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HBV and Viremia in HIV
Hepatitis B Reactivation and Low-level Viremia in People Living With HIV

Released: November 09, 2023

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Key Takeaways
  • The Swiss HIV Cohort Study and the Women’s Interagency HIV Study suggest that intermittent or persistent low-level viremia with HIV-1 RNA <200 copies/mL may be associated with an increased risk of virologic failure.
  • HBV reactivation, although rare, can occur if switching to an ART without HBV activity in people with hepatitis B core antibody.

Potential risks of antiretroviral therapy (ART) for the treatment of HIV include low-level viremia and hepatitis B virus (HBV) reactivation. At IDWeek 2023 and EACS 2023, there were 3 pivotal studies regarding treatment options for and risk of low-level viremia or HBV reactivation in people living with HIV.

Low-level Viremia: Swiss HIV Cohort Study
The Swiss HIV Cohort Study focused on HIV rebound and patients with low-level viremia. Dr Katharina Kusejko presented an interesting analysis on the relevance of low-level viremia for predicting the risk of ART failure in people living with HIV. Low-level viremia was defined as having detectable viremia between the assay cutoff of 50 and 200 copies/mL.

Persistent low-level viremia is seen in 4% to 8% of patients, whereas blips occur in up to 50% of patients. There is evidence from published work that HIV-1 RNA >200 copies/mL are clearly associated with antiviral drug resistance and treatment failure. However, because it is unclear what happens to people with HIV-1 RNA between 50 and 200 copies/mL, this study explored this question in-depth.

This study included 8132 people in Switzerland living with HIV who were receiving ART and had regular HIV-1 RNA monitoring, as well as ≥2 HIV-1 RNA tests 90 days apart. Participants were followed until the end of their follow-up period or virologic failure.

The researchers found that 7.7% of patients experienced virologic failure, 71.4% had an undetectable HIV-1 RNA throughout, and the remainder had intermittently detectable viremia. Those with low-level viremia were 3.5 times more likely to experience virologic failure, defined as a virus load >200 copies/mL, than those without.  However, the investigators did not distinguish between those in whom low-level viremia represented ongoing viral replication (as evidenced by emergence of new resistance mutations) versus those in whom low-level viremia merely represents release of virus from clonally expanded cells harboring provirus.  

This study certainly contributes to our understanding of the potential clinical significance of low-level viremia and reinforces that management needs to be individualized.

Low-level Viremia: Women’s Interagency HIV Study  
Dr Amalia Aldredge presented findings from the Women’s Interagency HIV Study of the consequences of low-level viremia among women in the United States. What the presence of low-level viremia means in terms of the risk for virologic failure remains an unanswered question. This prospective study was a nice complement to the Swiss HIV Cohort Study. It defined intermittent low-level viremia as having a nonconsecutive HIV-1 RNA of up to 199 copies/mL, and it followed patients from 2003-2020. Patients were required to have received ART for ≥1 year, as well as ≥2 consecutive HIV-1 RNA measurements. 

Of the 1598 women in the analysis, 275 had an episode of virologic failure, leaving 1323 women in the survival analysis. The investigators obtained 4 consecutive HIV-1 RNA measurements to determine if these patients had low-level viremia and whether it was intermittent. Approximately 19% of the women had intermittent low-level viremia, and 6% had persistent low-level viremia.

The risk of virologic failure among patients with intermittent and persistent low-level viremia was 1.9-fold and 2.3-fold, respectively. 

From these 2 very similar analyses, it can be suggested that intermittent or persistent low-level viremia with HIV-1 RNA  <200 copies/mL may be associated with an increased risk of virologic failure. It is important to note that it is unclear whether a change in regimen, adherence, or intervention may prevent these failures, so consistent patient monitoring is recommended. 

HBV Reactivation: Veterans Aging Cohort Study
Presented by Dr Rachel Denyer, the final study I would like to discuss focused on people living with HIV from the Veterans Aging Cohort Study who had a positive hepatitis B core antibody and negative surface antigen and were at risk for HBV reactivation.

Antiretroviral regimens used in HIV often include tenofovir, lamivudine, or emtricitabine, which also are recommended for those with HBV. But some newer 2-drug regimens—such as dolutegravir plus rilpivirine or cabotegravir plus rilpivirine—include no agents with anti-HBV activity. The investigators aimed to determine the risk of HBV reactivation among 5954 people living with HIV who had isolated hepatitis B core antibody, were at risk for HBV reactivation, and were switched to an ART regimen that lacked activity against HBV. 

The researchers found that HBV rebound occurred in 1.5% of people living with HIV who had hepatitis B core antibody after switching to a regimen that lacked HBV activity. Of note, patients who had prior history of surface antigen positivity were at a higher risk (20%) of having HBV rebound than those who did not. 

I believe this study suggests that, if there are compelling reasons to offer patients who are hepatitis B core antibody positive a regimen without tenofovir, one might be able to do that with reasonable safety and careful monitoring, especially if the patient has no history of surface antigen positivity. Although this approach is clearly outside treatment guidelines, there are certainly situations where tenofovir is not a viable option. In such situations, a history of surface antigen positivity is a factor that can help guide healthcare professionals to the correct regimen. 

Your Thoughts?
Which of the above studies will most affect your clinical practice? See more studies from IDWeek 2023 and EACS 2023, and get involved by posting a comment below.