Prevention of mother-to-child transmission of hepatitis B virus: a phase III, placebo-controlled, double-blind, randomized clinical trial to assess the efficacy and safety of a short course of tenofovir disoproxil fumarate in women with hepatitis B virus e-antigen.

BACKGROUND: Chronic hepatitis B virus (HBV) infection is complicated by cirrhosis and liver cancer. In Thailand, 6-7 % of adults are chronically infected with HBV. The risk of mother-to-child transmission (MTCT) of HBV has been estimated to be about 12 % when mothers have a high hepatitis B viral load, even if infants receive passive-active prophylaxis with HBV immunoglobulin (HBIg) and initiate the hepatitis B vaccine series at birth. We designed a study to assess the efficacy and safety of a short course of maternal tenofovir disoproxil fumarate (TDF) among women with a marker of high viral load for the prevention of MTCT of HBV. METHODS: The study is a phase III, multicenter (17 sites in Thailand), placebo-controlled, double-blind, randomized 1:1, two-arm clinical trial of TDF 300 mg once daily versus placebo among pregnant women from 28 weeks' gestation through 2-month post-partum. All infants receive HBIg at birth, and a hepatitis B (HB) vaccination series according to Thai guidelines: birth, and age 1, 2, 4 and 6 months. Participant women at study entry must be age ≥18 years, hepatitis B surface antigen (HBsAg) and e-antigen (HBeAg) positive, have alanine aminotransferase (ALT) level < 30 IU/L at screening (confirmed < 60 IU/L pre-entry), negative hepatitis C serology, creatinine clearance >50 mL/min, and no history of anti-HBV antiviral treatment. The target sample size of 328 mother/infant pairs assumed 156 evaluable cases per arm to detect a ≥9 % difference in MTCT transmission (3 % experimental arm versus 12 % placebo arm) with 90 % power. Mothers and infants are followed until 12 months after delivery. The primary infant endpoint is detection of HBsAg, confirmed by detection of HBV DNA at six months of age. Secondary endpoints are maternal and infant adverse events, acute exacerbations of maternal hepatitis B disease (ALT >300 IU/L, defined as a "flare") following discontinuation of study treatment, infant HBV infection status and growth up to 12 months of age. DISCUSSION: The results of this randomized trial will clarify the efficacy and safety of a short course of antiviral treatment to prevent mother-to-child transmission of HBV and inform international guidelines. TRIAL REGISTRATION: ClinicalTrials.gov Identifier NCT01745822 .

Building and Sustaining Optimized Diagnostic Networks to Scale-up HIV Viral Load and Early Infant Diagnosis.

BACKGROUND: Progress toward meeting the UNAIDS 2014 HIV treatment (90-90-90) targets has been slow in some countries because of gaps in access to HIV diagnostic tests. Emerging point-of-care (POC) molecular diagnostic technologies for HIV viral load (VL) and early infant diagnosis (EID) may help reduce diagnostic gaps. However, these technologies need to be implemented in a complementary and strategic manner with laboratory-based instruments to ensure optimization. METHOD: Between May 2019 and February 2020, a systemic literature search was conducted in PubMed, the Cochrane Library, MEDLINE, conference abstracts, and other sources such as Unitaid, UNAIDS, WHO, and UNICEF websites to determine factors that would affect VL and EID scale-up. Data relevant to the search themes were reviewed for accuracy and were included. RESULTS: Collaborations among countries, implementing partners, and donors have identified a set of framework for the effective use of both POC-based and laboratory-based technologies in large-scale VL and EID testing programs. These frameworks include (1) updated testing policies on the operational utility of POC and laboratory-based technologies, (2) expanded integrated testing using multidisease diagnostic platforms, (3) laboratory network mapping, (4) use of more efficient procurement and supply chain approaches such as all-inclusive pricing and reagent rental, and (5) addressing systemic issues such as test turnaround time, sample referral, data management, and quality systems. CONCLUSIONS: Achieving and sustaining optimal VL and EID scale-up within tiered diagnostic networks would require better coordination among the ministries of health of countries, donors, implementing partners, diagnostic manufacturers, and strong national laboratory and clinical technical working groups.