The University of Southampton
University of Southampton Institutional Repository

The impact of the 2013 WHO antiretroviral therapy guidelines on the feasibility of HIV population prevention trials

The impact of the 2013 WHO antiretroviral therapy guidelines on the feasibility of HIV population prevention trials
The impact of the 2013 WHO antiretroviral therapy guidelines on the feasibility of HIV population prevention trials
BACKGROUND: Several cluster-randomized HIV prevention trials aim to demonstrate the population-level preventive impact of antiretroviral therapy (ART). 2013 World Health Organization (WHO) guidelines raising the ART initiation threshold to CD4 <500/µL could attenuate these trials' effect size by increasing ART usage in control clusters.

METHODS: We used a computational model to simulate strategies from a hypothetical cluster-randomized HIV prevention trial. The primary model outcome was the relative reduction in 24-month HIV incidence between control (ART offered with CD4 below threshold) and intervention (ART offered to all) strategies. We assessed this incidence reduction using the revised (CD4 <500/µL) and prior (CD4 <350/µL) control ART initiation thresholds. Additionally, we evaluated changes to trial characteristics that could bolster the incidence reduction.

RESULTS: With a control ART initiation threshold of CD4 <350/µL, 24-month HIV incidence under control and intervention strategies was 2.46/100 person-years (PY) and 1.96/100 PY, a 21% reduction. Raising the threshold to CD4 <500/µL decreased the incidence reduction by more than one-third, to 12%. Using this higher threshold, moving to a 36-month horizon (vs 24-month), yearly control-strategy HIV screening (vs biannual), and intervention-strategy screening every 2 months (vs biannual), resulted in a 31% incidence reduction that was similar to effect size projections for ongoing trials. Alternate assumptions regarding cross-cluster contamination had the greatest influence on the incidence reduction.

CONCLUSIONS: Implementing the 2013 WHO HIV treatment threshold could substantially diminish the incidence reduction in HIV population prevention trials. Alternative HIV testing frequencies and trial horizons can bolster this incidence reduction, but they could be logistically and ethically challenging. The feasibility of HIV population prevention trials should be reassessed as the implementation of treatment guidelines evolves.
highly active antiretroviral therapy, HIV, prevention, randomized controlled trials
1528-4336
185-198
Ross, E.
6ad7beff-bca3-4209-8a94-6c7b2a308a57
Tanser, F.
b4ce79a2-0bf2-4021-89ad-0e759e2e2fc8
Pei, P.
d577f04c-6738-413e-b63b-e114d7e73d96
Newell, M.L.
c6ff99dd-c23b-4fef-a846-a221fe2522b3
Losina, E.
9e979600-32a8-4577-a763-c671ccf40045
Thiebaut, R.
3b6988b7-cf0e-465d-84e9-52660699a399
Weinstein, M.
052ff3c8-e587-4ef3-8348-7339ec82cd84
Freedberg, K.
216d3add-17cf-4142-a7dc-538fd8c19db1
Anglaret, X.
ec10389e-3eaa-4bec-a314-8873fbd6ae81
Scott, C.
2c763748-d634-401f-b8e6-62b5db6896b7
Dabis, F.
bc4396a5-e11c-4b6d-8d2d-11bf420db12f
Walensky, R.
27545875-6f11-4993-9b39-5074b5f34af2
Ross, E.
6ad7beff-bca3-4209-8a94-6c7b2a308a57
Tanser, F.
b4ce79a2-0bf2-4021-89ad-0e759e2e2fc8
Pei, P.
d577f04c-6738-413e-b63b-e114d7e73d96
Newell, M.L.
c6ff99dd-c23b-4fef-a846-a221fe2522b3
Losina, E.
9e979600-32a8-4577-a763-c671ccf40045
Thiebaut, R.
3b6988b7-cf0e-465d-84e9-52660699a399
Weinstein, M.
052ff3c8-e587-4ef3-8348-7339ec82cd84
Freedberg, K.
216d3add-17cf-4142-a7dc-538fd8c19db1
Anglaret, X.
ec10389e-3eaa-4bec-a314-8873fbd6ae81
Scott, C.
2c763748-d634-401f-b8e6-62b5db6896b7
Dabis, F.
bc4396a5-e11c-4b6d-8d2d-11bf420db12f
Walensky, R.
27545875-6f11-4993-9b39-5074b5f34af2

Ross, E., Tanser, F., Pei, P., Newell, M.L., Losina, E., Thiebaut, R., Weinstein, M., Freedberg, K., Anglaret, X., Scott, C., Dabis, F. and Walensky, R. (2014) The impact of the 2013 WHO antiretroviral therapy guidelines on the feasibility of HIV population prevention trials. HIV Clincial Trials, 15 (5), 185-198. (doi:10.1310/hct1505-185). (PMID:25350957)

Record type: Article

Abstract

BACKGROUND: Several cluster-randomized HIV prevention trials aim to demonstrate the population-level preventive impact of antiretroviral therapy (ART). 2013 World Health Organization (WHO) guidelines raising the ART initiation threshold to CD4 <500/µL could attenuate these trials' effect size by increasing ART usage in control clusters.

METHODS: We used a computational model to simulate strategies from a hypothetical cluster-randomized HIV prevention trial. The primary model outcome was the relative reduction in 24-month HIV incidence between control (ART offered with CD4 below threshold) and intervention (ART offered to all) strategies. We assessed this incidence reduction using the revised (CD4 <500/µL) and prior (CD4 <350/µL) control ART initiation thresholds. Additionally, we evaluated changes to trial characteristics that could bolster the incidence reduction.

RESULTS: With a control ART initiation threshold of CD4 <350/µL, 24-month HIV incidence under control and intervention strategies was 2.46/100 person-years (PY) and 1.96/100 PY, a 21% reduction. Raising the threshold to CD4 <500/µL decreased the incidence reduction by more than one-third, to 12%. Using this higher threshold, moving to a 36-month horizon (vs 24-month), yearly control-strategy HIV screening (vs biannual), and intervention-strategy screening every 2 months (vs biannual), resulted in a 31% incidence reduction that was similar to effect size projections for ongoing trials. Alternate assumptions regarding cross-cluster contamination had the greatest influence on the incidence reduction.

CONCLUSIONS: Implementing the 2013 WHO HIV treatment threshold could substantially diminish the incidence reduction in HIV population prevention trials. Alternative HIV testing frequencies and trial horizons can bolster this incidence reduction, but they could be logistically and ethically challenging. The feasibility of HIV population prevention trials should be reassessed as the implementation of treatment guidelines evolves.

Text
Ross_HIVClinTrials_2014.pdf - Version of Record
Download (407kB)

More information

Published date: September 2014
Keywords: highly active antiretroviral therapy, HIV, prevention, randomized controlled trials
Organisations: Faculty of Medicine

Identifiers

Local EPrints ID: 379615
URI: http://eprints.soton.ac.uk/id/eprint/379615
ISSN: 1528-4336
PURE UUID: 249143a1-73a9-432e-b378-d283d0fd1878
ORCID for M.L. Newell: ORCID iD orcid.org/0000-0002-1074-7699

Catalogue record

Date deposited: 14 Aug 2015 15:40
Last modified: 20 Jul 2019 00:38

Export record

Altmetrics

Contributors

Author: E. Ross
Author: F. Tanser
Author: P. Pei
Author: M.L. Newell ORCID iD
Author: E. Losina
Author: R. Thiebaut
Author: M. Weinstein
Author: K. Freedberg
Author: X. Anglaret
Author: C. Scott
Author: F. Dabis
Author: R. Walensky

University divisions

Download statistics

Downloads from ePrints over the past year. Other digital versions may also be available to download e.g. from the publisher's website.

View more statistics

Atom RSS 1.0 RSS 2.0

Contact ePrints Soton: eprints@soton.ac.uk

ePrints Soton supports OAI 2.0 with a base URL of http://eprints.soton.ac.uk/cgi/oai2

This repository has been built using EPrints software, developed at the University of Southampton, but available to everyone to use.

We use cookies to ensure that we give you the best experience on our website. If you continue without changing your settings, we will assume that you are happy to receive cookies on the University of Southampton website.

×