People with chronic hepatitis B who are at risk of acquiring HIV may experience the dual benefit of oral formulations of tenofovir-based PrEP that protect against HIV and reduce hepatitis B virus (HPV) burden; but may also experience an exacerbation of hepatitis when PrEP is discontinued. A recent review assesses the evidence for offering oral PrEP to this population and finds best practices to favor benefits over risks.
Amir Mohareb, MD, Medical Practice Evaluation Center Massachusetts General Hospital, Boston, MA, and colleagues point out that clinical practice guidelines provide little guidance on when and how to use PrEP safely in people with the disease. HBV, despite their risk of contracting HIV through the same route of infection.
“This lack of knowledge affects key populations and people in countries where HBV is endemic, who are at higher risk of living with chronic HBV, but who have the greatest benefits from using a tenofovir disoproxil fumarate therapy as PrEP to prevent HIV acquisition,” Mohareb and colleagues state.
With few published experiences assessing the risk of HBV reactivation in people with chronic HBV who take and stop PrEP, or use it sporadically or “on demand” around sexual activity, reviewers have reviewed the hepatology literature focusing on the safety or benefits of stopping antiviral treatment when treatment has reached undetectable levels of HBV DNA.
In a large observational study, 80% of 691 participants who discontinued antiviral therapy according to clinical society guidelines had HBV DNA reactivation; 61% had reactivation with an increase in ALT more than twice the upper limits of normal; and 41% required retreatment with antiviral therapy. These findings have prompted several clinical trials of stopping antivirals in people with HBeAg-negative infection.
Although Mohareb and colleagues recognize the differences between controlled HBV treatment withdrawal and inconsistent or short-term use of PrEP, they nevertheless find information in studies of HBV treatment withdrawal for PrEP safety and patient selection. They note that HBV DNA reactivation with discontinuation followed more often after long-term suppression. Some developed clinically apparent hepatitis flares; and those with pre-existing liver disease were most at risk of liver damage after discontinuation. Acute liver failure has occurred and, although rare, this is the major risk that must be weighed against the benefits of PrEP.
Based on their findings, Mohareb offers the following recommendations:
- All HBV-infected individuals who start tenofovir-based PrEP benefit from close follow-up and laboratory monitoring for HBV DNA, aminotransferases, and selected HBV serologies.
- Indefinite use of PrEP containing tenofovir should be considered in this population
- People who are losing HbsAg or who have low levels of quantitative HBsAg should consider stopping PrEP once the benefits of HIV prevention are no longer indicated
- When PrEP has been stopped, monitoring should be tailored to the person’s risk of reactivation and hepatitis. Optimally, laboratory testing for HBV DNA and aminotransferases should continue at least every 3 months for at least 1 year.
“All people with HBV who start PrEP should be informed of the risks of stopping tenofovir disoproxil fumarate and emtricitabine, the need for close laboratory monitoring, and the possibility of needing retreatment – which could be lifelong – for specific indications for HBV reactivation of hepatitis,” advised Mohareb and colleagues.