CROI 2020 Abstract eBook

Abstract eBook

Oral Abstracts

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MYELIN CONTENT IS ELEVATED IN VIROLOGICALLY UNSUPPRESSED PEOPLE LIVING WITH HIV Dimitre Tomov 1 , Sarah A.Cooley 1 , Casey Bowen 1 , Jeremy Strain 1 , Beau Ances 1 1 Washington University in St Louis, St Louis, MO, USA Background: HIV adversely affects myelin and leads to white matter pallor. With a recently developed method, myelin content can be assessed by T1-weighted (T1w) and T2-weighted (T2w) MRI. The overall pattern in the myelin maps is affected by disease with increases in the T1w/T2w ratio seen in neurodegenerative conditions. We hypothesized that older (> 50 years old) persons living with HIV (PLWH) who had virological failure (VF) would have an increase in the T1w/T2w ratio compared to individuals with virological suppression (VS) or healthy controls (HC). Methods: Structural T1w and T2w MRI scans were obtained from 424 participants including 206 HC, 140 PLWH with VS, and 78 PLWH with VF. T1w images were processed with FreeSurfer 6.0 to generate brain parcellations . Standard pipelines established for the Human Connectome Project (HCP) were used to derive myelin maps for each individual. Their myelin was estimated from the T1w to T2w ratio and assigned to the cortical surface of the brain. Individual brains were then registered to a common surface atlas. Average meylin for each FreeSurfer parcel was computed. Omnibus ANCOVA analysis with age as a covariate was used to identify the regions of interest (ROI) where myelin among VF, VS and HC groups was significantly different. Only ROI which survived corrected statistical threshold of 0.05 corrected for multiple comparisons, were then further assessed with pair-wise t-tests between each group. Spearman correlations were performed between viral load and myelin content in the VF group. Results: Exemplar myelin content maps from a characteristic PLWH are presented in Figure 1A. Regions of interest (ROI) from the Desikan-Killiany cortical atlas exhibited significantly elevated T1w/T2w ratio for PLWH with VF compared to PLWH with VS and HC. Areas that were significantly different included the right posterior cingulate, right inferior temporal, left orbitofrontal, right and left rostral middle frontal. Within PLWH with VF there was no significant correlation between the T1w/T2w ratio and VL for any of the regions. Conclusion: Our results suggest that PLWH who have VF have increases in myelin content compared to PLWH who have VS and HIV- controls. The observed increases in T1w/T2w ratio may reflect myelin damage or increases in inflammation and are similar to what has been observed in other neurodegenerative diseases. The T1w/T2w ratio does not measure virological failure.

Background: The 2-drug regimen of long-acting (LA) cabotegravir (CAB) and rilpivirine (RPV) dosed i.m. every 4 weeks (Q4W) was noninferior to daily oral 3-drug ART in Phase 3 studies. These results and supportive CAB+RPV LA pharmacokinetics enable regimen evaluation at a longer and potentially more convenient 8-week dosing interval (Q8W). Methods: ATLAS-2M is a multicenter, open-label, Phase 3b noninferiority (NI) study of CAB+RPV LA maintenance therapy administered Q8W (600mg CAB + 900mg RPV) or Q4W (400mg CAB + 600mg RPV) to treatment-experienced, HIV-infected adults. Virologically suppressed individuals on CAB+RPV LA Q4W (ATLAS study rollover) or oral standard-of-care were randomized 1:1 to receive CAB+RPV LA Q8W or Q4W. The primary endpoint at Week 48 was the proportion with plasma HIV-1 RNA ≥50 c/mL (Snapshot, ITT-exposed [ITTe]) with an NI margin of 4%. The key secondary endpoint was the proportion with HIV-1 RNA <50 c/mL (Snapshot, ITTe) with an NI margin of -10%. Results: 1045 participants were randomized and treated with CAB+RPV LA Q8W (n=522) or Q4W (n=523); 27%were female, 73%were white. Median age was 42 years (range 19–83); 63%were naïve to CAB+RPV LA while 37% transitioned from Q4W CAB+RPV LA in ATLAS. CAB+RPV LA Q8Wwas noninferior to Q4W dosing in both the primary (1.7% vs 1.0%) and secondary analysis (94.3% vs 93.5%; see Table). There were 8 and 2 confirmed virologic failures (CVFs; 2 sequential measures ≥200 c/mL) on Q8W and Q4W dosing, respectively; 5 and 0 CVFs, respectively, had archived resistance-associated mutations (RAMs) to RPV (E138A, Y188L, H221Y, Y181C) either alone (n=4) or with a CAB RAM (G140R, n=1) in baseline Peripheral blood mononuclear cells (PBMCs). On-treatment RAMs to RPV (K101E, E138K, M230L), CAB (N155H, Q148R, E138K), or both not present in baseline PBMCs were found in 5/8 Q8W CVFs and both Q4W CVFs. The safety profile was similar for Q4W and Q8W dosing (Table). Injection site reactions (ISRs) were mostly mild or moderate (98% overall) with a median duration of 3 days. Discontinuation for an adverse event occurred in 2% of patients (Q8W, n=12; Q4W, n=13), with 5 (1%) in each group due to ISRs. There was one death (Q8W; sepsis). Of those treated Q8W in ATLAS-2M after ≥48 weeks of Q4W dosing in ATLAS, 93% (115/124) expressed a preference for Q8W dosing. Conclusion: Q8W dosing of CAB+RPV LA was noninferior to Q4W dosing and well tolerated. These results support the therapeutic potential of CAB+RPV LA administered every 2 months.

Oral Abstracts

34 CABOTEGRAVIR + RILPIVIRINE EVERY 2 MONTHS IS NONINFERIOR TO MONTHLY: ATLAS-2M STUDY Edgar T. Overton 1 , Gary J. Richmond 2 , Giuliano Rizzardini 3 , Hans Jaeger 4 , Catherine Orrell 5 , Firaya Nagimova 6 , Fritz Bredeek 7 , Miguel García-Deltoro 8 , Paul D. Benn 9 , Yuanyuan Wang 10 , Krischan J. Hudson 11 , David A. Margolis 11 , Kimberly Smith 11 , Peter E. Williams 12 , William Spreen 11 1 University of Alabama at Birmingham, Birmingham, AL, USA, 2 Broward Health Medical Center, Ft Lauderdale, FL, USA, 3 Fatebenefratelli Sacco Hospital, Milan, Italy, 4 MVZ Karlsplatz HIV Research and Clinical Care Center, Munich, Germany, 5 Desmond Tutu HIV Foundation, Cape Town, South Africa, 6 Republic Tartarstan AIDS Center, Kazan, Russia, 7 Metropolis Medical, San Francisco, CA, USA, 8 Hospital General de Valencia, Valencia, Spain, 9 ViiV Healthcare, Brentford, UK, 10 GlaxoSmithKline, Collegeville, PA, USA, 11 ViiV Healthcare, Research Triangle Park, NC, USA, 12 Janssen, Beerse, Belgium

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PROSPECTIVE ENHANCED MONITORING OF DOLUTEGRAVIR-BASED FIRST LINE IN MALAWI Elvis Temfack 1 , Andreas Jahn 2 , Thokozani Kalua 2 , Joseph Bitilinyu-Bangoh 3 , Rose Nyirenda 2 , Anne-Geneviève Marcelin 4 , Vincent Calvez 4 , Diane Descamps 5 , Gilles Peytavin 5 , Sarala Nicholas 1 , David Maman 6 , Sofie Spiers 6 , Elisabeth Poulet 1 , Elisabeth Szumilin 7 , Birgitt Schramm 1 1 Epicentre, Paris, France, 2 Malawi Department of HIV and AIDS, Lilongwe, Malawi, 3 Queen Elizabeth Central Hospital, Blantyre, Malawi, 4 AP–HP, Hôpitaux Universitaires Pitié Salpêtrière, Paris, France, 5 AP–HP, Hôpital Bichat-Claude Bernard, Paris, France, 6 MSF, Lilongwe, Malawi, 7 MSF, Paris, France Background: In January 2019 the Ministry of Health of Malawi rolled-out tenofovir-lamivudine-dolutegravir (TLD) as national first-line antiretroviral therapy (ART). Transitioning of patients already on non-nucleoside-reverse-

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CROI 2020