Date of report 08 Oct 2026

Reported case interaction between
Lenacapavir LA and Rifabutin

In June 2025, a 30-year-old male with multidrug resistant HIV and a history of non-adherence (pre-admission CD4 count <10 cells/mm3, HIV RNA 28'000 copies/mL) was hospitalized for respiratory failure secondary to Pneumocystis jirovecii pneumonia along with disseminated Mycobacterium avium complex (MAC) infection. Treatment for HIV included dolutegravir, lamivudine, darunavir/ritonavir and tenofovir DF during hospitalization. In late July 2025, rifabutin was added to the MAC treatment regimen to enhance efficacy. A reduced dose of 150 mg daily was selected because of concomitant darunavir/ritonavir use. Following achievement of virological suppression (HIV RNA <20 copies/mL), ART was simplified to lenacapavir plus daily darunavir/ritonavir to address ongoing adherence challenges.

Of note, fostemsavir was considered suboptimal because of its twice-daily dosing schedule in a patient with adherence challenges, while ibalizumab was not an option because it was not routinely available in the country where this case occurred.

At the time of lenacapavir initiation, the patient had already been receiving rifabutin for one month; therefore, its maximal enzyme inducing effect was assumed to have been reached. To compensate for rifabutin-mediated induction, the oral lenacapavir loading dose was increased to 900 mg (instead of the 600 mg standard dose) on days 1 and 2. Similarly, the subcutaneous dose was increased to 1390 mg (instead of the standard 927 mg), administered on day 1 and every six month thereafter.

The decision to increase the lenacapavir dose was driven by the need to achieve adequate drug exposure without delay, considering that the maximal enzyme inducing effect of rifabutin had already been reached at the time of lenacapavir initiation. The original oral ART regimen was continued for the first following lenacapavir initiation. Therapeutic drug monitoring (TDM) of lenacapavir was performed daily during the first week, weekly for the first month, and subsequently at months 2 through 5. Lenacapavir concentrations consistently remained above the target threshold of 15.5 ng/mL. Specifically, lenacapavir concentrations were 3-fold above this threshold at week 1, 4-fold above it at weeks 2 and 3, and increased to 15-fold above the threshold at months 3 and 4, before declining to 1.2 fold above the threshold by month 6. Initial lenacapavir concentrations were comparable to those reported in real-world clinical practice (Le MP et al. CROI 2025), suggesting that the increased lenacapavir successfully compensated for rifabutin mediated induction. At months 3 and 4, lenacapavir concentrations exceeded twice the C_max  reported in the lenacapavir prescribing, potentially reflecting the effect of concomitant darunavir/ritonavir. Indeed, coadministration of lenacapavir with darunavir/cobicistat has been shown to increase lenacapavir AUC and Cmax by 94% and 130%, respectively. The patient viral load remained suppressed throughout lenacapavir therapy

This case demonstrates that dose adjusted lenacapavir can achieve therapeutic exposure despite the concurrent use of a moderate CYP3A4 inducer.

This case has been presented at the 27th International wokshop on HIV clinical pharmacology, Montreal, September 2-3, 2026.