*HIV/AIDS Unit, INMI “L. Spallanzani” IRCCS, Rome, Italy;†Medical Research Council Clinical Trials Unit at UCL, London, United Kingdom;‡Infectious Diseases Department, Hôpital Saint-Louis, University of Paris Diderot, INSERM U941, Paris, France;§Bordeaux Population Health Research Center, University of Bordeaux, INSERM, UMR 1219, Bordeaux, France;║Infectious Diseases Unit, Hospital de la Santa Creu I Sant Paul, Barcelona, Spain;¶Department of Infectious Diseases, Karolinska University Hospital, Stockolm, Sweden;#Infectious Diseases Unit, S. Maria Annunziata Hospital, Florence, Italy;**Chelsea and Westminster NHS Trust St Stephens Centre, London, United Kingdom; and††Infectious and Tropical Diseases Department, INSERM CIC 1413, CHU, Nantes, France.
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Background:The NEAT001/ANRS143 trial demonstrated noninferiority of ritonavir-boosted darunavir 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/mm3 and HIV-1 RNA ≥100,000 copies per milliliter. This preplanned ancillary study was conducted to assess whether differences in adherence might explain efficacy results.Setting:Phase III, open-label, randomized, multicenter study in 15 European countries (ClinicalTrials.gov, NCT01066962).Methods:Seven hundred seventy-four participants self-reported adherence (modified AIDS Clinical Trials Group questionnaire) over 96 weeks [383 RAL + DRV/r (twice daily; 5 pills/day), 391 TDF/FTC + DRV/r (once daily; 4 pills/day)]. Primary endpoint was ≥95% versus <95% adherence to prescribed doses recorded (1) over the last 4 days or (2) on the visual analogue scale over the last 30 days.Results:Characteristics, except age, were similar between arms; 9% had CD4+ <200 cells/mm3 and HIV-1 RNA ≥100,000 copies per milliliter. Adherence ≥95% in the last 4 days (P = 0.029) or at the visual analogue scale (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/mm3 and HIV-1 RNA ≥100,000 copies per milliliter was similar to the rest of the population, and not significantly associated with efficacy measures, with no significant differences between arms.Conclusion:Adherence was high and slightly better in the TDF/FTC + DRV/r than in the RAL + DRV/r arm. No convincing evidence was found that higher failure rate in the RAL + DRV/r arm in the subgroup with worse baseline viroimmunological status is caused by adherence differences.