Background: To assess efficacy in Central Nervous System (CNS), we evaluated neurocognitive performance in patients (pts) on atazanavir/ritonavir (ATV/r) monotherapy compared to ATV/r triple therapy.
Methods: MODAt (NCT01511809) is a multicentric, randomized, open-label, non-inferiority trial. Pts on ATV/r 300/100mg+2 N(t)RTIs since≥48 weeks, virologically suppressed since≥24 weeks, were randomized to ATV/r (arm A) or to maintain ATV/r+2N(t)RTIs (Arm B). This analysis included patients treated with either ATV/r triple therapy or monotherapy (with no re-intensification due to virological failure) who underwent neuropsychological (NP) evaluation at baseline, week 48 and, if not discontinued, at week 96. The NP tests assessed multiple cognitive domains including attention/concentration (Digit Symbol [DS]), learning/memory (Rey Auditory Verbal Learning Test [RAVLT], Rey Recall [RAVLT rec]); psychomotor speed (Trail Making Test–Part A [TMTA], Grooved Pegboard [GP]), executive functioning (TMT–Part B [TMTB]), language (Semantic [SF] and Phonemic fluency [PF]), and gross motor (finger tapping [FT]). Age, sex and education adjusted scores were used. Depression was assessed using the CES-D scale. Results are expressed as median (interquartile range). ANOVA for repeated measures and McNemar test were applied for longitudinal analysis.
Results: Sixty-five pts were examined (Arm A=28, Arm B=37): 88% males; age, 40 (35-46) years; education, 13 (12-15) years; duration of HIV-infection, 5 (2-7) years; CD4+ nadir, 293 (224-388) cells/μL; baseline CD4+, 610 (431-774) cells/μL, pre-ART HIV-RNA 4.67 (4-5.26) log10cp/mL; HCV co-infection (15%); none with AIDS diagnosis. Baseline NP findings were similar between the two arms with the exception of TMT-B scores that were worse in arm B compared to arm A (p=0.018). At baseline, CES-D score was abnormal (score>23) in 11 (17%) pts, borderline (score: 17-23) in 10 (15%) pts, with no significant changes of these proportions during follow-up. NP scores improved significantly over 96 weeks in five of nine tests [Figure] with no trend differences between arms. The proportion of pts with HIV-Associated Neurocognitive Disorders (HAND) dropped from 66% at baseline to 37% at week 96 with no differences between arms.
Conclusions: In subjects successfully treated for 96 weeks, we observed an improvement in the majority of explored NP test performances with similar trends in patients treated with ATV/r-monotherapy or ATV/r triple therapy.