighausen, Till
337d5ec4-e26e-40de-aa26-42e5c5c9b61e
Boyer, Sylvie
ac92cdf4-6029-44dd-8a57-11fea71b7077
de Oliveira, Tulio
0ec048ce-e4c0-4cf4-b837-16d9f711ae91
Rekacewicz, Claire
012e5486-851f-4441-92cf-495386a635e5
Bazin, Brigette
ff78a957-add4-47aa-af10-e612487fc16b
Newell, Maire-Louise
c6ff99dd-c23b-4fef-a846-a221fe2522b3
Pillay, Deenan
9b4da6c6-2220-4c60-aaca-f0f1a37c2ca8
Dabis, François
90f9de2e-aaba-4392-97d6-18776521b99f
ANRS 12249 TasP Study Group
Iwuji, Collins C
9172710f-6d53-4fc4-8948-2db34293c7ed
Orne-Gliemann, Joanna
2124c323-6911-49d3-9e50-bddb35f521f8
Larmarange, Joseph
8dc0592c-788f-4521-a3cb-4ff6c6aa06a3
Balestre, Eric
bd61dc3d-50e0-4457-8054-ae6229124d1e
Thiebaut, Rodolphe
3c607631-820e-4b01-b61b-74300e1a5ddd
Tanser, Frank
a7112c48-809b-4f7c-8662-eaef445891f4
Okesola, Nonhlanhla
0a55eb44-591c-4c9f-85a1-bd9268d845fc
Makowa, Thembisa
2609e3c2-face-480d-8856-934df629e7d5
Dreyer, Jaco
66cdb4a4-0837-4f68-bcc0-c903f1e10b9b
Herbst, Kobus
fab67269-11ef-4c52-91bc-635b00065504
Mcgrath, Nuala
b75c0232-24ec-443f-93a9-69e9e12dc961
Bärnighausen, Till
337d5ec4-e26e-40de-aa26-42e5c5c9b61e
Boyer, Sylvie
ac92cdf4-6029-44dd-8a57-11fea71b7077
de Oliveira, Tulio
0ec048ce-e4c0-4cf4-b837-16d9f711ae91
Rekacewicz, Claire
012e5486-851f-4441-92cf-495386a635e5
Bazin, Brigette
ff78a957-add4-47aa-af10-e612487fc16b
Newell, Maire-Louise
c6ff99dd-c23b-4fef-a846-a221fe2522b3
Pillay, Deenan
9b4da6c6-2220-4c60-aaca-f0f1a37c2ca8
Dabis, François
90f9de2e-aaba-4392-97d6-18776521b99f

Iwuji, Collins C, Orne-Gliemann, Joanna, Larmarange, Joseph, Balestre, Eric, Thiebaut, Rodolphe, Tanser, Frank, Okesola, Nonhlanhla, Makowa, Thembisa, Dreyer, Jaco, Herbst, Kobus, Mcgrath, Nuala, Bärnighausen, Till, Boyer, Sylvie, de Oliveira, Tulio, Rekacewicz, Claire, Bazin, Brigette, Newell, Maire-Louise, Pillay, Deenan and Dabis, François , ANRS 12249 TasP Study Group (2018) Universal Test and Treat and the HIV epidemic in rural South Africa: a phase 4, open-label, community cluster randomised trial. Lancet HIV, 5 (3), 116-125. (doi:10.1016/S2352-3018(17)30205-9).

Record type: Article

Abstract

Background

Universal antiretroviral therapy (ART), as per the 2015 WHO recommendations, might reduce population HIV incidence. We investigated the effect of universal test and treat on HIV acquisition at population level in a high prevalence rural region of South Africa.

Methods

We did a phase 4, open-label, cluster randomised trial of 22 communities in rural KwaZulu-Natal, South Africa. We included individuals residing in the communities who were aged 16 years or older. The clusters were composed of aggregated local areas (neighbourhoods) that had been identified in a previous study in the Hlabisa subdistrict. The study statisticians randomly assigned clusters (1:1) with MapInfo Pro (version 11.0) to either the control or intervention communities, stratified on the basis of antenatal HIV prevalence. We offered residents repeated rapid HIV testing during home-based visits every 6 months for about 4 years in four clusters, 3 years in six clusters, and 2 years in 12 clusters (58 cluster-years) and referred HIV-positive participants to trial clinics for ART (fixed-dose combination of tenofovir, emtricitabine, and efavirenz) regardless of CD4 cell count (intervention) or according to national guidelines (initially ≤350 cells per μL and <500 cells per μL from January, 2015; control). Participants and investigators were not masked to treatment allocation. We used dried blood spots once every 6 months provided by participants who were HIV negative at baseline to estimate the primary outcome of HIV incidence with cluster-adjusted Poisson generalised estimated equations in the intention-to-treat population after 58 cluster-years of follow-up. This study is registered with ClinicalTrials.gov, number NCT01509508, and the South African National Clinical Trials Register, number DOH-27-0512-3974.

Findings

Between March 9, 2012, and June 30, 2016, we contacted 26 518 (93%) of 28 419 eligible individuals. Of 17 808 (67%) individuals with a first negative dried blood spot test, 14 223 (80%) had subsequent dried blood spot tests, of whom 503 seroconverted after follow-up of 22 891 person-years. Estimated HIV incidence was 2·11 per 100 person-years (95% CI 1·84–2·39) in the intervention group and 2·27 per 100 person-years (2·00–2·54) in the control group (adjusted hazard ratio 1·01, 95% CI 0·87–1·17; p=0·89). We documented one case of suicidal attempt in a woman following HIV seroconversion. 128 patients on ART had 189 life-threatening or grade 4 clinical events: 69 (4%) of 1652 in the control group and 59 (4%) of 1367 in the intervention group (p=0·83).

Interpretation

The absence of a lowering of HIV incidence in universal test and treat clusters most likely resulted from poor linkage to care. Policy change to HIV universal test and treat without innovation to improve health access is unlikely to reduce HIV incidence.

Funding

ANRS, GiZ, and 3ie.

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More information

Accepted/In Press date: 2 November 2017
e-pub ahead of print date: 30 November 2017
Published date: March 2018

Identifiers

Local EPrints ID: 415678
URI: http://eprints.soton.ac.uk/id/eprint/415678
ISSN: 2352-3018
PURE UUID: cd674025-8520-416c-8b20-4c2a1e553daa
ORCID for Nuala Mcgrath: ORCID iD orcid.org/0000-0002-1039-0159
ORCID for Maire-Louise Newell: ORCID iD orcid.org/0000-0002-1074-7699

Catalogue record

Date deposited: 20 Nov 2017 17:30
Last modified: 15 Sep 2021 04:42

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Contributors

Author: Collins C Iwuji
Author: Joanna Orne-Gliemann
Author: Joseph Larmarange
Author: Eric Balestre
Author: Rodolphe Thiebaut
Author: Frank Tanser
Author: Nonhlanhla Okesola
Author: Thembisa Makowa
Author: Jaco Dreyer
Author: Kobus Herbst
Author: Nuala Mcgrath ORCID iD
Author: Till Bärnighausen
Author: Sylvie Boyer
Author: Tulio de Oliveira
Author: Claire Rekacewicz
Author: Brigette Bazin
Author: Deenan Pillay
Author: François Dabis
Corporate Author: ANRS 12249 TasP Study Group

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