Hepatitis C virus treatment for prevention among people who inject drugs: Modeling treatment scale-up in the age of direct-acting antivirals

Abstract

Substantial reductions in hepatitis C virus (HCV) prevalence among people who inject drugs (PWID) cannot be achieved by harm reduction interventions such as needle exchange and opiate substitution therapy (OST) alone. Current HCV treatment is arduous and uptake is low, but new highly effective and tolerable interferon-free direct-acting antiviral (DAA) treatments could facilitate increased uptake. We projected the potential impact of DAA treatments on PWID HCV prevalence in three settings. A dynamic HCV transmission model was parameterized to three chronic HCV prevalence settings: Edinburgh, UK (25%); Melbourne, Australia (50%); and Vancouver, Canada (65%). Using realistic scenarios of future DAAs (90% sustained viral response, 12 weeks duration, available 2015), we projected the treatment rates required to reduce chronic HCV prevalence by half or three-quarters within 15 years. Current HCV treatment rates may have a minimal impact on prevalence in Melbourne and Vancouver (<2% relative reductions) but could reduce prevalence by 26% in 15 years in Edinburgh. Prevalence could halve within 15 years with treatment scale-up to 15, 40, or 76 per 1,000 PWID annually in Edinburgh, Melbourne, or Vancouver, respectively (2-, 13-, and 15-fold increases, respectively). Scale-up to 22, 54, or 98 per 1,000 PWID annually could reduce prevalence by three-quarters within 15 years. Less impact occurs with delayed scale-up, higher baseline prevalence, or shorter average injecting duration. Results are insensitive to risk heterogeneity or restricting treatment to PWID on OST. At existing HCV drug costs, halving chronic prevalence would require annual treatment budgets of US $3.2 million in Edinburgh and approximately $50 million in Melbourne and Vancouver.

Conclusion: Interferon-free DAAs could enable increased HCV treatment uptake among PWID, which could have a major preventative impact. However, treatment costs may limit scale-up, and should be addressed.

Figure 1

Model schematic showing HCV disease transmission and treatment states (A) and behavioral states (B). (A) Compartments for uninfected PWID (X_j,k), acutely infected PWID (A_j,k), chronically infected PWID (C_j,k), PWID on antiviral treatment (T_j,k), and PWID treatment failures (F_j,k). (B) The population was stratified by risk (low/high, j = 0 or 1, respectively), and OST (off/on, k = 0 or 1, respectively). New PWID enter the model at a constant rate (θ) as uninfected, off OST, and either low or high risk. Uninfected PWID can become acutely infected with HCV, where a proportion (δ) of individuals spontaneously clear their acute infection after a duration of time (1/ψ), and return to the uninfected compartment. Those who do not spontaneously clear the acute infection (1-δ) progress to chronic infection, where they are eligible for antiviral treatment. Because PWID are unlikely to be diagnosed during acute infection, it was assumed that they are not treated during the acute stage. If treated, a proportion [α(t)] achieve SVR and return to the uninfected compartment. Those who do not attain SVR [1-α(t)] move to the treatment failure compartment, where they cannot be retreated. PWID exit all compartments due to permanent cessation of drug use (μ₁) or death due to drug or non–drug-related causes (μ₂). The base-case analysis assumed PWID transition between high/low risk stages, as well as on/off OST. Additional details are provided in the Supporting Information.

Figure 2

Chronic prevalence over time in (A) Edinburgh, (B) Melbourne, and (C) Vancouver. Simulations show no scale-up from baseline, or scale-up to 10, 20, 40, or 80 per 1,000 PWID treated annually. We assume no treatment prior to 2002, a linear scale-up to baseline treatment rates during 2002-2007, and baseline treatment rates during 2007-2012. A linear scale-up from baseline to scaled-up rate during 2015-2017 was modeled. HCV prevalence data points shown for comparison with 95% confidence intervals.

Figure 3

Relative prevalence reductions at 15 years (by 2027) with no treatment scale-up (8 per 1,000 PWID annually in Edinburgh, 3 per 1,000 PWID annually in Melbourne, and 5 per 1,000 PWID annually in Vancouver) and four treatment rate scenarios (10, 20, 40, and 80 per 1,000 PWID annually). Bars indicate the mean relative prevalence reductions, with whiskers representing the 95% CrI for the simulations.

Figure 4

Annual scaled-up treatment rate required to reduce prevalence by ¼, ½, or ¾ in Edinburgh, Melbourne, and Vancouver within 15 years (by 2027). Bars (and numbers) indicate the mean value, with whiskers representing the 95% CrI.

Figure 5

Results from the one-way sensitivity analyses; percent change from the base-case scenario of the predicted relative prevalence reduction at 15 years in Melbourne with scaled-up treatment rate of 10 per 1,000 PWID annually (from a baseline rate of 3 per 1,000 PWID annually). For the base-case, all chronically infected PWID (high/low risk or on/off OST) were eligible for treatment. Mo., months.