Infectious Disease · Medical Literature
Risk of Virological Failure After Switch to a Tenofovir-Sparing Dual Therapy in Virologically Suppressed People With HIV and Past HBV Infection.
Abstract
We compared the effectiveness of tenofovir (TFV)-based triple regimens (TT) to TFV-sparing dual therapies (DT) in virologically suppressed, HBsAg-/HBcAb+ people living with HIV (PLWH). We emulated a target trial including adults PLWH from five University Hospitals, with HBsAg-/HBcAb+ serostatus, starting a TT with unsuppressed serum HIV-RNA and reaching HIV-RNA 50 cp/mL or a single HIV-RNA ≥ 200 cp/mL) were estimated through a weighted Kaplan-Meier estimator. Overall, 415 PLWH were eligible for study analysis: 71 (17.1%) started a DT (3TC-based: 78.9%) during follow-up. They were mainly men (329, 79.3%), with a median age of 48 years. In the weighted analysis, the estimated probabilities of VF were: 29.3% for DT and 29.9% for TT at 5 years (difference: 0.5%; 95% CI: -28.7, +21.6). A higher VF risk was seen in the subset of PLWH with undetectable HBsAb at the longest follow-up available (4 years), independently of treatment group: 15.5% and 36.8% with DT and TT, respectively (difference: -21.3%; 95% CI: -30.3, -13.8). Switch to a TFV-sparing DT, compared with continuing a TT, was not associated with an increased risk of VF in PLWH and prior HBV infection.
Clinical relevance
This study addresses a clinically significant management dilemma in HIV-positive individuals with past HBV exposure (HBsAg-negative/HBcAb-positive): whether switching from tenofovir (TFV)-based triple therapy to TFV-sparing dual therapy risks virological failure, given that tenofovir serves dual antiviral roles in this population. This question is increasingly relevant as dual therapies gain traction for reducing long-term TFV-associated toxicities (renal, bone) in aging PLWH. The findings provide timely, real-world evidence to guide clinicians considering regimen simplification in this specific serological subgroup.
Key findings
1. In a target trial emulation of 415 virologically suppressed PLWH with HBsAg-/HBcAb+ serostatus, 71 (17.1%) switched to a TFV-sparing dual therapy (DT); 78.9% of DT regimens were 3TC-based. 2. At 5 years, the estimated probability of virological failure (VF; defined as two consecutive HIV-RNA >50 cp/mL or a single HIV-RNA ≥200 cp/mL) was 29.3% for DT vs. 29.9% for TFV-based triple therapy (TT); absolute difference: +0.5% (95% CI: -28.7%, +21.6%), indicating no statistically significant difference. 3. Inverse-probability weighting with a cloning-censoring approach was used to emulate randomization, minimizing indication bias inherent in observational switch studies. 4. In the subgroup with undetectable HBsAb at the longest available follow-up (4 years), VF probability was markedly lower in the DT arm: 15.5% vs. 36.8% for TT (difference: -21.3%; 95% CI: -30.3%, -13.8%), suggesting a paradoxically favorable signal for DT in this higher-risk subset. 5. The cohort was predominantly male (79.3%) with a median age of 48 years, reflecting the demographic most likely to harbor occult/past HBV and to be considered for regimen simplification. 6. DT regimens studied included 3TC + boosted PI or DTG, DTG + RPV, DOR + DTG, and long-acting CAB + RPV, representing the contemporary dual-therapy landscape.
Practice implications
Clinicians may reasonably consider switching virologically suppressed, HBsAg-negative/HBcAb-positive PLWH to evidence-based TFV-sparing dual therapies (e.g., DTG-based or long-acting CAB + RPV) without an apparent increase in 5-year virological failure risk, particularly when TFV-related toxicity (nephrotoxicity, osteopenia) is a concern. HBsAb serostatus at follow-up should be assessed prior to switch, as undetectable HBsAb was associated with notably higher VF rates regardless of regimen, identifying a subset warranting closer virological monitoring. Given the wide confidence intervals and observational design, these findings should be interpreted cautiously and prospective randomized data are needed before this can be adopted as definitive practice-changing guidance.