CROI 2016 Abstract eBook

Abstract Listing

Poster Abstracts

938 When to Start Antiretroviral Therapy in HIV-Positive Persons Aged Over 50 Years Sara Lodi ; for the HIV-CAUSAL Collaboration Harvard Sch of PH, Boston, MA, USA

Background: The START randomized controlled trial has shown that early initiation of combined antiretroviral therapy (cART) reduces the risk of serious AIDS and non-AIDS events in HIV-positive individuals. However, since the individuals included in START were relatively young and the number of deaths was low, it is unknown whether early initiation reduces mortality in older HIV-positive individuals. While earlier cART initiation may help decrease mortality associated with non-AIDS comorbidities, it might complicate clinical management because of polypharmacy and drug interactions. Our objective is to compare the risk of mortality in ART-naive and AIDS-free individuals aged≥50 years under i) immediate initiation and ii) initiation at AIDS or CD4 count <350 cells/mm 3 . Methods: We used data from the HIV-CAUSAL Collaboration of 12 HIV cohorts from Europe and the US. We included ART-naïve and AIDS-free individuals who were enrolled after 1999 with age≥50 years. Follow-up started at enrolment and ended at the earliest of death, 12 months with no laboratory measurement, or administrative censoring. We applied the parametric g-formula, a generalisation of standardisation, to estimate the 7-year risk of all-cause and non AIDS-related mortality under each cART initiation strategy. Estimates were adjusted for time-varying CD4 count, HIV-RNA and AIDS, and for baseline characteristics (calendar period, risk group, gender, geographical origin, and cohort). To interpret

these results, the same analyses were conducted on individuals in age groups 18-34 and 35-49 years at enrolment. Standard errors were computed using 200 bootstrap repetitions. Results: Of 9,837 eligible individuals with age≥50 at enrolment (84% men), 73% initiated cART during follow-up. Median [interquantile range (IQR)] age at baseline was 54 [51,59] years. Median [IQR] CD4 count at baseline and at cART initiation were 365 [209,532] and 258 [164,350] cells/mm 3 , respectively. During a median [IQR] follow-up of 37 [18,68] months, we identified 1085 deaths of which 468 were non AIDS-defining. The 7-year risk of all-cause and non AIDS-defining mortality for initiation with CD4<350 cells/mm 3 was lower compared with immediate initiation in individuals with age≥50 years (Table). There was a trend for increase benefit of early initiation with older age. Conclusions: Earlier initiation might be effective in reducing all-cause and non AIDS-related mortality in AIDS-free patients with age≥50 years. Earlier initiation should be prioritised in older patients.

939

Changes in Markers of T-Cell Senescence and ExhaustionWith HIV Therapy Theodoros Kelesidis 1 ; Carlee B. Moser 2 ; James H. Stein 3 ;ToddT. Brown 4 ;ThuyT.Tran 2 ; Heather J. Ribaudo 2 ; Michael Dube 5 ; Robert Murphy 6 ; OttoYang 1 ; Judith S. Currier 1 ; Grace A. McComsey 7 1 David Geffen Sch of Med at Univ of California Los Angeles, Los Angeles, CA, USA; 2 Harvard Sch of PH, Boston, MA, USA; 3 Univ of Wisconsin-Madison, Madison, WI, USA; 4 Johns Hopkins Univ, Baltimore, MD, USA; 5 Keck Sch of Med at the Univ of Southern California, Los Angeles, CA, USA; 6 Northwestern Univ, Feinberg Sch of Med, Chicago, IL, USA; 7 Case Western Reserve Univ, Cleveland, OH, USA

Background: Residual immune activation and immunosenescence may contribute to chronic comorbidities in treated HIV-1 infection. It is unclear whether the integrase inhibitor, raltegravir (RAL), which has increased penetration into the gastrointestinal and lymphoid tissues, affects immunosenescence and T cell exhaustion to a greater extent than ritonavir boosted protease inhibitors (PIs). Methods: A5260s is a substudy of a large prospective, randomized multicenter clinical trial that included HIV-1 infected treatment-naïve participants randomized to receive tenofovir disoproxil fumarate-emtricitabine (TDF/FTC) plus: atazanavir/ritonavir (ATV/r), darunavir/ ritonavir (DRV/r), or RAL. Analyses include 234 participants (71% of all A5260s participants) who achieved and maintained plasma HIV-1 RNA <50 copies/ml by week 24. Blood cellular markers of immunosenescence and exhaustion of both CD4+ and CD8+ T cell subsets included: %CD28-CD57+, %CD28-CD57+ PD1+ and % PD1+. Changes from baseline were examined at earlier (24 weeks) and later (96 weeks) time points as fold change and 95% confidence intervals. Pairwise treatment group comparisons used Wilcoxon rank-sum tests with p-values adjusted with false discovery rate control. Results: Sustained declines over time were evident in all treatment groups for all CD4+ T cell markers of immunosenescence and exhaustion, with no apparent differences between treatment groups. Markers of CD8+ T cell exhaustion (but not immunosenescence) declined over time in all groups, without major differences between groups. Conclusions: In this prospective randomized clinical trial of initially ART-naïve individuals initiating successful ART regimens of TDF/FTC with RAL, ATV/r or DRV/r, we did not find between groups differences in measured markers of T cell senescence or exhaustion after 96 weeks of ART. Despite successful ART therapy, markers of CD8+ T cell immunosenescence did not decrease by 96 weeks. These data support further the accumulating evidence of incomplete reversal of immune activation and senescence in the setting of current effective ART compared to ART naïve HIV-1 infected

Poster Abstracts

397

CROI 2016