Despite less injecting drug use, increased use of harm reduction services, and significant progress in reducing HIV infections, there has been a resurgence of hepatitis C among people who inject drugs in recent years in Baltimore, especially among people under the age of 40. This research, tracking changes over the past three decades, was presented by Eshan Patel to the recent Conference on Retroviruses and Opportunistic Infections (CROI 2024) in Denver.
Background
In the US, cases of acute hepatitis C infection continue to increase. There have also been HIV outbreaks among people who inject drugs in recent years linked to the opioid crisis. While combination prevention of both HIV and hepatitis C is the goal, it is unclear how effective this approach has been among people who inject drugs, especially during the implementation of universal test and treat for HIV, and the introduction of direct-acting antivirals to treat hepatitis C.
Combination prevention can be thought of as having both behavioural and biomedical components. Behavioural approaches encompass testing for HIV and hepatitis C, campaigns to promote harm reduction and syringe service programmes. Baltimore introduced a one-to-one needle exchange programme in 1994, which changed to allowing users to take as many syringes as needed from 2014. Biomedical approaches include the use of methadone and buprenorphine to manage opioid use disorder and treatment for both HIV and hepatitis C, which can also prevent onward transmission.
For HIV, treatment has changed dramatically since 1996, with the introduction of combination antiretroviral therapy (ART) as the primary form of treatment. Hepatitis C was mainly treated with interferon-based therapy before 2011, with some patients being offered direct-acting antivirals around 2012. However, direct-acting antivirals have only become more widely used as the primary treatment for hepatitis C in Baltimore since 2017.
The study
Participants were members of the AIDS Linked to the IntraVenous Experience (ALIVE) study cohort based in Baltimore, a US city an hour away from Washington DC. Since 1988, adults with a history of injection drug use have been eligible to participate and completed visits twice a year. At these visits, they completed surveys to report on recent drug use and engagement with prevention and medical interventions. They also provided blood for HIV and hepatitis C testing.
There were five enrolment periods: 1988 to 1989, 1994 to 1995, 1998, 2005 to 2006 and 2015 to 2018. Follow-up ended at the end of 2019. This allowed researchers to monitor changing patterns of infection over time, and link them to treatment and policy changes.
Overall, there were 5506 people in the cohort across all five enrolment periods, with a median age of 37, most of whom were male (74%) and Black (79%). However, the percentage of Black people injecting drugs has declined over time in the cohort, comprising 53% for the last period. Most had less than high school education (55%) and had injected drugs in the past six months (88%). A quarter of the cohort were HIV positive at enrolment, while over three-quarters tested positive for hepatitis C (78%).
HIV positivity was highest in 1998, at 39%, while hepatitis C positivity remained fairly constant during the study period (a low of 68% in the final period to a high of 81% between 1988 and 1989). In terms of overall follow-up, the median number of visits was six, with a total of 68,107 visits over the study period. Overall, 46% of cohort members have died. The lowest number of deaths was seen for those joining in the final enrolment period, at 11%.
New HIV and hepatitis C infections
Of 2657 participants who were HIV negative, there were 282 new HIV cases in the cohort over the five enrolment periods. There was decline in new cases from 4.1% in 1988 to 0.1% for the last period. Overall, incidence was 1.5% per year.
Of 593 participants who did not have hepatitis C at enrolment, there were 115 new cases. Incidence went down from 9.8% from 1988 to 4% in the last period, with an overall incidence of 3.2% per year. While incidence has fluctuated somewhat, it was at its lowest between 2011 and 2013, and has been on the increase since then.
Comparing 2017 to 2019 with 1988 to 1992, this shows a dramatic 98% reduction in the number of new HIV cases overall (Incident Rate Ratio = 0.02, 95% Confidence Interval = 0.00 to 0.13) and a much less dramatic 58% fall in hepatitis C cases (IRR = 0.42, 95% CI: 0.24 to 0.72).
A jarring finding was that once age and sex were controlled for, rates of new hepatitis C cases were not significantly different between 2014 to 2019, when compared to three decades ago, 1988 to 1992.
When looking at the differences in age groups more closely, in recent years there has been a sharp difference in new hepatitis C infections for those above and below the age of 40. Between 2014 and 2019, incidence was 17% for people under 40, while remaining below 5% for older people. While the rates for younger people were higher in 1988, there were various periods through the mid-1990s and 2000s when the number of new infections across age groups were similar.
For those participants with HIV, ART use increased dramatically from 55% in 2006 to 96% in 2019. In line with this, HIV viraemia (above 400) went down from 63% in 2007 to 36% in 2019. Similarly, among those with chronic hepatitis C infection, the percentage of people who had ever received treatment went up from 2% in 2014 to 56% in 2019, showing a steep uptake of direct-acting antivirals. Among those with hepatitis C antibodies, viraemia (above 500) went down from 84% in 2006 to 36% in 2019.
Over time, the number of cohort members who were active injecting drug users went down from a high of 89% in 1988 to 36% in 2019. Additionally, the uptake of harm reduction services among those who were injecting, such as attending syringe service programme, increased from 36% in 1998 (the first year of tracking) to 51% in 2019. A large increase was seen in the uptake of methadone treatment, from 10% in 1988 to 44% in 2019.
Conclusion
“Over this 30-year period, we saw decreases in injecting drug use that correlated with greater declines in HIV incidence as compared to hepatitis C incidence,” Patel concluded.
“Despite these improvements, it’s concerning that our current combination hepatitis C prevention efforts may not be sufficient, as we saw high, and potentially increasing, hepatitis C incidence among young people who inject drugs. To reach this population in this evolving drug use epidemic we have in the US, we may need additional approaches to how we implement our current prevention strategies as well as new tools to address the changing needs of people who inject drugs.”
Patel EU et al. Trends in HIV and HCV Prevention Efforts and Incidence Among People Who Inject Drugs in Baltimore. Conference on Retroviruses and Opportunistic Infections, Denver, abstract 160, 2024.