Introduction

People who inject drugs (PWID) bear a disproportionate burden of Hepatitis C virus (HCV) infections and face persistent barriers to healthcare access. HCV can cause an acute infection (acute hepatitis C), often asymptomatic, and more than half of these cases will progress to chronic infection. PWID who share injection paraphernalia like needles, syringes, or drug preparation equipment are at the greatest risk for acquiring and transmitting HCV [1, 2]. HCV prevalence among PWID has been alarmingly high, with 62% having been exposed (HCV antibody positive) and nearly half (44%) currently infected (HCV RNA positive) based on a 2018 study conducted in ten US cities [3]. Furthermore, PWID have an elevated risk for other bloodborne infections such as HIV, with HCV/HIV co-infection tripling the risk of cirrhosis and liver-related mortality [4].

Despite the availability of effective, simplified direct-acting antiviral therapies since 2015, recent data indicated limited progress in reducing HCV incidence among PWID in the United States [5]. A recent meta-analysis assessing HCV incidence before and after 2015 found that the incidence among PWID in U.S. remained high at 12.4 cases per 100 person-years (95% CI 6.4–23.6) during 2015–2021, showing no significant reduction compared to the pre-2015 incidence rate of 15.0 cases per 100 person-years (95% CI 9.9–22.6) [6]. Recent national surveillance data reported that after more than a decade of consecutive annual increases, reported acute hepatitis C has been relatively stable since 2021 [7]. Another national analysis found that HCV prevalence among U.S. adults remained unchanged from 2013 to 2016 to 2017–2020, but after accounting for increased rates of injection drug use, the adjusted estimate indicated a substantial increase in HCV RNA seroprevalence, indicative of current infections, from 0.9% (2013–2016) to 1.6% (2017–2020) [8, 9]. In 2020, the US Preventive Services Task Force (USPSTF) expanded screening recommendations from the previous focus on adults born between 1945 and 1965 and others at high risk to universal screening for all adults aged 18–79 years and all pregnant persons in each pregnancy [10]. Under the Affordable Care Act (ACA) these expanded HCV screening guidelines are covered at no cost for insured persons. Following these expanded screening guidelines, data from two national laboratories showed that 24% more HCV antibody tests were performed in 2021 than in 2019 [11]. In 2023, CDC recommended collecting HCV testing samples in a single visit with automatic HCV RNA testing for all reactive antibody results to increase the linkage of care and treatment of patients with current infections [12].

Certain demographic characteristics and risk behaviors have consistently been associated with HCV exposure in PWID including older age, high school degree or lower education, receptive syringe sharing/injection equipment, longer duration, and greater frequency of injection drug use [13,14,15,16]. The prevalence of HCV among those incarcerated with a history of injection drug use (IDU) is also disproportionately high [17, 18]. A study in North Dakota found that the odds of positive antibody HCV infection was more than seven times higher in incarcerated persons with a history of IDU compared to those without such a history [19]. Differences in HCV incidence have also been observed across demographic groups, with younger PWID and women who inject drugs experiencing higher HCV incidence [20, 21]. The demographic shift from older to younger PWID, including younger women of reproductive age, is linked closely to the opioid crisis and increasing injection drug use [22, 23].

In Los Angeles County, the reported acute hepatitis C rates have remained consistently below state and national levels and were estimated to be around 0.2 per 100,000 population, compared to 0.6 in California and 1.5 per 100,000 nationwide in 2023 [7, 24]. Syringe Service Programs (SSPs) has been established in Los Angeles County as a critical component of its public health intervention. Initiated in the early 1990 s by activists and community groups, SSPs grew from grassroots efforts to fully established public health services through the support and collaborations of the Los Angeles Police Department, city and county public officials, and legislative advancements. As of 2024, 22 certified programs are operating across the county, with extensive coverage through street-based, storefront, and clinic modalities [25]. Local SSPs offer a wide range of services, including HIV and HCV testing, linkage to care, naloxone distribution, and fentanyl testing strips, alongside the provision of sterile injection equipment and disposal services. And in response to the opioid crisis, many of these programs have increasingly integrated or facilitated access to medication-assisted treatment (MAT), such as buprenorphine (e.g., Suboxone) or methadone. Certain SSP locations also have started distributing safe drug smoking supplies, such as glass stems and pipes, due to an increasing number of PWID transitioning to smoking opioids, primarily fentanyl, and stimulants [26, 27].

Research has shown strong evidence that SSPs help reduce injection-related risk behaviors and HIV transmission among PWID but the evidence of the direct effect on HCV transmission is more limited in the United States [28, 29]. However, emerging data, including a recent study in New England, found that obtaining most syringes from pharmacies or directly from SSPs were modestly associated with lower HCV seroprevalence and strongly associated with a lower risk of borrowing used syringes, borrowing used injection equipment, and backloading [30]. Public health benefits that SSPS also provides include the safe disposal of used syringes and connecting people to substance use disorder treatment [31, 32]. Importantly, research has found no evidence that SSPs lead to increased drug use or crime [33, 34].

To address the impact of HCV, the Los Angeles County Department of Public Health (LAC-DPH) released the Los Angeles County Viral Hepatitis Action Plan in December 2022. The plan was developed in collaboration with Federally Qualified Health Center and pharmacy partners to align local efforts with the national viral hepatitis strategic plan. In 2023, LAC-DPH also published the Los Angeles County Viral Hepatitis Surveillance Report to characterize the local hepatitis burden and monitor progress towards national elimination goal [35]. Our study adds PWID-specific evidence for Los Angeles County by evaluating the long-term HCV prevalence trend and identifying its associated demographic and behavioral factors. To the knowledge of this study’s authors, this is the first surveillance-based study of HCV seroprevalence among PWID in Los Angeles County.

Materials and Methods

Study Setting and Population

National HIV Behavioral Surveillance (NHBS) is a surveillance system of HIV and risk behaviors funded by the Centers for Disease Control and Prevention (CDC). NHBS has collected and presented HIV-related information from men who have sex with men, PWID, and heterosexually active persons at increased risk for HIV infection in annual, rotating cycles since 2003 [36]. Respondent-driven sampling was used to recruit approximately 500 participants via an incentivized peer referral method in each study cycle. Since 2005, PWID participants were sampled in LAC every 3 years. While HIV has been the focus of NHBS, this system can be leveraged to study other important infections. In recent years, this included the expansion of biological testing activities such as testing for gonorrhea and chlamydia among MSM and HCV among PWID [3, 29]. HCV testing included only antibody testing in the 2012 and 2015 NHBS PWID cycles. Beginning in 2018, testing was expanded to include HCV RNA testing and continued in 2022 and 2024 [3]. The COVID-19 pandemic disrupted the NHBS schedule and resulted in the postponement of the planned PWID cycle from 2021 to 2022.

Eligibility criteria included participants who were 18 years of age or older, alert and able to complete the survey in English or Spanish, a resident of Los Angeles County, and reported any injection drug use other than being prescribed in the 12 months, which was confirmed by injection knowledge questions and/or inspection of injection track marks (e.g. visible signs of injection drug use and/or be willing to show interviewers and be able to accurately describe injection practices). The anonymous survey took approximately 40 min and was administered by trained NHBS interviewers. Interviews were conducted in private settings where other people could not overhear participant responses. The survey consisted of questions about demographics, health conditions, drug use, as well as questions about sexual and drug-related behaviors. All consented participants were screened on-site for HIV using a rapid-rapid testing algorithm with the Determine™ HIV-1/2 Ag/Ab Combo (Abbott Laboratories) as the first test, followed by a second rapid test with INSTI® HIV-1/HIV-2 antibody test (BioLytical Laboratories) for participants with a reactive result who were previously unaware of their HIV status. Samples that had discordant or uncertain results from the rapid tests were sent to the local laboratory for confirmatory testing. Participants received up to $120 in 2012, 2015, 2018, 2022, and 2024 for completing the survey, blood-based rapid HIV testing, and the rapid and/or lab-based HCV testing.

HCV Antibody and RNA Testing

Blood samples were collected by a certified phlebotomist trained in collecting and handling biological specimens within a mobile testing unit. HCV antibody results were obtained using the OraQuick HCV Rapid Antibody Test (OraSure Technologies) or through laboratory-based HCV antibody testing. Beginning with the NHBS-PWID 2018 cycle, blood samples were also sent to the Los Angeles County Public Health Laboratory for HCV-PCR RNA testing (performed with the Hologic Aptima HCV Quant Dx assay). All participants that tested positive on the HCV rapid test at the time of the NHBS encounter were counseled about avoiding behaviors such as sharing injection equipment that could spread HCV, avoiding use of alcohol and drugs that could accelerate liver damage, were informed about the availability of treatment for HCV infection, and received appropriate referrals based on their geographic locations. Consenting participants were given the option to either call back or come back to receive the lab-based HCV results within two weeks of participation.

Measures

We described study participants by sociodemographic characteristics including age (18–29, 30 + years), race/ethnicity (Non-Hispanic White, Non-Hispanic Black, Hispanic/Latino, Other), gender, education, current housing status, and lifetime incarceration. We also examined the types of drugs injected in the past 12 months, injection frequency (daily versus less-than-daily injection), duration of injection, exchanging sex for money or drugs, self-reported STI diagnosis in the past 12 months, and condom use at last vaginal or anal sex. Access to SSPs for clean syringes was defined as receiving sterile syringes or needles, at least once, from a SSP within 12 months prior to the interview. We assessed receptive syringe sharing (using a syringe that had previously been used by someone else for drug injection) and sharing of other injection equipment, including cookers, cottons, water, or backloading (dividing up drugs using a common syringe). Among HIV-negative participants, we also examined HIV pre-exposure prophylaxis (PrEP) use within the past 12 months.

Participants were also asked about lifetime history of HCV testing and treatment (“Have you ever been tested for hepatitis C infection?”; “Has a doctor, nurse, or other health care provider ever told you that you had hepatitis C?”; “Have you ever taken medicine to treat your hepatitis C infection?”). HCV antibody results were classified as “positive” if reactivity was detected using the rapid HCV antibody test. HCV RNA results were classified as either ‘Detected’ or ‘Not Detected.’ Participants from PWID in 2018, 2022 and 2024 with valid rapid antibody and RNA test results were categorized into four HCV infection categories: (1) acute (antibody non-reactive, RNA detected), (2) chronic (antibody reactive, RNA detected), (3) cleared (antibody reactive, RNA not detected), which may reflect either spontaneous clearance or clearance following successful treatment as NHBS does not collect clinical data or medical records, and (4) never infected (antibody non-reactive, RNA not detected).

Statistical Analysis

The five NHBS-PWID rounds with available rapid HCV results (in 2012, 2015, 2018, 2022, and 2024) were combined into a single analysis file for a statistical evaluation of time trends and multivariate analyses. We described demographic and behavioral characteristics for each survey round and evaluated differences in HCV antibody seropositivity among all PWID participants by the Pearson χ2 test. Trends in HCV antibody prevalence over time and its associated factors were assessed using a multivariable log-link Poisson model with robust standard errors. In the multivariate model, we reported adjusted prevalence ratios (aPRs) with 95% confidence intervals (CIs), incorporating a numeric variable for survey year and covariates that identified potential confounders based on previous literature. In additional to the main effect, we also investigated whether the effects of age or sex with HCV antibody positivity varied over time.

Previous studies suggest that male PWID who have sex with men (MSM/PWID) may have different drug use patterns and sexual and injection networks compared to other male PWID [37, 38]. Based on these findings, we conducted an exploratory sub-analysis among male PWID to compare injection-related risk factor and HCV prevalence between MSM/PWID and non-MSM/PWID. This allowed us to assess potential effect modification and then decide whether the final model should be restricted to non-MSM PWID. We used unweighted analyses, as prior work has noted methodological challenges with RDS weighting and shown that applying weights in Poisson regression may bias regression estimates [39]. A few variables had less than 2% missing data, with most variables having no missing observations. Therefore, all analyses were performed using a complete case approach in the multivariate models. All p-values were two-tailed and p < 0.05 was considered statistically significant. Statistical analyses were conducted in SAS 9.4.

Ethics

All participants gave their verbal informed consent to participate in the study. Study methods were approved by the Institutional Review Board of Los Angeles County and was considered as routine public health surveillance in 2018 and onward.

Results

Sample Characteristics Across Five Rounds

Tables 1 and 2 presents the demographic, socioeconomic, and behavioral characteristics of PWID across five rounds. A total of 2,323 NHBS-PWID participants were included in this analysis. Total participants for each round were distributed as follows: 430 (18.5%) in 2012 (Round 3), 433 (18.6%) in 2015 (Round 4), 504 (21.7%) in 2018 (Round 5), 467 (20.1%) in 2022 (Round 6), and 489 (21.1%) in 2024 (Round 7). The overall sample was predominantly male (69.1%) and largely composed of participants aged 30 years or older (85.1%). Across NHBS rounds, the proportion of younger participants (18–29 years old) varied, with the highest representation occurring in 2018 (21.6%) and the lowest in 2022 (6.2%). The racial/ethnic makeup remained stable over time with Hispanic/Latino participants being the largest racial group (42.3%), followed by White (36.2%), Black (12.7%), and other (8.6%). Overall, 78.6% were living at or below the federal poverty level, 60.0% reporting being unhoused at the time of the interview, 64.4% had a high school diploma or less education, and 89.6% reported a history of incarceration. The proportion of uninsured participants declined from 52.3% in 2012 to just 6.5% in 2024. Among male participants, reported male-to-male sex ranged from 8.4% to 14.3% across rounds. About two-thirds (64.2%) of participants reported condomless vaginal or anal sex at last intercourse and one fifth (18.9%) reported exchanging sex for drugs or money in the past year.

Table 1 Characteristics of NHBS-PWID participants across five NHBS rounds, Los Angeles County
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Table 2 Drug use characteristics of NHBS-PWID participants across five NHBS rounds, Los Angeles County
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About 4 in 5 (79%) participants reported prior HCV testing before the NHBS interview. Among participants who reported being told by a health care provider that they were HCV-positive, the proportion reporting ever taking HCV medicine increased from 15.1% in 2012 to 36.8% in 2024. Despite this treatment progress, treatment coverage remained suboptimal. Overall, 75.1% of self-reported HCV-positive participants reported no prior HCV treatment, and 63.2% remained untreated in 2024. HIV prevalence remained low, with a consistent rate of approximately 3.4% across NHBS rounds. A diagnosis of any bacterial sexually transmitted infection (STI) within the past 12 months was reported by 6.8% of participants, with the proportion increasing across NHBS rounds from 3.7% in 2012 to 9.8% in 2024. PrEP use within the past 12 months among HIV-negative participants remained very low (0.8%) and consistent across survey rounds.

Most PWID reported their first IDU between the ages of 18 and 24 years (36.2%), while nearly one-third began IDU before the age of 18 (29.3%). However, a downward trend was observed in the proportion of participants who initiated IDU before age 18, declining from 36.0% in 2012 to 21.5% in 2024 (31.9% in 2015, 30.4% in 2018, and 27.8% in 2022). Nearly half (46.7%) of participants reported more than 20 years of IDU and an additional 22.2% reported 11–20 years of IDU.

Injection practices among PWID participants shifted over time. Although the majority of participants reported daily injection (77.7% overall), daily heroin injection declined from 72.3% in 2012 to 33.5% in 2024. On the other hand, daily methamphetamine injection increased significantly from 6.5% in 2012 to 47.2% in 2024. Improvements in harm reduction were observed: the proportion of participants who reported always using a sterile needle increased from 36.7% in 2012 to 57.1% in 2024, and both receptive syringe sharing (used syringes that had been used by others) and the sharing of injection equipment declined from 33.0% to 17.4% and from 60.5% to 37.6%, respectively. Overall, 76.0% of participants reported using SSPs in the past 12 months. From 2018 to 2024, among participants who reported opioid or heroin use, the proportion who received medications such as methadone, buprenorphine, or Suboxone to treat opioid use in the past 12 months declined from 61.1% to 39.7%, with about half (49.8%) reporting MAT use overall.

Demographic and Behavioral Characteristics of PWID who Tested HCV Antibody Positive

Table 3 shows the demographic and behavioral characteristics of PWID participants who tested HCV antibody positive within NHBS rounds and overall. There was higher HCV antibody seroprevalence overall among Black participants (60.9%) compared with Hispanic/Latino (58.7%), White (56.1%), and other race/ethnicity group participants (49.2%). Participants aged 30 years or older had nearly double the HCV seroprevalence of those aged 18–29 (61.3% vs. 34.1%). Those with a history of incarceration had a higher HCV seroprevalence compared with those who had never been incarcerated (59.8% vs. 35.3%). Among male participants, men who have sex with men (MSM) recorded a lower HCV seroprevalence (38.6%) compared to non-MSM (62.6%). Among HCV antibody positive participants, the proportion of participants who were unaware of their HCV serostatus decreased from 57.8% in 2012 to 15.4% in 2024. Table 4 presents HCV seroprevalence by drug use behaviors among PWID across NHBS rounds.

Table 3 HCV antibody seropositivity of NHBS -PWID participants by characteristic and rounds, Los Angeles County
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Table 4 HCV antibody seropositivity of NHBS participants by drug use behaviors across five NHBS rounds, Los Angeles County
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Participants who injected heroin in the past 12 months had higher HCV seroprevalence (65.7%) compared with non-heroin injectors (27.5%), while participants who injected methamphetamine had lower HCV seroprevalence (48.3%) compared with non-methamphetamine injectors (73.9%). Higher HCV seroprevalence was also associated with daily injection, syringe sharing, longer injection duration, and use of SSPs.

MSM vs. Non-MSM PWID Participants

Among male PWID, those who reported sex with men (MSM/PWID; n = 189) were less likely to inject daily than other men who inject drugs (aPR = 0.79; 95% CI 0.71–0.88; p < 0.001), while receptive syringe sharing was similar between groups (aPR = 1.02; 95% CI 0.80–1.32; p = 0.86). Past-year methamphetamine injection was more common among MSM/PWID (aPR = 1.36; 95% CI 1.27–1.45; p < 0.001). HCV antibody positivity was lower for HIV-negative MSM/PWID compared to HIV-negative non-MSM PWID (38.2% vs. 58.8%) and lower for HIV-positive MSM/PWID compared to HIV-positive non-MSM PWID (38.6% vs. 61.8%).

While MSM/PWID and other men who inject drugs differed on some behaviors, a sub-analysis testing for effect modification among male PWID showed that key risk factors (daily injection, receptive syringe sharing, and past-year methamphetamine injection) and their associations with HCV antibody positivity did not differ significantly between MSM and non-MSM and did not substantively change other estimates or model fit (all p > 0.10). This indicated that the associations between these behaviors and HCV antibody positivity were consistent across MSM/PWID and non-MSM men. Therefore, MSM/PWID were included in the final model to provide a more comprehensive understanding of HCV risk factors among all PWID.

The Trend in HCV Antibody and HCV RNA Seropositivity

Table 1 demonstrated a steady decline in HCV antibody seroprevalence from 81.2% in 2012 to 64.9% in 2015, 59.1% in 2018, 50.1% in 2022 and 34.2% in 2024. During the observation years when both HCV rapid and RNA test results were available, chronic HCV infection (positive for both antibodies and RNA) similarly decreased from 37.1% in 2018 to 30.6% in 2022 and 18.2% in 2024, and acute HCV infections remained rare (≤ 0.5%). While the proportion of participants with cleared infection declined from 23.1% in 2018 to 14.6% in 2024 (Table 1), recalculating this measure among antibody-positive participants shows an increasing proportion who have cleared infection (treatment-induced or spontaneous viral clearance) over time from 38.4% in 2018 to 36.7% in 2022 and 44.2% in 2024, with an overall average of 39.4%. After adjusting for other factors, HCV prevalence continued to decrease at an average annual reduction of approximately 9% across the five NHBS rounds (aPR = 0.91, 95% CI 0.89–0.92, Table 5).

Factors Associated with HCV Antibody Seropositivity

Table 5 presents the multivariable-adjusted prevalence ratios (aPRs) and 95% confidence intervals (CIs) for factors associated with HCV antibody seropositivity among PWID across the five NHBS rounds. Participants aged 30 + had a more pronounced decline (aPR = 0.91, 95% CI 0.89–0.92) than those aged 18–29 years (aPR = 0.94, 95% CI 0.90–0.97). Regarding sex, the decline in HCV prevalence over time was faster among females (aPR = 0.91, 95% CI 0.89–0.92) compared to males (aPR = 0.95, 95% CI 0.94–0.96). White PWID had a higher prevalence of HCV compared with Hispanic/Latino PWID (aPR = 1.08, 95% CI 1.00–1.17).

A history of incarceration was also significantly associated with increased HCV positivity with ever-incarcerated participants showing a 36% higher prevalence (aPR = 1.36, 95% CI 1.14–1.61) than those never incarcerated. Participants with at least a high school education had a lower prevalence of HCV (aPR = 0.91, 95% CI 0.85–0.97) compared to the those who received less than high school education. Interestingly, those with health insurance at the time of the survey had a 12% higher HCV prevalence (aPR = 1.12; 95% CI 1.03–1.22) compared with those without insurance. This may be because many insured participants were covered by expanded Medicaid under the ACA, which provided health insurance coverage for low-income adults. This may also explain the higher HCV prevalence observed among participants living at or below the poverty line (aPR = 1.16; 95% CI 1.06–1.27).

Table 5 Factors associated with HCV antibody seropositivity among NHBS-PWID participants, 2012–2024
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Participants who injected daily had 41% higher HCV seroprevalence compared to those who injected less frequently (aPR = 1.41; 95% CI 1.26–1.56). Receptive syringe sharing increased the prevalence by 8% (aPR = 1.08, 95% CI 1.01–1.16). Participants accessing SSPs for clean syringes had a 32% higher prevalence of HCV than those who did not (aPR = 1.32; 95% CI 1.19–1.45). No significant associations were detected between HCV antibody positivity and housing status, HIV infection, or self-reported bacterial STI.

Discussion

The findings of this study highlight significant temporal and injection behavioral shifts in HCV prevalence among PWID in Los Angeles County, with approximately three-quarters accessing local SSPs. From 2012 to 2024, we documented an annual decrease of approximately 9% in HCV antibody prevalence, with a parallel decline in HCV RNA prevalence observed from 2018 to 2024. Concurrently, more participants became aware of their HCV-positive status, along with an increase in HCV treatment uptake. More participants reported always using sterile syringes while fewer engaged in receptive syringe sharing or shared other injection paraphernalia. These interconnected trends suggest that local harm reduction efforts have made meaningful progress in reducing HCV transmission risk among local PWID.

However, such reduction was uneven across demographic groups. Younger PWID participants (18–29 years) and males showed weaker declines of 5.9% and 4.9%, respectively, compared to older (9.1%) and female (9.1%) participants. The weaker downward trend among participants aged 18–29 highlights the persistent elevated risk for HCV for this group. Two studies conducted in New York City indicated a flattened prevalence of HCV antibody among young PWID of 31% for those aged 18–29 during 2014–2016 and 30% for those aged 18–30 during 2018–2021 though these analyses largely relied on pooled trends and made no direct comparisons across age groups [40, 41]. To our knowledge, no existing research has conducted a trend analysis stratified by age among PWID. Our study addresses this gap by showing that, unlike older age groups, younger PWID have not experienced the same level of decline in HCV prevalence over time. This age-stratified trend analysis provides evidence that current harm reduction strategies may be insufficiently tailored or inaccessible to younger PWID. The local Los Angeles County DPH surveillance data from the NHBS-PWID 2022 cycle found that younger PWID showed higher proportions of sharing injection equipment (56% vs. 45%), sharing syringes receptively (31% vs. 18%), exchanging sex for money or drugs (21% vs. 14%), and recent STI diagnoses (18% vs. 9%) including chlamydia, gonorrhea, or syphilis compared with those who were 30 years of age or older [42]. These findings match other studies linking syringe sharing among young PWID to homelessness and serious mental health problems [43, 44]. Our data suggests a need for refreshed youth-focused programs, especially for those less engaged in routine medical care that integrate public health and community services with clinical care. Programs should expand access to clean supplies through SSPs, mobile and drop-in outreach, secondary distribution, and vending machines, and address their basic social needs like housing and mental health care [45]. With universal HCV screening now recommended for adults aged 18–79, community and shelter-based clinics should adapt their screening and linkage models to better reach younger adults at risk for HCV and to provide more integrated HIV/STI prevention and care, including PrEP and doxycycline post-exposure prophylaxis (DoxyPEP).

Our finding of a slower decline in HCV antibody prevalence among male PWID diverges from a previous bio-behavioral surveillance from Catalonia in Spain, which identified males as the primary drivers of declining HCV prevalence, while women continued to experience elevated or increasing risks [46]. A 2023 review found that women who inject drugs face a 1.2 times greater risk of acquiring HCV than men and a 2024 meta-analysis reported that women were significantly more likely to engage in receptive syringe sharing than men (RR: 1.12, 95% CI 1.01–1.23), suggesting higher ongoing exposure and slower prevalence decline among female PWID [20, 47]. More recent U.S. national surveillance data also show that, since 2020, acute HCV case rates among males have consistently been approximately twice as high as those among females [7]. These varied findings suggest that local contexts and differences in harm reduction engagement may shape HCV trends. In Los Angeles County, HCV testing and treatment have expanded within community clinics that also provide women’s health and sexual health services, as well as within women-focused homeless programs that include hepatitis C education, screening, and linkage to care for women experiencing homelessness [48, 49]. Although these services have not been evaluated specifically among women who inject drugs, they are consistent with service access patterns that could support greater decline in HCV prevalence among women in our sample. Additional studies are needed to better understand the factors underlying these sex-specific HCV patterns in Los Angeles. While the steeper decline observed among women is encouraging, the slower decline among men indicates potential disparity and emphasizes the need for interventions that more effectively engage men who inject drugs in HCV prevention and treatment.

Our findings confirmed that high frequency IDU is strongly associated with an increased risk of HCV infection, with 77.7% of participants injecting daily, resulting in a 41% higher HCV positivity rate compared to those who inject less frequently. Unsafe injection practices remain a concern with 27.3% reporting receptive syringe sharing, resulting in an 8% higher HCV positivity rate. While both daily injection and syringe sharing are long-established infection risk factors and often practiced together, their continued prevalence in this population emphasizes the need for expanded access to sterile syringes [6, 50]. This risk is further compounded by the ongoing synthetic opioid and stimulant crisis [51]. Our data (Table 2) revealed marked increase in past 12-month methamphetamine use from 33.5% to 84.7%, and previous analysis from local surveillance data found that three quarters of PWID in the 2022 survey reported using drugs that they suspected contained fentanyl, representing a 27% increase compared to participants in the 2018 survey [50]. Co-use of methamphetamine and fentanyl has therefore become an increasingly concerning trend in Los Angeles County. Urine drug screening data from 2023 revealed that 73% of fentanyl-positive specimens in Los Angeles County also tested positive for methamphetamine, and the county health department data showed nearly two-thirds (64%) of methamphetamine overdose deaths in the county also involved synthetic opioids, particularly illicitly-manufactured fentanyl [52, 53]. Given fentanyl’s shorter half-life compared to heroin, fentanyl exposure may contribute to more frequent injection and greater syringe demand, which can increase opportunities for syringe sharing when sterile supplies are insufficient [54]. A study conducted in Philadelphia reported rising fentanyl use compels frequent injections (a median of 8 times per day among SSP users), making it harder for sterile syringe supplies to meet demand and increasing the likelihood of syringe sharing [55]. In our data, heroin injection in the past 12 months, particularly daily heroin injection, was associated with higher HCV antibody seroprevalence, whereas methamphetamine injection was associated with lower HCV antibody seropositivity across rounds (Table 4). Our findings are consistent with prior studies showing differences in HCV infection by substance use patterns. A recent study in rural U.S. communities reported that HCV antibody prevalence was highest among PWID who injected opioids, either alone or in combination with stimulants, and lowest among those who injected only stimulants [56]. Our data do not differentiate opioid only from opioid/stimulant injection, and substances reported in the past 12 months do not capture lifetime exposure or cumulative risk. Despite these limitations, the observed associations suggest that opioid (including fentanyl) injection may be linked to greater cumulative exposure through higher frequency injection, longer injection duration, equipment sharing, and/or barriers to consistent access to sterile syringes, all of which increase opportunities for HCV acquisition.

Consistent with previous studies that show a disproportionate prevalence of HCV among the incarcerated population, participants with a history of incarceration had 36% higher HCV positivity compared to those never incarcerated [18, 22, 57, 58]. Incarceration settings often lack consistent access to harm reduction resources such as sterile syringe access, safe tattooing and MAT [59]. In Los Angeles County jails, documented operational barriers (short stays, unpredictable release dates, limited phlebotomy hours, funding constraints, and challenges engaging and linking patients to care after release) complicate HCV care delivery [60]. Expanding testing and treatment in correctional facilities therefore provides a significant opportunity to reduce individual disease burden and lower community-level HCV incidence and prevalence [61].

The increase in self-reported bacterial STI diagnoses from 3.7% in 2012 to 9.8% in 2024 is consistent with broader STI trends in Los Angeles County, where syphilis rates increased 2.5 times, gonorrhea rates increased 1.8 times and chlamydia rates increased 1.1 times from 2014 to 2023, although recent data shows a slowdown since 2023 [62]. While HCV transmission among PWID occurs primarily through sharing injection equipment, STI diagnoses may serve as indicators of sexual risk behaviors that could contribute to HCV transmission risk, particularly in the context of other risk factors such as exchanging sex for money or drugs and inconsistent condom use.

Our sample suggests that our PWID participants face significant economic and social marginalization, as evidenced by their dependence on public insurance, unstable housing, and low socioeconomic status. PWID participants living at or below the poverty line or with lower education had higher HCV positivity rates, reflecting socioeconomic vulnerability as foundational drivers of HCV transmission [63]. At the same time, our data show elevated HCV positivity among participants using SSPs, reflecting that these programs effectively reach PWID at the greatest risk. Such association reinforce the critical role that SSPs play as trusted and safe environments that connect the most marginalized individuals to harm reduction service and education [64]. During the study period, many local SSPs increased both their fixed and mobile site locations, expanded partnerships with methadone clinics, extended office hours, maintained anonymity with minimal intake processes, and removed limits on the number of syringes distributed. Our findings that show reduced syringe sharing and increased consistent use of sterile needles among PWID participants might reflect this increased access to SSPs. Although SSPs remain the primary source for sterile syringes among NHBS PWID participants, local data (not presented in the tables) suggest that approximately 25% to 49% of PWID in recent years also obtain sterile syringes from pharmacies. These positive trends are further reflected in the consistently low rates of acute HCV cases, which remained below 1%, and less than 5% HIV prevalence among our participants.

Our data also show improvement in viral clearance, with overall 39% classified as treated or resolved among HCV antibody-positive PWID across the 2018, 2022 and 2024 rounds. For broader context beyond PWID, Los Angeles County’s viral hepatitis surveillance report suggest about 30% of chronic HCV cases were treated or resolved between 2019 and 2023 [35, 65]. And the CDC estimated that only 34% of individuals with diagnosed HCV achieved viral clearance based on HCV testing data over the 10-year span of 2013–2022 [66]. Both local and national estimates fall well short of the national targets of 58% HCV viral clearance by 2025 and 80% by 2030 [67]. Global examples show that delivering HCV care through active case management, mobile teams, and onsite treatment can increase treatment coverage and reduce disease burden [68]. The country of Georgia’s national HCV elimination program reported a remarkable decline in new cases of chronic HCV infections among the general population, including PWID, by prioritizing mass screening, seamless linkage to care, and access to free treatment from 2015–2024 [69]. In Rwanda, mobile test-and-treat HCV clinics reached more patients in much less time than traditional clinics and lowered out-of-pocket costs for patients [70]. These findings suggest that expanding onsite testing and treatment thorough syringe service programs, mobile outreach, correctional settings, and community pharmacies (pharmacy-dispensed direct-acting antivirals under collaborative practice) could also accelerate progress toward HCV elimination in Los Angeles County [71].

Limitations

This study has some limitations. First, the participants may not represent all PWID in Los Angeles County; they are likely more reflective of local PWID who engage in harm reduction programs, as nearly 75% used SSPs in the past 12 months. These findings are based on a sample of PWID in Los Angeles County recruited through respondent-driven sampling (RDS) with incentives, which may attract individuals who are of lower socioeconomic status. Second, drug use behaviors variables included in the analysis were based on past 12 months rather than lifetime data, which may not fully capture the cumulative risk exposure associated with HCV infection. Moreover, self-reported data likely introduces potential recall and social desirability biases. Third, the analysis was limited to participants with available blood-based antibody HCV results (either rapid or lab-based results). The unavailability of a phlebotomist was the primary reason that participants did not receive an HCV. This group represented between 3% and 10% of participants who completed interviews across the different cycle years. Fourth, NHBS-PWID recruitment relied on RDS from seeds at syringe service programs and our sample likely underrepresents PWID on the outskirts of the county (e.g., Antelope Valley, Santa Clarita, and Pomona) and those who are not engaged with services, which could limit countywide generalizability. Fifth, the COVID-19 pandemic disrupted harm reduction programs and clinical services in Los Angeles County. Many SSPs experienced temporary closures, reduced hours, and staffing shortages. These changes likely limited HIV and HCV testing, clinical evaluation, and treatment access during the 2022 round. At the same time, some providers adopted telehealth and limited onsite services to keep people connected. When compared with 2018, a higher proportion of participants in 2022 reported receiving clean injection equipment and fewer reported sharing syringes. This suggests that some harm reduction supply remained available and may have buffered injection risk.

Conclusion

This study found that overall HCV antibody prevalence among PWID participants decreased from 2012 to 2024, and the decrease was mostly driven by those 30 years and older and female PWID. Decreases in HCV antibody and RNA prevalence, along with improved sterile injection practices, greater awareness of HCV status, and modest increases in treatment uptake, suggest that local harm reduction strategies have contributed substantially to reducing HCV transmission. High frequency injection, syringes sharing, and socioeconomic vulnerability continue to drive risk. Expanding onsite test-and-treat services in harm reduction programs through mobile outreach, in correctional settings, and providing case management services may further reduce HCV prevalence in Los Angeles County.