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

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)

Download Full-text

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

Open Forum Infectious Diseases ◽

10.1093/ofid/ofab466.1029 ◽

2021 ◽

Vol 8 (Supplement_1) ◽

pp. S508-S509

Author(s):

Ronald D’Amico ◽

Paul Benn ◽

Shanker Thiagarajah ◽

Susan L Ford ◽

Eileen Birmingham ◽

...

Keyword(s):

Research And Development ◽

Injection Site ◽

Virologic Failure ◽

Hcv Rna ◽

Virologic Suppression ◽

Efficacy And Safety ◽

Modes Of Transmission ◽

Long Acting ◽

Chronic Hcv ◽

Hiv 1

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)

Download Full-text

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)

Download Full-text

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).

Download Full-text

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)

Download Full-text

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.

Download Full-text

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

Download Full-text

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.

Download Full-text

A retrospective clinical audit of general practices in Australia to determine the motivation for switch to dolutegravir/abacavir/lamivudine and clinical outcomes

International Journal of STD & AIDS ◽

10.1177/0956462417730474 ◽

2017 ◽

Vol 29 (3) ◽

pp. 300-305 ◽

Cited By ~ 7

Author(s):

Pedro E Ferrer ◽

Mark Bloch ◽

Norman Roth ◽

Robert Finlayson ◽

David Baker ◽

...

Keyword(s):

Virologic Failure ◽

Clinical Audit ◽

Integrase Inhibitor ◽

Suppressive Therapy ◽

Virologic Suppression ◽

Kaplan Meier ◽

Single Pill ◽

General Practices ◽

Hiv 1 ◽

Viable Treatment

The most common reasons for switching HIV-1 therapy in patients with virologic suppression are treatment regimen simplification and resolving tolerability issues. Single-pill regimens that include an integrase inhibitor are recommended options. A retrospective clinical audit was performed to determine the motivations for switching to dolutegravir (DTG)/abacavir (ABC)/lamivudine (3TC) at high HIV-caseload general practice clinics in Australia. The most common reasons for switching from a prior suppressive therapy to DTG/ABC/3TC were simplification of regimen, resolving toxicity/intolerance and patient preference (73%, 13% and 12%, respectively). Kaplan–Meier analysis showed that the probability of patients remaining on DTG/ABC/3TC therapy at 12 months was 95.1%. Switching to DTG/ABC/3TC from a range of other regimens was associated with a discontinuation rate of 3.2%, with 2.5% of patients discontinuing due to adverse events and no patients discontinuing due to virologic failure. Switching to DTG/ABC/3TC was a viable treatment strategy in this cohort of Australian patients.

Download Full-text

Safety and Effectiveness of Switching to Abacavir/Lamivudine Plus Rilpivirine for Maintenance Therapy in Virologically Suppressed HIV-1 Patients in Singapore (SEALS)

10.21203/rs.3.rs-100235/v1 ◽

2020 ◽

Author(s):

Alvin ZC Lim ◽

Grace SR ◽

Junhao Ang ◽

Christine BC Teng ◽

Li Wei Ang ◽

...

Keyword(s):

Adverse Events ◽

Maintenance Therapy ◽

Primary Outcome ◽

Virologic Failure ◽

Resistance Testing ◽

Virologic Suppression ◽

International Studies ◽

Resistance Mutations ◽

Hiv 1

Abstract BackgroundThe efficacy and tolerability of an antiretroviral regimen are important considerations for selection of HIV-1 infection maintenance therapy. Abacavir/lamivudine plus rilpivirine (ABC/3TC+RPV) has been shown in international studies to be effective and well-tolerated in virologically suppressed patients. This study evaluated the effectiveness and safety of switching to ABC/3TC+RPV as maintenance therapy in virologically suppressed HIV-1 infected patients in Singapore.MethodsIn this retrospective, single-centre study, we included patients who were prescribed ABC/3TC+RPV, had HIV-1 RNA <50 copies/ml immediately pre-switch, and had no documented history of resistance mutations or virologic failure to any of the components. Patients were followed up for 48+12 weeks. The primary outcome was the proportion of patients who maintained virologic suppression of HIV-1 RNA <50 copies/ml at the end of follow-up period based on on-treatment analysis. The secondary outcomes were the resistance profiles associated with virologic failure, changes in immunologic and metabolic parameters, and the safety profile of ABC/3TC+RPV.ResultsA total of 222 patients were included in the study. The primary outcome was achieved in 197 patients [88.8%, 95% confidence interval: 83.7%-92.4%]. There were 21 patients (9.5%) who discontinued treatment for non-virologic reasons. The remaining 4 patients experienced virologic failure, of whom, 3 of these patients had developed emergent antiretroviral resistance and had HIV-1 RNA >500 copies/ml at the end of the 48+12 weeks follow-up period. The remaining patient experienced sustained low level viremia and subsequently achieved viral suppression without undergoing resistance testing. A total of 49 adverse events were observed in 31 out of 222 patients (14.0%), which led to 13 patients discontinuing therapy. Neuropsychiatric adverse events were most commonly observed (57.1%). A statistically significant increase in CD4 was observed (p<0.01), with a median absolute change of 31 cells/uL (interquartile range: -31.50 to 140.75). No significant changes in lipid profiles were detected. ConclusionABC/3TC+RPV is a safe and effective switch option for maintenance therapy in virologically suppressed HIV-1 patients with in Singapore.

Download Full-text

626. The Efficacy and Safety of Maintenance with Doravirine Plus Two NRTIs after Initial Suppression in Adults with HIV-1 in the DRIVE-FORWARD Clinical Trial: Results from the Study Extension through 192 Weeks

Open Forum Infectious Diseases ◽

10.1093/ofid/ofab466.824 ◽

2021 ◽

Vol 8 (Supplement_1) ◽

pp. S417-S417

Author(s):

Pedro Cahn ◽

Jean-michel Molina ◽

Johan Lombaard ◽

Kathleen Squires ◽

Sushma Kumar ◽

...

Keyword(s):

Weight Gain ◽

Panel Member ◽

Virologic Suppression ◽

Efficacy And Safety ◽

Open Label ◽

Review Panel ◽

Double Blind ◽

Open Label Extension ◽

Favorable Safety ◽

Hiv 1

Abstract Background DRIVE-FORWARD is a phase 3 trial with a completed double-blind period comparing doravirine (DOR) 100 mg with ritonavir-boosted darunavir (DRV/r) 800/100 mg, both administered with two nucleos(t)ide reverse transcriptase inhibitors (NRTIs; tenofovir and emtricitabine, or abacavir and lamivudine), and an ongoing open-label extension. At Week (W) 48, DOR demonstrated non-inferior efficacy to DRV/r, with a superior lipid profile. Those results were sustained at W96. Here we present efficacy and safety results through W192. Methods Participants who completed the 96-week double-blind phase and met inclusion criteria were eligible to receive open-label DOR plus two NRTIs in a 96-week extension. Efficacy and safety at W192 were assessed in two groups: participants initially randomized to DOR and maintained on DOR (n=259) and those who switched from DRV/r to DOR at W96 (n=233). Results HIV-1 RNA < 50 copies/mL were maintained through W192 in 81.1% of participants who continued DOR and 80.7% of those who switched from DRV/r to DOR. The mean increase in CD4 T-cell counts from W96 to W192 was similar for participants maintained on DOR (47 cells/mm3) and those switched from DRV/r (53 cells/mm3). Protocol-defined virologic failure occurred in 3.1% and 5.6% of participants maintained on DOR and switched from DRV/r, respectively, and development of genotypic resistance was low in both groups (Table 1). Discontinuation due to adverse events was also low (Table 1). Fasting LDL-cholesterol, non-HDL-cholesterol, and triglycerides showed minimal increase in participants maintained on DOR and were reduced in those switched from DRV/r to DOR (Table 1). Participants maintained on DOR had minimal weight gain after W96 (median 1 kg), and a small increase overall (median 1.9 kg, Day 1 through W192); participants who switched to DOR had a small increase after W96 (median 1.5 kg), similar to the median weight gain in the base study (DOR 1.8 kg; DRV/r 0.7 kg). Conclusion Among participants who continued DOR in the DRIVE-FORWARD open-label extension, virologic suppression and favorable safety were maintained for an additional 96 weeks. Participants who switched from DRV/r to DOR maintained virologic suppression and demonstrated favorable safety for 96 weeks. Disclosures Pedro Cahn, MD, PHD, Merck (Advisor or Review Panel member)ViiV Healthcare (Grant/Research Support, Advisor or Review Panel member) Kathleen Squires, MD, Merck (Employee) Sushma Kumar, PhD, Merck (Employee) Hong Wan, PhD, Merck (Employee) Valerie Teal, MS, Merck (Employee) Ernest Asante-Appiah, PhD, Merck (Employee) Peter Sklar, MD, Merck (Employee) Elizabeth A. Martin, DO, MPH, MBA, Merck (Employee) Rima Lahoulou, n/a, Merck (Employee)

Download Full-text