Long-Acting HIV Therapy Doesn’t Elevate Hepatitis B Reactivation Risk, Study Finds
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A new study indicates that switching to long-acting injectable antiretroviral therapy (ART) does not appear to increase the risk of hepatitis B virus (HBV) reactivation or new infection in people living with HIV. However, researchers emphasize the importance of careful pre-switch assessment and ongoing monitoring, particularly for individuals with chronic HBV. The findings, published in Clinical Infectious Diseases, offer reassurance as long-acting ART gains wider adoption.
Long-acting injectable ART represents a significant advancement in HIV treatment, offering a convenient alternative to daily oral medications and potentially improving sustained viral suppression. However, the medications cabotegravir (CAB) and rilpivirine (RPV), commonly used in these long-acting formulations, lack activity against HBV. This raised concerns that individuals with prior HBV exposure or incomplete immunity could experience viral reactivation or new infections. Until now, robust evidence from real-world clinical settings has been limited.
Prospective Study Evaluates HBV Risk with CAB/RPV
To address this knowledge gap, researchers in Spain conducted a prospective cohort study at Hospital Clínic Barcelona, following adults with HIV who initiated long-acting CAB/RPV between February 2023 and February 2025. The study meticulously evaluated participants’ baseline HBV serologic profiles and tracked the incidence of HBV reactivation and new infections following the switch to the injectable regimen. Participants underwent comprehensive baseline testing, including serological assessments, vaccination status checks, and liver function evaluations. Follow-up monitoring occurred at predetermined intervals and whenever abnormal laboratory or clinical findings warranted further investigation. Statistical analysis employed a range of methods, including chi-squared, Fisher exact, Mann-Whitney U, and Student t-tests.
Key Findings: No Increased Risk in Most Patients
The final analysis included 741 patients, with a median age of 43 years (range 35-52), and 92% identified as cisgender men. The median duration of HIV diagnosis was 12 years (IQR, 7-18), and participants had previously received 2- or 3-drug ART for a median of 8 years (IQR, 2-14) before transitioning to the long-acting regimen. Baseline testing revealed that 61% of patients had immunity to HBV based on vaccination, while approximately 25% showed evidence of prior exposure, and 3% tested positive for isolated hepatitis B core antibody.
During a median follow-up period of 54 weeks (IQR, 28-77), the researchers observed no instances of HBV reactivation or new infection among patients without a history of chronic HBV infection. This included those with isolated core antibody positivity or evidence of previously resolved infection.
However, among the four patients who were switched to long-acting regimens despite having chronic HBV infection, two experienced HBV reactivation. Both individuals subsequently resumed ART regimens that included medications active against HBV. The incidence rate of HBV reactivation in patients with chronic HBV was notably high, at 118.95 per 100 person-years (95% CI, 14.41-429.69), while no reactivation events were observed in those without a history of chronic disease.
Mild Liver Enzyme Elevations Common, But Rarely Linked to HBV
Liver enzyme elevations were observed during follow-up, but these were generally mild and not consistently associated with baseline HBV status. Severe transaminase elevations were infrequent and transient, with only a small proportion directly attributable to HBV reactivation.
The study acknowledged several limitations, including its retrospective design, potential for reduced generalizability, the possibility of undetected subclinical reactivations, incomplete vaccination records, and the use of qualitative data.
“These findings underscore the importance of thorough HBV screening before initiating long-acting ART, particularly in individuals with known chronic infection,” a senior official stated.
Disclosure: Multiple study authors reported affiliations with biotechnology, pharmaceutical, and/or medical device companies. A complete list of disclosures is available in the original publication.
This article originally appeared on Infectious Disease Advisor.
