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Nevirapine-induced hepatotoxicity and pharmacogenetics: a retrospective study in a population from Mozambique

    Cinzia Ciccacci

    Department of Biopathology & Diagnostic Imaging, Section of Genetics, Tor Vergata University, Rome, Italy.

    Irccs Centro Neurolesi ’Bonino Pulejo‚ Messina, Italy

    ,
    Paola Borgiani

    † Author for correspondence

    Department of Biopathology & Diagnostic Imaging, Section of Genetics, Tor Vergata University, Rome, Italy.

    , ,
    Elisabetta Sirianni

    Department of Biopathology & Diagnostic Imaging, Section of Genetics, Tor Vergata University, Rome, Italy.

    , ,
    Anna M Doro Altan

    Department of Public Health, Tor Vergata University, Rome, Italy

    ,
    Giovanna Paturzo

    Department of Public Health, Tor Vergata University, Rome, Italy

    ,
    Placido Bramanti

    Irccs Centro Neurolesi ’Bonino Pulejo‚ Messina, Italy

    ,
    Giuseppe Novelli

    Department of Biopathology & Diagnostic Imaging, Section of Genetics, Tor Vergata University, Rome, Italy.

    Medical Genetics Unit, San Pietro Hospital, Rome, Italy

    &
    Leonardo Palombi

    Department of Public Health, Tor Vergata University, Rome, Italy

    Published Online:https://doi.org/10.2217/pgs.09.142

    Aims: Nevirapine is widely used to treat HIV-1 infection to prevent mother-to-child transmission; unfortunately adverse drug reactions have been reported. Our aim was to identify genes/variants involved in nevirapine-induced hepatotoxicity. Materials & methods: Patients from Mozambique, 78 with nevirapine-induced hepatotoxicity and 78 without adverse events, were genotyped for ABCB1, CYP2B6, CYP3A4 and CYP3A5 gene variants. We conducted a case–control association study and a genotype/phenotype correlation analysis. Results: The ABCB1 c.3435C>T SNP was associated with hepatotoxicity (p = 0.038), with the variant T allele showing a protective effect (odds ratio: 0.42). Moreover, four SNPs in the CYP2B6 and CYP3A5 genes resulted significantly correlated with transaminase values. In particular, for the CYP2B6 c.983T>C SNP, the difference in the alanine aminotransferase mean values were highly significant between TT and TC genotypes (p < 0.001). Conclusion: Our preliminary results confirm the contribution of the ABCB1 c.3435C>T SNP in nevirapine-induced hepatotoxicity risk and, at the same time, suggest the necessity for further studies.

    Papers of special note have been highlighted as: ▪ of interest ▪▪ of considerable interest

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