BACKGROUND AND AIMS
Among hepatitis B virus (HBV) core antibody positive (cAb+) people with HIV, suppressive HBV treatment, including either tenofovir disoproxil fumarate (TDF) or tenofovir alafenamide (TAF), is recommended to prevent HBV reactivation and possibly fulminant or fatal hepatitis.1,2 The risk of HBV resistance is high if lamivudine is used without TDF or TAF, whereas the risk of HIV resistance is high if entecavir is used without TDF or TAF. The authors describe TDF/TAF interruptions and HBV monitoring practices in the USA, as well as assess the incidence of HBV reactivation and hepatitis flares during TDF/TAF interruptions in the OPERA cohort.
METHOD
The OPERA cohort includes electronic health records from >142,000 people with HIV receiving routine clinical care in the USA (96 clinics, 22 states, 1 USA territory), representing approximately 13% of people with diagnosed HIV infection in the USA at the time of this study.3 All TDF/TAF interruptions among HBV surface antigen positive (sAg+) and/or cAb+ people with HIV were categorised by risk of reactivation (high: sAg+; moderate: sAg-/cAb+/HBV surface antibody negative [sAb-]; low: sAg-/cAb+/sAb+).The presence of HBV DNA, sAg, and alanine transaminase (ALT) testing was assessed before (within ≤12 months) and during the interruption. The incidence of HBV reactivation and hepatitis flares (American Association for the Study of Liver Diseases definitions) was assessed with Poisson regression.
RESULTS
Of 30,549 people co-infected with HBV/HIV, 5,343 (17%) had ≥1 interruption, for a total of 6,252 interruptions (11% high, 19% moderate, 70% low-risk) and the median duration was 23 months (interquartile range: 4–53). There were no DNA tests before (high: 56%; moderate: 94%; low: 92%) or during interruptions (high: 48%; moderate: 91%; low: 95%). There was no sAg test in 75% of high, 69% of moderate, and 72% of low-risk interruptions. HBV reactivation occurred in 117 high-risk interruptions (17% overall, 32% of those with DNA tests) for an incidence rate [IR] of 9.92 per 100 person-years (95% CI: 8.28, 11.89). Reactivation occurred in 24 moderate-risk interruptions (2% overall, 6% of those with DNA and/or sAg tests), with an IR of 0.67 (95% CI: 0.45, 1.00). Only 10 low-risk interruptions resulted in HBV reactivation (<1% overall; <1% of those with DNA and/or sAg tests), with an IR of 0.08 (95% CI: 0.04, 0.15). ALT tests were available before (high: 91%; moderate: 91%; low: 93%) and during interruptions (high: 99%; moderate: >99%; low: >99%). Hepatitis flares occurred in 68 (10%) high-risk interruptions (IR per 100 person-years: 5.53; 95% CI: 4.36, 7.01), 59 (5%) moderate-risk interruptions (IR: 1.74; 95% CI: 1.35,2.24), and 162 (4%) low-risk interruptions (IR: 1.31; 95% CI: 1.13, 1.53).
CONCLUSION
In this large USA cohort of sAg+ and/or cAb+ people with HIV receiving care in primary or HIV care clinics, TDF/TAF interruptions were common and lengthy, and HBV lab monitoring was sub-optimal, suggesting that primary and HIV care providers tend to be unaware of HBV status or overlook HBV monitoring and management in people with co-infection. While sAg+ individuals had the highest HBV reactivation and hepatitis flare risk, all were at risk regardless of serology. Given infrequent testing, many reactivations were likely missed. Primary and HIV care providers need to incorporate HBV monitoring in their standard of care and proceed with caution if considering a TDF/TAF interruption for people with
HBV/HIV co-infection.
