833. Efficacy and Safety of Long-Acting Cabotegravir + Rilpivirine in Participants with HIV/HCV Co-infection: ATLAS-2M 48-Week Results

Abstract Background The phase IIIb ATLAS-2M study demonstrated non-inferiority of long-acting (LA) cabotegravir (CAB) + rilpivirine (RPV) dosed every 8 weeks (Q8W) compared with every 4 weeks (Q4W) for maintenance of virologic suppression. Hepatitis C virus (HCV) co-infection occurs in ~6% of people with HIV due to shared modes of transmission. We report efficacy and safety of CAB + RPV LA in participants with HIV/HCV co-infection in ATLAS-2M. Methods Participants with HIV-1 RNA < 50 c/mL receiving CAB + RPV LA Q4W (transitioned from ATLAS [NCT02951052]) or oral comparator ART were randomized 1:1 to receive CAB + RPV LA Q4W or Q8W. Baseline HCV RNA was assessed by polymerase chain reaction. Participants with symptomatic chronic HCV infection requiring treatment within 12 months or liver enzymes not meeting entry criteria were excluded. Week 48 assessments included proportion with HIV-1 RNA ≥50 and < 50 c/mL (Snapshot algorithm), general and hepatic safety, and pharmacokinetics. Results HIV/HCV co-infection was present in 10 (1%) of 1045 participants, 60% of whom were female at birth. At Week 48, 9/10 (90%) and 972/1035 (94%) participants with HIV/HCV co-infection and HIV mono-infection, respectively, had HIV-1 RNA < 50 c/mL (adjusted difference, 4.1; 95% CI, −14.5 to 22.6). No participants with HIV/HCV co-infection had HIV-1 RNA ≥50 c/mL (vs 14/1035 [1%] with HIV mono-infection) or confirmed virologic failure through Week 48 (vs 10 [1%] with HIV mono-infection); 1/10 (10%) discontinued for reasons other than adverse events (AEs). Excluding injection site reactions (ISRs), AEs and serious AEs were reported in 4 (40%) and 0 participants with HIV/HCV co-infection, respectively; the only AE reported in >1 participant was injection site pain (n=5; 50%). In participants with HIV/HCV co-infection, all ISRs were grade 1/2; none led to withdrawal. No hepatic laboratory abnormalities were reported in participants with HIV/HCV co-infection through Week 48; rates were low in those with HIV mono-infection (Table). Plasma CAB and RPV concentrations were similar between groups. Conclusion CAB + RPV LA was effective and well tolerated in this small cohort of participants with HIV and asymptomatic HCV co-infection. Disclosures Ronald D’Amico, DO, MSc, GlaxoSmithKline (Shareholder)ViiV Healthcare (Employee) Paul Benn, MB ChB FRCP, ViiV Healthcare (Employee) Shanker Thiagarajah, MB ChB, GlaxoSmithKline (Employee, Shareholder) Susan L. Ford, PharmD, GlaxoSmithKline (Shareholder)ViiV Healthcare (Employee) Eileen Birmingham, MD, MPH, Janssen Research and Development (Employee, Shareholder) Ojesh R. Upadhyay, MPH, MBA, GlaxoSmithKline (Employee) Louise Garside, PhD, GlaxoSmithKline (Employee) Rodica Van Solingen-Ristea, MD, Janssen Research and Development (Employee)ViiV Healthcare (Employee) Kati Vandermeulen, M.SC., Janssen Research and Development (Employee) William Spreen, PharmD, GlaxoSmithKline (Shareholder)ViiV Healthcare (Employee)

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877. North American Phase 3/3b Experience with Long-Acting Cabotegravir and Rilpivirine: Efficacy, Safety, and Virologic Outcomes

Open Forum Infectious Diseases ◽

10.1093/ofid/ofab466.1072 ◽

2021 ◽

Vol 8 (Supplement_1) ◽

pp. S530-S531

Author(s):

Babafemi O Taiwo ◽

Darrell Tan ◽

Parul Patel ◽

Paula Teichner ◽

Joseph Polli ◽

...

Keyword(s):

Treatment Guidelines ◽

Virologic Failure ◽

Descriptive Analysis ◽

Injection Site Reaction ◽

Treatment Preference ◽

Virologic Suppression ◽

Research Support ◽

Phase 3 ◽

Long Acting ◽

Hiv 1

Abstract Background Cabotegravir (CAB) plus rilpivirine (RPV) is the first complete long-acting (LA) regimen recommended by treatment guidelines for the maintenance of HIV-1 virologic suppression. CAB+RPV LA dosed every 4 weeks (Q4W) or every 8 weeks (Q8W) demonstrated noninferior efficacy in multinational Phase 3/3b trials. This post hoc descriptive analysis summarizes efficacy, virologic outcomes, safety, and treatment preference for US and Canadian (CAN) participants through Week (W) 48. Methods This analysis focuses on data for US/CAN participants naive to CAB+RPV (n=376) from the larger pooled population of the ATLAS, FLAIR, and ATLAS-2M Phase 3/3b studies (N=1245). Endpoints included the proportion of participants with plasma HIV-1 RNA ≥ 50 and < 50 c/mL at W48 (FDA Snapshot algorithm), incidence of confirmed virologic failure (CVF; 2 consecutive HIV-1 RNA ≥ 200 c/mL), safety, and treatment preference through W48. Results 376 US/CAN participants received CAB+RPV LA Q4W or Q8W. Median (range) age was 39y (20–74); 14.9% were female, 66.0% were White. At W48, 93.1% (350/376) maintained virologic suppression (HIV-1 RNA < 50 c/mL), 1.9% (7/376) had HIV-1 RNA ≥ 50 c/mL, and 0.8% (3/376) met the CVF criterion, consistent with the overall global pooled population (Table 1). Two of the three participants with CVF had ≥ 2 of the three baseline factors (archived RPV resistance-associated mutations [RAMs], HIV subtype A6/A1, body mass index [BMI] ≥ 30 kg/m2) previously associated with CVF. Among the US/CAN participants with a single baseline factor, none met CVF. Overall, archived RPV RAMs were observed in 3.2% (12/376), HIV subtype A6/A1 in 1.1% (4/376), and BMI ≥ 30 kg/m2 in 26.3% (99/376) of participants. Safety and injection site reaction findings were similar to the overall pooled population (Table 2). Most participants (120/134, 89.6%) preferred LA over oral dosing (7/134, 5.2%). Table 1. Snapshot outcomes following CAB+RPV LA Q4W and Q8W at Week 48 in participants naive to CAB+RPV from ATLAS, FLAIR, and ATLAS-2M (ITT-E population) Table 2. Safety summary through Week 48 following CAB+RPV LA Q4W and Q8W or comparator ART in participants naive to CAB+RPV from ATLAS, FLAIR, and ATLAS-2M Conclusion In US/CAN Phase 3/3b trial participants, CAB+RPV LA was highly effective and well tolerated, with outcomes consistent with the overall pooled population. Baseline prevalence of archived RPV RAMs and subtype A6/A1 was low and aligned with regional prevalence/surveillance data. CAB+RPV LA provides a tolerable and effective injectable LA treatment option for virologically suppressed US/CAN individuals with HIV. Disclosures Babafemi O. Taiwo, MBBS, Gilead (Consultant)Merck (Consultant)ViiV Healthcare (Consultant) Darrell Tan, MD PhD, Abbvie (Grant/Research Support)Gilead (Grant/Research Support)GlaxoSmithKline (Scientific Research Study Investigator)ViiV Healthcare (Grant/Research Support) Parul Patel, PharmD, GlaxoSmithKline (Shareholder)ViiV Healthcare (Employee) Paula Teichner, PharmD, GlaxoSmithKline (Shareholder)ViiV Healthcare (Employee) Joseph Polli, PhD, FAAPS, GlaxoSmithKline (Shareholder)ViiV Healthcare (Employee) Louise Garside, PhD, GlaxoSmithKline (Employee) Ronald D’Amico, DO, MSc, GlaxoSmithKline (Shareholder)ViiV Healthcare (Employee) Christine L. Talarico, M.S., GlaxoSmithKline (Shareholder)ViiV Healthcare (Employee) Rodica Van Solingen-Ristea, MD, Janssen Research and Development (Employee)ViiV Healthcare (Employee) Bryan Baugh, MD, Janssen, Johnson & Johnson (Employee, Shareholder) William Spreen, PharmD, GlaxoSmithKline (Shareholder)ViiV Healthcare (Employee) Michael Aboud, MBChB, MRCP, GlaxoSmithKline (Shareholder)ViiV Healthcare (Employee) Matthew Bosse, DO, GlaxoSmithKline (Shareholder)ViiV Healthcare (Employee)

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Impact of Integrase Sequences From HIV-1 Subtypes A6/A1 on the In Vitro Potency of Cabotegravir or Rilpivirine

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.01702-21 ◽

2022 ◽

Author(s):

Jerry L. Jeffrey ◽

Marty St. Clair ◽

Ping Wang ◽

Chunfu Wang ◽

Zhufang Li ◽

...

Keyword(s):

Virologic Failure ◽

Fold Change ◽

Effective Capacity ◽

Virologic Suppression ◽

Subtype B ◽

Long Acting ◽

Breakthrough Experiments ◽

The Impact ◽

Hiv 1

The FLAIR study demonstrated noninferiority of monthly long-acting cabotegravir + rilpivirine vs daily oral dolutegravir/abacavir/lamivudine for maintaining virologic suppression. Three participants who received long-acting therapy had confirmed virologic failure (CVF) at Week 48, and all had HIV-1 that was originally classified as subtype A1 and contained the baseline integrase polymorphism L74I; updated classification algorithms reclassified all 3 as HIV-1 subtype A6. Retrospectively, the impact of L74I on in vitro sensitivity and durability of response to cabotegravir in HIV-1 subtype B and A6 backgrounds was studied. Site-directed L74I and mutations observed in participants with CVF were generated in HIV-1 subtype B and a consensus integrase derived from 3 subtype A6 CVF baseline sequences. Rilpivirine susceptibility was assessed in HIV-1 subtype B and A1 containing reverse transcriptase mutations observed in participants with CVF. HIV-1 subtype B L74I and L74I/G140R mutants and HIV-1 subtype A6 I74L and I74/G140R mutants remained susceptible to cabotegravir; L74I/Q148R double mutants exhibited reduced susceptibility in HIV-1 subtypes B and A6 (half maximal effective capacity fold change, 4.4 and 4.1, respectively). Reduced rilpivirine susceptibility was observed across HIV-1 subtypes B and A1 with resistance-associated mutations K101E or E138K (half maximal effective capacity fold change, 2.21 to 3.09). In cabotegravir breakthrough experiments, time to breakthrough was similar between L74 and I74 viruses across HIV-1 subtypes B and A6; Q148R was selected at low cabotegravir concentrations. Therefore, the L74I integrase polymorphism did not differentially impact in vitro sensitivity to cabotegravir across HIV-1 subtype B and A6 integrase genes (ClinicalTrials.gov identifier: NCT02938520).

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Indirect comparison of 48-week efficacy and safety of long-acting cabotegravir and rilpivirine maintenance every 8 weeks with daily oral standard of care antiretroviral therapy in participants with virologically suppressed HIV-1-infection

10.21203/rs.3.rs-72129/v1 ◽

2020 ◽

Author(s):

Vasiliki Chounta ◽

Sonya J Snedecor ◽

Sterling Wu ◽

Nicolas Van de Velde

Keyword(s):

Subgroup Analysis ◽

Drug Class ◽

Active Drug ◽

Standard Of Care ◽

People Living With Hiv ◽

Virologic Suppression ◽

Efficacy And Safety ◽

Treatment Comparison ◽

Long Acting ◽

Hiv 1

Abstract BackgroundEfficacy and safety of long-acting cabotegravir (CAB) + rilpivirine (RPV) every 8 weeks (Q8W) versus daily oral standard of care (SoC) maintenance in treatment-experienced individuals with virologically suppressed human immunodeficiency virus type 1 (HIV-1) has not been directly compared in randomized clinical trials. This analysis aimed to indirectly compare these regimens. MethodsAn adjusted indirect treatment comparison of CAB + RPV Q8W with daily oral SoC was performed, using Phase 3 data from studies of CAB + RPV every 4 weeks vs SoC (Q4W; ATLAS/FLAIR, n=591 per group) and a Phase 3b trial of CAB + RPV Q8W vs Q4W (ATLAS-2M [excluding participants with prior CAB + RPV exposure]; n=327 per group). Eligible participants were virologically suppressed (viral load <50 HIV-1 ribonucleic acid (RNA) copies/mL), treatment-experienced individuals with HIV-1-infection. Treatment efficacy and safety at Week 48 included virologic suppression and lack of virologic suppression (proportion of participants with plasma HIV-1 RNA <50 copies/mL or ≥50 copies/mL, respectively; both as per FDA snapshot algorithm), CD4-cell count change from baseline, no virologic data, discontinuations due to adverse events (AEs), and overall AEs, serious AEs and Grade 3–5 AEs excluding injection-site reactions. Baseline characteristics between the Q4W arms of ATLAS/FLAIR and ATLAS-2M showed no significant differences or differences were not judged to be clinically relevant, apart from participants switching from a baseline third active drug class; more participants switched from integrase strand inhibitors in ATLAS/FLAIR, and from non-nucleoside reverse transcriptase inhibitors in ATLAS-2M. A subgroup analysis stratified by baseline third active drug class was performed. ResultsInjections of CAB + RPV Q8W showed no significant differences across efficacy and safety outcomes versus daily oral SoC. The subgroup analysis found there were no significant differences on virologic suppression or lack of virologic suppression for any baseline third active drug class subgroups. These results suggest that CAB + RPV Q8W is non-inferior to daily oral SoC.ConclusionsThis analysis supports the therapeutic potential of CAB + RPV Q8W for virologically suppressed people living with HIV-1 infection seeking an alternative maintenance treatment option to daily oral SoC.Trial registrationNCT02938520, NCT02951052, NCT03299049

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887. Implementation of Long-acting Injectable Cabotegravir/Rilpivirine for HIV-1 Treatment at a Ryan White-funded Clinic in the U.S. South

Open Forum Infectious Diseases ◽

10.1093/ofid/ofab466.1082 ◽

2021 ◽

Vol 8 (Supplement_1) ◽

pp. S535-S535

Author(s):

Lauren F Collins ◽

Della Corbin-Johnson ◽

Meron Asrat ◽

Tonya Rankins ◽

...

Keyword(s):

Virologic Failure ◽

Panel Member ◽

Proton Pump Inhibitor Therapy ◽

Source Distribution ◽

Virologic Suppression ◽

Screening Criteria ◽

Medication Access ◽

Ryan White ◽

Long Acting ◽

Hiv 1

Abstract Background In January 2021, the first ever long-acting injectable (LAI) antiretroviral therapy (ART), cabotegravir/rilpivirine (CAB/RPV), was approved for maintenance HIV-1 treatment in select patients with virologic suppression. LAI-ART has the potential to improve ART adherence, reduce HIV stigma, and promote equity in care outcomes, however, implementation in real-world settings has yet to be evaluated. Methods We launched a pilot LAI-ART program at the largest Ryan White-funded HIV clinic in the Southeast. From 4/14/21 to 5/14/21, providers referred patients interested and willing to switch to LAI-CAB/RPV who met screening criteria. Our interdisciplinary LAI team (Clinician-Pharmacy-Nursing) verified clinical eligibility (HIV-1 < 200 c/ml ≥6 months and no history of virologic failure, resistance to either drug, or chronic HBV infection) and pursued medication access for 28-day oral lead-in and monthly injectable CAB/RPV. We describe demographic and clinical variables of referred PWH and early outcomes in accessing LAI-ART. Results Among 42 referrals, median age was 40.5 (Q1-Q3, 32-52) years, 83% were men, and 76% Black. Payor source distribution was 26% Private, 19% Medicare, 10% Medicaid, and 45% ADAP. At the time of referral, median CD4 count was 583 (Q1-Q3, 422-742) cells/mm3 and median sustained HIV-1 RNA < 200 c/ml was 1427 (Q1-Q3, 961-2534) days. A total of 35 patients (74%) met clinical eligibility for LAI-CAB/RPV, including 4 patients who required a transition off proton pump inhibitor therapy to accommodate oral RPV. Ineligible PWH were excluded due to evidence of RPV resistance (n=5), possible RPV hypersensitivity (n=1), and HIV non-suppression (n=1). The table summarizes the process of pursuing LAI-ART access for the initial 10 enrollees by insurance status. Conclusion Our experience implementing LAI-ART at a Ryan White-funded HIV clinic in the Southern U.S. has been challenged by substantial human resource capital to attain drug, delayed therapy initiation due to insurance denials, and patient ineligibility primarily due to concern for potential RPV resistance. These barriers may perpetuate disparities in ART access and virologic suppression among PWH and need to be urgently addressed so that LAI-ART can be offered equitably. Disclosures Lauren F. Collins, MD, MSc, Nothing to disclose Bradley L. Smith, Pharm.D., AAHIVP, Gilead Sciences, Inc (Advisor or Review Panel member) Wendy Armstrong, MD, Nothing to disclose Jonathan Colasanti, MD, Integritas CME (Consultant, develop and deliver CME content around Rapid Entry/Rapid ART)

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Week 48 Results of EMERALD: A Phase 3, Randomized, Non-inferiority Study Evaluating the Efficacy and Safety of Switching from Boosted-protease Inhibitors (bPI) Plus Emtricitabine (FTC)/Tenofovir Disoproxil Fumarate (TDF) Regimens to the Once Daily (QD), Single-tablet Regimen (STR) of Darunavir/Cobicistat/Emtricitabine/Tenofovir Alafenamide (D/C/F/TAF) in Virologically Suppressed, HIV-1-infected Adults

Open Forum Infectious Diseases ◽

10.1093/ofid/ofx180.009 ◽

2017 ◽

Vol 4 (suppl_1) ◽

pp. S737-S738 ◽

Cited By ~ 2

Author(s):

Chloe Orkin ◽

Jean-Michel Molina ◽

Joel Gallant ◽

Eugenia Negredo ◽

Joseph Gathe ◽

...

Keyword(s):

Virologic Failure ◽

Study Drug ◽

Virologic Suppression ◽

Efficacy And Safety ◽

Open Label ◽

Genetic Barrier ◽

Significant Difference ◽

Safety Parameters ◽

Hiv 1 ◽

Research Grant

Abstract Background EMERALD is evaluating the efficacy and safety of switching from bPI + FTC/TDF regimens (control) to D/C/F/TAF 800/150/200/10 mg in virologically suppressed, HIV-1-infected adults. We present Week 48 primary results. Method EMERALD (NCT02269917) is a randomized, active-controlled, open-label, international, multicenter, parallel-group, non-inferiority trial. Virologically suppressed (viral load [VL] < 50 c/mL for ≥2 months), HIV-1-infected adults were randomized (2:1) to switch to D/C/F/TAF or continue control. The FDA-stipulated primary endpoint was non-inferiority of D/C/F/TAF vs. control regarding % virologic rebound (confirmed VL ≥ 50 c/mL or premature discontinuations with last VL ≥ 50 c/mL) cumulative through Week 48 (4% margin). Result 1141 patients were randomized and treated (N = 763 D/C/F/TAF; N = 378 control); median age 46; 18% women; 76% white; 58% on >2 previous ARVs (prior to screening regimen); 15% with previous non-DRV virologic failure (VF). Virologic rebound through Week 48 was non-inferior for D/C/F/TAF (2.5%; n = 19) vs. control (2.1%; n = 8) (Δ0.4%, 95% CI: –1.5%; 2.2%; P < 0.001). Most rebounders (12/19 [63%] vs. 4/8 [50%]) resuppressed by Week 48 without change in therapy. Week 48 virologic suppression rates (VL < 50 c/mL; FDA Snapshot) were 94.9% vs. 93.7% (Δ1.2%, 95% CI: −1.7%;4.1%) and VF rates (VL ≥ 50 c/mL; Snapshot) were 0.8% vs. 0.5% (Δ0.3%, 95% CI: −0.7%;1.2%), with no discontinuations for VF. No resistance-associated mutations related to any study drug were observed. Adverse events (AEs) were similar between arms: AE-related discontinuations (1.4% vs. 1.3%); grade 3–4 AEs (6.8% vs. 8.2%); serious AEs (4.6% vs. 4.8%); and no deaths. Renal and bone parameters favored D/C/F/TAF vs. control. TC and LDL-C slightly favored control vs. D/C/F/TAF, with no clinically significant difference in TC/HDL-C ratio between arms (Table 1). Conclusion Percentage of virologic rebound after switching to D/C/F/TAF was non-inferior to control cumulative through Week 48, with high suppression rates (94.9%), no resistance development, better bone and renal safety parameters and similar TC/HDL-C ratio. D/C/F/TAF maintains the high genetic barrier to resistance of darunavir with the safety advantages of TAF, even in patients with a history of non-DRV VF. Disclosures C. Orkin, Janssen Pharmaceuticals: Grant Investigator, Scientific Advisor and Speaker’s Bureau, Consulting fee, Research grant, Speaker honorarium and Travel bursary to attend conference. MSD: Grant Investigator, Scientific Advisor and Speaker’s Bureau, Consulting fee, Research grant, Speaker honorarium and Travel bursary to attend conference. Viiv Healthcare: Grant Investigator, Scientific Advisor and Speaker’s Bureau, Consulting fee, Research grant, Speaker honorarium and Travel bursary to attend conference. Gilead Sciences: Grant Investigator, Scientific Advisor and Speaker’s Bureau, Consulting fee, Research grant, Speaker honorarium and Travel bursary to attend conference. J. M. Molina, Merck / Gilead: Scientific Advisor, Research grant. Janssen / Viiv / BMS / Teva: Scientific Advisor, Speaker honorarium. Gilead: Speaker’s Bureau, Speaker honorarium. J. Gallant, Janssen Therapeutics: Investigator, Research support. E. Negredo, Janssen: Board Member, Scientific Advisor and Speaker’s Bureau, Speaker honorarium. J. Gathe, Janssen: Consultant and Investigator, Research grant and Speaker honorarium. J. Eron, Janssen: Consultant and Grant Investigator, Consulting fee and Grant recipient. E. Van Landuyt, Janssen: Employee and Shareholder, Salary. E. Lathouwers, Janssen: Employee and Shareholder, Salary. V. Hufkens, Janssen: Employee and Shareholder, Salary. R. Petrovic, Janssen: Employee and Shareholder, Salary. M. Opsomer, Janssen: Employee and Shareholder, Salary.

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1021. HIV-1 RNA Blips and Low-Level Replication During Phase III/IIIb Cabotegravir + Rilpivirine Long-Acting Studies Are Similar to Oral 3-Drug Therapy and Not Associated with Week 48 Virologic Outcome

Open Forum Infectious Diseases ◽

10.1093/ofid/ofaa439.1207 ◽

2020 ◽

Vol 7 (Supplement_1) ◽

pp. S540-S541

Author(s):

Christine L Talarico ◽

Sterling Wu ◽

Ojesh R Upadhyay ◽

Marty St Clair ◽

Veerle Van Eygen ◽

...

Keyword(s):

Viral Load ◽

Virologic Failure ◽

Phase Iii ◽

Individual Study ◽

Treatment Groups ◽

Qualitative And Quantitative ◽

Low Level ◽

Long Acting ◽

Study Participants ◽

Hiv 1

Abstract Background Phase III/IIIb studies demonstrated cabotegravir (CAB) + rilpivirine (RPV) long-acting (LA) dosed every 4 weeks (Q4W) was noninferior to current antiviral regimen (CAR) (FLAIR and ATLAS) and CAB + RPV LA dosed every 8 weeks (Q8W) was noninferior to Q4W (ATLAS-2M) through Week 48 (W48). HIV-1 ribonucleic acid (RNA) blips (viral load [VL] ≥50 to < 200 c/mL) are common during antiretroviral therapy (ART) and generally not associated with subsequent virologic failure (2 consecutive HIV-1 RNA ≥200 c/mL). We compared the frequency of HIV-1 RNA blips and low-level qualitative and quantitative HIV-1 RNA replication among participants treated with CAB+RPV LA and oral CAR and assessed impact on virologic outcome. Methods Plasma samples collected at study visits were analyzed for HIV-1 RNA viral load using the Abbott RealTime HIV-1 assay and qualitative target detected (TD) or target not detected (TND) outcomes were provided for HIV-1 RNA < 40 c/mL. The HIV-1 SuperLow assay (bioMONTR Labs) was used to measure HIV-1 RNA < 2 c/mL at Baseline and W48. Results The proportion of participants with HIV-1 RNA blips was similar overall between Q4W CAB + RPV LA and CAR arms in FLAIR (38/283 [13%] vs 39/283 [14%]) and ATLAS (17/308 [6%] vs 23/308 [7%]). Presence of HIV-1 RNA blips in either arm was not associated with virologic non-response at W48 (HIV-1 RNA ≥50 c/mL per US Food and Drug Administration Snapshot). In ATLAS-2M, HIV-1 RNA blips were observed in 32/523 (6%; Q4W) and 18/522 (3%; Q8W) of participants, with W48 virologic nonresponse in 2 Q4W and 0 Q8W participants. TD outcomes at individual study visits were comparable between study arms for the 3 studies. At W48, the proportion of participants with HIV-1 RNA < 2 c/mL was similar to Baseline and similar between treatment groups in all studies. Conclusion The proportions of study participants with HIV-1 RNA blips, TD viral load results, and HIV-1 < 2 c/mL were similar between the Q4W and Q8W CAB+RPV LA and the oral 3-drug CAR arms through W48 in phase III/IIIb studies. HIV-1 RNA blips did not predict virologic nonresponse (Snapshot analysis) at W48. Disclosures Christine L. Talarico, M.S, GlaxoSmithKline (Shareholder)ViiV Healthcare (Employee) Sterling Wu, PhD, GlaxoSmithKline (Employee, Shareholder) Marty St. Clair, GlaxoSmithKline (Shareholder)ViiV Healthcare (Employee) Veerle Van Eygen, MSc, Janssen Pharmaceutica NV (Employee) Krischan J. Hudson, PhD, MPH, GlaxoSmithKline (Shareholder)ViiV Healthcare (Employee) Sandy Griffith, PharmD, GlaxoSmithKline (Shareholder)ViiV Healthcare (Employee) Conn M. Harrington, BA, ViiV Healthcare (Employee) Jan van Lunzen, MD, PhD, GlaxoSmithKline (Shareholder)ViiV Healthcare (Employee) David Margolis, MD, MPH, GlaxoSmithKline (Shareholder)ViiV Healthcare (Employee) William Spreen, PharmD, ViiV Healthcare (Employee, Shareholder)

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Long-term Outcomes in a Large Randomized Trial of HIV-1 Salvage Therapy: 96-Week Results of AIDS Clinical Trials Group A5241 (OPTIONS)

The Journal of Infectious Diseases ◽

10.1093/infdis/jiz281 ◽

2019 ◽

Vol 221 (9) ◽

pp. 1407-1415 ◽

Cited By ~ 3

Author(s):

Rajesh T Gandhi ◽

Karen T Tashima ◽

Laura M Smeaton ◽

Vincent Vu ◽

Justin Ritz ◽

...

Keyword(s):

Clinical Trials ◽

Salvage Therapy ◽

Virologic Failure ◽

Virologic Suppression ◽

Cumulative Activity ◽

Antiretroviral Medications ◽

Resistant Group ◽

Aids Clinical Trials ◽

Hiv 1

Abstract Background Short-term (48-week) results of the OPTIONS trial showed that nucleoside reverse transcriptase inhibitors (NRTIs) can be safely omitted from salvage therapy as long as the regimen has a cumulative activity of >2 active antiretroviral medications. The long-term durability of this approach and outcomes in persons who have more-extensive HIV-1 drug resistance are uncertain. Methods Participants with virologic failure and anticipated antiretroviral susceptibility received an optimized regimen and were randomized to omit or add NRTIs. A separate group with more resistance (cumulative activity ≤2 active agents) received an optimized regimen including NRTIs. Results At week 96, among 360 participants randomized to omit or add NRTIs, 70% and 65% had HIV-1 RNA <200 copies/mL, respectively. Virologic failure was uncommon after week 48. Younger age and starting fewer new antiretroviral medications were associated with higher odds of virologic failure. In the highly resistant group, 53% had HIV-1 RNA <200 copies/mL at week 96. Conclusions HIV-1 salvage therapy can safely omit NRTIs without compromising efficacy or durability of response as long as the new regimen has a cumulative activity of >2 active drugs. Younger people and those receiving fewer new antiretrovirals require careful monitoring. Even among individuals with more-extensive resistance, most achieve virologic suppression. Clinical Trials Registration NCT00537394.

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Predictors of HIV-1 virologic failure to long-acting cabotegravir and rilpivirine

AIDS ◽

10.1097/qad.0000000000002883 ◽

2021 ◽

Vol Publish Ahead of Print ◽

Author(s):

Amy G. Cutrell ◽

Jonathan M. Schapiro ◽

Carlo F. Perno ◽

Daniel R. Kuritzkes ◽

Romina Quercia ◽

...

Keyword(s):

Virologic Failure ◽

Long Acting ◽

Hiv 1

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Clinical and Virologic Outcomes Following Initiation of Antiretroviral Therapy Among Seroconverters in the Microbicide Trials Network-020 Phase III Trial of the Dapivirine Vaginal Ring

Clinical Infectious Diseases ◽

10.1093/cid/ciy909 ◽

2018 ◽

Vol 69 (3) ◽

pp. 523-529 ◽

Cited By ~ 2

Author(s):

Sharon A Riddler ◽

Jennifer E Balkus ◽

Urvi M Parikh ◽

John W Mellors ◽

Carolyne Akello ◽

...

Keyword(s):

Antiretroviral Therapy ◽

Disease Progression ◽

Virologic Failure ◽

Vaginal Ring ◽

Phase Iii ◽

Virologic Suppression ◽

Cell Counts ◽

The Impact ◽

Hiv 1

Abstract Background A vaginal ring containing dapivirine, a non-nucleoside human immunodeficiency virus (HIV)-1 reverse transcriptase inhibitor (NNRTI), was safe and effective in preventing HIV-1 infection in African women. We examined the impact of dapivirine ring use at the time of HIV-1 acquisition on subsequent HIV-1 disease progression and responses to NNRTI-containing antiretroviral therapy (ART). Methods HIV-1 disease progression and virologic failure following initiation of ART were assessed among women who acquired HIV-1 while participating in Microbicide Trials Network–020, a randomized, placebo-controlled trial of a monthly, dapivirine vaginal ring. Results Among the 158 participants who acquired HIV-1 (65 dapivirine, 93 placebo), no differences between dapivirine and placebo participants were observed in CD4+ cell counts or plasma HIV-1 RNA over the first year after infection (prior to ART). During follow-up, 100/158 (63%) participants initiated NNRTI-containing ART (dapivirine: 39/65; placebo: 61/93); the median time to HIV-1 RNA <200 copies/ml was approximately 90 days for both dapivirine and placebo ring recipients (log-rank P = .40). Among the 81 participants with at least 6 months of post-ART follow-up, 19 (24%) experienced virologic failure (dapivirine: 6/32, 19%; placebo: 13/39, 27%; P = .42). Conclusions The acquisition of HIV-1 infection during dapivirine or placebo treatment in ASPIRE did not lead to differences in HIV-1 disease progression. After the initiation of NNRTI-containing ART, dapivirine and placebo participants had similar times to virologic suppression and risks of virologic failure. These results provide reassurance that NNRTI-based ART regimens are effective among women who acquired HIV-1 while receiving the dapivirine vaginal ring. Clinical Trials Registration NCT016170096 and NCT00514098.

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1768. Efficacy and Safety of Switching From Boosted-Protease Inhibitors (bPI) Plus Emtricitabine/Tenofovir Disoproxil Fumarate (F/TDF) Regimens to the Once Daily (QD), Single-Tablet Regimen (STR) of Darunavir/Cobicistat/Emtricitabine/Tenofovir Alafenamide (D/C/F/TAF) in Virologically Suppressed, HIV-1-Infected Adults: Week 96 Results of the Phase 3, Randomized, Non-Inferiority EMERALD Trial

Open Forum Infectious Diseases ◽

10.1093/ofid/ofy209.153 ◽

2018 ◽

Vol 5 (suppl_1) ◽

pp. S65-S65 ◽

Cited By ~ 1

Author(s):

Joseph Eron ◽

Chloe Orkin ◽

Douglas Cunningham ◽

Federcio Pulido ◽

Frank Post ◽

...

Keyword(s):

Extension Phase ◽

Virologic Suppression ◽

Efficacy And Safety ◽

Research Support ◽

Open Label ◽

Genetic Barrier ◽

Independent Contractor ◽

Grant Recipient ◽

Hiv 1 ◽

Research Grant

Abstract Background The QD STR D/C/F/TAF 800/150/200/10 mg was noninferior to bPI + F/TDF at 48 weeks in EMERALD. Efficacy and safety of D/C/F/TAF through week 96 are presented. Methods EMERALD (NCT02269917) is a randomized, active-controlled, open-label, international, multicenter noninferiority trial. Virologically suppressed (VL<50 c/mL for ≥2 months) ART experienced (previous non-DRV VF allowed) HIV-1-infected adults were randomized (2:1) to switch to D/C/F/TAF or continue bPI + F/TDF over 48 weeks. Patients could then continue on D/C/F/TAF or switch from bPI + F/TDF to D/C/F/TAF at week 52 (Late switch, 44 weeks D/C/F/TAF exposure) in a single-arm extension phase until week 96. The percentage of patients with virologic rebound (confirmed VL ≥50 c/mL) cumulative through week 48 and week 96 were primary and secondary endpoints, respectively. Results Of 1141 randomized and treated patients (58% had received ≥5 previous ARVs including screening ARVs; 15% had previous non-DRV VF), 1,080 continued in the extension phase (N = 728 D/C/F/TAF; N = 352 late switch). Few patients had virologic rebound cumulative through week 96 in the D/C/F/TAF arm (3.1%, 24/763). Virologic rebound occurred in 2.3% (8/352) in the late switch arm over 44 weeks D/C/F/TAF treatment. Many rebounders (14/24 and 2/8) resuppressed by week 96. At week 96 a high percentage of patients in the D/C/F/TAF arm (90.7%, 692/763) were suppressed (VL<50 c/mL). In the late switch arm, 93.8% (330/352) maintained virologic suppression after 44 weeks of treatment. No DRV, primary PI, TFV, or FTC RAMs were seen post baseline. Few serious AEs and AE related discontinuations occurred in either arm (Table 1). Improvements in renal and bone parameters were maintained in the D/C/F/TAF arm and seen in the late switch arm (week 52–96), with a small change in TC/HDL-C ratio (Table 1). Conclusion Switching to D/C/F/TAF maintained high virologic suppression rates (>90%) at week 96 with no resistance development, and was well tolerated over 96 weeks with bone, renal, and lipid safety consistent with known TAF and cobicistat profiles. Efficacy and safety results in the late switch arm were consistent with week 48 results in the D/C/F/TAF arm. D/C/F/TAF combines the efficacy and high genetic barrier to resistance of DRV with the safety benefits of TAF, even in patients with a history of non-DRV VF. Disclosures J. Eron Jr., Gilead: Consultant and Grant Investigator, Consulting fee and Research grant. Janssen: Consultant, Consulting fee and Research grant. C. Orkin, AbbVie, Abbott, Boehringer Ingelheim, BMS, Gilead, GSK, Janssen, ViiV: Grant Investigator and Research Contractor, Research grant and Research support. D. Cunningham, Janssen: Investigator, Research grant. Gilead: Investigator, Research grant. F. Pulido, Janssen: Consultant, Investigator and Scientific Advisor, Consulting fee, Research support and Speaker honorarium. F. Post, Gilead: Consultant and Grant Investigator, Consulting fee and Grant recipient. Viiv: Grant Investigator, Grant recipient. Janssen: Consultant, Consulting fee. MSD: Consultant, Consulting fee. S. De Wit, Janssen: Investigator, Research grant. E. Lathouwers, Janssen: Employee and Shareholder, Salary. V. Hufkens, Janssen: Employee and Shareholder, Salary. R. Petrovic, Janssen R&D: Independent Contractor, Consulting fee. E. Van Landuyt, Janssen: Employee and Shareholder, Salary.

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