Patient Self-Reported Adherence to Ritonavir-Boosted Darunavir Combined with Either Raltegravir or Tenofovir Disoproxil Fumarate /Emtricitabine in the Neat 001/Anrs 143 Trial.

BACKGROUND: The NEAT 001/ANRS 143 trial demonstrated non-inferiority of darunavir-ritonavir combined with either raltegravir (RAL+DRV/r) or tenofovir disoproxil fumarate/emtricitabine (TDF/FTC+DRV/r) in HIV-positive, antiretroviral-naive adults. In post-hoc analyses however, RAL+DRV/r showed inferiority in patients with baseline CD4+ <200/mm and HIV-1 RNA ≥100,000 copies/mL. This pre-planned ancillary study was conducted to assess whether differences in adherence might explain efficacy results SETTING:: Phase III, open-label, randomized, multicentre study in 15 European countries (ClinicalTrials.gov, NCT01066962).

METHODS: 774 participants self-reported adherence (modified ACTG questionnaire) over 96 weeks (383 RAL+DRV/r [BID; 5 pills/daily], 391 TDF/FTC+DRV/r [QD; 4 pills/daily]. Primary endpoint was >95% versus <95% adherence to prescribed doses recorded a) over the last 4 days, or b) on the visual analogue scale (VAS) over the last 30 days RESULTS:: Characteristics, except age, were similar between arms; 9% had CD4+ <200 cells/mm and HIV-1 RNA ≥100,000 copies/mL. Adherence >95% in the last 4 days (p=0.029) or at VAS (p=0.0072) was higher with TDF/FTC+DRV/r than with RAL+DRV/r. Adherence >95% over the last 4 days was associated with lower probability of virological failure (p=0.015). Adherence in patients with baseline CD4+ <200 cells/mm and HIV-1 RNA ≥100,000 copies/mL was similar to the rest of the population, and not significantly associated with efficacy measures, with no significant differences between arms. Adherence was not different between baseline CD4 and HIV-1 RNA subgroups, overall and across arms (adherence ≥95% over the last 4 days: 90% for RAL+DRV/r versus 93% for TDF/FTC+DRV/r, p=0.91 for interaction of baseline strata with arm; adherence ≥95% on VAS: 89% versus 91%, respectively, p=0.86 for interaction of baseline strata with arm) CONCLUSION:: Adherence was high and slightly better in the TDF/FTC+DRV/r than in the RAL+DRV/r arm. Adherence differences did not explain inferiority of RAL+DRV/r in patients with CD4 <200/mm3 and HIV-1 RNA >100.000 copies/mL. No convincing evidence was found that higher failure rate in the RAL+DRV/r arm in the subgroup with worse baseline viro-immunological status is caused by adherence differencesThis is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal.