CROI 2017 Abstract e-Book

Abstract eBook

Poster and Themed Discussion Abstracts

1 NIAID, Bethesda, MD, USA, 2 Weill Cornell Med, New York, NY, USA, 3 Leicester Royal Infirmary, Leicester, UK, 4 Med Univ of Vienna, Vienna, Austria, 5 Hosp Italiano de Buenos Aires, Buenos Aires, Argentina, 6 Kirby Inst, Sydney, Australia Background: The benefit of immediate antiretroviral therapy (ART) was established in the strategic timing of antiretroviral treatment (START) study. This benefit was evident across a number of baseline subgroups including plasma viral load (pVL). The aim of this sub-analysis of the START trial was to assess the effects of immediate versus deferred ART on CD4+ count and pVL during follow-up, outcomes for which there is greater power, among participants with pVL ≤3000 c/mL (lowest quartile). This is an important subgroup due to their low risk of clinical outcomes. Methods: Participants with pre-ART pVL ≤3000c/mL were included in this sub-analysis provided they had no current or previous history of ART use (N=1138 including 347 with pVL≤400c/mL and 94 with pVL≤50 c/mL). All analyses were ITT. We compared immediate (Imm) with deferred (Def) ART in terms of the CD4 cell count and pVL results at study time points. Results: Participants with pVL≤3000c/mL had a pre-ART median age of 37 years and 40%were female. 4% of participants were HCV antibody + and 3%were HBsAg+. The median CD4 cell count was 714 cells/µL (IQR 617, 854) and median pVL was 971 c/mL (IQR 293, 1830). 538 out of 557 (97%) in the Imm arm started ART at a median of 6 days (IQR 1, 14) and 168 out of 581 (29%) in the Def arm at a median of 694 days (IQR 396, 1033) after randomization respectively. Primary endpoints were observed in 11 (0.67 per 100 person years) and 12 (0.72 per 100 person years) participants in the Imm and Def arms respectively (hazard ratio=0.92, 95% confidence interval 0.41 to 2.08). Mean CD4 counts and percentage of participants with pVL≤200 c/mL and >3000 c/mL by randomization arm at 12 and 24 months are shown in Table 1. The mean CD4 count difference between treatment arms at 12 months was 126 cells/µL (95% confidence interval 94 to 157). Conclusion: In this sub-analysis of START participants with pre-treatment pVL <3000 c/mL randomized to Imm vs Def ART. The Imm ART group had higher CD4 cell counts and greater suppressed viremia during follow-up. The clinical benefits of these differences will require long-term follow-up.

Poster and Themed Discussion Abstracts

474 BENEFIT OF CONTINUOUS/IMMEDIATE ART ON DISEASE RISK: SMART & START COMBINED ANALYSIS Álvaro H. Borges 1 , Jacqueline Neuhaus 2 , Shweta Sharma 2 , James Neaton 2 , Keith Henry 3 , Olga Anagnostou 4 , Therese Staub 5 , Sean Emery 6 , Jens D. Lundgren 1 , for the INSIGHT SMART & START Study Groups 1 RigsHosp, Copenhagen, Denmark, 2 Univ of Minnesota, Minneapolis, MN, USA, 3 Hennepin County Med Cntr, Minneapolis, MN, USA, 4 Univ of Athens, Athens, Greece, 5 Cntr Hosp de Luxembourg, Luxembourg, Luxembourg, 6 Kirby Inst, Sydney, Australia Background: The SMART and START trials established continuous/immediate ART as the standard of care for HIV+ persons. The CD4 difference between treatment groups during follow-up in each trial was approximately 200 cells/µL. We hypothesized that treatment hazard ratios (HRs) were similar in each trial and the pooled analysis of the two studies would better estimate the effect of continuous/immediate ART on disease risk. Methods: The drug conservation arm in SMART and the deferred ART arm in START were pooled as the “immune impairment group” (IIG) and the viral suppression arm in SMART and the early ART arm in START as “immune preservation group” (IPG). Endpoints assessed were AIDS or AIDS-death (AIDS), serious non-AIDS or non-AIDS-death (SNA), cardiovascular disease (CVD), cancer, and all-cause death. HRs from Cox models were obtained for IIG vs IPG for each study and heterogeneity assessed. For the pooled cohort we 1) obtained estimated HRs, 2) assessed mediators of IPG benefit frommodels adjusting for baseline demographics, CVD and cancer risk factors, and time-updated CD4 and HIV RNA, and 3) performed subgroup analyses based on baseline demographics, CVD and cancer risk factors, CD4 count and geographical region. Results: Among 10157 participants (median age 40y; 27% female; 51%MSM; median baseline CD4 634 cells/µL; 37% smokers), there were 123 AIDS, 244 SNA, 117 cancers, 103 CVD, 118 deaths, and 359 AIDS or SNA. Nadir median CD4 counts in SMART and START were 250 and 553 cells/µL, respectively. HRs for endpoints were similar for both trials without evidence of heterogeneity (Figure). Unadjusted pooled HRs (95% CI) of IIG vs IPG were for AIDS 3.60 (2.35, 5.51); SNA 1.59 (1.23-2.06); CVD 1.60 (1.07-2.37); cancer 1.86 (1.27-2.72); death 1.82 (1.25-2.65), and AIDS or SNA 2.03 (1.63-2.53). Adjustment for time-updated CD4 and HIV RNA attenuated the pooled HRs for SNA (1.35, 1.00-1.82) and death (1.21, 0.78- 1.87). IIG was consistently associated with increased risk of the various endpoints across all subgroups investigated (interaction p>0.1), except that the risk of cancer associated with IIG was higher among those ≤ 35 years (HR 3.16 vs 1.86, interaction p=0.05). Conclusion: Continuous/immediate ART use reduced the risk of AIDS and SNA events among HIV+ persons consistently in SMART and START despite a difference in nadir CD4 count of 300 cells/µL. Pooled treatment differences were similar across a number of subgroups except for age and cancer risk. 475 NO PER-PATIENT COST INCREASE UNDER IMMEDIATE ART FOR ALL: EVIDENCE FROM SWAZILAND Shaukat Khan 1 , Emma Mafara 1 , Pascal Geldsetzer 2 , Salinda Phanitsiri 3 , Cebele Wong 1 , Charlotte Lejeune 1 , Fiona Walsh 3 , Velephi Okello 4 , Till Baernighausen 5 1 Clinton Hlth Access Initiative, Mbabane, Swaziland, 2 Harvard Univ, Boston, MA, USA, 3 Clinton Hlth Access Initiative, Boston, MA, USA, 4 Swaziland Ministry of Hlth, Mbabane, Swaziland, 5 Heidelberg Univ, Heidelberg, Germany Background: Swaziland has one of the highest adult HIV prevalence rates (26%) worldwide. As Swaziland and many other countries in sub-Saharan Africa are moving to universal test-and-treat (UTT), or Early Access to ART for All (EAAA), policies, it is critical to understand the cost implications of this change to inform long-term financial planning. The study presented here is one of the first empirical costing study of EAAA in a public-sector health setting. We compare average patient costs under standard-of-care (SOC) vs. under EAAA.

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