Randolph Ngwafor, MD, MSc
Nominated From: University of Hawai’i
Research Site: Cameroon
Research Area: Infectious Disease
Primary Mentor: Dr. Cecilia Shikuma
Genetic diversity of NAT2 and CYP2C9 in HIV positive patients, with or without cotrimoxazole prophylaxis
Co-trimoxazole prophylaxis has been shown to reduce morbidity and mortality to opportunistic infections and is thus recommended for all HIV-exposed children born to mothers living with HIV, regardless of the HIV status of these infants.The long duration of prophylaxis is adequate to prevent opportunistic infections in these infants and also to HIV positive patients. The majority of previous studies conducted evaluate the influence of the use of Co-trimoxazole on polymorphisms in the NAT2 and CYP2C9 genes in affections like renal transplantation (Kagaya et al 2012), acute lymphoblastic leukemia (Kamel et al 2015) and sulfonamide hypersensitivity (Zielinska et al 1998(a), Sacco et al 2012, O’Neil et al 2002, Zielinska et al 1998(b)).
Not much is known about Co-trimoxazole prophylaxis in HIV patients in Cameroon, and it is unknown if prolonged use of Co-trimoxazole can enhance individuals with NAT2 and CYP2C9 polymorphisms to increase susceptibility to other disease conditions. Thus, this research seeks to demonstrate if the prolonged use of Co-trimoxazole in adults with eventual NAT2 or CYP2C9 polymorphisms are susceptible to having opportunistic infections or hypersensitivity reactions. Study participants will be recruited from antiretroviral therapy (ART) clinics and inpatient/internal medicine-infectiology services in the Yaounde Central Hospital and Cite Verte District Hospital. Blood samples will be analyzed at the Laboratory for Public Health Research Biotechnology, where DNA extraction, PCR and restriction fragment length polymorphism will be carried out to determine mutations of the NAT2 and CYP 2C9 genes.
Aim 1: Determine the prevalence of HIV positive adults who receive Co-trimoxazole prophylaxis. We will systematically identify all HIV positive patients, and determine if they are on Co-trimoxazole. This will be done through interviewing the patients and checking their record books.
Aim 2: Determine polymorphisms of NAT2 and CYP2C9 metabolizing enzymes in these adults, with and without Co-trimoxazole prophylaxis. We will collect blood samples on filter paper from HIV-positive adults with and without Co-trimoxazole prophylaxis, and perform a PCR and restriction fragment length polymorphism to determine the presence of polymorphisms in the NAT2 and CYP2C9 enzymes.
Aim 3: Identify all HIV patients with NAT2 or CYP2C9 polymorphisms and verify of any history of hypersensitivity and opportunistic infections in these patients. We will identify all HIV patients with polymorphisms and check their record books for any hypersensitivity reactions or opportunistic infections. This will help us correlate the disease condition to the polymorphisms.
Data acquired from this study will generate important knowledge about the existence of the prevalence and nature of these polymorphisms in HIV patients and an eventual correlation with hypersensitivity reactions and opportunistic infections in these patients. This may warrant an alternative preventive strategy in these patients with mutations to prevent opportunistic infections.