March 1, 2023
Minimal Monitoring During Hepatitis C Virus Treatment Works, With Some CaveatsBy Erica Kaufman West, MD
Hepatitis C virus (HCV) treatment can be effectively treated with pan-genotypic direct-acting antiviral (DAA) medications. Around the world, costs of medication and those associated with treatment are prohibiting wide-scale cure. The AIDS Clinical Trials Group A5360 Minimal Monitoring (MINMON) trial examined the feasibility of minimal in-person monitoring while treating patients with HCV and compensated cirrhosis with interferon-free, ribavirin-free DAAs. The results were reported in The Lancet Gastroenterology and Hepatology.
Adult, HCV-treatment-naïve patients were recruited across five countries (Brazil, South Africa, Thailand, Uganda and the USA). Patients had to have an HCV viral load of at least 1,000 IU/mL within 35 days of study entry, and fibrosis stage was determined by fibrosis-4 (FIB-4, which uses age, aspartate aminotransferase, alanine aminotransferase and platelet count). Patients with compensated cirrhosis were admitted but capped at 80 participants. Patients with HIV were admitted, but only if they had HIV-viral suppression on non-efavirenz containing regimens or were HIV-treatment naïve with a CD4 count of at least 350 cells per μL. Patients with active hepatitis B virus were excluded, as these patients require laboratory monitoring, but patients with resolved HBV were included (hepatitis B core antibody positive, with or without HBV surface antibodies).
Patients were given a single-tablet combination of 400 mg of sofosbuvir and 100 mg of velpatasvir on the first visit, with instruction to take one daily for 12 weeks with or without food. Specifically, no genotype was done, all 84-days were dispensed on the first visit, no scheduled clinic or laboratory monitoring visits were made, and two points of remote contact at week 4 and week 22 were scheduled. At week 22, a final outcome assessment visit would be scheduled. Unplanned visits were allowed, but patients had to initiate those visits by calling the contact number they were given at the first visit.
A total of 400 patients were enrolled, mostly in the U.S., Brazil and Thailand, with only 27 participants from Africa’s two sites. Week 4 remote contact was successful in 394 (99%) patients, and week 22 remote contact was successful in 335 (84%). Only 3 patients reported losing study drug, and 2 were given replacements due to treatment interruption being less than 14 days. Overall, 355 (89%) of patients reported taking 100% of medications. In total, 15 (4%) of patients had 21 unplanned in-person visits, and none of these were associated with treatment discontinuation. Two patients were lost to follow-up, 1 had medication loss, 1 did not return for final lab testing, and 1 discontinued treatment due to a grade 1 adverse reaction. Of the rest, 370 (95%) achieved a sustained virologic response.
This study is extremely encouraging regarding the safety and efficacy of direct-acting antivirals for HCV treatment and could allow us to make great gains in reaching the World Health Organization’s goal of HCV elimination by 2030. However, unless U.S. health care payers agree to dispense the entire treatment duration upfront and stop asking for unnecessary labs to “prove” compliance, little will change here.
(Solomon et al. Lancet Gastroenterol Hepatol. 2022;7(4):307-317.)
