CROI 2016 Abstract eBook

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Poster Abstracts

Methods: ATLAS-M (NCT 2011-001060-21) is a phase IV, multicenter, open-label, randomized, non-inferiority trial. Patients (pts) on ATV/r+2NRTIs, without previous virological failure, with HIV-RNA<50copies/mL and CD4>200cells/mm 3 for>6months were randomized to switch to ATV/r+3TC(dual therapy, DT) or to maintain the 3-drug regimen(triple therapy, TT). At baseline(BL) and W48, NP was evaluated. Exclusion criteria for NP testing were: active psychiatric disorders, alcohol/drug abuse, and linguistic difficulties for non native pts. Raw scores obtained at each task were Z-transformed using normative data. A composite Z-score was calculated to explore global NP. Cognitive impairment was defined according to Frascati criteria. Factors associated with the evolution of NP were identified by linear regression analysis. Results: A total of 266 pts (78%males, median age 44 yrs, median CD4 603cells/µL) were enrolled. W48 NP data were available in 151 pts, of which 81 and 70 in DT and TT arms, respectively. Pts with an available NP testing showed shorter time from HIV diagnosis(p=0.024) and cART initiation(p=0.049), higher CD4 nadir(p=0.04), lower proportions of females(p=0.003), HCV co-infection(p=0.008) and past IDU(p=0.004) compared to the 115 participants not included in the sub-study. At BL, pts in the DT and TT arms did not differ for the main characteristics and showed a similar proportion of cognitive impairment(16% vs 21%,p=0.41). Overall, no change in the prevalence of cognitive impairment was observed at W48(p=0.39). DD and TT confirmed a comparable global NP(-0.04 vs -0.003,p=0.78); also in all cognitive domains we observed no difference. However, both groups showed a decreased memory performance when compared to BL: mean change DT -0.42(p<0.001) and TT -0.27(p=0.01); no difference were observed between the two arms in the mean memory change(p=0.29). Analyzing factors associated with the evolution of the global NP (W48-BL composite z-score), we found no significant effect of DT compared with TT(β=0.10;p=0.11), after adjusting for time on cART(β=-0.01;p=0.09) and CD4 nadir(β=0.04 for 100 cells increase;p=0.04). Conclusions: Simplification to DT was apparently CNS safe. Cognitive evolution will be further investigated at the scheduled W96 follow-up. 418 Neurocognitive Improvement With NRTI-Sparing Treatment in Acute HIV Infection Cynthia Gay 1 ; SarahWillils 1 ; JoAnn D. Kuruc 1 ; Kara S. McGee 2 ; Angela Kashuba 1 ; Mehri S. McKellar 2 ; Charles B. Hicks 3 ; Joseph J. Eron 1 ; David M. Margolis 1 ; Kevin R. Robertson 1 1 Univ of North Carolina at Chapel Hill, Chapel Hill, NC, USA; 2 Duke Univ, Durham, NC, USA; 3 Univ of California San Diego, San Diego, CA, USA Background: HIV accesses the CNS within days of infection and persistent neurocognitive impairment (NI) may occur despite viral suppression due to ongoing low level viral replication causing persistent immune activation. Therefore, early antiretroviral therapy (ART) in Acute HIV infection (AHI) may improve neurocognitive function by limiting CD4 nadir. Methods: In a single arm, open-label pilot study, AHI patients were treated within 30 days of diagnosis with ritonavir-boosted darunavir 800mg once daily plus etravirine, 400mg once daily or 200mg twice daily for 48 weeks. Neuropsychological performance (NP) was assessed at baseline, week 24 and week 48 in the following domains: Premorbid/ language, Learning, Memory, Speed of Processing, Attention, Fine motor, and Executive functioning. Best available demographically corrected normative data were utilized to create z scores and then deficit scores for impairment ratings. Results: Between August 2009 and November 2012, 15 AHI patients started treatment, 13 (87%) of whom achieved HIV RNA <200 copies/mL by week 24 of ART. Among 12 patients retained through week 48, 9 (75%) suppressed to <50 copies/mL by week 48. Median time from ART initiation to HIV RNA <200 copies/mL and <50 copies/mL was 59 days and 86 days, respectively. 13 patients completed 32 NP assessments; 8 patients at all 3 time points, 2 at baseline and week 24 or 48 and 2 at baseline only. 61%were impaired at baseline, 33% at 24 weeks and 30% at 48 weeks. There was a statistically significant improvement in overall neurocognitive performance (NP) over time (F(2,17)= 4.23, p= 0.03), with most improvement occurring from baseline to week 24 (baseline mean z = -0.69, (.14), week 24 mean z= -0.40 (15), and week 48 mean z= -45 (.15)). 2 of 3 persons who did not achieve improvement in overall neurocognitive function also did not suppress HIV RNA by week 24. There was no association with CD4 nadir and NP (r=.19, ns). Self-report of current cognitive or physical problems at baseline was noted for 23%, but not there was no association with overall NP (r=-.22, ns). Conclusions: Most AHI patients achieving HIV RNA suppression on ART experienced neurocognitive improvement in contrast to those who did not achieve HIV suppression, 2/3 of whom remained impaired. While psychological distress of HIV infection was noted in some, there was no significant relationship to NP. Early institution of ART during AHI may improve overall neurocognitive function and reduce the risk of subsequent neurocognitive impairment. 419 HIV Associated Neurocognitive Impairment: A Randomized Controlled Trial of Lithium Background: HIV-associated neurocognitive disorders (HAND) remain highly prevalent despite effective anti-retroviral therapy (ART). The incidence of severe HAND has decreased but with longer life expectancy and associated cerebro-vascular risk factors, the overall prevalence is probably rising. Severe HAND is associated with high rates of morbidity and mortality. There is an urgent need to identify suitable neuroprotective adjunctive treatments for HAND. Lithium is a low-cost drug and widely available in public service settings in low and middle-income countries. Two pilot studies investigating lithium in HAND have been conducted. Lithium improved neurocognitive impairment in one study and neuronal integrity in both studies. However, these studies were limited by the lack of a comparator arm, and the short duration of lithium treatment. Methods: We conducted a 24 week randomized placebo-controlled trial to study lithium as an adjunctive treatment in patients with severe HAND [Global Deficit Score (GDS) > 0.5] stabilised on ART for at least 6 months with suppressed viral loads. The primary objective was to measure the change in neuropsychological function as determined by the GDS from baseline to week 24. Results: We randomized 66 Xhosa patients to lithium (n=34) or placebo (n= 32) and 61 completed the study (lithium arm= 30; placebo arm= 31). Fifty eight were women and 8 men who at enrolment had a mean age of 39.3 and 40.6 years and a mean CD4+ T-cell count of 502 and 498 cells/µL respectively in the lithium and placebo arms. The median GDS for both the lithium and placebo arms at enrolment were 1.11. The median change in GDS score between baseline and week 24 for the lithium and placebo arms were -0.57 (95% CI -0.77, -0.32) and -0.56 (-0.69, -0.34) respectively, with a mean difference of -0.054 (-0.26, 0.15); p = 0.716. The study drug was well tolerated with no statistically significant difference (p = 0.413) in adverse events between the 2 study arms. Six serious adverse events occurred but none were considered related to the study drug. Four participants were withdrawn with 1 loss to follow-up. Conclusions: We found that adjunctive lithium in virologically suppressed patients with HAND was well tolerated but had no additional benefit on neurocognitive impairment. 420 Week48 Cognitive Improvement in HAND After Switch to HAART Based on CHARTER Score +3 Gilles Force 1 ;Valerie Hahn 2 ; Helene Defferriere 3 ; Natacha Darchy 4 ; Jacques Ropers 5 ; Philippe Aegerter 5 ; Constance Delaugerre 6 ; Gilles Peytavin 7 ; Pierre DeTruchis 3 1 Hosp Franco-Britannique, Levallois-Perret, France; 2 Cntr Hospier Sainte-Anne, Paris, France; 3 Hosp Raymond Poincaré, APHP, Garches, France; 4 Inst Hospier Franco-Britannique, Levallois- Perret, France; 5 Hosp Ambroise Paré, APHP, Boulogne, France; 6 Hosp Saint Louis et Univ Paris Diderot, Paris, France; 7 IAME, INSERM UMR 1137, Univ Paris 7 UF 301, Paris, France Background: Neuro+3 is a pilot open-label study which evaluates the cognitive status in patients with HAND (HIV-Associated Neurocognitive Disorders), despite effective ARV therapy for more than one year. After inclusion, the initial ARV treatment (T) was changed to a new combination with enhanced Charter score (+3) and the same battery of cognitive tests was planned after 48 and 96 weeks. Week 48 data are analyzed in the present study. Methods: 63 pts were screened with BREF≤15/18 or mHIVDS≤10/12 in 8 investigational centers. 31pts were included with at least 2 ability domains >1SD for the following tests after depression assessment using Beck Depression Inventory BDI II: Grooved Pegboard (d and nd), Verbal Fluency, CVLT, Digit span, PASAT, Digit symbol, Wisconsin Card Sorting Test (6 domains). Results: Median range characteristics of the 31 enrolled pts were: 26 men, 54 years (33-64), HIV duration 20 years (2-29), Nadir CD4 165/mm 3 (4-1465), and at screening CD4 count was 622/mm 3 (125-2130). Plasma HIV-RNA was <20 copies/ml at screening except in 2pts (31 and 79 copies/ml), and at baseline except in 2 other pts (24 and 22 copies/ Eric H. Decloedt 1 ; Carla S. Freeman 2 ; Maia S. Lesosky 2 ; Gary Maartens 2 ; John Joska 2 1 Stellenbosch Univ, Tygerberg, South Africa; 2 Univ of Cape Town, Cape Town, South Africa

Poster Abstracts

159

CROI 2016