Fostemsavir Tromethamine

Other key data to be presented from ViiV Healthcare’s innovative pipeline and portfolio include the exploration of different mechanisms of action through broadly neutralising antibodies as well as real-world insights from established long-acting and 2-drug regimens LONDON--(BUSINESS WIRE)-- ViiV Healthcare, the global specialist HIV company majority owned by GSK, with Pfizer and Shionogi as shareholders, today announced the presentation of 64 abstracts that includes highlights of the company’s next-generation pipeline advancements, alongside data from its diverse portfolio of marketed HIV treatment and prevention options at the Conference on Retroviruses and Opportunistic Infections (CROI 2024) being held in Denver, Colorado, from 3 – 6 March 2024. Kimberly Smith, M.D., MPH, Head of Research & Development at ViiV Healthcare, said: “As leaders in developing long-acting injectables for the treatment of HIV, we’re excited to present new data setting the stage for ViiV’s next generation of medicines and demonstrating how key pipeline assets will target HIV in different ways. These findings, as well as the breadth of data we’ll present on our marketed products, including new interim results from the LATITUDE study, reflect a portfolio and future-looking pipeline focused on ending the HIV epidemic. We look forward to sharing them with the scientific and HIV communities at CROI 2024.” Key abstracts to be presented at CROI 2024 by ViiV Healthcare and its study partners will include: Data introducing our next generation of potential ultra long-acting medicines for HIV: ViiV Healthcare will share findings from a phase I study evaluating different formulations of cabotegravir and their potential for dosing every four months. The ongoing, open-label, single-dose, dose-escalation phase I study in 70 healthy adults assessed both the 200 mg/mL formulation of cabotegravir in combination with recombinant human hyaluronidase PH20 (rHuPH20), as well as a new formulation of cabotegravir (CAB ULA) administered by itself.1 Researchers will share safety and pharmacokinetic findings from both ultra long-acting approaches and their potential for future clinical development. Findings advancing different mechanisms of action in HIV research: New phase IIa findings from the BANNER study of VH3810109 (N6LS), an investigational, broadly neutralising antibody (bNAb), will be presented. Researchers will share findings of the bNAb administered intravenously and the first efficacy findings of its subcutaneous administration.2 Findings from the SPAN study of N6LS, examining the safety and tolerability of the highest subcutaneous and intravenous N6LS doses administered to date, with and without PH20, will also be presented.3 Additionally, efficacy and safety data from a non-ViiV owned bNAb asset, VRC07-523LS, in a phase II, open-label clinical trial used in combination with long-acting CAB for maintenance antiretroviral therapy (ART) will be presented.4 New data on long-acting therapy vs daily oral standard of care, in traditionally non-adherent populations: Interim analysis of the LATITUDE phase III trial will be presented showing that, the injectable antiretroviral treatment for HIV, Cabenuva (cabotegravir and rilpivirine [CAB+RPV LA]), demonstrates superior efficacy compared to daily oral standard of care (SOC) in individuals with a history of antiretroviral adherence challenges. The NIAID/ACTG also announced a modification to the study, where further randomisation has been stopped and participants in the SOC arm are being given the option to switch to the long-acting therapy arm.5 Real-world evidence from across our treatment and prevention portfolios: New findings from SEARCH, a randomised study evaluating the real-world impact of the inclusion of long-acting cabotegravir for PrEP in an HIV prevention coverage package compared to the standard-of-care of oral PrEP and PEP alone in rural Uganda and Kenya, will also be presented.6 Real-world evidence findings for the complete long-acting HIV treatment regimen Cabenuva will be presented from the OPERA cohort examining ART-experienced, virally suppressed adults living with HIV who switched to CAB+RPV LA or to an oral regimen.7 Findings for the 2-drug regimen, Dovato (dolutegravir, lamivudine [DTG/3TC]), will include the InfCare HIV study, which presents three-year switch data, from 3-drug regimen to Dovato, in a long-term real-world Swedish cohort.8 This study adds to the body of real-world evidence to date that includes more than 40,000 people living with HIV.9 Here is a list of ViiV Healthcare-sponsored or supported studies to be presented at CROI 2024: Title First Author Presentation Number Presentation Dolutegravir A single once-daily ABC/DTG/3TC tablet predicts safe and effective exposures in children 3 to <6kg H. Chandasana 02770 Poster Tuesday, March 5 2:30-4:00pm MST Population pharmacokinetics of ABC/DTG/3TC FDC to support dosing in peds with HIV-1 (IMPAACT 2019) H. Chandasana 03110 Poster Tuesday, March 5:30-4:00pm MST Dolutegravir and growth in pediatric populations with HIV-1: IMPAACT P1093 and IMPAACT 2019 M. McKenna 01783 Poster Tuesday, March 5 2:30-4:00pm MST Switching to DTG+3TC vs 3-drug regimens in routine clinical care: long-term Swedish data E. Sörstedt 01838 Poster Tuesday, March 5 2:30-4:00pm MST Temporal trends of cardiovascular disease incidence in people with HIV from 2001-2021 N. Jaschinski 02263 Poster Tuesday, March 5 2:30-4:00pm MST Increased cancer risk with low CD4 counts persists despite over 2 years of virological suppression J. Hoy 01462 Poster Wednesday, March 6 2:30-4:00pm MST Cabotegravir for Treatment Long-acting Injectable CAB/RPV is Superior to Oral ART in PWH with adherence challenges: ACTG A5359 A. Rana 03579 Oral Wednesday, March 6 12:51-1:00pm MST Real-world utilization of cabotegravir + rilpivirine in the US: data from Trio Health cohort J. J. Eron 01374 Poster Monday, March 4 2:30-4:00pm MST Real-world effectiveness of cabotegravir + rilpivirine vs. standard of care oral regimens in the US R. K. Hsu 01952 Poster Monday, March 4 2:30-4:00pm MST HIV-1 RNA blips and low-level viral replication: SOLAR (CAB+RPV LA vs. BIC/FTC/TAF) C. Latham 00138 Poster Monday, March 4 2:30-4:00pm MST Model based comparison of cabotegravir pharmacokinetics following thigh and gluteal injections K. Han 03157 Poster Wednesday, March 6 2:30-4:00pm MST Cabotegravir for PrEP SEARCH Randomized trial of Dynamic Choice HIV Prevention including injectable cabotegravir (CAB-LA) J. Kabami 03405 Late-Breaker Oral Tuesday, March 5 10:00-12:00pm MST Pre-exposure prophylaxis with cabotegravir long-acting injectable in the OPERA cohort A. Mills 01400 Poster Monday, March 4 2:30-4:00pm MST Real-world use of cabotegravir long acting for pre-exposure prophylaxis: TRIO cohort K. Mayer 01907 Poster Monday, March 4 2:30-4:00pm MST Cabotegravir PopPK analysis of adults and adolescents living with HIV or at risk for HIV receiving PrEP Y. Lin 03038 Poster Tuesday, March 5 2:30-4:00pm MST Interest in long-acting injectable PrEP among transgender women in the United States E. E. Cooney 00621 Poster Wednesday, March 6 2:30-4:00pm MST Healthcare staff acceptability and feasibility of telehealth delivery of cabotegravir for PrEP A. Liu 03080 Poster Wednesday, March 6 2:30-4:00pm MST Fostemsavir Temsavir treatment enhances bNAb recognition and subsequent clearance of HIV-1 infected cells R. Ferris 02971 Poster Monday, March 4 2:30-4:00pm MST Pipeline: Ultra Long-Acting Cabotegravir Phase I study of cabotegravir long-acting injectable formulations supports ≥4-monthly dose interval K. Han 00251 Oral Monday, March 4 10:00-12:00pm MST Pipeline: Broadly Neutralising Antibodies VH3810109 (N6LS) in antiretroviral therapy–naive adults with HIV-1: phase IIa BANNER efficacy data P. Leone 01911 Oral Monday, March 4 10:00-12:00pm MST Safety and efficacy of VRC07-523LS plus long-acting cabotegravir in the phase 2 ACTG A5357 Trial B. Taiwo 02254 Oral Monday, March 4 10:00-12:00pm MST High-dose VH3810109 (N6LS) ± recombinant human hyaluronidase PH20: phase I SPAN study safety results B. Win 01988 Poster Wednesday, March 6 2:30-4:00pm MST Pipeline: Maturation Inhibitors Next-generation maturation inhibitor GSK3640254 showed broad spectrum potency without MI resistance B. McAuliffe 03095 Poster Wednesday, March 6 2:30-4:00pm MST The preclinical pro maturation inhibitor VH3739937 J. Jeffrey 02819 Poster Wednesday, March 6 2:30-4:00pm MST General HIV Resistance in young children newly diagnosed with HIV in Western Cape, South Africa K. Anderson 01012 Poster Tuesday, March 5 2:30-4:00pm MST DOVATO (dolutegravir and lamivudine) tablets INDICATION 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. IMPORTANT SAFETY INFORMATION BOXED WARNING: PATIENTS CO-INFECTED WITH HEPATITIS B VIRUS (HBV) AND HIV-1: EMERGENCE OF LAMIVUDINE-RESISTANT HBV AND EXACERBATIONS OF HBV All patients with HIV-1 should be tested for the presence of HBV prior to or when initiating Dovato. Emergence of lamivudine-resistant HBV variants associated with lamivudine-containing antiretroviral regimens has been reported. If Dovato is used in patients co-infected with HIV-1 and HBV, additional treatment should be considered for appropriate treatment of chronic HBV; otherwise, consider an alternative regimen. Severe acute exacerbations of HBV have been reported in patients who are co-infected with HIV-1 and HBV and have discontinued lamivudine, a component of Dovato. Closely monitor hepatic function in these patients and, if appropriate, initiate anti-HBV treatment. CONTRAINDICATIONS Do not use Dovato in patients with previous hypersensitivity reaction to dolutegravir or lamivudine Do not use Dovato in patients receiving dofetilide WARNINGS AND PRECAUTIONS Hypersensitivity Reactions: Hypersensitivity reactions have been reported with dolutegravir and were characterized by rash, constitutional findings, and sometimes organ dysfunction, including liver injury Discontinue Dovato immediately if signs or symptoms of severe skin or hypersensitivity reactions develop, as a delay in stopping treatment may result in a life-threatening reaction. Clinical status, including liver aminotransferases, should be monitored and appropriate therapy initiated Hepatotoxicity: Hepatic adverse events have been reported, including cases of hepatic toxicity (elevated serum liver biochemistries, hepatitis, and acute liver failure), in patients receiving a dolutegravir-containing regimen without pre-existing hepatic disease or other identifiable risk factors Patients with underlying hepatitis B or C or marked elevations in transaminases prior to treatment may be at increased risk for worsening or development of transaminase elevations with use of Dovato. In some cases, the elevations in transaminases were consistent with immune reconstitution syndrome or hepatitis B reactivation, particularly in the setting where anti-hepatitis therapy was withdrawn Monitoring for hepatotoxicity is recommended Embryo Fetal Toxicity: Assess the risks and benefits of Dovato and discuss with the patient to determine if an alternative treatment should be considered at the time of conception through the first trimester of pregnancy due to the risk of neural tube defects Pregnancy testing is recommended before initiation of Dovato. Individuals of childbearing potential should be counseled on the consistent use of effective contraception Lactic Acidosis and Severe Hepatomegaly With Steatosis: Fatal cases have been reported with the use of nucleoside analogs, including lamivudine. Discontinue Dovato if clinical or laboratory findings suggestive of lactic acidosis or pronounced hepatotoxicity develop, including hepatomegaly and steatosis in the absence of marked transaminase elevations. Adverse Reactions or Loss of Virologic Response Due to Drug Interactions with concomitant use of Dovato and other drugs may occur (see Contraindications and Drug interactions). Immune Reconstitution Syndrome, including the occurrence of autoimmune disorders with variable time to onset, has been reported with the use of Dovato. Adverse reactions The most common adverse reactions (incidence ≥2%, all grades) with Dovato were headache (3%), nausea (2%), diarrhea (2%), insomnia (2%), fatigue (2%), and anxiety (2%). Drug interactions Consult full Prescribing Information for Dovato for more information on potentially significant drug interactions Dovato is a complete regimen. Coadministration with other antiretroviral medications for the treatment of HIV-1 infection is not recommended Drugs that induce or inhibit CYP3A or UGT1A1 may affect the plasma concentrations of dolutegravir Administer Dovato 2 hours before or 6 hours after taking polyvalent cation-containing antacids or laxatives, sucralfate, oral supplements containing iron or calcium, or buffered medications. Alternatively, Dovato and supplements containing calcium or iron can be taken with food Use in specific populations Pregnancy: There are insufficient human data on the use of Dovato during pregnancy to definitively assess a drug-associated risk for birth defects and miscarriage. An Antiretroviral Pregnancy Registry has been established. Advise individuals of childbearing potential of the potential risk of neural tube defects. Assess the risks and benefits of Dovato and discuss with the patient to determine if an alternative treatment should be considered at the time of conception through the first trimester of pregnancy or if pregnancy is confirmed in the first trimester Lactation: Breastfeeding is not recommended due to the potential for HIV-1 transmission, developing viral resistance in HIV-positive infants, and adverse reactions in a breastfed infant Females and Males of Reproductive Potential: Pregnancy testing is recommended before initiation of Dovato. Counsel individuals of childbearing potential taking Dovato on the consistent use of effective contraception Renal Impairment: Dovato is not recommended for patients with creatinine clearance <30 mL/min. Patients with a sustained creatinine clearance between 30 and 49 mL/min should be monitored for hematologic toxicities, which may require a dosage adjustment of lamivudine as an individual component Hepatic Impairment: Dovato is not recommended in patients with severe hepatic impairment (Child-Pugh Score C) For more information, please see full US Prescribing Information for Dovato: https://gskpro.com/content/dam/global/hcpportal/en_US/Prescribing_Information/Dovato/pdf/DOVATO-PI-PIL.PDF CABENUVA (cabotegravir; rilpivirine) extended-release injectable suspensions INDICATION CABENUVA is indicated as a complete regimen for the treatment of HIV-1 infection in adults and adolescents 12 years of age and older and weighing at least 35 kg to replace the current antiretroviral regimen in those who are virologically suppressed (HIV-1 RNA <50 copies/mL) on a stable antiretroviral regimen with no history of treatment failure and with no known or suspected resistance to either cabotegravir or rilpivirine. IMPORTANT SAFETY INFORMATION CONTRAINDICATIONS Do not use CABENUVA in patients with previous hypersensitivity reaction to cabotegravir or rilpivirine Do not use CABENUVA in patients receiving carbamazepine, oxcarbazepine, phenobarbital, phenytoin, rifabutin, rifampin, rifapentine, systemic dexamethasone (>1 dose), and St John’s wort WARNINGS AND PRECAUTIONS Hypersensitivity Reactions: Serious or severe hypersensitivity reactions have been reported in association with other integrase inhibitors and could occur with CABENUVA Hypersensitivity reactions, including cases of drug reaction with eosinophilia and systemic symptoms (DRESS), have been reported during postmarketing experience with rilpivirine-containing regimens. While some skin reactions were accompanied by constitutional symptoms such as fever, other skin reactions were associated with organ dysfunctions, including elevations in hepatic serum biochemistries Discontinue CABENUVA immediately if signs or symptoms of hypersensitivity reactions develop. Clinical status, including liver transaminases, should be monitored and appropriate therapy initiated. Cabotegravir and rilpivirine oral lead-in may be used to help identify patients who may be at risk of a hypersensitivity reaction Post-Injection Reactions: Serious post-injection reactions (reported in less than 1% of subjects) were reported within minutes after the injection of rilpivirine, including dyspnea, bronchospasm, agitation, abdominal cramping, rash/urticaria, dizziness, flushing, sweating, oral numbness, changes in blood pressure, and pain (e.g., back and chest). These events may have been associated with accidental intravenous administration and began to resolve within a few minutes after the injection Carefully follow the Instructions for Use when preparing and administering CABENUVA. The suspensions should be injected slowly via intramuscular injection and avoid accidental intravenous administration. Observe patients briefly (approximately 10 minutes) after the injection. If a post-injection reaction occurs, monitor and treat as clinically indicated Hepatotoxicity: Hepatotoxicity has been reported in patients receiving cabotegravir or rilpivirine with or without known pre-existing hepatic disease or identifiable risk factors Patients with underlying liver disease or marked elevations in transaminases prior to treatment may be at increased risk for worsening or development of transaminase elevations Monitoring of liver chemistries is recommended and treatment with CABENUVA should be discontinued if hepatotoxicity is suspected Depressive Disorders: Depressive disorders (including depressed mood, depression, major depression, mood altered, mood swings, dysphoria, negative thoughts, suicidal ideation, suicide attempt) have been reported with CABENUVA or the individual products Promptly evaluate patients with depressive symptoms Risk of Adverse Reactions or Loss of Virologic Response Due to Drug Interactions: The concomitant use of CABENUVA and other drugs may result in known or potentially significant drug interactions (see Contraindications and Drug Interactions) Rilpivirine doses 3 and 12 times higher than the recommended oral dosage can prolong the QTc interval CABENUVA should be used with caution in combination with drugs with a known risk of Torsade de Pointes Long-Acting Properties and Potential Associated Risks with CABENUVA: Residual concentrations of cabotegravir and rilpivirine may remain in the systemic circulation of patients for prolonged periods (up to 12 months or longer). Select appropriate patients who agree to the required monthly or every-2-month injection dosing schedule because non-adherence could lead to loss of virologic response and development of resistance To minimize the potential risk of developing viral resistance, it is essential to initiate an alternative, fully suppressive antiretroviral regimen no later than 1 month after the final injection doses of CABENUVA when dosed monthly and no later than 2 months after the final injections of CABENUVA when dosed every 2 months. If virologic failure is suspected, switch the patient to an alternative regimen as soon as possible ADVERSE REACTIONS The most common adverse reactions in adults (incidence ≥2%, all grades) treated with CABENUVA were injection site reactions, pyrexia, fatigue, headache, musculoskeletal pain, nausea, sleep disorders, dizziness, and rash The safety of CABENUVA in adolescents is expected to be similar to adults DRUG INTERACTIONS Refer to the applicable full Prescribing Information for important drug interactions with CABENUVA, VOCABRIA (cabotegravir), or EDURANT (rilpivirine) Because CABENUVA is a complete regimen, coadministration with other antiretroviral medications for the treatment of HIV-1 infection is not recommended Drugs that are strong inducers of UGT1A1 or UGT1A9 are expected to decrease the plasma concentrations of cabotegravir. Drugs that induce or inhibit CYP3A may affect the plasma concentrations of rilpivirine CABENUVA should be used with caution in combination with drugs with a known risk of Torsade de Pointes USE IN SPECIFIC POPULATIONS Pregnancy: There are insufficient human data on the use of CABENUVA during pregnancy to adequately assess a drug-associated risk for birth defects and miscarriage. Discuss the benefit-risk of using CABENUVA during pregnancy and conception and consider that cabotegravir and rilpivirine are detected in systemic circulation for up to 12 months or longer after discontinuing injections of CABENUVA. An Antiretroviral Pregnancy Registry has been established Lactation: Potential risks of breastfeeding include HIV-1 transmission, developing viral resistance in HIV-positive infants, and adverse reactions in a breastfed infant For more information, please see full US Prescribing Information for Cabenuva: APRETUDE (cabotegravir) extended-release injectable suspensions INDICATION APRETUDE is indicated in at-risk adults and adolescents weighing at least 35 kg for pre-exposure prophylaxis (PrEP) to reduce the risk of sexually acquired HIV-1 infection. Individuals must have a negative HIV-1 test prior to initiating APRETUDE (with or without an oral lead-in with oral cabotegravir) for HIV-1 PrEP. IMPORTANT SAFETY INFORMATION BOXED WARNING: RISK OF DRUG RESISTANCE WITH USE OF APRETUDE FOR HIV-1 PRE-EXPOSURE PROPHYLAXIS (PrEP) IN UNDIAGNOSED HIV-1 INFECTION Individuals must be tested for HIV-1 infection prior to initiating APRETUDE or oral cabotegravir, and with each subsequent injection of APRETUDE, using a test approved or cleared by the FDA for the diagnosis of acute or primary HIV-1 infection. Drug-resistant HIV-1 variants have been identified with use of APRETUDE by individuals with undiagnosed HIV-1 infection. Do not initiate APRETUDE for HIV-1 PrEP unless negative infection status is confirmed. Individuals who become infected with HIV-1 while receiving APRETUDE for PrEP must transition to a complete HIV-1 treatment regimen. CONTRAINDICATIONS Do not use APRETUDE in individuals: with unknown or positive HIV-1 status with previous hypersensitivity reaction to cabotegravir receiving carbamazepine, oxcarbazepine, phenobarbital, phenytoin, rifampin, and rifapentine WARNINGS AND PRECAUTIONS Comprehensive Management to Reduce the Risk of HIV-1 Infection: Use APRETUDE as part of a comprehensive prevention strategy, including adherence to the administration schedule and safer sex practices, including condoms, to reduce the risk of sexually transmitted infections (STIs). APRETUDE is not always effective in preventing HIV-1 acquisition. Risk for HIV-1 acquisition includes, but is not limited to, condomless sex, past or current STIs, self-identified HIV risk, having sexual partners of unknown HIV-1 viremic status, or sexual activity in a high prevalence area or network. Inform, counsel, and support individuals on the use of other prevention measures (e.g., consistent and correct condom use; knowledge of partner[s] HIV-1 status, including viral suppression status; regular testing for STIs) Use APRETUDE only in individuals confirmed to be HIV-1 negative. HIV-1 resistance substitutions may emerge in individuals with undiagnosed HIV-1 infection who are taking only APRETUDE, because APRETUDE alone does not constitute a complete regimen for HIV-1 treatment. Prior to initiating APRETUDE, ask seronegative individuals about recent (in past month) potential exposure events and evaluate for current or recent signs or symptoms consistent with acute HIV-1 infection (e.g., fever, fatigue, myalgia, skin rash). If recent (<1 month) exposures to HIV-1 are suspected or clinical symptoms consistent with acute HIV-1 infection are present, use a test approved or cleared by the FDA as an aid in the diagnosis of acute HIV-1 infection When using APRETUDE, HIV-1 testing should be repeated prior to each injection and upon diagnosis of any other STIs Additional HIV testing to determine HIV status is needed if an HIV-1 test indicates possible HIV-1 infection or if symptoms consistent with acute HIV-1 infection develop following an exposure event. If HIV-1 infection is confirmed, then transition the individual to a complete HIV-1 treatment Counsel HIV-1 uninfected individuals to strictly adhere to the recommended dosing and testing schedule for APRETUDE Potential Risk of Resistance with APRETUDE: There is a potential risk of developing resistance to APRETUDE if an individual acquires HIV-1 either before, while taking, or following discontinuation of APRETUDE. To minimize this risk, it is essential to clinically reassess individuals for risk of HIV-1 acquisition and to test before each injection to confirm HIV-1–negative status. Individuals who are confirmed to have HIV-1 infection must transition to a complete HIV-1 treatment. If individuals at continuing risk of HIV-1 acquisition discontinue APRETUDE, alternative forms of PrEP should be considered and initiated within 2 months of the final injection of APRETUDE Long-Acting Properties and Potential Associated Risks with APRETUDE: Residual concentrations of cabotegravir may remain in the systemic circulation of individuals for prolonged periods (up to 12 months or longer). Take the prolonged-release characteristics of cabotegravir into consideration and carefully select individuals who agree to the required every-2-month injection dosing schedule because non-adherence or missed doses could lead to HIV-1 acquisition and development of resistance Hypersensitivity Reactions: Serious or severe hypersensitivity reactions have been reported in association with other integrase inhibitors and could occur with APRETUDE Discontinue APRETUDE immediately if signs or symptoms of hypersensitivity reactions develop. Clinical status, including liver transaminases, should be monitored and appropriate therapy initiated Hepatotoxicity: Hepatotoxicity has been reported in a limited number of individuals receiving cabotegravir with or without known pre-existing hepatic disease or identifiable risk factors Clinical and laboratory monitoring should be considered and APRETUDE should be discontinued if hepatotoxicity is suspected and individuals managed as clinically indicated Depressive Disorders: Depressive disorders (including depression, depressed mood, major depression, persistent depressive disorder, suicidal ideation or attempt) have been reported with APRETUDE Promptly evaluate patients with depressive symptoms Risk of Reduced Drug Concentration of APRETUDE Due to Drug Interactions: The concomitant use of APRETUDE and other drugs may result in reduced drug concentration of APRETUDE Refer to the full Prescribing Information for steps to prevent or manage these possible and known significant drug interactions, including dosing recommendations. Consider the potential for drug interactions prior to and during use of, and after discontinuation of APRETUDE; review concomitant medications during use of APRETUDE ADVERSE REACTIONS The most common adverse reactions (incidence ≥1%, all grades) with APRETUDE were injection site reactions, diarrhea, headache, pyrexia, fatigue, sleep disorders, nausea, dizziness, flatulence, abdominal pain, vomiting, myalgia, rash, decreased appetite, somnolence, back pain, and upper respiratory tract infection. DRUG INTERACTIONS Refer to the full Prescribing Information for important drug interactions with APRETUDE Drugs that induce UGT1A1 may significantly decrease the plasma concentrations of cabotegravir USE IN SPECIFIC POPULATIONS Lactation: Assess the benefit-risk of using APRETUDE to the infant while breastfeeding due to the potential for adverse reactions and residual concentrations in the systemic circulation for up to 12 months or longer after discontinuation Pediatrics: Not recommended in individuals weighing less than 35 kg For more information, please see full US Prescribing Information for APRETUDE: RUKOBIA (fostemsavir) extended-release tablets INDICATION RUKOBIA, in combination with other antiretrovirals (ARVs), is indicated to treat HIV-1 infection in heavily treatment-experienced adults with multidrug-resistant HIV-1 infection failing their current ARV regimen due to resistance, intolerance, or safety considerations. IMPORTANT SAFETY INFORMATION CONTRAINDICATIONS Do not use in patients with previous hypersensitivity to fostemsavir or any of the components of RUKOBIA. Do not use RUKOBIA in patients receiving strong cytochrome P450 (CYP)3A inducers, including but not limited to enzalutamide, carbamazepine, phenytoin, rifampin, mitotane, and St John’s wort (Hypericum perforatum). WARNINGS AND PRECAUTIONS Immune Reconstitution Syndrome, including the occurrence of autoimmune disorders with variable time to onset, has been reported with the use of RUKOBIA. QTc Prolongation with Higher than Recommended Dosages: RUKOBIA at 2,400 mg twice daily has been shown to significantly prolong the QTc interval of the electrocardiogram. Use RUKOBIA with caution in patients with a history of QTc interval prolongation or in patients with relevant pre-existing cardiac disease or who are taking drugs with a known risk of Torsade de Pointes. Elderly patients may be more susceptible to drug-induced QT interval prolongation. Elevations in Hepatic Transaminases in Patients with Hepatitis B or C Virus Co-infection: Monitoring of liver chemistries is recommended in patients with hepatitis B and/or C co-infection. Diligence should be applied in initiating or maintaining effective hepatitis B therapy when starting RUKOBIA in patients co-infected with hepatitis B. Adverse Reactions or Loss of Virologic Response Due to Drug Interactions with concomitant use of RUKOBIA and other drugs may occur (see Contraindications and Drug Interactions). Adverse reactions The most common adverse reaction (all grades, randomized cohort) observed in ≥5% of subjects was nausea (10%). 81% of adverse reactions reported with RUKOBIA were mild or moderate in severity. Drug interactions See the full Prescribing Information for RUKOBIA for a complete list of significant drug interactions. Temsavir may increase plasma concentrations of grazoprevir and voxilaprevir. Use an alternative hepatitis C virus regimen if possible. Use the lowest possible starting dose for statins and monitor for statin-associated adverse events. Patients receiving RUKOBIA should not take doses of estrogen-based therapies, including oral contraceptives, that contain more than 30 mcg/day of ethinyl estradiol. Caution is advised particularly in patients with additional risk factors for thromboembolic events. Use in specific populations Pregnancy: There are insufficient human data on the use of RUKOBIA during pregnancy to definitively assess a drug-associated risk for birth defects and miscarriage. An Antiretroviral Pregnancy Registry has been established. Lactation: Breastfeeding is not recommended due to the potential for HIV-1 transmission, developing viral resistance, and adverse reactions in a breastfed infant. For more information, please see full US Prescribing Information for RUKOBIA: 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 the company's Annual Report on Form 20-F for 2022, and Q4 Results for 2023. Registered in England & Wales: GSK plc ViiV No. 3888792 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 Han, et al. Phase I Study of Cabotegravir Long-Acting Injectable Formulations Supports ≥4-Monthly Dose Interval. Presented at 31st Conference on Retroviruses and Opportunistic Infections (CROI). March 2024. 2 Leone, et al. VH3810109 (N6LS) in Antiretroviral Therapy–Naive Adults With HIV-1: Phase IIa BANNER Efficacy Data. Presented at 31st Conference on Retroviruses and Opportunistic Infections (CROI). March 2024. 3 Win, et al. High-Dose VH3810109 (N6LS) ± Recombinant Human Hyaluronidase PH20: Phase I SPAN Study Safety Results. Presented at 31st Conference on Retroviruses and Opportunistic Infections (CROI). March 2024. 4 Taiwo, et al. Safety and Efficacy of VRC07-523LS plus Long-Acting Cabotegravir in the Phase 2 ACTG A5357 Trial. Presented at 31st Conference on Retroviruses and Opportunistic Infections (CROI). March 2024. 5 Rana, et al. Long-acting Injectable CAB/RPV is Superior to Oral ART in PWH with adherence challenges: ACTG A5359. Presented at 31st Conference on Retroviruses and Opportunistic Infections (CROI). March 2024. 6 Kamya, et al. SEARCH Randomized trial of Dynamic Choice HIV Prevention including injectable cabotegravir (CAB-LA). Presented at 31st Conference on Retroviruses and Opportunistic Infections (CROI). March 2024. 7 Hsu, et al. Real-World Effectiveness of Cabotegravir + Rilpivirine vs. Standard of Care Oral Regimens in the US. Presented at 31 Conference on Retroviruses and Opportunistic Infections (CROI). March 2024. 8 Sörstedt, et al. Switching to DTG+3TC vs 3-drug regimens in routine clinical care: long-term Swedish data. Presented at 31st Conference on Retroviruses and Opportunistic Infections (CROI). March 2024. 9 Data on File

▎药明康德内容团队编辑自1981年首个艾滋病病例进入人们的视线以来，在短短40多年的时间内，艾滋病治疗领域就发生了天翻地覆的变化。随着鸡尾酒疗法的问世，人类免疫缺陷病毒（HIV）感染者的预期寿命几乎已能与健康人相当。然而，2020年在JAMA Network Open上发表的一项研究表明，HIV感染者即使接受了抗逆转录病毒治疗（ART）并有效地抑制了HIV病毒的复制，与未曾感染过HIV病毒的人群相比，在预期无主要慢性合并症（包括慢性肝病、慢性肾病、慢性肺病、糖尿病、癌症和心血管疾病）寿命方面仍然存在着约15年左右的差距。研究发现，造成这一差距的原因包括感染后无法完全恢复的免疫功能障碍和HIV病毒引起的持续存在的慢性炎症。在ART治疗取得成功后，HIV感染者的血液中已检测不到HIV病毒，那究竟是什么造成了如此巨大的差距？对于这个问题，来自加拿大蒙特利尔大学CHUM研究中心的研究人员将目光投向了HIV-1包膜糖蛋白，尤其是在HIV病毒传播过程中起关键作用的包膜糖蛋白gp120。经过研究他们发现，可在艾滋病患者的血浆和组织中检测到的可溶性gp120（sgp120）很可能就是导致HIV病毒感染者过早形成合并症的罪魁祸首，并将研究结果发表在The Journal of Infectious Diseases杂志上。gp120是一种暴露在HIV病毒包膜表面的糖蛋白，能够从病毒颗粒和感染的细胞表面自发脱落释放。因此，即使在接受ART期间，sgp120仍然能够在HIV感染者的血浆和组织中被检测到。有研究表明，除了能够帮助病毒进入细胞，这种的糖蛋白还能与多种免疫细胞表面的CD4结合，使这些免疫细胞产生多种细胞因子，进而引发慢性炎症。除此以外，sgp120还能与未感染的旁观者CD4+ T细胞上的CD4互相作用，使这些细胞对HIV+血浆介导的抗体依赖性细胞毒性（ADCC）敏感。也就是说，即使在长期接受抗病毒治疗、血液中无法检测到病毒的情况下，sgp120仍然可能引起持续的炎症反应，从而增加并发症的发病风险。为了证明这一假设，在这项研究中，研究人员通过优化基于ELISA的方法，对386名ART治疗时间较长、血浆中无法检测到病毒的HIV感染者进行了研究，以探究sgp120和ADCC介导抗体（特别是anti-cluster A抗体）的存在与免疫功能障碍、慢性炎症和亚临床心血管疾病的相关性，并深入探讨了gp120触发慢性炎症的机制，以期为艾滋病未来的治疗和健康管理提供新的认识和可能性。▲检测不到sgp120的人群与sgp120阳性人群的特征（图片来源：参考资料[1]）结果显示，72.3%的样本（n=279）检测不到sgp120，17.6%（n=68）的样本的sgp120水平较低，10.1%（n=39）的样本的sgp120水平高。与检测不到sgp120的HIV感染者和未感染过HIV的对照人群相比，sgp120低水平和高水平HIV感染者的血浆IL-6水平显著升高。此外，高水平的sgp120和anti-cluster A抗体与CD4计数和CD4:CD8比率呈负相关。在具有可检测的动脉粥样硬化斑块和可检测的sgp120的受试者中，anti-cluster A抗体及其与sgp120水平的组合与动脉粥样硬化斑块的总体积呈正相关。对于这些结果，研究人员认为sgp120具有免疫调节作用，可能导致了HIV感染者的免疫功能障碍、慢性炎症和并发症的过早形成。因此，靶向gp120的疗法有望对其免疫调节作用进行“解毒”，为HIV感染者提供更全面的健康管理。对于这一可能性，研究人员已进行了初步的探索，他们认为一种小分子gp120抑制剂fostemsavir或许有望治疗gp120引起的相关健康问题。Fostemsavir是temsavir（一种小分子HIV-1附着抑制剂）的前药，已于2020年获美国FDA批准用于治疗HIV感染者。该研究小组发现，temsavir能够减少gp120的释放，并且经temsavir处理的细胞产生的sgp120失去了与未感染的旁观者CD4+ T细胞相互作用的能力，保护了这些细胞免受ADCC反应和sgp120介导的细胞因子释放的影响。而fostemsavir是否可以帮助HIV感染者减轻sgp120介导的慢性炎症和免疫功能障碍，尚有待进一步的研究。研究人员表示，sgp120有望成为未来治疗HIV感染的重要靶点，需要更深入的研究以进一步理解gp120释放的机制，探索潜在的抗病毒疗法，并开展针对性的大规模临床试验。这将为HIV感染者提供更全面的治疗选择，进一步弥合HIV感染者与健康人之间的整体健康状况差距。药明康德为全球生物医药行业提供一体化、端到端的新药研发和生产服务，服务范围涵盖化学药研发和生产、生物学研究、临床前测试和临床试验研发、细胞及基因疗法研发、测试和生产等领域。如您有相关业务需求，欢迎点击下方图片填写具体信息。▲如您有任何业务需求，请长按扫描上方二维码，或点击文末“阅读原文/Read more”，即可访问业务对接平台，填写业务需求信息▲欲了解更多前沿技术在生物医药产业中的应用，请长按扫描上方二维码，即可访问“药明直播间”，观看相关话题的直播讨论与精彩回放参考资料：[1] Benlarbi, M., et al. (2023). Plasmatic HIV-1 soluble gp120 is associated with immune dysfunction and inflammation in ART-treated individuals with undetectable viremia. The Journal of Infectious Diseases.Doi: https://doi-org.libproxy1.nus.edu.sg/10.1093/infdis/jiad503[2] Marcus JL, Leyden WA, Alexeeff SE, Anderson AN, Hechter RC, Hu H, Lam JO, Towner WJ, Yuan Q, Horberg MA, Silverberg MJ. Comparison of Overall and Comorbidity-Free Life Expectancy Between Insured Adults With and Without HIV Infection, 2000-2016. JAMA Netw Open. 2020 Jun 1;3(6):e207954. doi: 10.1001/jamanetworkopen.2020.7954. PMID: 32539152; PMCID: PMC7296391.免责声明：药明康德内容团队专注介绍全球生物医药健康研究进展。本文仅作信息交流之目的，文中观点不代表药明康德立场，亦不代表药明康德支持或反对文中观点。本文也不是治疗方案推荐。如需获得治疗方案指导，请前往正规医院就诊。版权说明：本文来自药明康德内容团队，欢迎个人转发至朋友圈，谢绝媒体或机构未经授权以任何形式转载至其他平台。转载授权请在「药明康德」微信公众号回复“转载”，获取转载须知。分享，点赞，在看，聚焦全球生物医药健康创新