786 – Impact of Rifabutin on Bictegravir Ctrough and Viral Control in PWH With Mycobacterial Infection

Background

Mycobacterial infection is an important opportunistic infection in people with HIV (PWH), which often requires rifamycin-containing anti-mycobacterial therapy. Rifabutin (RFT), a cytochrome P450 3A4 inducer, may significantly reduce bictegravir trough concentrations (BIC C_trough), but the impact of this drug-drug interaction on viral control is rarely assessed.

Methods

This prospective multi-center study enrolled PWH receiving concurrent RFT-containing anti-mycobacterial therapy and bictegravir/emtricitabine/tenofovir alafenamide (BIC/FTC/TAF) for ≥28 days. We assessed BIC C_trough levels and plasma HIV RNA loads. The primary end-point was the proportion of BIC C_trough levels above the protein-adjusted 95% effective concentration (paEC95) of 162 ng/mL. UHPLC-MS/MS determined RFT C_peak and BIC C_trough levels. 

Results

Between Oct 2023 and Jun 2025, 18 PWH receiving RFT-containing therapy and BIC/FTC/TAF were enrolled. The median age was 41 years (IQR 33-50), 94.4% were men, and 83.3% were men who have sex with men. Three had tuberculosis and 15 had nontuberculous mycobacterial infection. At the initiation of concurrent therapy, the participants had received a median duration of ART for 114.5 days (IQR 79.8-312.3), 28% had achieved plasma HIV RNA <50 copies/mL, and 11% had CD4 counts >200 cells/mm³. Two PWH started BIC/FTC/TAF 133 and 155 days, respectively, after RFT initiation, while 16 PWH had received BIC/FTC/TAF for a median duration of 98 days (IQR 30-131) before RFT initiation. When taking RFT concurrently, median BIC C_trough level decreased significantly to 438.3 ng/mL (IQR 400-781) compared with 3,261.0 (IQR 1,957-4,696) without RFT (Figure), representing a median of 86% reduction (IQR 72-90%). Median RFT C_peak level was 399 ng/mL (IQR 237-516). Despite this substantial decrease, only one (5.6%) participant had a BIC C_trough level <162 ng/mL (144.2 ng/mL) but he continued to maintain plasma HIV RNA <50 copies/m. During one-year follow-up of concurrent use of RFT and BIC/FTC/TAF, the proportions of participants achieving plasma HIV RNA loads <50 copies/mL increased progressively: 50% at month 1, 62% at month 3, 86% at month 6, and 100% at months 9 and 12.

Conclusions

Despite significant drug-drug interaction between RFT and BIC/FTC/TAF that substantially reduce BIC C_trough levels, PWH receiving both therapies can achieve and maintain viral suppression over one year of follow-up, with adequate BIC C_trough levels for effective HIV control.

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