– New Data Evaluating the Efficacy and Safety Profile of Biktarvy for the Treatment of People with HIV and Hepatitis B or Tuberculosis will be Presented –

– Retrospective Analysis Evaluating HIV Resistance-Associated Mutations Reinforces Importance of Treatment Selection in HIV Management –

Gilead Sciences, Inc. (NASDAQ:GILD) today announced new data from three studies evaluating the efficacy and safety profile of Biktarvy® (bictegravir 50 mg/emtricitabine 200 mg/tenofovir alafenamide 25 mg tablets, B/F/TAF) for a broad range of people with HIV, including those with HIV/hepatitis B (HBV) coinfection and HIV/tuberculosis (TB) coinfection. These data and other studies supporting the important role of Biktarvy in the HIV treatment landscape were presented at the 31st Conference on Retroviruses and Opportunistic Infections (CROI).

"People with HIV and comorbid conditions or pre-existing treatment resistance can often face complex and evolving treatment needs. These studies were conducted to help bridge the unmet HIV treatment gap and better understand the potential of Biktarvy in a broad range of people and communities affected by HIV and their diverse health needs, said Jared Baeten, MD, PhD, Vice President, HIV Clinical Development, Gilead Sciences. "The data presented at CROI contribute to the growing body of long-term evidence for Biktarvy and reinforce Gilead's commitment to a person-centric approach to HIV treatment research."

HIV/HBV Coinfection

ALLIANCE (NCT03547908) is an ongoing Phase 3 study evaluating the efficacy and safety of Biktarvy compared to dolutegravir 50 mg (DTG) + emtricitabine 200 mg/tenofovir disoproxil fumarate 300 mg, F/TDF, DTG+F/TDF, in adults with HIV/HBV coinfection initiating treatment. The ALLIANCE trial is the first randomized clinical trial of TAF- vs TDF-based regimens in treatment naïve adults with HIV /HBV coinfection. Its goal is to evaluate treatment regimens that may effectively suppress both HIV and HBV. Previously reported Week 96 results demonstrated the efficacy of both antiretroviral regimens. Additionally, ALLIANCE participants treated with Biktarvy exhibited numerically higher levels of HBV viral suppression and seroconversion. Further results from the trial showed that safety findings were similar between the Biktarvy and DTG+F/TDF groups. Adverse events (AEs) included upper respiratory tract infection (19.8% vs. 14.8%), COVID-19 (38% vs. 36.1%), pyrexia (12.4% vs. 13.1%), ALT increase (8.3% vs. 12.3%), and nasopharyngitis (12.4% vs. 6.6%).

A new exploratory analysis presented at CROI further investigated the factors associated with the HBV treatment response observed with Biktarvy compared to DTG+F/TDF. This subgroup analysis compared the HBV treatment responses according to baseline demographics, HBV genotype, and markers of HIV-1/HBV disease severity for all participants (n=243) at two years.

Consistent with the overall population, the present analysis suggests that in people with HIV/HBV coinfection, the treatment response of TAF- versus TDF-based therapy for many HBV treatment outcomes may be greater for certain subgroups, supporting the continued evaluation of Biktarvy in this population. Some of the subgroups that showed treatment differences favoring Biktarvy included younger age, those with certain levels or types of HBV DNA/genotypes and those with higher-than-normal liver enzymes, among others. The use of Biktarvy in individuals with HIV/HBV is investigational, and the safety and efficacy of this use have not been established.

HIV/TB Coinfection

TB is the leading cause of death among people with HIV. In 2022, approximately 167,000 people died from HIV-associated TB, with the WHO African Region having the highest prevalence. While significant progress has been made in early detection and treatment of HIV-associated TB, there are still significant therapeutic challenges. The interactions between antiretrovirals and TB medications complicate the management of individuals with dual infections. These interactions primarily occur during the metabolism of the drugs. The drug-drug interactions involving the first-line TB drug, rifampicin, are particularly clinically relevant for a number of antiretroviral agents.

Integrase strand transfer inhibitors (INSTIs) are recommended by major standard guidelines for HIV treatment. Several clinical research gaps exist when combining the INSTIs and drugs used for the treatment of tuberculosis, which need to be addressed to inform HIV and tuberculosis co-treatment. INSIGHT (NCT04734652) is an ongoing Phase 2b open-label study conducted in collaboration with a range of organizations, including the Centre for the AIDS Programme of Research in South Africa (CAPRISA), investigating the efficacy, safety, and pharmacokinetics of Biktarvy and dolutegravir 50 mg (DTG) + lamivudine 300mg/ tenofovir disoproxil fumarate 300mg, TLD, in adults initiating treatment for HIV/TB coinfection who have been receiving a rifampicin-based treatment regimen for at least eight weeks.

Participants were randomly allocated to receive Biktarvy or TLD in a 2:1 ratio. Biktarvy was taken twice a day during rifampicin-containing TB treatment and 2 weeks after stopping TB treatment. Thereafter, Biktarvy was taken once daily. Once-daily TLD plus dolutegravir 50mg evening dose was taken during TB treatment and for two weeks after completion of TB treatment. Thereafter, TLD was taken once daily – as per standard of care, until 48 weeks. The primary outcome measure is viral suppression rates at Week 24, defined as HIV-1 RNA ˂50 copies/mL.

Preliminary week 24 results presented at CROI showed that 97% percent (71/73) of participants treated with Biktarvy achieved viral suppression (HIV-1 RNA < 50 copies /ml) as did 97% (36/37) of participants treated with the DTG-based regimen. Serious adverse events (AEs) were common in this population with advanced HIV disease and TB. However, none of the reported AEs were deemed related to the study drug. A similar number of Grade 3 and Grade 4 AEs were reported in both arms.

"South Africa has the largest HIV epidemic in the world, with more than 7 million people with HIV, over half of whom have latent TB co-infection," said Anushka Naidoo, BPharm, MMedSc, PhD, Research Scientist, Centre for AIDS Programme of Research in South Africa (CAPRISA), and Principal Investigator of the INSIGHT study. "The availability of antiretroviral therapy options, including within drug classes, is important, particularly in high HIV/TB burden settings. The key findings from this landmark study presented at CROI support the continued evaluation of Biktarvy in people with HIV and TB as a potential treatment to bridge a critical gap for the individuals and communities who bear the disproportionate burden of co-infection."

The INSIGHT trial will continue through Week 48 to determine longer-term safety and efficacy. Biktarvy is contraindicated for coadministration with rifampin, also known as rifampicin, by the U.S. FDA. The use of Biktarvy in individuals with HIV/TB coinfection is investigational, and the safety and efficacy of this use have not been established.

Resistance-Associated Mutations in Switch Trials

Genetic changes occur in HIV by chance. Some of these changes stop HIV medicines from working; these changes are called resistance mutations. To understand the length of time that resistance mutations stay in the body, researchers looked at the genetic patterns of HIV (called HIV genotype) over time in people who took part in three clinical studies.

Genotype data were collected at the beginning of the clinical trials, and for some participants, earlier genotyping reports were also available. Researchers looked at these reports to find out whether resistance mutations persisted, newly appeared, or disappeared in a cohort of participants (n=242) from three trials who switched to Biktarvy treatment after achieving viral suppression for at least three months on their previous antiretroviral regimen.

The majority of resistance-associated mutations in the analysis were detected 100% of the time or were newly detected and did not disappear over time. Drug resistance mutations archived in cells may persist despite viral suppression, posing a risk for transmission of drug-resistant virus in cases of virological failure, treatment interruption or non-adherence. Healthcare providers must consider all previous drug treatments and genotype reports and should not assume that resistance mutations are no longer present simply because they are not reported in the most recent genotype report, as they may reemerge at a later time. These findings highlight the importance of understanding an individual's treatment history and prior resistance mutation status for treatment management.

In February 2024, the U.S. FDA approved a new, expanded indication for Biktarvy to treat virologically suppressed people with HIV with M184V/I resistance, a common form of treatment resistance.

Additional research studies evaluating Biktarvy presented at CROI 2024 explore safety and efficacy data in older populations, as well as treatment effects on immune activation biomarkers and weight change in people with HIV who are virologically suppressed.

Please see below for U.S. Indications and Important Safety Information for Biktarvy, including BOXED WARNING.

There is currently no cure for HIV or AIDS.