Genetic Diversity of Cytochrome P450 2C9 (CYP2C9) in HIV/AIDS Positive Patients Regarding Side Effects Induced by Cotrimoxazole at the ALNADJMA Multipurpose Center in N'Djamena, Chad
Abstract
Introduction: HIV is a retrovirus that destroys the immune system. In Chad, HIV prevalence is 1.1%. Cotrimoxazole is a prophylactic drug that effectively reduces the morbidity associated with opportunistic infections. The genetic diversity of drug-metabolising enzymes, such as CYP2C9, influences the metabolism of cotrimoxazole in the occurrence of side effects. Although cotrimoxazole prophylaxis is common and cost-effective, clear guidelines are lacking in countries such as Chad. The aim of this study is to evaluate and compare CYP2C9 gene variants in HIV-positive patients at the Alnadjama centre and to analyse their impact on cotrimoxazole tolerance in order to support personalised therapeutic approaches.
Methods: A case-control study was conducted from May 2022 to September 2024 at the Alnadjama Multipurpose Center in N'Djamena, Chad, with molecular analyses performed at LAPHER-Biotech, University of Yaoundé I, Cameroon. HIV-positive patients aged 18–60 years on cotrimoxazole prophylaxis were divided into groups based on the presence or absence of side effects. After informed consent, interviews and blood samples were collected, and medical records reviewed. DNA was extracted using the Chelex-100 method, CYP2C9 gene amplified by PCR, digested with BstNI enzyme, and fragments analyzed by agarose gel electrophoresis. Statistical analyses included allele frequencies, Chi-square tests, odds ratios (OR), and 95% confidence intervals, with significance set at p < 0.05.
Results: Among 160 patients, 120 received cotrimoxazole, with 58 (48.3%) reporting side effects. The CYP2C9*2 wild-type genotype (C/C) predominated (98.3%), with the mutant (T/T) rare (1.7%), regardless of side effects. For CYP2C9*3, the heterozygous genotype (A/C) was most common (96.6–98.4%), and the mutant (C/C) was rare (1.6–3.4%), with no significant differences between groups. Association tests showed no significant correlation between CYP2C9*2 or *3 variants and cotrimoxazole adverse effects (OR near 1, p not significant).
Conclusion: CYP2C9*2 and *3 variants were not significantly associated with cotrimoxazole side effects in this HIV-positive cohort. The findings highlight the value of pharmacogenetics and recommend further research incorporating multiple genes and clinical factors to better predict adverse drug reactions in these patients.
Keywords: N'Djamena, Side effects, Cotrimoxazole, CYP2C9, HIV, Genetic diversity, Chad, Polymorphism.
Keywords:
N'Djamena, Side effects, Cotrimoxazole, CYP2C9, HIV, Metabolizer, Chad, Genetic diversityDOI
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Copyright (c) 2025 Moudiné Ouadjonré François , Calvino Fomboh Tah , Faysala Oscar , Mahamat Nour Aguid Abakar , Ledjébaye Joseph , Brahim Boy Otchom , Wilfred Fon Mbacham
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