The goal of this study is to improve HCV care continuum outcomes for people who inject drugs (PWID), reduce potential onward transmission to others and improve HIV outcomes among those who are HIV/HCV coinfected. The study will evaluate whether HCV treatment outcomes (sustained virologic response, treatment completion, adherence) and post treatment outcomes (HCV reinfection, HIV viral suppression) in HCV mono- and HIV/HCV co-infected PWID can be optimized by tailoring treatment support in 7 PWID-focused integrated HIV/HCV prevention and treatment centers in India.
The primary objective is to evaluate whether the intensity of treatment adherence support affects sustained virologic response rates in HCV mono- and HIV/HCV co-infected participants receiving HCV direct-acting antivirals (DAA) in PWID-focused centers. Secondary objectives are: 1. To evaluate whether the intensity of treatment adherence support affects HCV treatment completion rates. 2. To evaluate whether the intensity of treatment adherence support affects HCV treatment adherence. 3. To estimate the incidence and correlates of HCV reinfection among HCV mono- and HIV/HCV coinfected PWID who achieve HCV cure. 4. To evaluate the impact of HCV cure on HIV viral suppression among HIV/HCV coinfected PWID. Investigators will evaluate this via a 3-arm, individual-level randomized clinical trial, in which treatment assignment probabilities vary according to participants' estimated propensity for treatment failure at baseline (precision randomization). An estimated 3,000 persons will be enrolled and randomized at 7 community-based integrated care centers (ICCs) across India across a duration of 18 - 24 months. Data from these 7 ICCs on early HIV treatment refills/viral suppression (3-6 months after antiretroviral therapy (ART) initiation) will be used to develop and validate an algorithm to predict propensity for HCV treatment failure. Prior to treatment initiation, each participant will undergo a questionnaire to capture information on barriers/ facilitators to treatment adherence identified in the prediction model in order to determine the propensity for HCV treatment failure (minimal or elevated risk). Individuals will be preferentially randomized to the support level that matches their failure risk. Those at elevated risk for treatment failure will be randomized at an allocation ratio of 3:2:1 for Arm 3 (high intensity support), Arm 2 (medium intensity support) and Arm 1 (low intensity support), respectively. Conversely, those at minimal risk will be randomized at a ratio of 1:2:3 to Arm 3 (high intensity support), Arm 2 (medium intensity support) and Arm 1 (low intensity support), respectively. Participants and study staff will be blinded to the risk classification (minimal, elevated) but, because of the nature of the interventions, blinding to intervention assignment is not possible. Persons will be treated for HCV according to the standard of care in India. Minimal laboratory monitoring will be used except when clinically indicated. Participants with decompensated cirrhosis will be excluded from treatment. All HIV/HCV co-infected participants and those HCV monoinfected participants who achieve SVR will be followed post-treatment. These individuals will be followed every six months after the SVR assessment to assess HCV reinfection and HIV viral suppression (among HIV/HCV coinfected participants) for up to 30 months after SVR.
A 28-day supply of medication will be dispensed to participants at entry, 4 weeks, and 8 weeks. Participants will receive standard adherence counseling at entry and every refill pickup/home or field delivery. Participants will have access to all of the services available at the ICC including facilitated linkage to referrals as needed. Site staff will routinely track clients who miss refill appointments in real-time using standard tracking measurements
The medium intensity intervention will include standard of care dispensation of a 28-day supply of medication at entry, 4 weeks and 8 weeks. Participants will be assigned to a patient navigator (PN) and receive tailored patient navigation support for medication reminders, picking up medication refills (or home or field delivery of study medications), overcoming barriers as well as service linkage. Participant will be contacted by the PN at least once every two weeks.
YR Gaitonde Centre for AIDS Research and Education
Chennai, Tamil Nadu, India
Sustained Virologic Response (SVR) by Intervention Group Stratified by Defined Risk for Treatment Failure (Minimal vs Elevated)
The percentage of participants who achieved SVR defined as HCV RNA \< lower limit of quantification (LLOQ). HCV RNA \< lower limit of quantification (LLOQ, 30 IU/ml) was measured 12 weeks (range 10 - 60 weeks) after treatment completion.
Time frame: Between 10 and 60 weeks after scheduled end of treatment.
HCV Treatment Completion
The percentage of participants who completed the prescribed course of treatment (12 or 24 weeks). Participants with compensated cirrhosis and genotype 3 infection would have received 24 weeks of treatment. All other participants would have received treatment for 12 weeks. All participants in this study received 12 weeks of treatment.
Time frame: Measured at the end of prescribed course of treatment (12 or 24 weeks)
Adherence >90% (Self-report)
The percentage of participants who self-report taking \>90% of doses during treatment.
Time frame: Measured at the end of prescribed course of treatment (12 or 24 weeks)
Adherence >90% (Medication Records)
The percentage of participants in possession of \>90% of doses during treatment based on medication refills and pill counts.
Time frame: Measured at the end of prescribed course of treatment (12 or 24 weeks)
Adherence Level (Self-report)
The percentage of doses taken during treatment as self-reported by the participant.
Time frame: Measured at the end of prescribed course of treatment (12 or 24 weeks)
Adherence Level (Medication Records)
The percentage of doses participants had in their possession during treatment based on medication refills and pill counts.
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Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
3,000
The high intensity intervention will involve patient-centered DOT with flexibility in terms of the frequency of pickup and the site of DOT (ICC, field-based) with a minimum of at least 1 observed dose per week. Participants in this arm will also receive PN support for overcoming barriers and service linkage similar to participants in Arm 2. The main differences between Arms 2 and 3 are: (i) medications will not be dispensed for more than one week at a time (to coincide with opioid agonist therapy (OAT) dosing, where applicable); and (ii) ≥1 dose/week will be observed.
Time frame: Measured at the end of prescribed course of treatment (12 or 24 weeks)
HCV Reinfection
The percentage of participants who test positive for HCV Core Antigen after achieving SVR.
Time frame: Measured at 6 month intervals after confirmation of SVR for up to 36 months.
HIV Viral Suppression Among HIV/HCV Coinfected Participants
The percentage of HIV/HCV co-infected participants with HIV RNA less than LLOQ after the SVR assessment. HCV RNA abstracted from chart reviews.
Time frame: After assessment of SVR for up to 36 months.