Uzbekistan Hepatitis Elimination Project (UHEP)

Pilot Concept

A catalytic investment is used to cover up-front costs to purchase the first round of diagnostics and medicines. All participants receive free testing (Table 1). An estimated 20% of patients receive free treatment using an existing mechanism where neighborhood councils determine eligibility for free medical services based on income level. A mark-up on treatment pricing to the 80% who can afford to pay, funds the purchase of subsequent rounds of diagnostics and medicine and repays the catalytic investment at program conclusion.

The cost of hepatitis B or hepatitis C medication was determined by summing the total cost of the respective supplies/programs divided by the estimated number of respective patients who will seek treatment and are able to pay.

Training was provided to all nurses on use of RDTs, motivational interviewing, and patient registry. The University of Maryland provide training to all doctors, including Polyclinic GPs, on study protocols with special attention to how simplified testing and treatment algorithms differ from current national guidelines. Training also included interpretation of laboratory results, medicine contraindications, drug-drug interactions, comorbidities, recommended dosing, and use of the REDCAP patient registry.

Study Protocol

The project is overseen by a medical advisory board consisting of international experts who advise on hepatitis B or hepatitis C testing algorithms and treatment strategies. A study protocol was developed by the project team, reviewed by the medical advisory board and approved by the national Institutional Review Board and MoH before the Uzbekistan Hepatitis Elimination Pilot (UHEP) was launched on December 6, 2019.

Simplified testing algorithms were developed to minimize the number of tests required before initiating treatment. Patients are screened using HBsAg rapid diagnostic test (RDT) followed by rapid HIV and creatinine tests if patient tested HBsAg positive. All HIV positive patients are referred to HIV clinics for treatment. All other patients are referred to the Polyclinic General Practioner (GP) for consultation and to receive a prescription.

An HCV RDT is conducted at the same time as the HBsAg test, to test for anti-HCV. Patients who test anti-HCV positive have their blood drawn and samples are sent for HCV core antigen, creatinine, aspartate aminotransferase (AST) and platelet tests. An AST to Platelet Ratio Index (APRI) is calculated to estimate cirrhosis. Glomerular Filtration Rate (eGFR) is calculated to determine renal function. Cirrhotic patients (APRI >1.5) or patients with impaired renal function (eGFR <30 ml/min/1.73 m2) are referred to RIV for consultation with a specialist physician. All other patients are scheduled to see a Polyclinic GP when test results are available (approximately 3 days after testing).

The HBsAg positive patients receive a prescription for 12 months of tenofovir disoproxil fumarate with instruction to come back after 12 months for free follow up tests (HBsAg, HIV and creatinine). All eligible HCV infected patients receive a 3-month prescription for sofosbuvir/daclatasvir if non-cirrhotic or a 3-month prescription for sofosbuvir/velpatasvir if cirrhotic. They weraree instructed to return after 12 weeks following completion of treatment for a free HCV core antigen test to determine sustained virologic response (SVR) i.e., cure.

Motivational Interview

Prior to being referred to a doctor, all patients who tested positive for HBsAg or HCV antibody meet with a nurse who has been trained to administer a brief motivational interview.  This technique has been used in drug and alcohol abuse settings to increase participants’ internal desire to link to care and adhere to treatment

Patient Registry

All patient consent, contact information, medical history, test results and doctors’ notes are entered into an open-source REDCAP electronic medical registry that was developed to monitor patient progress through the program. All polyclinics and RIV medical staff are provided with low-cost digital tablets and laptops, including cellular wireless routers where needed, to allow for recording and near real-time uploading of patient data. The registry system prevents repeat testing and provides a mechanism for follow up when patients are not linked to care.

Negotiated Pricing

Quality-assured medicines and diagnostics are purchased at high volumes and low prices through the Global Procurement Fund (GPRO), a non-profit procurement service. The Uzbekistan government agreed to waive most import duties and fees and provided human resources, clinic space, laboratory equipment, and disposables. A national pharmacy chain, OxyMED, was contracted to sell medicines at only a 5% markup.

Test Locations

A total of 13 polyclinics in Tashkent, the capital city, were recruited to test an estimated 250,000 adults age >18 years over a period of 12 months. Three to four operate at any given time. Each quarter, three to four new polyclinics among the 13 selected polyclinics will be opened for testing and the polyclinics working in prior months will cease testing.

Training

Training was provided to all nurses on use of RDTs, motivational interviewing, and patient registry. The University of Maryland provide training to all doctors, including Polyclinic GPs, on study protocols with special attention to how simplified testing and treatment algorithms differ from current national guidelines. Training also included interpretation of laboratory results, medicine contraindications, drug-drug interactions, comorbidities, recommended dosing, and use of the REDCAP patient registry.