CROI 2020 Abstract eBook
resistant HIV-1 infection who are unable to form a viable regimen from fully active ARV agents. We present the impact of key baseline (BL) factors on short- term virologic outcome and durability of response to FTR in the Randomized Cohort (RC). Methods: RC participants, with 1-2 fully active ARVs were randomized (3:1) to blinded FTR 600 mg (n=203) or placebo (n=69) BID plus failing regimen for 8 days of functional monotherapy, followed by open-label FTR 600mg BID plus optimized background therapy (OBT; n=272). The impact of BL factors: gp120 polymorphisms, TMR IC 50 fold-change (FC), and HIV-1 subtype, on change in HIV-1 RNA from Day 1 to 8, proportion of participants with a clinically relevant (>0.5log 10 ) decrease in HIV-1 RNA at Day 8, and HIV-1 RNA <40 c/mL at W96, was evaluated. Results: Overall, 46% (122/263) of evaluable RC participants had a relevant gp120 polymorphism present at BL. Median change in HIV-1 RNA at Day 8 was lower among monotherapy participants with vs without BL gp120 polymorphisms of interest (-0.65 log 10 vs -1.03 log 10 ). However, 55% (48/88) of participants with BL gp120 polymorphisms achieved a viral load reduction >0.5 log 10 at Day 8. BL TMR IC 50 FC from reference was observed over a broad range (0.05 to >5,000-fold; median 0.99-fold) with 74% (195/263) and 87% (229/263) of evaluable participants with TMR IC 50 FC <10- and <100-fold, respectively. While monotherapy participants with TMR IC 50 FC >100-fold at BL had a median change in HIV-1 RNA of <0.5 log 10 at Day 8, this did not prevent a decline >0.5 log 10 . In fact, 38% (8/21) of participants with BL TMR IC 50 FC >100- fold achieved >0.5 log 10 decline over this time. The majority of participants in the RC (79%, 216/272) had HIV-1 subtype B virus. Similar proportions of monotherapy participants with subtype B (66%, 108/163) vs non-B (65%, 26/40) virus achieved >0.5 log 10 decline in HIV-1 RNA at Day 8; although the number of participants with non-B subtype, including AE, was small (n= 40 and 1, respectively). Conclusion: In BRIGHTE, BL gp120 polymorphisms of interest, TMR IC 50 FC, and HIV-1 subtype did not reliably predict virologic outcome at Day 8 of FTR functional monotherapy and did not impact durability of response (HIV-1 RNA <40 c/mL) to FTR + OBT through 96 weeks of therapy, among HTE participants in the RC.
502 NO SIGNIFICANT CHANGE ON RESERVOIR IN QUATUOR: A 4/7 DAYS A WEEK MAINTENANCE STRATEGY Sidonie Lambert-Niclot 1 , Lambert Assoumou 1 , Pierre De Truchis 2 , Djeneba Bocar Fofana 3 , Karine Amat 4 , Jonathan Bellet 5 , François Raffi 6 , Philippe Morlat 7 , Christine Katlama 8 , Cecile Moins 1 , Dominique Costagliola 9 , Pierre-Marie Girard 10 , Roland Landman 11 , Laurence Morand-Joubert 12 , for the ANRS 170 QUATUOR Study Group 1 INSERM, Paris, France, 2 Assistance Publique – Hôpitaux de Paris, Garches, France, 3 Assistance Publique – Hôpitaux de Paris, Paris, France, 4 Institut de Médecine et d'Epidémiologie Appliquée, Paris, France, 5 Institut Pierre Louis d'Epidemiologie et de Santé Publique, Paris, France, 6 CHU Hôtel-Dieu, Nantes, France, 7 CHU de Bordeaux, Bordeaux, France, 8 AP–HP, Hôpitaux Universitaires Pitié Salpêtrière, Paris, France, 9 Institut Pierre Louis d'Epidémiologie et de Santé Publique, Paris, France, 10 Saint- Antoine Hospital, Paris, France, 11 AP–HP, Hôpital Bichat-Claude Bernard, Paris, France, 12 Laboratoire de Virologie Hôpital Saint Antoine, Paris, France Background: ANRS 170 QUATUOR study demonstrated the non-inferiority of a 4/7 days maintenance strategy vs a 7/7 days regimen in patients with controlled viral load (VL) under triple therapy with either PI, NNRTI, or InSTI based regimen at week 48 (W48). The aims of these virological sub-studies were to assess HIV cellular reservoir size, HIV residual viremia and HIV RNA quantification in semen until W48. Methods: HIV total DNA was measured using the real-time PCR kit GENERIC HIVDNA Cell® (Biocentric®, Bandol, France) with a limit of quantification [LOQ] of 10 copies/PCR. Ultra-sensitive plasma VL (USpVL) and semen HIV VL (1/5 dilution) were determined using COBAS® HIV-1, v2.0 (Roche Molecular Systems, Branchburg, NJ, USA). For USpVL, the limit of detection (LOD) was defined as an undetected PCR signal. Generalized estimating equation was used to compare the changes from baseline of total HIV DNA, plasma seminal VL and plasma blood residual viremia within and between the 2 groups over time. Results: Characteristics of sub-study population were similar to those of global trial population. Paired D0 and W48 HIV total DNA were obtained in 119 patients. 45% and 44% of patients showed a HIV DNA below the LOQ at D0 and W48 respectively. Median (IQR) HIV DNA was 1.7 log 10 c/10 6 PBMC (<1.3-2.3) at D0 and 1.6 (<1.3-2.4) at W48 in the 4D arm versus 1.9 (<1.3-2.3) and 1.7 (<1.3- 2.3) in the 7D arm. Plasma residual viremia was measured in 116 patients at D0 and W48 with a proportion of patients with USpVL detectable of 17.3 % and 26.9% respectively in the 4D arm and 21.9% and 29.7 % in the 7D arm. Semen HIV RNA was measured in 78 patients with a proportion of semen VL detectable in 2.3% at D0 and 6.7% at W48 in the 4D arm versus 6.1% and 9.1 % in the 7D arm. There is no significant evolution in HIV DNA, residual viremia and semen VL maintenance therapy in plasma residual viremia level or in HIV cellular reservoir size, as in the 7/7 days. These findings are reassuring the potency of a 4D/7 maintenance strategy on virological suppression at the level of residual viremia. 503 CLINICAL SIGNIFICANCE OF gp120 POLYMORPHISMS, TMR IC 50 FC AND HIV-1 SUBTYPE IN BRIGHTE Margaret Gartland 1 , Peter Ackerman 2 , Frank Mannino 3 , Louise K. Garside 4 , Andrew Clark 5 , Amy Pierce 1 , Mark Krystal 2 , Cyril C. Llamoso 2 , Max Lataillade 2 1 ViiV Healthcare, Research Triangle Park, NC, USA, 2 ViiV Healthcare, Branford, CT, USA, 3 GlaxoSmithKline, Collegeville, PA, USA, 4 GlaxoSmithKline, Uxbridge, UK, 5 ViiV Healthcare, London, UK Background: The ongoing Ph3 BRIGHTE study is evaluating Fostemsavir (FTR), an investigational prodrug of the first-in-class attachment inhibitor temsavir (TMR), in heavily treatment-experienced (HTE) participants with multi-drug between D0 and W48 and no significant difference between arms. Conclusion: No change was observed during the first year of 4/7 days
504 A HIGHLY POTENT AND SAFE ALLOSTERIC HIV-1 INTEGRASE INHIBITOR, STP0404 Seohyun Ahn 1 , Uk-Il Kim 1 , Won Young Seo 1 , Seongmi Choi 1 , Tatsuya Maehigashi 2 , Jared Lindenberger 3 , Mamuka Kvaratskhelia 3 , Baek Kim 2 , Kyungjin Kim 1 1 ST Pharm Co, Ltd, Seoul, South Korea, 2 Emory University, Atlanta, GA, USA, 3 University of Colorado Anschutz Medical Campus, Aurora, CO, USA Background: Allosteric HIV-1 integrase inhibitors (ALLINIs) are a new class of HIV-1 inhibitors, targeting HIV-1 maturation process. While great efforts have been made for the discovery of ALLINIs, clinical development of ALLINIs
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