CROI 2019 Abstract eBook

Abstract eBook

Oral Abstracts

in rural Kenya and Uganda. All HIV+ persons with CD4<350 were eligible for ART. In 16 intervention communities, ART was delivered via patient-centered streamlined care including supported linkage and rapid ART start. In 16 control communities, ART was delivered via country standard of care. Mortality was ascertained after 3 years via comprehensive outreach. We evaluated (1) identification of HIV+ persons with CD4<350 at baseline, (2) among these persons, the effect of streamlined care on ART start and mortality, and (3) gender differences in mortality. Comparisons between study arms used cluster- level TMLE; survival estimates used Kaplan-Meier; estimates of ART start among ART-naïve persons treated death as a competing risk. Results: Among 13,266 baseline HIV+ residents, 22% (N=2,956) had CD4<350. Of these, 33% (988/2,956) were new diagnoses and 10% (282/2,956) were diagnosed but ART-naive. HIV+men (N=4,597) were twice as likely as HIV+ women (N=8,669) to have CD4<350 and untreated (18% vs. 9%, respectively). Among persons with CD4<350, streamlined care reduced mortality by 27% vs. control (RR=0.72; 95%CI:0.57, 0.93; p=0.02). Mortality was reduced substantially more among men (RR=0.60; 95%CI:0.43, 0.86; p=0.005) than women (RR=0.90; 95%CI:0.62, 1.31; p=0.56). Despite immediate ART eligibility in both arms, persons with CD4<350 started ART faster under streamlined care vs. control (76% vs. 43% by 12 months, respectively, p<0.001). Within each arm, time to ART start was similar between men and women. However, more men vs. women had baseline HIV RNA>100,000 copies/mL (29% vs. 19%, respectively), placing men at elevated risk of HIV progression/death. Conclusion: After population-based HIV testing, SEARCH streamlined care accelerated ART start and reduced mortality at a population level among HIV+ persons with CD4<350, particularly among men. These interventions may play a key role in meeting the UNAIDS goal of eliminating AIDS deaths. Susan Swindells 1 , Jaime-Federico Andrade-Villanueva 2 , Gary J. Richmond 3 , Giuliano Rizzardini 4 , Axel Baumgarten 5 , Maria Del Mar Masia 6 , Gulam Latiff 7 , Vadim Pokrovsky 8 , Joseph M. Mrus 9 , Jenny O. Huang 10 , Krischan J. Hudson 9 , David A. Margolis 9 , Kimberly Smith 9 , Peter E. Williams 11 , William Spreen 9 1 University of Nebraska Medical Center, Omaha, NE, USA, 2 University of Guadalajara, Guadalajara, Mexico, 3 Broward Health Medical Center, Fort Lauderdale, FL, USA, 4 Fatebenefratelli Sacco Hospital, Milan, Italy, 5 MIB Infectious Disease Medical Center, Berlin, Germany, 6 Hospital General Universitario de Elche, Elche, Spain, 7 Maxwell Centre, Durban, South Africa, 8 Russia AIDS Federal Center, Moscow, Russian Federation, 9 ViiV Healthcare, Research Triangle Park, NC, USA, 10 GlaxoSmithKline, Mississauga, Ontario, Canada, 11 Janssen, Beerse, Belgium Background: ATLAS, a phase 3, open-label, multicenter study, was designed to establish whether switching to monthly long-acting (LA) Cabotegravir (CAB) + Rilpivirine (RPV) LA is noninferior to continuing current 3-drug oral ART in adults with virologically suppressed HIV-1 infection. Methods: Eligible participants had HIV-1 RNA <50 c/mL for ≥6 months without virologic failure on oral regimens comprising 2 NRTI + 1 INSTI, NNRTI, or PI. Participants were randomly assigned (1:1) to continue current ART (CART arm) or switch to the LA arm. The LA arm participants received oral CAB 30mg + RPV 25mg once daily for 4 weeks for safety monitoring, then single 3 mL loading doses of CAB LA 600mg (200 mg/mL) and RPV LA 900mg (300 mg/mL) by IM injection, followed by 2 mL IM injections every 4 ± 1 weeks of CAB LA 400mg and RPV LA 600mg. The primary endpoint was HIV-1 RNA ≥50 c/mL at W48, using the FDA snapshot algorithmwith a 6% noninferiority margin. Results: 616 participants initiated treatment (308/arm; ITT-E). Median age was 42 yrs (26%≥50 yrs); 33%were female and 68%white. Baseline regimens included 2 NRTI + 1 NNRTI (50%), INSTI (33%), or PI (17%). At W48, 5 participants (1.6%) in the LA arm and 3 (1.0%) in the CART arm had HIV-1 RNA ≥50 c/mL, meeting noninferiority criteria for the primary endpoint (Table). Similarly, the LA armwas noninferior to CART for the key secondary endpoint of HIV-1 RNA <50 c/mL (93% vs 95%). Three LA and 4 CART participants had confirmed virologic failure (CVF, HIV-1 RNA ≥200 c/mL in consecutive samples). The LA CVFs included 1 with RAM E138A, 1 with E138A+V108I (both having E138A in baseline DNA), and 1 with RT-E138E/K and IN-N155H. The 4 CART CVFs included 1 each of RAMs M184I, M184V+G190S, M230M/I, and 1 with no RAMs. In the LA arm, 231 participants (75%) had injection site pain with 4 participants (1%) withdrawing for these events. Incidences of grade 3/4 and serious AEs were similar across the LA and CART arms; there was 1 death (CART arm). Of the 275

LA arm participants completing HIVTSQc at W48, 98%were more satisfied with CAB LA + RPV LA compared with their daily oral treatment at study entry. Conclusion: The regimen of monthly injections of CAB LA + RPV LA was noninferior to continued 3-drug oral ART at W48. The LA regimen was generally well tolerated, with low rates of serious AEs and drug- or injection-related withdrawals. Virologic failure was infrequent in both arms. Overall, these results support the therapeutic potential of once-monthly CAB LA + RPV LA.

Oral Abstracts

139 LONG-ACTING CABOTEGRAVIR + RILPIVIRINE AS MAINTENANCE THERAPY: ATLAS WEEK 48 RESULTS

140LB LONG-ACTING CABOTEGRAVIR + RILPIVIRINE FOR HIV MAINTENANCE: FLAIR WEEK 48 RESULTS Chloe Orkin 1 , Keikawus Arastéh 2 , Miguel Górgolas Hernández-Mora 3 , Vadim Pokrovsky 4 , Edgar T. Overton 5 , Pierre-Marie Girard 6 , Shinichi Oka 7 , Ronald D’Amico 8 , David Dorey 9 , Sandy Griffith 8 , David A. Margolis 8 , Peter E. Williams 10 , Wim Parys 10 , William Spreen 8 1 Queen Mary University of London, London, UK, 2 EPIMED GmbH, Berlin, Germany, 3 Fundacion Jimenez Diaz, Madrid, Spain, 4 Central Research Institute of Epidemiology, Moscow, Russian Federation, 5 University of Alabama at Birmingham, Birmingham, AL, USA, 6 Hôpital Saint Antoine, Paris, France, 7 National Center for Global Health and Medicine, Tokyo, Japan, 8 ViiV Healthcare, Research Triangle Park, NC, USA, 9 GlaxoSmithKline, Mississauga, Canada, 10 Janssen Research & Development, Beerse, Belgium Background: The 2-drug long-acting (LA) injectable regimen of the INSTI cabotegravir (CAB) and the NNRTI rilpivirine (RPV) is being developed to reduce dose frequency, pill taking and drug exposure. FLAIR, a phase 3, open-label, multicenter study is investigating whether switching to monthly CAB+RPV is noninferior to dolutegravir/abacavir/lamivudine (DTG/ABC/3TC). Methods: ART-naïve participants received induction therapy with oral DTG/ ABC/3TC (CAR & ) for 20 weeks. Those with HIV-1 RNA <50 c/mL at 16 weeks were eligible to enter the maintenance phase and randomly assigned (1:1) to continue CAR or switch to LA. Participants in the LA arm received an oral lead-in of CAB 30mg + RPV 25mg once daily for 4 weeks to assess tolerability before receiving CAB+RPV as intramuscular monthly LA injectable therapy. The primary endpoint was viral load (VL) ≥50 c/mL at W48 by FDA snapshot algorithm (NI margin 6%). Safety, tolerability and confirmed virologic failure (CVF) were secondary endpoints. Results: 566/629 participants who initiated induction therapy were randomly assigned to the LA or CAR arm (283/arm). The median age was 34 yr (11%≥50 yr); 22%were female and 74%were white. At the induction phase start, median CD4 count was 444 cells/mm³ (7%<200 cells/mm³), median VL was 4.49 log 10 c/ mL (20%≥100,000 c/mL). Six participants in the LA arm (2.1%) and 7 in the CAR arm (2.5%) had HIV-1 RNA ≥50 c/mL at W48, meeting noninferiority criteria for the primary endpoint (Table) and for the key secondary endpoint of HIV-1

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CROI 2019