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Additional ACTG Presentations Address Muscle Density and Area among People Living with HIV and COVID-19 TreatmentLOS ANGELES, July 23, 2024 (GLOBE NEWSWIRE) -- ACTG, a global clinical trials network focused on HIV and other infectious diseases, will present an exploratory analysis from the REPRIEVE trial demonstrating that former and current use of abacavir was associated with a higher incidence of major adverse cardiovascular events at AIDS 2024 in Munich, Germany. The oral presentation will take place on July 26, 2024, as part of the session Comorbidities: The Heart of the Matter, from 10:30-11:30 am CEST at Hall B0b/Channel 5 and virtually. “This carefully constructed analysis adds to the body of evidence that abacavir use is associated with a higher risk of cardiovascular events like heart attacks and strokes,” said ACTG Chair Judith Currier, M.D., M.Sc., University of California Los Angeles. “These data align with prior studies that had been considered somewhat controversial because no exact mechanism was clearly demonstrated and should be taken into account by clinicians when they evaluate treatment options for people living with HIV.” These are the latest findings from REPRIEVE, the first large-scale clinical trial to test a primary prevention strategy to reduce the increased risk of cardiovascular disease among people living with HIV. It found that participants who took pitavastatin calcium (a daily statin pill that lowers cholesterol) reduced their risk of major adverse cardiovascular events by 36 percent compared with those receiving a placebo over a median duration of five years of follow up. The analysis being presented at AIDS 2024 evaluated the role of prior and current use of select antiretroviral treatments (including abacavir, tenofovir, thymidine analogs, and protease inhibitors) on the development of major cardiovascular events. These antiretrovirals were selected based upon prior association with cardiovascular risk and kidney impairment (future analyses are planned to examine the role of other antiretrovirals). Among 7,769 participants, 31.3 percent were born female and 65.2 percent were not white. The median age was 50, LDL (low-density lipoprotein, a kind of cholesterol) was 108 mg/dL, CD4 count was 621 cell/mm3, and 88 percent had a viral load under 400 copies/mL. Participants had been taking HIV treatment for a median of 9.5 years. Researchers found that current or past use of abacavir increased the risk of major adverse cardiovascular events by 42 and 50 percent, respectively, while current or past use of other antiretroviral treatments caused no such increase. “This analysis is important as we seek to tease out the various factors that may help reduce cardiovascular risk in people living with HIV,” said lead study author Carl Fichtenbaum, M.D., University of Cincinnati. “While the association between abacavir and cardiovascular risk is disappointing, it is not a surprise. It is, however, reassuring that the other HIV therapies included in the analysis like tenofovir were not associated with a higher risk.” REPRIEVE had a number of unique aspects: study participants had no known prior history of cardiovascular disease, the global cohort from 12 countries had low-to-moderate risk for cardiovascular disease, and all study endpoints were independently vetted by the national study Thrombolysis in Myocardial Infarction (TIMI). REPRIEVE began in 2015 as cooperative agreements (HL12339, HL123336, HL164284, and HL164285) and was a collaborative effort between the National Institutes of Health’s National Heart, Lung, and Blood Institute (NHLBI) and the National Institute of Allergy and Infectious Diseases (NIAID), two of the largest NIH institutes. It received additional funding from the NIH Office of AIDS Research, Kowa Pharmaceuticals America, Inc. (providers of pitavastatin calcium and placebo), Gilead Sciences, Inc., and ViiV HealthCare. The trial is led by Steven Grinspoon, M.D. (Chair) and Pamela S. Douglas, M.D. (Co-chair), who led the Clinical Coordinating Center and Heather Ribaudo, Ph.D. (Lead Statistician) and Michael Lu, M.D., M.P.H. (Protocol Chair, Mechanistic Substudy of REPRIEVE), who led the Data Coordinating Center. To learn more, please visit www.reprievetrial.org. In addition to these data from REPRIEVE, ACTG will also make the following presentations at AIDS 2024: No Evidence of Pitavastatin Effect on Muscle Density or Area Among People with HIV (REPRIEVE; Poster Presentation: Tuesday, July 23rd, 12:00-1:00 pm CEST, Poster Exhibition Hall) Kristine Erlandson, et al. This analysis from the REPRIEVE mechanistic substudy found that statins did not reduce muscle density or area. This two-year study of middle-aged people living with HIV at low-to-moderate risk of cardiovascular disease, confirmed through imaging that statins were safe and did not cause significant muscle damage. This is reassuring to people who want to use statins to lower their risk of cardiovascular events like heart attacks and strokes. Efficacy and Safety of Ensitrelvir in Non-Hospitalized Adults at Standard or High-Risk of Progression to Severe COVID-19: the SCORPIO-HR Phase 3, Randomized, Double-Blind Placebo-Controlled Trial (ACTG 5407; Poster Presentation: Tuesday, July 23rd, 12:00-1:00 pm CEST, Poster Exhibition Hall) Kara Chew, et al. While the oral protease inhibitor ensitrelvir demonstrated anti-viral activity, safety, and a trend toward shorter time to symptom resolution compared to placebo, SCORPIO-HR (ACTG 5407) did not meet its primary endpoint of time to two or more days sustained resolution of 15 COVID-19 symptoms in outpatient participants at standard and higher risk for severe disease. About ACTG ACTG is the world’s largest and longest running clinical trials network focused on HIV and other infectious diseases and the people living with them. It is funded by NIAID and collaborating NIH Institutes under award numbers UM1 AI068636, UM1 AI107716, and UM1 AI068634. Founded in 1987, ACTG conducts research to improve the management of HIV and its comorbidities; develop a cure for HIV; and innovate treatments for tuberculosis, hepatitis B, and emerging infectious diseases. It comprises thousands of dedicated researchers, staff, and community members who are pursuing research into novel treatments and cures for infectious diseases at 65 locations across four continents, with the ultimate goal of advancing science that meaningfully impacts the lives of the people we serve. Disclaimer: This content is solely the responsibility of ACTG and does not necessarily represent the official views of the NIH. Media Contact:Jenna Conley, ACTGjenna@conleycommunications.net

LONDON--( BUSINESS WIRE )--ViiV Healthcare, the global specialist HIV company majority owned by GSK, with Pfizer and Shionogi as shareholders, announces 48-week findings from PASO DOBLE (GeSIDA 11720 study), the largest head-to-head, phase IV randomised clinical trial (RCT) investigating the 2-drug regimen Dovato (dolutegravir/lamivudine [DTG/3TC]) compared to the 3-drug regimen Biktarvy (bictegravir/emtricitabine/tenofovir alafenamide fumarate [BIC/FTC/TAF]) for the treatment of HIV-1 in people who are virologically suppressed and who could benefit from treatment optimisation. 1 Findings showed that switching to DTG/3TC in virologically suppressed adults living with HIV demonstrated non-inferior efficacy in maintaining viral suppression compared with switching to BIC/FTC/TAF. 1 These data will be presented at the 25 th International AIDS Conference (AIDS 2024), held in Munich, Germany (22-26 July). Harmony P. Garges, M.D., MPH, Chief Medical Officer at ViiV Healthcare, said: “ The results from PASO DOBLE show that Dovato demonstrated non-inferior efficacy compared to Biktarvy , and that the average weight gain for trial participants taking DTG/3TC was significantly lower than those taking BIC/FTC/FTC over the course of the year. This is a meaningful outcome, as treatment-related weight gain is an important topic for many people living with HIV. At ViiV Healthcare we're dedicated to bringing innovative HIV treatments to people living with HIV that are not only safe and effective, but also address their specific needs beyond viral suppression.” In the PASO DOBLE clinical trial, 553 people living with HIV and virally suppressed switched treatment to either DTG/3TC (n=277) or BIC/FTC/TAF (n=276). 1 The study population included individuals who were on therapy that could be optimised, such as multiple tablet regimens, or those containing pharmacokinetic boosting agents or drugs with cumulative toxicity, such as efavirenz or tenofovir disoproxil fumarate (TDF). 2 The study met its primary endpoint when DTG/3TC demonstrated non-inferior efficacy versus BIC/FTC/TAF based on the proportion of participants with viral RNA ≥50 copies/mL at 48 weeks using the FDA snapshot and a 4% non-inferiority margin in the exposed intention-to-treat population. 1 At 48 weeks, DTG/3TC was non-inferior to BIC/FTC/TAF (risk difference between DTG/3TC [2.2%] minus BIC/FTC/TAF [0.7%] of 1.4%, 95% CI -0.5 to 3.4). One participant in the BIC/FTC/TAF arm and zero in the DTG/3TC arm had protocol-defined confirmed virological failure through week 48 (HIV-1 RNA ≥50 c/mL followed by a second consecutive HIV-1 RNA assessment ≥200 c/mL). 1 The study found in a key secondary endpoint that weight increased significantly more in participants who switched to BIC/FTC/TAF (adjusted mean change 1.81kg, 95% CI 1.28-2.34) than in those who switched to DTG/3TC (adjusted mean change 0.89kg, 95% CI 0.37-1.41) [difference 0.92kg, 95% CI 0.17-1.66] through week 48. Equally, the proportion of participants with weight gain greater than 5% at week 48 was significantly higher at 29.9% for BIC/FTC/TAF compared to 20% for DTG/3TC (adjusted OR 1.81, 95% CI 1.19-2.76). 1 Weight change with DTG/3TC did not differ between men and women or based on the previous regimen of participants, whereas the proportion of trial participants experiencing greater than 5% weight gain with BIC/FTC/TAF was approximately 45% higher than those taking DTG/3TC when switching from a regimen with abacavir (30.6% BIC/FTC/TAF vs 21.1% DTG/3TC), and about 2-fold higher when switching from a regimen with TDF (40.7% BIC/FTC/TAF vs 19.5% DTG/3TC). Safety was comparable through week 48 and consistent with known safety profiles. There were few discontinuations due to adverse events in both study arms (DTG/3TC = 1, 0.4%; BIC/FTC/TAF = 2, 0.7%), with no differences between arms. 1 Esteban Martínez, MD, PhD, Chief Executive Investigator of the PASO DOBLE study and Senior Consultant in Infectious Diseases at Hospital Clínic of Barcelona, Spain said: “ The HIV treatment regimens that are commonly prescribed today are all highly effective, which makes it critical that we study the impact of these therapies beyond just viral suppression. The results from PASO DOBLE show Dovato , a 2-drug regimen, not just demonstrated the same efficacy as a 3-drug regimen, but also showed less weight gain compared to BIC/FTC/TAF through 48 weeks.” About PASO DOBLE 1,2 The PASO DOBLE (NCT04884139) randomised clinical trial is a phase IV, open-label, randomised multicentre clinical trial evaluating the efficacy of DTG/3TC versus BIC/FTC/TAF for the maintenance of virologic suppression in people living with HIV-1, conducted in 30 sites across Spain. Virologically suppressed people living with HIV on regimens containing ≥1 pill/day, boosters, or drugs with cumulative toxicity such as efavirenz or TDF were eligible and were randomised (1:1) to switch to either DTG/3TC or BIC/FTC/TAF. The primary endpoint was the proportion of people living with HIV with RNA ≥50 copies/mL at 48 weeks (FDA snapshot, 4% non-inferiority margin) in the intention-to-treat exposed population. Secondary outcomes measured included, among others, absolute weight gain, BMI change, and the proportion of participants with weight change greater than 5%. About Dovato Dovato is indicated as a complete regimen to treat HIV-1 infection in adults with no antiretroviral (ARV) treatment history or to replace the current ARV regimen in those who are virologically suppressed (HIV-1 RNA <50 copies/mL) on a stable ARV regimen with no history of treatment failure and no known resistance to any component of Dovato . Dovato is approved in the US, Europe, Japan, Australia, and other countries worldwide. Please consult the full Summary of Product Characteristics for all the safety information: Dovato 50 mg/300 mg film-coated tablets . Trademarks are owned by or licensed to the ViiV Healthcare group of companies. About SEIMC-GeSIDA Foundation (FSG) The SEIMC-GeSIDA Foundation (FSG) was created to encourage, promote, and support scientific and technical research and development, training, and publication of findings in the field of clinical microbiology and infectious diseases and associated conditions. FSG was founded by investigators from the Spanish Society of Clinical Microbiology and Infectious Diseases as a tool to promote high-quality investigation in the field of HIV infection and other infectious diseases. The Foundation also aims to respond to the scientific concerns of the group’s members. FSG is composed of qualified professionals with experience in the field of clinical trials and multicentre studies. Its streamlined infrastructure facilitates performance of clinical studies and responds to the needs of investigators in terms of methodology/statistical analysis and of logistics and management of trials and other multicentre studies. We also provide staff to run events such as scientific meetings and conferences (national and international) and to organise courses, lectures, talks, seminars, round-table talks, and specialised workshops. For more information on the FSG, please visit https://fundacionseimcgesida.org/en/quienes-somos/ About ViiV Healthcare ViiV Healthcare is a global specialist HIV company established in November 2009 by GSK (LSE: GSK) and Pfizer (NYSE: PFE) dedicated to delivering advances in treatment and care for people living with HIV and for people who are at risk of acquiring HIV. Shionogi became a ViiV shareholder in October 2012. The company’s aims are to take a deeper and broader interest in HIV and AIDS than any company has done before and take a new approach to deliver effective and innovative medicines for HIV treatment and prevention, as well as support communities affected by HIV. For more information on the company, its management, portfolio, pipeline, and commitment, please visit viivhealthcare.com. About GSK GSK is a global biopharma company with a purpose to unite science, technology, and talent to get ahead of disease together. Find out more at gsk.com. Cautionary statement regarding forward-looking statements GSK cautions investors that any forward-looking statements or projections made by GSK, including those made in this announcement, are subject to risks and uncertainties that may cause actual results to differ materially from those projected. Such factors include, but are not limited to, those described under Item 3.D “Risk factors” in GSK’s Annual Report on Form 20-F for 2023, and GSK’s Q1 Results for 2024. Registered in England & Wales: GSK plc No. 3888792 ViiV Healthcare Limited No. 06876960 Registered Office: GSK plc 980 Great West Road Brentford, Middlesex United Kingdom TW8 9GS ViiV Healthcare Limited GSK Medicines Research Centre Gunnels Wood Road, Stevenage United Kingdom SG1 2NY References 1 P. Ryan, et al. Non-inferior efficacy and less weight gain when switching to DTG/3TC than when switching to BIC/FTC/TAF in virologically suppressed people with HIV (PWH): the PASODOBLE (GeSIDA 11720) randomised clinical trial. Presented at the 25th International AIDS Conference. July 2024 2 Clinical Trials.gov - DTG/​3TC vs. BIC/​FTC/​TAF Maintenance Therapy in People Living With HIV: (PASO-DOBLE). Available at https://clinicaltrials.gov/ct2/show/NCT04884139 . Last accessed July 2024