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New Data on HIV-1 Treatments, Including Biktarvy and Novel Lenacapavir Combination Regimen, Presented at CROI 2025
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Results highlight promising advancements in novel treatments for patients with HIV-1, including a combination regimen with broadly neutralizing antibodies and long-term data on bictegravir, emtricitabine, and tenofovir alafenamide (Biktarvy).
Presentations from Gilead Sciences at the Conference on Retroviruses and Opportunistic Infections (CROI) 2025 highlight advancements in potential treatments for HIV-1 infection, including positive long-term outcomes in patients with HIV and hepatitis B virus (HBV) coinfection with the combination of bictegravir, emtricitabine, and tenofovir alafenamide (TAF) (Biktarvy; Gilead Sciences, Inc) and promising results from a phase 2 study of a twice-yearly investigational combination of lenacapavir (LEN, Sunlenca; Gilead Sciences, Inc) and broadly neutralizing antibodies (bNAbs).1
HIV can lead to a lifetime burden of adherence to medications. | Image Credit: © Corona Borealis - stock.adobe.com
Data from these presentations showcases the continued research into HIV treatments to eventually provide a cure for infected patients. Affecting over a million individuals in the United States alone, HIV remains a major health burden for impacted patients and their families, despite the availability of preexposure prophylaxis (PrEP) and major advancements in therapeutic options. It is essential for pharmacists to be aware of novel treatments in the clinical trial pipeline, as their presence in specialty settings for HIV care continues to evolve and expand.2
Bictegravir, emtricitabine, and tenofovir alafenamide (Biktarvy)
At CROI, investigators presented new data from ALLIANCE (NCT03547909), an ongoing phase 3 trial investigating Biktarvy versus dolutegravir 50 mg (DTG) and emtricitabine 200 mg/tenofovir disoproxil fumarate (TDF) 300 mg; F/TDF; and DTG+F/TDF, in adults with HIV-1 and HBV coinfection initiating treatment. Investigations into treatments for coinfection are critical, as around 5% to 15% of US patients with HIV also have chronic HBV infection, which hastens progression to adverse liver outcomes.3,4
In the open-label extension phase of ALLIANCE, which is the first randomized clinical trial evaluating TAF- versus TDF-based regimens in treatment-naïve adults with HIV/HBV coinfection, week 48 outcomes indicated that Biktarvy induced high rates of HIV-1 (95.4%) and HBV (86.6%) virologic suppression in participants (n = 89) that switched to the treatment after 96 weeks of treatment with DTG + F/TDF. In the previously conducted 96-week randomized phase, investigators demonstrated efficacy of both regimens in coinfected patients.1,5
Importantly, regarding the HBV end point, investigators observed a normalization of alanine transaminase (ALT) levels, a critical enzyme found in the liver, in patients with coinfection who reported abnormal ALT levels prior to the switch to Biktarvy from DTG + F/TDF, according to Anchalee Avihingsanon, MD, PhD, an investigator in the ALLIANCE trial, who discussed the results in an interview.6
“This is very important, because if we switch this patient and they still have abnormal ALT, it means that they can have increased [risk] of liver inflammation, liver fibrosis, liver cirrhosis, and liver cancer later on,” Avihingsanon said in the interview. Regarding the rate of treatment-emergent adverse events (TEAEs), which were only reported in 19% of participants and included weight gain and cholesterol increases, Avihingsanon said that this prevalence was clinically insignificant, indicating that the regimen is “quite safe” in this population.6
Lenacapavir and bNAbs
Investigators also presented data from the phase 2 open-label study (NCT05729568) of lenacapavir (LEN) with bNAbs (teropavimab [GS-5423, TAB] and zinlirvimab [GS-2872, ZAB]) (LTZ) as a long-acting, twice-yearly combination regimen for patients with HIV-1. Recently, the FDA granted breakthrough therapy designation to LTZ, which makes the regimen poised to receive expedited review and speedier investigation on its path towards possible FDA approval to become the first long-acting combination regimen with twice-yearly dosing.1,7
In the phase 2 trial, investigators examined outcomes when virologically suppressed adults switched to LTZ every 6 months compared with staying on a stable baseline antiretroviral regimen (SBR). The primary end point of the trial was met, which was the proportion of patients with HIV-1 RNA of 50 copies/mL or more at week 26, as determined by an FDA-defined algorithm. At week 26, 96% (n = 51/53) of participants who received LTZ and 96% (n = 26/27) who received SBR remained virologically suppressed, a key indicator of effectiveness. Furthermore, CD4 counts increased from baseline to week 26 in each cohort.1
“Moving forward, we think this is a regimen that should be very palatable to patients who are really desiring longer-acting therapies to ease the burden of having to take medications too frequently,” Onyema Ogbuagu, MBBCh, FACP, FIDSA, associate professor of medicine and pharmacology at Yale School of Medicine and principal investigator in the phase 2 trial, said in an interview. “Our hope is that the strategy being advanced is applicable to individuals who struggle with daily pill adherence.”8
Importantly, there were no serious AEs related to treatment with LTZ, and no infusion reactions related to either of the bNAb. Ogbuagu noted that pharmacists can play a role in patient education on what to expect regarding the injection site, while counseling them on how to make the injection experience more tolerable. Pharmacists can prescribe pain mitigation measures and local therapies to treat injection site reactions, according to Ogbuagu.1,8
“We intend to, in short order, present 1-year data [from this trial] to show that we are inducing much longer-term efficacy and safety, and thereafter, an open label phase [will begin],” Ogbuagu explained. “We’re excited to see where that takes us, and hopefully, this will inform plans about future trials that lead to licensure.”8
