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

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.