CROI 2019 Abstract eBook

Abstract eBook

Poster Abstracts

Conclusion: We found no difference in treatment outcomes between people in Uganda infected with subtype A1 or D HIV-1 and initiated on NNRTI -based therapy over 7-years of observation.

for a hazard ratio and complicate the interpretation of the study findings. The restricted mean survival time (RMST) measure have not been used as primary measure of efficacy in HIV/AIDS clinical trials and may offer a powerful alternative to the hazard ratio. We compared analysis based on the difference in RMST (Δ-RMST) measure with 2 treatment-effect measures in a recent HIV equivalence trial, and investigated the performance and characteristics of Δ-RMST-based analysis. Methods: Primary and secondary virologic failure (VF) outcome measures from ACTG A5257 were reanalyzed using hazard ratio (HR) and Δ-RMST estimands and compared the to the original study results based on risk difference estimated by Kaplan-Meier (RDKM). A5257 equivalence bounds were transformed for each estimand assuming exponential VF distributions and A5257 design characteristics. The performance and operating characteristics of Δ-RMST-based analysis in the setting of non-proportional hazards ratio were investigated in a simulation study. Results: Table summarizes results of the analyses in the ACTG 5257 study and alternative analyses. Analyses based on Δ-RMST globally led to similar conclusions as the published finding based on RDKM. In contrast, analyses based on HR provided some discordant equivalence conclusions compared both with the initial analyses based on RDKM and the Δ-RMST despite that appeared driven by very low failure rates in one group. Results of our simulation study indicated that the violation of the proportional hazards assumption may negatively an impact the probability of declaring equivalence for a Δ-RMST based analysis. Conclusion: The RMST based analysis could be a promising alternative measure of efficacy in HIV/AIDS clinical trials although further discussion to define non- inferiority bounds is needed.

508 HIV CONTROLLERS MAINTAIN VIRAL SUPPRESSION DESPITE WANING T-CELL RESPONSES ON ART Nikolaus Jilg 1 , Pilar Garcia-Broncano 2 , Michael Peluso 3 , Florencia Pereyra 4 , Ronald Bosch 5 , Carla Roberts-Toler 5 , Cornelius N. Van Dam 6 , Michael Keefer 7 , Daniel R. Kuritzkes 4 , Alan Landay 8 , Steven G. Deeks 3 , Xu G. Yu 2 , Paul E. Sax 4 , Jonathan Z. Li 4 1 Massachusetts General Hospital, Boston, MA, USA, 2 Ragon Institute of MGH, MIT and Harvard, Cambridge, MA, USA, 3 University of California San Francisco, San Francisco, CA, USA, 4 Brigham and Women’s Hospital, Boston, MA, USA, 5 Harvard University, Boston, MA, USA, 6 University of North Carolina at Chapel Hill, Chapel Hill, NC, USA, 7 University of Rochester, Rochester, NY, USA, 8 Rush University, Chicago, IL, USA Background: Robust HIV-specific T cell responses are a hallmark of HIV controllers (HCs). We assessed the impact of antiretroviral therapy (ART) on HIV-specific T cell responses and the ability of HCs to maintain HIV suppression after discontinuation of ART. Methods: A5308 is a prospective, open-label study of rilpivirine, emtricitabine and tenofovir disoproxil fumarate (RPV/FTC/TDF) in ART-naive HCs with viral loads (VLs) <500 cp/mL for ≥12 months. HIV-specific T cell responses were measured by intracellular cytokine staining assays in response to HIV gag pool stimulation. Outcomes were evaluated by repeated measures GEE models. In addition, viral load outcomes from HCs in the UCSF SCOPE cohort were included if they had been treated with ART with subsequent VL measurements after ART discontinuation. Results: Thirty-five HCs completed ≥24 weeks of ART in A5308 and were analyzed. Before ART, higher levels of HIV-specific CD4+ and CD8+ T cell responses were associated with undetectable viremia either by the integrase- single copy assay or the Abbott viral load assay. After 24-48 weeks of ART, significant decreases were observed in a broad range of HIV-specific CD4+ and CD8+ T cell responses. These included CD4+ T cells expressing IFN-γ (-0.32 percentage points (%) [95% confidence interval -0.50%, -0.14%], p<0.001), IL2 (-0.19% [-0.37%, -0.02%], p=0.03), TNFα (-0.53% [-1.1%, 0.02%], p=0.06), and CD8+ cells expressing IFN-γ (-0.23% [-0.47%, 0%], p=0.05), TNFα (-0.32% [-0.58%, -0.07%], p=0.01), and CD107 (-0.38% [-0.82%, 0.06%], p=0.09). Furthermore, significant reductions were found in the percentages of polyfunctional HIV-specific CD4+ and CD8+ cells expressing multiple cytokines (CD4+ IFN-γ+ TNFα+ CD107+: -0.08%, p=0.004; CD8+ IFN-γ+ TNFα+ CD107+: -0.13%, p=0.001). Four HCs from A5308 and 6 HCs from the UCSF SCOPE study discontinued ART after a median [Q1, Q3] of 33 [25, 65] weeks of treatment. Two of the HCs had detectable VLs immediately preceding ART initiation. In the first 24 weeks after ART discontinuation, only 1 of the 10 HCs had a detectable VL (107 HIV-1 RNA copies/mL). This participant also had the highest pre-ART VL (53 HIV-1 RNA copies/mL). Conclusion: ART significantly reduces both HIV-specific CD4+ and CD8+ T cell responses in HIV controllers. ART did not adversely affect controller status as HIV controllers maintained a low viral load after ART discontinuation. 509 RESTRICTED MEAN SURVIVAL TIME AS A TREATMENT MEASURE IN HIV/ AIDS CLINICAL TRIALS Xian Abulizi 1 , Philippe Flandre 1 , Heather Ribaudo 2 1 INSERM, Paris, France, 2 Harvard T.H. Chan School of Public Health, Boston, MA, USA Background: Under- or over-estimation of the hypothesized failure rates in the definition of non-inferiority bounds for a hazard ratio (HR) estimand can significantly impact on the probability of a trial demonstrating non-inferiority

Poster Abstracts

510 HOME VS SELF-INITIATED ART REFILL: CLINICAL, IMMUNOLOGICAL, AND VIROLOGIC OUTCOMES Rory F. Leisegang 1 , Jane Ball 1 , Mark Cotton 2 , David Dowdy 3 , Keri Calkins 3 , Susan Cleary 1 , Gary Maartens 1 , Jean B. Nachega 4 1 University of Cape Town, Cape Town, South Africa, 2 Stellenbosch University, Tygerberg, South Africa, 3 Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA, 4 University of Pittsburgh, Pittsburgh, PA, USA Background: Antiretroviral therapy (ART) delivery by courier to the patient’s home (home refill) is a novel intervention that may improve clinical outcomes and reduce indirect costs for individuals in low- and middle-income countries (LMICs). We aimed to compare clinical and virologic outcomes for patients obtaining medication refills at their local pharmacy (self refill) vs. home refill in Aid for AIDS (AFA), a large South African private sector HIV/AIDS programme. Methods: Retrospective cohort analysis of ART naïve HIV-infected adults in AFA who initiated first line NNRTI based ART regimen between January 2002 and July 2010 was performed. Patients were selected to switch to home refill based on the discretion of AFA. Primary endpoint was all-cause mortality; secondary endpoints were viral suppression (VL< 400 copies/mL) and median CD4+ T-cell response (cells/µl) (from baseline) at 6-month intervals. We compared the crude survival between self-refill and home refill using Kaplan–Meier plots and a log-rank test. We performed Cox regressions to model the individual and simultaneous effects of baseline variables and mode of ART delivery on all-cause mortality, adjusting for propensity score. Results: 40,939 patients, contributing 66,204 years of follow-up were recorded. The most common first line regimen was efavirenz + lamuvidine + zidovudine, followed by efavirenz + emtricitabine + tenofovir in later years. Emerging at 24 months, the home refill group had improved median CD4+ T-cell count response (451 vs. 387, respectively, p < 0.01), and the likelihood of

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