K43TW011957

Development of a Multiplex Quantitative PCR Assay for HIV and Hepatitis B Virus, for Low- and Middle-Income Countries - Summary

Human Immunodeficiency Virus (HIV) and Hepatitis B Virus (HBV) share the same blood-borne modes of transmission, primarily through sexual contact and injection drug use. Individuals at risk for HIV are also at a higher risk for HBV infection. Globally, an estimated 257 million people live with chronic HBV infection (2015), while in 2019, 38 million people were living with HIV (PLHIV). Africa, particularly Sub-Saharan Africa (SSA), is the most affected region in the world, with 70% (25.7 million) of PLHIV and approximately 6% of the adult population infected with HBV.

Importantly, it is estimated that chronic HBV infection affects 5-20% of PLHIV. HBV is an asymptomatic liver disease, making its early detection difficult and leading to serious complications such as cirrhosis, hepatocellular carcinoma, and early death. Knowledge of HBV status at the initiation of HIV antiretroviral therapy (ART) is essential for appropriate selection of an initial ART regimen. Tenofovir disoproxil fumarate (TDF) should be combined with lamivudine (3TC) or emtricitabine (FTC), which suppress both HIV and HBV replication, and for monitoring treatment.

Mali, a low- and middle-income country (LMIC) in West Africa, has an HIV/AIDS prevalence rate of over 1% of the general population (over 20 million). Specific adult population groups, such as pregnant women, students, and blood donors, have HBsAg positive rates ranging from 10 to 18.8%. While HIV RNA and HBV DNA quantification assays are recommended to better guide and monitor treatment, access to such assays in SSA is very limited or not even available. In most of Africa, HIV patients are screened only for HBsAg. Thus, patients with occult hepatitis B (OBI), despite having HBV-DNA in serum and/or in the liver but HBsAg negativity, will not be detected and will miss an important opportunity to initiate treatment. OBI is usually asymptomatic, but its reactivation commonly occurs in immunosuppressed individuals, such as HIV-infected persons. Measurement of viral nucleic acids plays a critical role in determining the phase of infection, selecting treatment, and is informative about the efficacy of antiviral therapy.

This K43 application seeks to develop a multiplex, real-time, quantitative PCR (RT-QPCR) assay for simultaneous quantification of HIV RNA and HBV DNA. The assay will be specifically designed to detect regional genetic variants, using an "open" system platform that is economically, environmentally, and within the technical capabilities of laboratory staff in SSA. My proposed career development will be supervised by both American and Malian mentors and focus on gaining expertise and skills in the design and development of new multiplexed PCR assays, methods to evaluate new diagnostic tests, and implementation strategies for new tests. This includes stakeholder engagement, as well as strengthening my career skills in research leadership and team science.

Des Techniques Et Des Technologies De Bamako Usttb Universite Des Sciences

THE JOHN E. FOGARTY INTERNATIONAL CENTER (FIC) SUPPORTS RESEARCH AND RESEARCH TRAINING TO REDUCE DISPARITIES IN GLOBAL HEALTH AND TO FOSTER PARTNERSHIPS BETWEEN U.S. SCIENTISTS AND THEIR COUNTERPARTS ABROAD. FIC SUPPORTS BASIC BIOLOGICAL, BEHAVIORAL, AND SOCIAL SCIENCE RESEARCH, AS WELL AS RELATED RESEARCH TRAINING AND CAREER DEVELOPMENT. THE RESEARCH PORTFOLIO IS DIVIDED INTO SEVERAL PROGRAMS THAT SUPPORT A WIDE VARIETY OF FUNDING MECHANISMS TO MEET PROGRAMMATIC OBJECTIVES.

93.989 - International Research and Research Training

Fogarty International Center (FIC) [HHS - NIH]

Mali

Foreign

Emerging Global Leader Award (K43 Independent Clinical Trial Not Allowed) (PAR-19-098)

Amendment Since initial award the total obligations have increased 401% from $99,640 to $499,480.