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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
Iwuji, Collins
9172710f-6d53-4fc4-8948-2db34293c7ed
Orne-Gliemann, J.
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Larmarange, J.
a9f884ad-88f1-45f9-8dba-01dc50337598
E., Balestre
bd61dc3d-50e0-4457-8054-ae6229124d1e
Thiebaut, R.
3b6988b7-cf0e-465d-84e9-52660699a399
Tanser, F.
b4ce79a2-0bf2-4021-89ad-0e759e2e2fc8
Okesola, N.
738c55d8-6127-4951-82c1-fe2d538251f1
T., Makowa
2609e3c2-face-480d-8856-934df629e7d5
J., Dreyer
5f48d79f-b720-4e5b-80c6-4493ec6de43e
Herbst, K.
2f558167-fbfc-478f-9170-f632d1bcfa9b
Mcgrath, N.
b75c0232-24ec-443f-93a9-69e9e12dc961
Bärnighausen, T
173f79c5-c1d3-4b20-9562-59eeb2a7ebf1
Boyer, S.
c941ad47-1356-457d-af3d-e608823dbd0b
T., De Oliveira
4635e7b7-aa51-4f4e-a84e-cbb6f11c06f7
Rekacewicz, C.
012e5486-851f-4441-92cf-495386a635e5
Bazin, B.
ff78a957-add4-47aa-af10-e612487fc16b
Newell, M-L.
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Pillay, D.
f5be10ef-edf2-46b9-9c80-61d6a6ed7ce4
Dabis, F.
bc4396a5-e11c-4b6d-8d2d-11bf420db12f
Iwuji, Collins
9172710f-6d53-4fc4-8948-2db34293c7ed
Orne-Gliemann, J.
2bd7211f-7f44-48bb-9606-d717e00aca26
Larmarange, J.
a9f884ad-88f1-45f9-8dba-01dc50337598
E., Balestre
bd61dc3d-50e0-4457-8054-ae6229124d1e
Thiebaut, R.
3b6988b7-cf0e-465d-84e9-52660699a399
Tanser, F.
b4ce79a2-0bf2-4021-89ad-0e759e2e2fc8
Okesola, N.
738c55d8-6127-4951-82c1-fe2d538251f1
T., Makowa
2609e3c2-face-480d-8856-934df629e7d5
J., Dreyer
5f48d79f-b720-4e5b-80c6-4493ec6de43e
Herbst, K.
2f558167-fbfc-478f-9170-f632d1bcfa9b
Mcgrath, N.
b75c0232-24ec-443f-93a9-69e9e12dc961
Bärnighausen, T
173f79c5-c1d3-4b20-9562-59eeb2a7ebf1
Boyer, S.
c941ad47-1356-457d-af3d-e608823dbd0b
T., De Oliveira
4635e7b7-aa51-4f4e-a84e-cbb6f11c06f7
Rekacewicz, C.
012e5486-851f-4441-92cf-495386a635e5
Bazin, B.
ff78a957-add4-47aa-af10-e612487fc16b
Newell, M-L.
c6ff99dd-c23b-4fef-a846-a221fe2522b3
Pillay, D.
f5be10ef-edf2-46b9-9c80-61d6a6ed7ce4
Dabis, F.
bc4396a5-e11c-4b6d-8d2d-11bf420db12f

Iwuji, Collins, Orne-Gliemann, J., Larmarange, J., E., Balestre, Thiebaut, R., Tanser, F., Okesola, N., T., Makowa, J., Dreyer, Herbst, K., Mcgrath, N., Bärnighausen, T, Boyer, S., T., De Oliveira, Rekacewicz, C., Bazin, B., Newell, M-L., Pillay, D. and Dabis, F. (2017) Universal Test and Treat and the HIV epidemic in rural South Africa: a phase 4, open-label, community cluster randomised trial. Lancet HIV. (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: 1 December 2017

Identifiers

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

Catalogue record

Date deposited: 20 Nov 2017 17:30
Last modified: 19 Jul 2019 04:13

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