Hepatitis C reinfection common in treated drug users

According to a secondary analysis of the randomized HERO trial, among injecting drug users treated for hepatitis C virus (HCV) infection, the rate of new infections was high shortly after a sustained virologic response but decreased with longer follow-up.

In 415 participants followed for up to 42 months, the overall reinfection rate was 11.4 per 100 person-years of risk (95% CI 8.7-14.7) over 518 person-years of follow-up, reported researchers led by Alain Litwin, MD, MPH, of the University of South Carolina School of Medicine in Greenville, in JAMA network opened.

However, with increasing follow-up after sustained virologic response, there was a significant decline in new infections. The rate was 15.5 per 100 person-years in the first six months of follow-up, but decreased to 4.3 per 100 person-years between 18 and 3 years of follow-up (P=0.008).

“Our findings support previous reports showing that most reinfections occur within 24 weeks of a sustained virologic response, highlighting the need to provide effective interventions early to prevent reinfection,” Litwin and colleagues wrote.

Reinfection rates have more than doubled among those who tested positive for methamphetamine compared to those who did not test positive (adjusted incidence rate ratio [aIRR] 2.41, 95% CI 1.22–4.76) and was more than three times higher among those who reported injection drug use within the last three months than among those who had not recently used drugs (aIRR 3.33, 95% CI 1.86–5.97).

The higher rates of new infections in this analysis compared with other studies likely reflect the at-risk population included in the HERO trial, Litwin's group said. Over time, the untreated HCV population will include a higher proportion of individuals who are more difficult to treat due to severe substance use disorders, polyuse, mental and medical comorbidities, homelessness, lack of social support and poor transportation. These characteristics were common among all HERO participants, they noted.

However, the high rates of reinfection suggest that high-risk groups are uptake of treatment, they added. This high-risk group is a final obstacle on the path to eliminating HCV infection; the reinfections are easily treatable with simple, accessible, direct-acting antiviral therapies. “While minimizing HCV reinfection is an important health care goal, the occurrence of reinfections is also an indication that treatment is reaching high-risk groups,” they explained.

“These data will form the basis for public health strategies to eliminate HCV,” the authors conclude, “and minimize reinfection by identifying high-risk behaviors and implementing appropriate interventions for PWID.” [people who inject drugs] who require more intensive or more frequent follow-up and immediate retreatment.”

In an accompanying editorial, Marianne Martinello, MBBS, PhD, and Gail Matthews, MBChB, PhD, of the University of New South Wales in Sydney, Australia, noted that more than 2 million people in the United States—mostly injection drug users—are living with HCV infection.

“The higher rate of new infections in the HERO trial should not be a cause for concern,” they wrote. “First, it is important to be aware that new HCV infection will occur when DAA [direct-acting antiviral] Treatment intensity will be increased, particularly in population groups at highest risk of transmission.”

While there may be an initial increase, the number of new infections will fall as HCV prevalence in the population decreases, they added. “A successful strategy to eliminate HCV must take this into account, and neither clinicians nor politicians should be discouraged by this, but be prepared to continue to integrate surveillance, prevention and management of new infections into their approach.”

Primary results from the HERO (Hepatitis C Real Options) trial, which compared the effectiveness of modified directly observed therapy and patient navigation in opioid treatment programs and community health centers from 2016 to 2018, showed no significant difference in sustained virologic response between the two treatment groups (73.9% versus 74.5%, P=0.35).

The secondary analysis conducted in 2022 included 415 participants from the original study with sustained virologic response after treatment with direct-acting antiviral therapy. The mean age was 44.7 years and 72.8% were men. Overall, 72.8% reported recent injection drug use, 46.3% were living in unstable housing, and 75.4% had recently received methadone or buprenorphine for opioid use disorder.

Reinfection rates varied considerably among the included opioid treatment programs and community health centers, ranging from 2.9 per 100 person-years of risk (95% CI 0.1–16.3) to 25.2 per 100 person-years of risk (95% CI 15.6–38.5; P=0.006).

Limitations of the study, according to Litwin and his team, included the predominantly urban setting and the significant differences in new infection rates between study sites. They pointed out that more than a third of new infections were reported at a single site.

In addition, many of the participants lost to follow-up had characteristics associated with a higher risk of reinfection, such as taking methadone for opioid use disorder. “Although the number of patients lost to follow-up was small, this overlap in characteristics suggests that the patients lost to follow-up represented a cohort with higher-risk behaviors, potentially leading to an underestimation of true reinfection rates,” they explained.