Direct-acting antiviral therapy for hepatitis C delivered by non-specialists such as primary care physicians and nurse practitioners is safe and effective – even for the most difficult-to-treat patients – and could potentially help increase the number of people receiving treatment, according to findings from the ASCEND study presented at the Conference on Retroviruses and Opportunistic Infections (CROI 2016) last month in Boston.
Interferon-based therapy for hepatitis C is long and difficult and can cause side effects that lead many patients to stop treatment prematurely. It also requires expertise to determine who needs treatment due to progressive liver disease and when to discontinue therapy that is likely to be futile, as it only produces a cure about half the time. The advent of direct-acting antivirals increased the emphasis on viral load monitoring and drug-resistance mutations. As such, treatment in the interferon era was generally managed by specialists such as hepatologists or gastroenterologists, later joined by infectious disease doctors.
Interferon-free direct-acting antiviral regimens have made treatment much easier, better tolerated, and more effective. Most people can now be cured with 12 or even 8 weeks of therapy and side effects are generally mild. The latest AASLD/IDSA guidelines recommend that everyone with chronic hepatitis C virus (HCV) infection should be considered for treatment rather than waiting until they develop advanced liver disease. But challenges remain, including the high cost of therapy and the lack of enough specialists to treat everyone living with the disease.
Sarah Kattakuzhy from the University of Maryland and colleagues conducted a longitudinal trial to evaluate the safety and effectiveness of hepatitis C treatment driven by primary care providers. This open-label, Phase 4 trial enrolled 600 chronic hepatitis C patients at 3 community health centers in Washington, DC, who started treatment between May and November 2015.
About 70% were men, almost all (96%) were black/African American, the average age was about 59 years, and nearly a quarter were coinfected with HIV. A majority (72%) had hard-to-treat HCV genotype 1a (the rest had 1b), 18% had prior hepatitis C treatment experience, and 20% had compensated liver cirrhosis. Participants were allocated in a non-randomised manner to receive treatment managed by either a hepatologist or infectious disease specialist (n=294), a primary care physician (n=156), or a nurse practitioner (n=150). Providers underwent a uniform 3-hour training on the AASLD/IDSA guidelines.
All patients were treated with sofosbuvir/ledipasvir (the drugs in Harvoni) according to label directions. Only 29 (5%) qualified for 8 weeks of treatment, with the rest assigned to 12 weeks (90%) or 24 weeks (5%).
The primary outcome was sustained virological response, or undetectable HCV RNA at 12 weeks after completion of treatment (SVR12). Efficacy was reported for 304 people with available SVR12 data, and follow-up is ongoing. Adherence was reported for 409 participants who completed 12 weeks of treatment, using a composite of adherence at weeks 4, 8, and 12.
Overall, 49 patients discontinued treatment early, mostly due to loss to follow-up (31 people). The overall SVR12 rate was 93.8% in an interim per-protocol analysis of 304 patients with available data.
There were no significant differences in SVR12 rates according to provider type: primary care physicians: 96.7% (58 of 60); nurse practitioners: 94.9% (75 of 79); and specialists: 92.1% (152 of 165).
HIV co-infection status had no impact on SVR12 overall (92.0%) or SVR12 by provider type (89.0%, 90.9%, and 93.0%, respectively). However, among the 409 patients who completed 12 weeks of therapy, adherence was significantly higher among people treated by nurse practitioners (51.4%) or primary care physicians (49.0%) compared to specialists (19.2)%.
“The ASCEND investigation demonstrates that HCV treatment administered independently by primary care providers and nurse practitioners is safe and equally effective as care observed with experienced specialists, inclusive of challenging subpopulations of the epidemic, and within the largest African-American cohort described to date,” the researchers concluded.
“The ASCEND model could increase the availability of community-based, non-specialist providers to significantly expand the scale of HCV therapy, and bridge existing gaps in the hepatitis C care cascade,” they added.
The hepatitis C (HCV) care cascade in the US is limited by the number of specialists able to treat HCV. Given the advent of directly acting antiviral therapy, we conducted a large-scale, longitudinal trial to evaluate the efficacy and safety of primary care driven HCV treatment
In this multi-center, open label, phase IV clinical trial, chronic HCV-infected patients of community health centers in Washington DC were identified by their providers, consented, and distributed in a non-randomized manner to receive treatment from either a specialist (ID/Hepatology), primary care physician (PCP), or nurse practitioner (NP). Providers underwent uniform training on IDSA-AALSD therapeutic guidelines. Patients were treated with ledipasvir and sofosbuvir (LDV/SOF) as per label. The primary outcome was defined as unquantifiable HCV RNA viral load 12 weeks after completion of therapy (SVR12). Adherence to visits at 4, 8, and 12 weeks (all -7 to +14 days), were categorized by a composite score of attendance. Statistical analysis included chi-squared or Fisher’s exact test and logistic regression using SAS, version 9.3
600 patients began treatment with LDV/SOF from May to November 2015, with follow up ongoing. 14 patients discontinued treatment early, including 4 due to adverse events and 1 death unrelated to study participation. Patients were predominantly black (96%) and genotype 1a (72%); 24% were HIV/HCV-coinfected, 18% were treatment experienced, and 20% were CPA cirrhotic, with comparable baseline characteristics between provider groups. Of 181 patients with available results, 169 achieved SVR12 (93.4% per protocol; 86.7% intention-to-treat including early discontinued). Of 12 patients with virologic failure, 1 had breakthrough and 11 had relapse. There was no significant difference (p=0.67) between per protocol SVR12 and provider type: NPs (47/49;95.9%), PCPs (36/38;94.7%), and specialists (86/94;91.5%). HIV status had no impact on SVR12 or SVR12 by provider type. Of 419 patients who completed 12 weeks of therapy, composite adherence was significantly associated with provider type: 50% in NPs, 41% in PCPs, and 19% in specialists (P<0.001)
For the first time, we demonstrate that HCV treatment administered independently by PCPs and NPs is safe and effective, inclusive of challenging subpopulations of the epidemic, and within the largest African-American cohort described to date. Community-based non-specialist providers could significantly expand the scale of HCV therapy