Impact of Recent Drug Use on the Efficacy of Elbasvir/Grazoprevir for HCV-infected People on Opioid Agonist Therapy

Juan Macías; Francisco Téllez; Ignacio de los Santos; Luis E. Morano; Dolores Merino; Rafael Granados; Francisco Vera-Mendez; Alejandro González-Serna; Esther Campo-Moneo; Lucio García-Fraile; Federico García; Luis M. Real; Juan A. Pineda

Disclosures

J Viral Hepat. 2021;28(6):878-886. 

In This Article

Results

Baseline Characteristics of the Patients

Overall, 384 patients were prescribed EBR/GZR up to September 2019, four did not start treatment and were excluded. Three hundred and eighty patients included in the cohorts started EBR/GZR, 347 (91%) have reached the end of treatment response, and 336 have an evaluable SVR12. Out of them, 145 (43%) individuals referred to have never injected drugs. Among 191 PWID, 66 (35%) of them were receiving OAT (methadone, n = 58; buprenorphine, n = 4; buprenorphine/naloxone, n = 4). Data on illicit drug use were available among 310 (92%) individuals. Overall, recent drug use was reported by 7.7% (n/N = 24/310) patients and 28% (n/N = 17/61) PWID on OAT. The characteristics of the patients at the date of starting EBR/GZR are summarized in Table 1. All patients with cirrhosis were compensated at the date of starting EBR/GZR. Two patients had previous liver events, one hepatocellular carcinoma (PWID without OAT) and one ascites (non-PWID). These two patients showed Child-Pugh-Turcotte score A at the date of starting EBR/GZR. There were significant differences among the groups in factors such as the frequency of HIV coinfection, HCV genotype distribution or pretreatment with peg-interferon plus ribavirin.

Response to Treatment

Three hundred and eighteen [95%, 95% confidence interval (95% CI): 92%–98%] patients achieved SVR12 (ITT analysis). SVR12 was 97% (95% CI: 93%–99%, n/N = 141/145) among people who never used injecting drugs, 94% (95% CI: 88%–97%, n/N = 117/125) among PWID not receiving OAT and 91% (95% CI: 81%–97%, n/N = 60/66) among PWID receiving OAT (p = 0.134, Figure 1). Five (1.5%) patients showed relapses after the end of treatment response, and two (0.6%) individuals showed virological breakthrough before the end of treatment. Three of five (60%) relapses could be evaluated by phylogenetic analysis of samples at baseline and at the date of SVR12 evaluation. None were classified as reinfections by phylogenetic analysis. Virological and non-virological outcomes by study group are summarized in Table 2. In the mFAS analysis, 99% (n/N = 141/143) patients that never injected drugs, 98% (n/N = 117/120) PWID without OAT and 97% (n/N = 60/62) PWID on OAT reached SVR12 (p = 0.646). No patient suffered liver events after starting EBR/GZR and up to SVR12.

Figure 1.

Response to elbasvir/grazoprevir among patients who never injected drugs, PWIDs without OAT and PWIDs with OAT. p-values refer to the chi-squared test or, where appropriate, Fisher's test

The rates of SVR12 (ITT) for recent drug users were 67% (n/N = 16/24) compared with 97% (n/N = 278/286) for individuals without recent drug use (p < 0.001). Among the 24 recent drug users, three (13%) showed relapses after the end of treatment, and five (21%) were lost-to-follow-up. The three relapses were assessed by phylogenetic analysis and reinfection was ruled out. Plasma HCV RNA was undetectable in two recent drug users lost-to-follow-up assessed 12–24 months after the scheduled end of treatment. Among recent drug users, there were no discontinuations due to adverse effects nor viral breakthrough. Considering the two patients lost-to-follow-up with undetectable HCV RNA, the overall curation rate for recent drug users was 83% (n/N = 20/24). In the mFAS analysis, the SVR12 among PWID with recent drug use was 85% (n/N = 17/20) compared with 99% (n/N = 277/280) individuals without recent drug use (p = 0.004).

Management and Response According to HCV Genotype

The overall SVR (ITT) rates by genotype were 92% (n/N = 76/83) for genotype 1a, 96% (n/N = 136/142) for genotype 1b, 100% (n/N = 19/19) for genotype 1 other subtypes and 96% (n/N = 86/90) for genotype 4. Two (2.4%) patients with genotype 1a, two (1.4%) with genotype 1b and 1 (1.1%) with genotype 4 relapsed. Breakthroughs were observed in 1 (1.2%) patient with genotype 1a and 1 (1.1%) with genotype 4. The SVR (mFAS) rates by genotype were 96% (n/N = 76/79) for genotype 1a, 99% (n/N = 136/138) for genotype 1b, 100% (n/N = 19/19) for genotype 1 other subtypes and 98% (n/N = 86/88) for genotype 4.

Figure 2 summarizes the management of patients with genotype 1a infection. Out of 83 individuals, 53 (64%) showed baseline HCV RNA ≥800,000 IU/ml. Among those, the presence of baseline RASs was assessed in 23 (43%) individuals. Ribavirin was added to EBR/GZR in six (20%) of the 30 patients with HCV RNA viremia ≥800,000 IU/ml., and treatment was extended to 16 weeks in five of them. Thus, 24 (45%) patients with genotype 1a and baseline HCV RNA ≥800,000 IU/ml were not managed following EBR/GZR recommendations of use. The characteristics of individuals with relapses or viral breakthrough are displayed in Table 3. Of seven virological failures, three could be regarded as not managed following the package insert recommendations. None of them was a recent drug user.

Figure 2.

Management of genotype 1a patients treated with elbasvir/grazoprevir (n = 83)

Factors Associated With Response to Treatment

In the univariate analysis, recent drug use and HCV genotype 1a were associated with lower rates of SVR12 (Table 4). There was a trend for lower SVR12 rates among PWID on OAT (Table 4). After multivariate analysis, adjusted by age and gender, only recent drug use was independently associated with SVR12 (Table 4).

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