Interested participants were screened using the pre‐enrolment criteria,28 and eligible participants signed informed consent forms. GPs took short medical histories and referred them to on‐site laboratory technicians (Figure 1 ).
Technicians took 10‐11 mL of blood, then conducted the WHO prequalified PoC rapid diagnostic test (RDT) for anti‐HCV (SD BIOLINE). Following a reactive RDT result, HCV on‐site RNA testing involved the WHO prequalified Xpert hepatitis C VL assay on the GeneXpert® System (Cepheid). All HCV‐RNA‐positive participants then had HIV and HBV RDTs, liver function tests, renal function tests and a full blood examination. RDTs were conducted on‐site and all other blood tests at a private laboratory nearby, with samples collected from study sites daily and results emailed within 24 hours. The aspartate aminotransferase to platelet ratio index (APRI) score was calculated to assess cirrhosis and inform length of treatment (12 or 24 weeks). The APRI score is calculated as:
Participants were asked to return for review of pre‐treatment assessments; GPs performed a clinical assessment for physical signs of decompensated cirrhosis, and determined whether the participant required hepatologist or other specialist evaluation. Participants with (i) ALT or AST >200 U/L, (ii) bilirubin above 1.14 mg/dL, (iii) albumin <3.5 g/dL without other obvious cause, or with past or current, (iv) jaundice, (v) ascites, (vi) hepatic encephalopathy or (vii) haematemesis and melena met the criteria for hepatologist review. Participants reviewed by a specialist then returned to the GP for DAA initiation, if deemed appropriate. Participants were ineligible for DAA therapy if they presented with (i) HIV co‐infection, (ii) hepatitis B co‐infection, (iii) active tuberculosis, (iv) eGFR <30 mL/min/1.73 m2, (v) or pregnancy or (vi) were taking medications with serious interactions with sofosbuvir/daclatasvir.
For eligible participants, GPs prescribed and dispensed generic oral sofosbuvir 400 mg and daclatasvir 60 mg on‐site. The APRI cut‐off for cirrhosis was 2.0 as per the 2017 Myanmar National Guidelines,25 but was changed to 1.5 on 6 September 2019 in line with the second edition.26 Participants with an APRI score below the national cut‐off received a 12‐week course, and those with APRI score above cut‐off received a 24‐week course. Participants returned to the clinic every four weeks for short on‐treatment study‐related monitoring visits, which included medication dispensing and questions about alcohol use, injecting drug use, medication adherence and side effects.
Participants’ blood was tested using the hepatitis C VL assay on the GeneXpert® System (Cepheid) 12 weeks after completing treatment to assess sustained virological response (SVR12), defined as no HCV RNA detected. Participants with HCV detectable, VL <10 IU/mL were asked to return for a second HCV RNA test at SVR24; if the result was ‘not detected’, this was classified as SVR12 achieved.
Technicians took 10‐11 mL of blood, then conducted the WHO prequalified PoC rapid diagnostic test (RDT) for anti‐HCV (SD BIOLINE). Following a reactive RDT result, HCV on‐site RNA testing involved the WHO prequalified Xpert hepatitis C VL assay on the GeneXpert® System (Cepheid). All HCV‐RNA‐positive participants then had HIV and HBV RDTs, liver function tests, renal function tests and a full blood examination. RDTs were conducted on‐site and all other blood tests at a private laboratory nearby, with samples collected from study sites daily and results emailed within 24 hours. The aspartate aminotransferase to platelet ratio index (APRI) score was calculated to assess cirrhosis and inform length of treatment (12 or 24 weeks). The APRI score is calculated as:
Participants were asked to return for review of pre‐treatment assessments; GPs performed a clinical assessment for physical signs of decompensated cirrhosis, and determined whether the participant required hepatologist or other specialist evaluation. Participants with (i) ALT or AST >200 U/L, (ii) bilirubin above 1.14 mg/dL, (iii) albumin <3.5 g/dL without other obvious cause, or with past or current, (iv) jaundice, (v) ascites, (vi) hepatic encephalopathy or (vii) haematemesis and melena met the criteria for hepatologist review. Participants reviewed by a specialist then returned to the GP for DAA initiation, if deemed appropriate. Participants were ineligible for DAA therapy if they presented with (i) HIV co‐infection, (ii) hepatitis B co‐infection, (iii) active tuberculosis, (iv) eGFR <30 mL/min/1.73 m2, (v) or pregnancy or (vi) were taking medications with serious interactions with sofosbuvir/daclatasvir.
For eligible participants, GPs prescribed and dispensed generic oral sofosbuvir 400 mg and daclatasvir 60 mg on‐site. The APRI cut‐off for cirrhosis was 2.0 as per the 2017 Myanmar National Guidelines,
Participants’ blood was tested using the hepatitis C VL assay on the GeneXpert® System (Cepheid) 12 weeks after completing treatment to assess sustained virological response (SVR12), defined as no HCV RNA detected. Participants with HCV detectable, VL <10 IU/mL were asked to return for a second HCV RNA test at SVR24; if the result was ‘not detected’, this was classified as SVR12 achieved.
