Dolutegravir 50mg / Abacavir 600mg / Lamivudine 300mg tablets

INTRODUCTION: With longer life expectancy in people living with HIV (PLWH) on antiretroviral therapy, cardiovascular disease (CVD) has become a common cause of mortality among them. Abacavir has been associated with an increased risk of myocardial infarction, but the mechanism is unknown. Additionally, abacavir may be obesogenic which could mediate an additional risk factor of CVD. We aim to investigate if discontinuation of abacavir will have a favourable impact on body weight and cardiac parameters in PLWH. METHODS AND ANALYSIS: Randomised, controlled, superiority trial of virologically suppressed PLWH on dolutegravir, abacavir and lamivudine (DTG/ABC/3TC) for ≥6 months. In total, 70 PLWH will be randomised 1:2 to either continue DTG/ABC/3TC or to switch to dolutegravir and lamivudine (DTG/3TC) providing the power of 80% at alpha 5% to detect a mean difference in weight change of 2 kg (Δ) given an SD of 2.7 kg. Follow-up will be 48 weeks. Data will be collected at baseline and week 48. Primary outcome will be change in mean body weight from baseline to week 24 and 48 evaluated in a linear mixed model. Secondary outcomes will be changes in cardiac, inflammatory and metabolic parameters, fat distribution, coagulation, endothelial, platelet function, quality of life and virological control from baseline to week 48. Measurements include CT of thorax and abdomen, external carotid artery ultrasound, liver elastography and dual energy X-ray absorptiometry and blood analysis. Plasma HIV RNA will be measured at baseline, week 4, 24 and 48. Forty participants (20 from each arm) will be included in a substudy involving cardiac MRI at baseline and week 48. Twenty non-HIV-infected controls will be included with a single scan to compare with baseline scan data. ETHICS AND DISSEMINATION: Result from this study will lead to a better understanding of the association between antiretroviral therapy and the impact on weight and risk of CVD. Findings will be useful for both clinicians and PLWH in the guidance of a more individualised HIV treatment. Results from the main study and the substudies will be submitted for publication in a peer-reviewed journal(s). The AVERTAS study is approved by the Ethics Committee of the Capital Region, Denmark (H-20011433), Danish Medicines Agency (EudraCT no. 2019-004999-19) and Regional Data Protection Centre (P-2020-207). TRIAL REGISTRATION NUMBER: Pre-results registration at ClinicalTrials.gov Identifier: NCT04904406, registered 27 May 2021. PROTOCOL VERSION: Protocol version 9.0, 4 April 2023, approved 10-05-2023 by Ethics Committee of the Capital Region, Denmark (H-20011433). Danish Medicines Agency (EudraCT no. 2019-004999-19). Regional Data Protection Centre (P-2020-207) ClinicalTrials.gov.

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INTRODUCTION: Central nervous system adverse events (AE) have been a cause of discontinuation of dolutegravir-containing therapy, especially in combination with abacavir. The main aim of the study was to evaluate whether the switch to bictegravir/emtricitabine/tenofovir alafenamide (BIC/FTC/TAF) was associated with a reduction in severity and incidence of neuropsychiatric symptoms compared to continued dolutegravir/abacavir/lamivudine (DTG/ABC/3TC). METHODS: DOBINeuro is a randomized trial enrolling people living with HIV (PLWH) treated with DTG/ABC/3TC for > 6 months and with HIV-RNA < 50 cps/ml for > 12 months. At baseline, PLWH are randomized to continue DTG/ABC/3TC or switch to BIC/FTC/TAF. The original sample size was 50 PLWH per arm, but the enrollment was prematurely stopped due to a delayed recruitment process. Neuropsychiatric symptoms were evaluated by the self-report Symptom Checklist (SCL)-90-R and the Mini-International Neuropsychiatric Interview Plus. RESULTS: A total of 41 PLWH were enrolled and underwent randomization: 20 were randomized to continue DTG/ABC/3TC and 21 to switch to BIC/FTC/TAF. At baseline, clinical and laboratory characteristics were homogeneous in the two arms. Switching from DTG/ABC/3TC to BIC/FTC/TAF in virologically suppressed PLWH was associated with an improvement in sleep disorders but not in any other neuropsychiatric symptom. CONCLUSIONS: Although limited by a low sample size, this study suggests neuropsychiatric tolerability may improve when switching virologically suppressed PLWH from DTG to BIC-based strategies.

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Purpose: To review published evidence on alternative administration methods for antiretroviral therapy in patients unable to swallow tablets. Methods: We conducted a scoping review using PubMed, Web of Science, and Google Scholar databases from 2011 to 2025. We included studies reporting pharmacokinetic data, clinical outcomes, or safety data on crushed, dispersed, or enterally administered antiretroviral formulations. Four independent reviewers screened 1,474 articles after duplicate removal, with 12 studies meeting selection criteria. Results: We identified 12 studies (8 case reports, 2 case series, 2 cohort studies) describing alternative administration of antiretrovirals. Key findings included: (1) Bictegravir/emtricitabine/tenofovir alafenamide was associated with viral suppression when dissolved and administered enterally; (2) Dolutegravir/abacavir/lamivudine crushed via nasogastric tube was associated with viral suppression within 10 months; (3) Dolutegravir requires separation from enteral feeds containing polyvalent cations to avoid chelation and reduced absorption. (4) Most nucleoside reverse transcriptase inhibitors (NRTIs) could be crushed or dissolved, while non-nucleoside reverse transcriptase inhibitors (NNRTIs) showed variable stability. (5) Therapeutic drug monitoring was recommended for integrase inhibitors administered enterally. Conclusion: This review provides evidence suggesting the use of modified ART formulations when standard oral administration is not possible. In situations where swallowing difficulties prevent the use of whole tablets, alternative methods such as crushing, or dissolving may offer a practical approach to maintain treatment continuity. Alternative administration ART, namely INSTI-based regimens and NRTIs, may help maintain viral suppression in these settings, provided that drug-specific pharmacokinetic considerations and enteral feeding interactions are addressed. Further prospective studies with therapeutic drug monitoring are needed to establish standardized protocols.

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Abstract Background Bictegravir, emtricitabine and tenofovir alafenamide (B/F/TAF) is a guidelines-recommended single-tablet regimen (STR) for people living with HIV-1 (PLWH). Week (W) 48 primary endpoint results of this phase 3 study switching to B/F/TAF from dolutegravir (DTG), abacavir (ABC) and lamivudine (3TC) established the safety and efficacy of B/F/TAF. Here we report outcomes from an open-label (OL) extension of B/F/TAF. Methods Adults virologically suppressed on DTG, ABC, and 3TC were randomized 1:1 to switch to B/F/TAF once daily or continue their current regimen as a STR in a double blind (DB) manner. Unblinding occurred after the W48 primary endpoint, then participants received B/F/TAF in an OL extension while transitioning off the study. All participants who received B/F/TAF in the DB or OL phases are included in analyses. Efficacy was assessed as the proportion with HIV-1 RNA &amp;lt; 50 copies/mL at each study visit using missing=excluded (M=E) analysis, efficacy in in subgroups with pre-existing resistance was assessed using last observation carried forward. Safety was assessed by adverse events (AEs) and laboratory results. Results 563 participants were randomized and treated (282 B/F/TAF, 281 ABC/DTG/3TC); 524 (93%) completed the DB phase and received OL B/F/TAF; a total of 547 participants received B/F/TAF in DB and/or OL phases: 11% women, 21% Black, median age 47 yrs (range 21, 71). The median duration of B/F/TAF was 96 weeks (IQR 49-119). HIV-1 RNA &amp;lt; 50 c/mL was maintained in 99-100% at all timepoints (M=E) through a maximum of 168 weeks, including high efficacy in those with archived resistance (Table 1). No participant developed resistance to B/F/TAF. Study drug-related AEs occurred in 7% on B/F/TAF; most were grade 1; the most common was headache (1.6%). 7 (1%) participants had an AE leading to premature study drug discontinuation, only 1, headache, occurred in the OL phase. Estimated GFR and lipids were mostly stable with slightly increased LDL at W96; weight changes are noted at W48 and W96. (Table 2). Table 1. Table 2. Conclusion Extended follow-up to the study of switching to B/F/TAF from DTG/ABC/3TC, demonstrates continued high rates of virologic suppression with no resistance and excellent safety and tolerability of B/F/TAF through a maximum of 168 weeks for treatment of PLWH. Disclosures Indira Brar, MD, Gilead (Speaker’s Bureau)janssen (Speaker’s Bureau)ViiV (Speaker’s Bureau) Peter Ruane, MD, AbbVie (Consultant, Grant/Research Support, Speaker’s Bureau)Bristol-Myers Squibb (Grant/Research Support)Gilead Sciences Inc. (Consultant, Grant/Research Support, Scientific Research Study Investigator, Shareholder, Speaker’s Bureau)Idenix (Consultant)Janssen (Grant/Research Support, Speaker’s Bureau)Viiv Healthcare (Grant/Research Support) Douglas Ward, MD, Gilead Sciences Inc. (Grant/Research Support, Scientific Research Study Investigator, Advisor or Review Panel member, Speaker’s Bureau)Merck (Advisor or Review Panel member)Viiv Healthcare (Advisor or Review Panel member, Speaker’s Bureau) Jean-michel Molina, MD, PhD, Bristol-Myers Squibb (Advisor or Review Panel member)Gilead Sciences Inc. (Grant/Research Support, Scientific Research Study Investigator, Advisor or Review Panel member)Janssen (Advisor or Review Panel member)Merck (Advisor or Review Panel member)Teva (Advisor or Review Panel member)Viiv Healthcare (Advisor or Review Panel member) Anthony Mills, MD, Gilead (Grant/Research Support, Advisor or Review Panel member)Janssen Pharmaceutica (Grant/Research Support, Advisor or Review Panel member)Merck (Grant/Research Support, Advisor or Review Panel member)Shionogi (Grant/Research Support)ViiV Healthcare (Grant/Research Support, Advisor or Review Panel member) Mezgebe Berhe, MD, Gilead Sciences Inc. (Grant/Research Support, Scientific Research Study Investigator) Cynthia Brinson, MD, Gilead (Advisor or Review Panel member, Speaker’s Bureau)ViiV Healthcare (Advisor or Review Panel member, Speaker’s Bureau) Moti Rampogal, MD, Gilead Sciences (Consultant, Research Grant or Support, Speaker’s Bureau)Janssen (Consultant, Research Grant or Support, Speaker’s Bureau)Merck (Consultant, Research Grant or Support)ViiV Healthcare (Consultant, Research Grant or Support, Speaker’s Bureau) Keith Henry, MD, Gilead (Research Grant or Support, Paid to institution)GSK/ViiV (Research Grant or Support, Paid to institution)Janssen (Research Grant or Support, Paid to institution)Merck (Research Grant or Support, Paid to institution) Hailin Huang, PhD, Gilead Sciences Inc. (Employee, Shareholder) Kristen Andreatta, MSc, Gilead Sciences (Employee, Shareholder) Hal Martin, MD, MPH, Gilead Sciences Inc. (Employee, Shareholder)

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