A new study published in The Lancet Microbe reports the first twice-yearly injectable HIV treatment regimen—combining lenacapavir, teropavimab, and zinlirvimab—has achieved high rates of viral suppres...

A new study published in The Lancet Microbe reports the first twice-yearly injectable HIV treatment regimen—combining lenacapavir, teropavimab, and zinlirvimab—has achieved high rates of viral suppres...

A new study published in The Lancet Microbe reports the first twice-yearly injectable HIV treatment regimen—combining lenacapavir, teropavimab, and zinlirvimab—has achieved high rates of viral suppression and demonstrated a favorable safety profile at 26 weeks.

A new study published in The Lancet Microbe reports the first twice-yearly injectable HIV treatment regimen—combining lenacapavir, teropavimab, and zinlirvimab—has achieved high rates of viral suppression and demonstrated a favorable safety profile at 26 weeks. Led by Joe Eron, MD, a researcher with the UNC Institute for Global Health and Infectious Diseases, the findings mark a significant milestone toward what could become the first complete long-acting HIV regimen requiring dosing only twice per year.

Over the last few years a number of studies aiming to cure HIV or at least achieve long-term viral suppression off antiretroviral therapy (ART) have produced tantalising results. These studies have given participants one or both of the long-acting versions of two broadly neutralising antibodies (bnAbs), 3BNC117 (teropavimab) and 10-1074 (zinlirvimab), sometimes in conjunction with immune boosting oral drugs.

High rates of virologic suppression were observed in the Phase 1b study (NCT04811040) investigating lenacapavir and two broadly neutralizing antibodies (bNAb), teropavimab (30 mg/kg) and zinlirvimab (10 or 30 mg/kg), in virologically suppressed people with HIV-1 susceptible (IC90 ≤ 2 μg/mL) to both (primary cohort, n = 20) or either (pilot cohort, n = 10) bNAb. We describe resistance analyses through Week (W) 26.MethodsPost-baseline resistance analyses were conducted at virologic failure, and exploratory resistance analyses performed for participants with virologic rebound. Low copy number genotyping methods for capsid and a 1 kb stretch of gp120 from rebound virus were developed, and phenotypic susceptibility assessed.ResultsVirologic failure was observed in 1/30 participants. This primary cohort participant had HIV RNA 155 copies/mL at W16 and developed Q67H in capsid (lenacapavir fold-change 4.7), without resistance to bNAbs; the participant resuppressed on oral antiretrovirals. Two pilot cohort participants, experienced virologic rebound at W26 (55 and 72 copies/mL) and restarted oral antiretrovirals. In exploratory analyses, neither had emergent lenacapavir resistance or altered bNAb susceptibility.ConclusionsLenacapavir, teropavimab, and zinlirvimab maintained a high rate of virologic suppression through W26, with rare emergent lenacapavir resistance and no bNAb resistance, supporting further Phase 2 evaluation.

Resistance analysis from a Phase 1b study of lenacapavir with broadly neutralizing antibodies teropavimab and zinlirvimab showed rare emergent lenacapavir

Resistance analysis from a Phase 1b study of lenacapavir with broadly neutralizing antibodies teropavimab and zinlirvimab showed rare emergent lenacapavir

High rates of virologic suppression were observed in the Phase 1b study (NCT04811040) investigating lenacapavir and two broadly neutralizing antibodies (bNAb), teropavimab (30 mg/kg) and zinlirvimab (10 or 30 mg/kg), in virologically suppressed people with HIV-1 susceptible (IC90 ≤2 μg/mL) to both (primary cohort, n=20) or either (pilot cohort, n=10) bNAb. We describe resistance analyses through Week (W)26.MethodsBaseline genotypic and phenotypic analyses of proviral gag and envelope DNA were performed. Post-baseline resistance analyses were conducted at virologic failure, and exploratory resistance analyses performed for participants with virologic rebound. For participants with HIV-1 RNA ≥50 to <1000 copies/mL, standard viral RNA genotyping methods were unsuccessful; therefore, low copy number genotyping methods for both capsid and a 1 kb stretch of gp120 from rebound virus were developed, and phenotypic susceptibility assessed.ResultsVirologic failure was observed in 1/30 participants through W26. This primary cohort participant had HIV-1 RNA 155 copies/mL at W16 and developed Q67H in capsid (lenacapavir fold-change 4.7), without resistance to bNAbs; the participant resuppressed on oral antiretrovirals. Two pilot cohort participants, one with baseline susceptibility to teropavimab and one to zinlirvimab, experienced virologic rebound at W26 (55 and 72 copies/mL, respectively) and restarted oral antiretrovirals per protocol. In exploratory analyses, neither had baseline or emergent lenacapavir resistance or altered bNAb susceptibility.ConclusionsLenacapavir, teropavimab, and zinlirvimab maintained a high rate of virologic suppression through W26, with a low rate of emergent lenacapavir resistance and no bNAb resistance, supporting further evaluation of this combination in Phase 2.

The combination of two broadly neutralizing antibodies (bNAbs), teropavimab and zinlirvimab, plus the capsid inhibitor lenacapavir, is a potential twice-yearly regimen for HIV-1 treatment.

The combination of two broadly neutralizing antibodies (bNAbs), teropavimab and zinlirvimab, plus the capsid inhibitor lenacapavir, is a potential twice-yearly regimen for HIV-1 treatment. The level of bNAb susceptibility to maintain virologic suppression is unknown; therefore, we evaluated this combination in participants meeting stringent viral sensitivity criteria to only one of the two bNAbs.MethodsPilot study within a proof-of-concept Phase 1b study (NCT04811040).ResultsNo serious treatment-emergent adverse events occurred and 8/10 participants remained virologically suppressed at Week 26.ConclusionsMore inclusive bNAb susceptibility criteria may be appropriate for future studies of this combination treatment.

A single dose of Lenacapavir, Teropavimab, and Zinlirvimab maintained virological suppression for 6 months in 8 of 10 people with HIV-1 highly susceptible

Onyema Ogbuagu, MBBCh, FACP, FIDSA discussed 96% virologic suppression with lenacapavir-based therapy, showing similar results to daily oral regimens.

Two broadly neutralising antibodies, teropavimab and zinlirvimab, might be good partners for lenacapavir (Sunlenca) in a long-acting HIV treatment regimen, according to study results presented yesterd...

Two broadly neutralising antibodies, teropavimab and zinlirvimab, might be good partners for lenacapavir (Sunlenca) in a long-acting HIV treatment regimen, according to study results presented yesterd...

Two broadly neutralising antibodies, teropavimab and zinlirvimab, might be good partners for lenacapavir (Sunlenca) in a long-acting HIV treatment regimen, according to study results presented yesterd...

Two broadly neutralising antibodies, teropavimab and zinlirvimab, might be good partners for lenacapavir (Sunlenca) in a long-acting HIV treatment regimen, according to study results presented yesterd...

Two broadly neutralising antibodies, teropavimab and zinlirvimab, might be good partners for lenacapavir (Sunlenca) in a long-acting HIV treatment regimen, according to study results presented yesterd...

Two broadly neutralising antibodies, teropavimab and zinlirvimab, might be good partners for lenacapavir (Sunlenca) in a long-acting HIV treatment regimen, according to study results presented yesterd...

Un essai de phase II a évalué l’administration semestrielle du lénacapavir (LEN) associé à deux anticorps neutralisants à large spectre (bNAbs), en comparaison avec un traitement antirétroviral oral standard.

Two broadly neutralising antibodies, teropavimab and zinlirvimab, might be good partners for lenacapavir (Sunlenca) in a long-acting HIV treatment regimen, according to study results presented yesterday at the Conference on Retroviruses and Opportunistic Infections (CROI 2025) in San Francisco.