Analysis of TPH-2 single nucleotide polymorphisms and depressive symptoms in a Mexican cohort of HIV-1 patients treated with efavirenz- and atazanavir

Abstract

Abstract Background Depressive disorders have been associated with TPH2 gene polymorphisms. Additionally, HIV-1 antiretroviral drugs (ART) such as efavirenz (EFV) have been reported to cause neuropsychiatric adverse effects. Objective This study aimed to determine the genotypes and allelic frequencies of TPH2 SNPs (rs120074175, rs1386493, rs4570625, and rs7305115) in a Mexican cohort of ART-naive patients, and healthy volunteers as control, and assess the severity of their depressive symptoms using the Beck Depression Inventory (BDI). Methods In a prospective study conducted from January 2017 to December 2018, eigthy-one HIV-1-positive ART-naive patients were recruited from the Infectious Disease Hospital, National Medical Center “La Raza”, Mexico City; 39 were treated with EFV, and 42 treated with atazanavir (ATV). Additionally, 59 healthy subjects were included as controls. Blood samples were collected and genomic DNA obtained from peripheral blood polymorphonuclear cells. All DNA samples were subjected to qPCR using TaqMan probes for the TPH2 SNPs. Additionally, all subjects were evaluated using the BDI. Results The frequencies and distributions of alleles among the SNPs studied showed that the genotype frequencies resulted in Hardy-Weinberg equilibrium (HWE) for all SNPs evaluated, except for the rs120074175 in the people living with HIV (PLWH), and controls with the wild-type allele (GG genotype, 100%). Three of the four analyzed SNPs did not show statistically significant differences in the distribution of the rs1386493, rs4570625 and rs7305115 alleles between patients and controls. A total of 64.1% of PLWH, who were treated with EFV had depression according to the initial BDI score, and after four weeks, 90.4% of them had severe depression. Among patients treated with ATV, 73.8% had severe depression at the baseline and, at 4 weeks, 87.5% had severe depression. The increase in depressive symptoms was more evident in patients treated with EFV (EFV X2: 19.085; df: 1; p < 0.0001; ATV X2: 5.383; df: 1; p = 0.0203). Conclusion In this study, we showed that 69.13% of patients with HIV diagnosis have severe depression from started. The severity of depressive symptoms was higher in the group of patients treated with EFV after four weeks of treatment. It will be important to consider a psychiatric monitoring of each patient to contain adverse effects and/or provide timely antidepressant treatment.