Study population

The OST clinic was started at the ICMR-RMRIMS, Patna in January 2014 as a part of NACO’s mission (funded by Ministry of Health & Family Welfare, India) to reduce the transmission of HIV among PWID. Whenever a patient visits OST center (to seek services), the OST medical officer conducts a structured interview and examination of the patient to assess demographic, behavioral, and clinical history including drug use and opioid dependency and enroll him/her based on the OST suitability criteria: (a) Opioid dependence with a long history; (b) Current use of injection drug; (c) Age ≥18 years; (d) No medical contraindication to OST; (e) Ability to give informed consent; (f) Failed attempts at achieving abstinence through other means (detoxification); (g) Feasibility to comply with requirements of OST center (such as staying close by and ability to visit the center on daily basis). Once enrolled in OST center, the trained medical officer starts buprenorphine at the clinic. The OST patients are supposed to visit the center on daily basis to receive the directly observed buprenorphine drug therapy. All patients at baseline also undergo testing to detect HIV, HBV antigen, and HCV antibody, which are routinely done at the ICMR-RMRIMS, Patna. If found HIV positive, the medical officer links patients to the designated ART centers to receive appropriate HIV management. However, for HBV antigen positive and HCV seropositive patients, the medical officer only counsels patients and refer to tertiary healthcare center for further management.

The study complied with the principles of Helsinki Declaration and obtained ethics approvals from the ICMR-RMRIMS, Patna ethics committee. As we were using the archived data collected as a part of routine national program activity, the ethics committee of the ICMR-RMRIMS, Patna waived the requirement for informed consent from the participants (Approval letter no. RMRI/EC/34/2022; Dated: 03 August, 2022). For this study, we included OST patients who were enrolled and had undergone HCV serostatus assessment (at the time of enrollment) from January 2014 to December 2022 at the ICMR-RMRIMS. During this time, total 268 patients were enrolled and had undergone the HCV serostatus assessment.

Variables and data sources

This study utilized routinely collected and de-identified data from the OST center at the ICMR-RMRIMS, Patna. Authors have abstracted information for various exposures and outcome variable from the medical records of OST patients.

Outcome variable

‘HCV sero-status’ was the primary outcome of the study. The ‘HCV serostatus’ is being routinely assessed at the ICMR-RMRIMS using in-vitro qualitative enzyme linked immunosorbent assay (J. Mitra and Co. Ltd., New Delhi, India) for the detection of antibodies against HCV (anti-HCVs) in human serum and considered as HCV sero-positive if they have HCV antibody.

Exposure variables

The extracted information on exposure variables include: ‘Socio-demographic variables’ such as age in years (completed), age of injection drug onset in years, sex (male; female), education level (illiterate, upto higher secondary, and more than higher secondary), marital status (unmarried, married and separated or divorced), and occupation (student, employed, unemployed, part-time and full time employment); ‘Drug history’ included type of drugs used (such as buprenorphine, pentazocin, heroin, cannabis, chlorpheniramine etc.), type of drug administration, and frequency of drug administration in years, and history of injection equipment sharing.

Statistical analyses

We have used mean, standard deviation, frequencies, percentage, medians, and interquartile ranges (IQR) to describe the distribution of variables in the participants. Across HCV status (absent vs. present): (a) Age was expressed as means and standard deviation (SD) and compared using unpaired t-test; (b) Number of injection years and total number of drug used as medians and interquartile range (IQR) and compared using Mann-Whitney-U test; and (c) Categorical variables such as marital status, education, occupation, type of drug use, HIV-, HAV-, HBV-, HEV-status were expressed in percentages and compared using Pearson’s chi-squared test.

We also examined the prevalence of HCV across the categories of age (18 to 20, 21 to 25, 26 to 30, 31 to 35, 36 to 40, and >40 years) and categories of number of years of injection use (≤2, 2.1 to 5, 5.1 to 10, and >10 years) and assessed the significance using linear trend test. We used Poisson regression with a robust variance estimator [14] to calculate unadjusted and adjusted prevalence ratio (PR) for various socio-demographic variables and clinical parameters (with HCV status as an outcome). All p-values were two-tailed and a p-value <0.05 was considered as significant. Stata version 14.2 (Stata Corp, College Station, TX, USA) was used for all statistical analyses.

Burden of HCV sero-positivity in OST center attendees

The high prevalence of HCV among OST attendees in ICMR-RMRIMS is consistent with other regions of India [1]. The observed HCV prevalence of 28% among OST patients in Bihar was significantly less than the 44.7% prevalence reported by Goel et al. in their systematic analysis of HCV in PWID across India [1]. This finding may reflect differences between the OST patients and community-based sample of PWID with regard to education attainment, social support, behavioural risks, or years of injection drug use etc. The differences in HCV sero-prevalence could also be attributed to geographical disparities in terms of access to injectable opioids [11]. Nevertheless, our findings suggest that approximately 30% of patients enrolled in OST center was HCV seropositive, which is worrisome and demands urgent attention from policymakers. The observed HCV sero-prevalence is ~33 times higher than the HCV sero-prevalence reported in the general population of India i.e. 0.85% (95%CI: 0.00%-3.98%) [1, 2]. Several clinical, social and behavioural factors may drive the higher prevalence of HCV among PWID. The level of exposure to adverse risk environments is found to be higher in PWID compared to others [7]. Compared with the general population, PWID are at greater risk of police arrest, incarceration, sex work, and the experience of homelessness or unstable housing, all of which are associated with increased blood-borne virus transmission [7]. Unfortunately, the available clinical records for the OST attendees in ICMR-RMRIMS do not provide any information about the mentioned adverse exposures, prohibiting comparison with other studies [7].

Determinants of HCV sero-positivity and comparison with other studies

The determinants of HCV sero-positivity (such as education, employment and years of injection drug use) observed in this study are very similar to those reported in other studies among PWID. Consistent with the previously reported literature, we found the robust positive association between years of injection use and high HCV sero-positivity [15–18]. Similarly, HCV sero-positivity was lower among educated- and employed-patients [15–18]. In this study, 31% (95% CI: 25.5%– 36.9%) PWID were age less than or equal to 25 years (considered as ‘young PWID’). This is consistent with the estimates reported by Degenhardt et al. 27.8% (95% CI: 19.0%– 36.7%) for South Asia [7]. We also observed a sharp increase in the HCV sero-positive status after the age of 25 years. There was a positive linear trend for HCV positive status with increase in age of participants.

Public health significance of the findings

The findings of the study may further support the Bihar government’s initiative to integrate HCV care into OST center for several reasons. First, an OST center provides an ideal opportunity to screen high risk group for HCV. Second, the high prevalence of HCV seropositivity among OST center attendees means easy and early access to many HCV patients (which generally are hard to reach population) and initiation of prompt treatment to reduce a reservoir pool of HCV. Third, the directly observed buprenorphine therapy (at the OST center) stabilizes PWID (as it provides slower onset but longer duration of action) [9], reduces their cravings for injections and improves patients’ compliance with HCV therapy and thus, may prevent further HCV transmission in a community. Fourth, an OST center provides an enabling environment to provide HCV treatment along with risk-reducing behaviour measures–a well-established way to treat HCV and prevent re-infection as well as HIV transmission [9]. Fifth, OST center requires patients to visit either daily or at short intervals (to receive directly observed buprenorphine therapy) thus may provide an ideal setting to monitor HCV care across continuum from point-of-care diagnosis to treatment and follow-up care and reinfection prevention counselling. The OST center set-up has been successfully utilized to provide HIV management in multiple national and international settings [9, 19]. The approaches used and lessons learned from these settings could be utilized in Indian context to efficiently integrate the HCV care in existing OST center set-up to reduce occurrence of new cases as well as treatment of prevalent cases.

Strengths and limitations

The strength of the study include: (a) Complete data on HCV sero-status for all enrolled patients; and (b) Standardized sero-status assessment of patients at the ICMR-RMRIMS, Patna. There are several limitations to this study that should be taken into account. First, a very small sample size; The OST center had enrolled, on average, fewer than 30 patients every year. The barriers to entry were—active injection use, daily or near daily visits to the center, failure of non-medication treatment for oral use of drugs—made for not only a small but potentially very biased sample. Second, limited external validity of findings; the study included only opioid dependent PWID, who were seeking services from the OST center. Moreover, all the enrolled participants were males. Therefore, we believe that the study participants may not represent the true population of PWID in the community. Third, the medical records at the OST center in ICMR-RMRIMS, Patna has information for limited number of determinants (mostly limited to socio-demographic and years of injection use). As per the NACO guidelines for OST centers in India [11], the OST centers are supposed to collect complete information on socio-demographics, complete drug use history, clinical history, mental health, psychosocial health, adverse exposures etc. However, the medical records of the study participants had no information about behavioural risk factors (such as smoking, alcohol etc.) as well as adverse exposures such as history of police arrest, incarceration, sex work, sharing of injection equipment or experience of homelessness or unstable housing. Nevertheless, the primary objective of the study was to understand the burden of HCV seropositive status; and all the study participants had undergone through a standardized process to assess their HCV antibody status. Fourth, OST center has information for HCV antibody (an evidence of past infection that could have become chronic) and not the viral load which is a better indicator of current HCV infection. Fifth, the availability of directly acting agents through OST center in Patna (since 2022) could have increased the enrolment of HCV patients at the OST center (potentially inflating the HCV seropositive burden among OST attendees). However, this is very unlikely in our study as only one seropositive patient was enrolled at the OST center in the year 2022.