Gilead Sciences presented new research data from its HIV treatment portfolio and pipeline at the International Congress on Drug Therapy in HIV Infection (HIV Glasgow 2024), showcasing advancements in long-term efficacy, resistance patterns, and novel dosing strategies. The data include four-year outcomes from the BICSTaR study on Biktarvy, insights from the ROSETTA registry on INSTI resistance, and findings from the ALLIANCE trial on HIV/HBV co-infection.
Long-Term Efficacy and Safety of Biktarvy
The BICSTaR study (NCT03580668), a multinational, prospective, observational cohort study, evaluated the effectiveness, safety, and tolerability of Biktarvy in treatment-naïve (TN) and treatment-experienced (TE) people with HIV in routine clinical practice. The four-year outcomes from participants in Canada, France, and Germany demonstrated that Biktarvy maintained high levels of effectiveness and tolerability. Virologic suppression (HIV-1 RNA <50 copies/mL) was maintained in 98% of TN and 97% of TE participants. No treatment-emergent resistance to Biktarvy was reported. Discontinuation due to drug-related adverse events occurred in 7% of participants overall, with weight change being the most commonly reported reason (4%).
An analysis of self-reported treatment adherence through 24 months in TE participants (n=1,496) who switched to Biktarvy showed high and sustained virologic suppression (HIV-1 RNA <50 copies/mL) through 24 months (96% overall), with no treatment-emergent resistance. Mean adherence scores were high at both baseline and 24 months (95% and 97%, respectively).
Resistance Patterns with Integrase Strand Transfer Inhibitors
The ROSETTA registry, which collects data on virologic failure with INSTI-based regimens, presented an interim analysis including 125 clinical datasets and 124 sequences. The analysis revealed that 19.4% of participants had been previously exposed to earlier INSTIs. Major INSTI resistance mutations were selected in 33 cases (26.6%): 28 cases with Dolutegravir (DTG) failure, 3 with Bictegravir (BIC), and 2 with Cabotegravir (CAB). Notably, two of the mutations seen, G118R and R263K, were not observed in cases with earlier INSTI exposure, suggesting different resistance pathways based on past exposure.
Biktarvy in HIV/HBV Co-infection
The ALLIANCE trial (NCT03547908), a Phase III study, evaluated Biktarvy versus dolutegravir 50 mg (DTG) + emtricitabine 200 mg/tenofovir disoproxil fumarate 300 mg (F/TDF) in adults with HIV-1/HBV co-infection initiating treatment. Week 144 outcomes from the open-label extension phase showed that Biktarvy maintained high rates of HIV-1 and HBV virologic suppression, defined as HIV RNA <50 copies/ mL and HBV RNA <29 IU/ mL, respectively. At Week 144, Biktarvy maintained high levels of HIV-1 RNA (99.0%) and HBV DNA (80.2%) suppression. Study drug-related treatment-emergent adverse events (TEAEs) were reported in 32% of participants, with only 1% (n=1) of discontinuations due to TEAEs.
Investigational Regimens: Bictegravir and Lenacapavir Combination
ARTISTRY-1 (NCT05502341), an ongoing Phase 2/3 study, compares the investigational once-daily combination of bictegravir (BIC) and lenacapavir (LEN) versus current therapy in people with HIV who require a complex treatment regimen to maintain virologic suppression. Week 48 results demonstrated that parameters measuring lipids and glucose levels generally improved after switching from a baseline regimen to BIC+LEN. At Week 48, fasting lipid parameters generally improved from baseline in both BIC+LEN groups versus the complex antiretroviral regimen group with a median change in total cholesterol, -12.3% and -8.1%, respectively, versus +1.8%. Results from a pharmacokinetic (PK) analysis support the use of BIC 75 mg +LEN 50 mg fixed-dose combination (FDC) for Phase 3.
Novel Weekly Oral Combination HIV Treatment
GS-1720, a selective integrase strand transfer inhibitor (INSTI), is being evaluated as part of a novel, investigational once-weekly antiretroviral agent combination. Phase 1b study (NCT05585307) data showed that in participants with GS-1720 concentrations at day 11 above 2-fold the inhibitory quotient, robust antiviral activity (≥1.5 log10 copies/mL reduction in HIV-1 RNA from baseline) was observed. No participant had primary resistance-associated mutations in integrase at screening, and no resistance to the INSTI-class was detected at day 11, across a range of GS-1720 concentrations.
Long-Acting, Twice-Yearly Regimen of Lenacapavir and Broadly Neutralizing Antibodies (bNAbs)
A pooled analysis of efficacy and safety outcomes from a Phase 1b study (NCT04811040) evaluating the treatment responses of participants receiving lenacapavir with bNAbs [teropavimab (GS-5423, TAB) + zinlirvimab (GS-2872, ZAB)] showed that at Week 26, 21% (n=3) of participants who received LEN + TAB and the low dose of ZAB and 0% (n=0) participants who received LEN +TAB and the high dose of ZAB had an HIV viral load ≥50 copies/mL (per FDA Snapshot).
