Partner-based adherence intervention for second-line antiretroviral therapy (ACTG A5234): A multinational randomised trial

The ACTG 5234 team

Research output: Contribution to journalArticle

Abstract

Background: Adherence is key to the success of antiretroviral therapy. Enhanced partner support might benefi t patients with previous treatment failure. We aimed to assess whether an enhanced partner-based support intervention with modifi ed directly observed therapy would improve outcomes with second-line therapy in HIV-infected patients for whom fi rst-line therapy had failed. Methods: We did a multicentre, international, randomised clinical trial at nine sites in Botswana, Brazil, Haiti, Peru, South Africa, Uganda, Zambia, and Zimbabwe. Participants aged 18 years or older for whom fi rst-line therapy had failed, with HIV RNA concentrations greater than 1000 copies per mL and with a willing partner, were randomly assigned (1:1), via computer-generated randomisation, to receive partner-based modifi ed directly observed therapy or standard of care. Randomisation was stratifi ed by screening HIV RNA concentration (≤10 000 copies per mL vs >10 000 copies per mL). Participants and site investigators were not masked to group assignment. Primary outcome was confi rmed virological failure (viral load >400 copies per mL) by week 48. Analysis was by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT00608569. Findings: Between April 23, 2009, and Sept 29, 2011, we randomly assigned 259 participants to the modifi ed directly observed therapy group (n=129) or the standard-of-care group (n=130). 34 (26%) participants in the modifi ed directly observed therapy group achieved the primary endpoint of virological failure by week 48 compared with 23 (18%) participants in the standard-of-care group. The Kaplan-Meier estimated cumulative probability of virological failure by week 48 was 25.1% (95% CI 17.7-32.4) in the modifi ed directly observed therapy group and 17.3% (10.8-23.7) in the standard-of-care group, for a weighted diff erence in standard of care versus modifi ed directly observed therapy of -6.6% (95% CI -16.5% to 3.2%; p=0.19). 36 (14%) participants reported at least one grade 3 or higher adverse event or laboratory abnormality (n=21 in the modifi ed directly observed therapy group and n=15 in the standard-of-care group). Interpretation: Partner-based training with modifi ed directly observed therapy had no eff ect on virological suppression. The intervention does not therefore seem to be a promising strategy to increase adherence. Intensive follow-up with clinic staff might be a viable approach in this setting. Funding AIDS Clinical Trials Group and the National Institute of Allergy and Infectious Diseases, US National Institutes of Health.

Original languageEnglish (US)
Pages (from-to)e12-e19
JournalThe Lancet HIV
Volume2
Issue number1
DOIs
StatePublished - Jan 1 2015
Externally publishedYes

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Directly Observed Therapy
Standard of Care
HIV
Therapeutics
Random Allocation
National Institute of Allergy and Infectious Diseases (U.S.)
RNA
Botswana
Haiti
Zambia
Zimbabwe
Peru
Intention to Treat Analysis
Uganda
National Institutes of Health (U.S.)
South Africa
Viral Load
Treatment Failure
Brazil
Acquired Immunodeficiency Syndrome

ASJC Scopus subject areas

  • Epidemiology
  • Immunology
  • Infectious Diseases
  • Virology

Cite this

Partner-based adherence intervention for second-line antiretroviral therapy (ACTG A5234) : A multinational randomised trial. / The ACTG 5234 team.

In: The Lancet HIV, Vol. 2, No. 1, 01.01.2015, p. e12-e19.

Research output: Contribution to journalArticle

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abstract = "Background: Adherence is key to the success of antiretroviral therapy. Enhanced partner support might benefi t patients with previous treatment failure. We aimed to assess whether an enhanced partner-based support intervention with modifi ed directly observed therapy would improve outcomes with second-line therapy in HIV-infected patients for whom fi rst-line therapy had failed. Methods: We did a multicentre, international, randomised clinical trial at nine sites in Botswana, Brazil, Haiti, Peru, South Africa, Uganda, Zambia, and Zimbabwe. Participants aged 18 years or older for whom fi rst-line therapy had failed, with HIV RNA concentrations greater than 1000 copies per mL and with a willing partner, were randomly assigned (1:1), via computer-generated randomisation, to receive partner-based modifi ed directly observed therapy or standard of care. Randomisation was stratifi ed by screening HIV RNA concentration (≤10 000 copies per mL vs >10 000 copies per mL). Participants and site investigators were not masked to group assignment. Primary outcome was confi rmed virological failure (viral load >400 copies per mL) by week 48. Analysis was by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT00608569. Findings: Between April 23, 2009, and Sept 29, 2011, we randomly assigned 259 participants to the modifi ed directly observed therapy group (n=129) or the standard-of-care group (n=130). 34 (26{\%}) participants in the modifi ed directly observed therapy group achieved the primary endpoint of virological failure by week 48 compared with 23 (18{\%}) participants in the standard-of-care group. The Kaplan-Meier estimated cumulative probability of virological failure by week 48 was 25.1{\%} (95{\%} CI 17.7-32.4) in the modifi ed directly observed therapy group and 17.3{\%} (10.8-23.7) in the standard-of-care group, for a weighted diff erence in standard of care versus modifi ed directly observed therapy of -6.6{\%} (95{\%} CI -16.5{\%} to 3.2{\%}; p=0.19). 36 (14{\%}) participants reported at least one grade 3 or higher adverse event or laboratory abnormality (n=21 in the modifi ed directly observed therapy group and n=15 in the standard-of-care group). Interpretation: Partner-based training with modifi ed directly observed therapy had no eff ect on virological suppression. The intervention does not therefore seem to be a promising strategy to increase adherence. Intensive follow-up with clinic staff might be a viable approach in this setting. Funding AIDS Clinical Trials Group and the National Institute of Allergy and Infectious Diseases, US National Institutes of Health.",
author = "{The ACTG 5234 team} and Robert Gross and Lu Zheng and Rosa, {Alberto La} and Xin Sun and Rosenkranz, {Susan L.} and Cardoso, {Sandra Wagner} and Francis Ssali and Rob Camp and Catherine Godfrey and Cohn, {Susan E.} and Robbins, {Gregory K.} and Anthony Chisada and Wallis, {Carole L.} and Nancy Reynolds and Darlene Lu and Safren, {Steven A.} and Lara Hosey and Patrice Severe and Collier, {Ann C.}",
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T1 - Partner-based adherence intervention for second-line antiretroviral therapy (ACTG A5234)

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AU - The ACTG 5234 team

AU - Gross, Robert

AU - Zheng, Lu

AU - Rosa, Alberto La

AU - Sun, Xin

AU - Rosenkranz, Susan L.

AU - Cardoso, Sandra Wagner

AU - Ssali, Francis

AU - Camp, Rob

AU - Godfrey, Catherine

AU - Cohn, Susan E.

AU - Robbins, Gregory K.

AU - Chisada, Anthony

AU - Wallis, Carole L.

AU - Reynolds, Nancy

AU - Lu, Darlene

AU - Safren, Steven A.

AU - Hosey, Lara

AU - Severe, Patrice

AU - Collier, Ann C.

PY - 2015/1/1

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N2 - Background: Adherence is key to the success of antiretroviral therapy. Enhanced partner support might benefi t patients with previous treatment failure. We aimed to assess whether an enhanced partner-based support intervention with modifi ed directly observed therapy would improve outcomes with second-line therapy in HIV-infected patients for whom fi rst-line therapy had failed. Methods: We did a multicentre, international, randomised clinical trial at nine sites in Botswana, Brazil, Haiti, Peru, South Africa, Uganda, Zambia, and Zimbabwe. Participants aged 18 years or older for whom fi rst-line therapy had failed, with HIV RNA concentrations greater than 1000 copies per mL and with a willing partner, were randomly assigned (1:1), via computer-generated randomisation, to receive partner-based modifi ed directly observed therapy or standard of care. Randomisation was stratifi ed by screening HIV RNA concentration (≤10 000 copies per mL vs >10 000 copies per mL). Participants and site investigators were not masked to group assignment. Primary outcome was confi rmed virological failure (viral load >400 copies per mL) by week 48. Analysis was by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT00608569. Findings: Between April 23, 2009, and Sept 29, 2011, we randomly assigned 259 participants to the modifi ed directly observed therapy group (n=129) or the standard-of-care group (n=130). 34 (26%) participants in the modifi ed directly observed therapy group achieved the primary endpoint of virological failure by week 48 compared with 23 (18%) participants in the standard-of-care group. The Kaplan-Meier estimated cumulative probability of virological failure by week 48 was 25.1% (95% CI 17.7-32.4) in the modifi ed directly observed therapy group and 17.3% (10.8-23.7) in the standard-of-care group, for a weighted diff erence in standard of care versus modifi ed directly observed therapy of -6.6% (95% CI -16.5% to 3.2%; p=0.19). 36 (14%) participants reported at least one grade 3 or higher adverse event or laboratory abnormality (n=21 in the modifi ed directly observed therapy group and n=15 in the standard-of-care group). Interpretation: Partner-based training with modifi ed directly observed therapy had no eff ect on virological suppression. The intervention does not therefore seem to be a promising strategy to increase adherence. Intensive follow-up with clinic staff might be a viable approach in this setting. Funding AIDS Clinical Trials Group and the National Institute of Allergy and Infectious Diseases, US National Institutes of Health.

AB - Background: Adherence is key to the success of antiretroviral therapy. Enhanced partner support might benefi t patients with previous treatment failure. We aimed to assess whether an enhanced partner-based support intervention with modifi ed directly observed therapy would improve outcomes with second-line therapy in HIV-infected patients for whom fi rst-line therapy had failed. Methods: We did a multicentre, international, randomised clinical trial at nine sites in Botswana, Brazil, Haiti, Peru, South Africa, Uganda, Zambia, and Zimbabwe. Participants aged 18 years or older for whom fi rst-line therapy had failed, with HIV RNA concentrations greater than 1000 copies per mL and with a willing partner, were randomly assigned (1:1), via computer-generated randomisation, to receive partner-based modifi ed directly observed therapy or standard of care. Randomisation was stratifi ed by screening HIV RNA concentration (≤10 000 copies per mL vs >10 000 copies per mL). Participants and site investigators were not masked to group assignment. Primary outcome was confi rmed virological failure (viral load >400 copies per mL) by week 48. Analysis was by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT00608569. Findings: Between April 23, 2009, and Sept 29, 2011, we randomly assigned 259 participants to the modifi ed directly observed therapy group (n=129) or the standard-of-care group (n=130). 34 (26%) participants in the modifi ed directly observed therapy group achieved the primary endpoint of virological failure by week 48 compared with 23 (18%) participants in the standard-of-care group. The Kaplan-Meier estimated cumulative probability of virological failure by week 48 was 25.1% (95% CI 17.7-32.4) in the modifi ed directly observed therapy group and 17.3% (10.8-23.7) in the standard-of-care group, for a weighted diff erence in standard of care versus modifi ed directly observed therapy of -6.6% (95% CI -16.5% to 3.2%; p=0.19). 36 (14%) participants reported at least one grade 3 or higher adverse event or laboratory abnormality (n=21 in the modifi ed directly observed therapy group and n=15 in the standard-of-care group). Interpretation: Partner-based training with modifi ed directly observed therapy had no eff ect on virological suppression. The intervention does not therefore seem to be a promising strategy to increase adherence. Intensive follow-up with clinic staff might be a viable approach in this setting. Funding AIDS Clinical Trials Group and the National Institute of Allergy and Infectious Diseases, US National Institutes of Health.

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