The influence of extrinsic apoptosis gene expression on immunological reconstitution of male ART-treated PLHIV

Abstract

The primary goal of antiretroviral therapy (ART) is to suppress viral replication to undetectable levels (< 50 copies/mL). Despite achieving complete viral suppression, 10-40% of individuals on ART do not adequately restore their CD4 + T-cell count, being defined as immunological non-responders (INR). Factors such as sex, age at treatment initiation, coinfections, and pre-ART CD4 + T-cell count may influence this insufficient recovery. This impairment can also result from poor production or exacerbated destruction of CD4 + T-cells, particularly through extrinsic pathway-mediated apoptosis involving Fas/FasL and caspase-3. Thus, this study aimed to evaluate the expression profile of extrinsic apoptosis pathway genes (CASP3, FAS, FASLG) in adult male HIV patients on ART. The patients were stratified as immunological responders (n = 25) and immunological non-responders (n = 8) based on the increase and total count of CD4 + T-cells. Significant differences for CASP3 (FC = 1.39, p = 0.047) and FASLG (FC = 1.94, p < 0.0001) gene expressions were identified between IR and INR groups, but not for FAS (FC=-1.2, p = 0.638). This study indicates increased apoptotic pathway gene expression in INR and highlights the influence of cell destruction mechanisms on immunological recovery.

Keywords: CASP3; CD4 + T-cell recovery; FAS; FASL; cell death; immunological non-responders.

Fig. 1

Differential gene expression of the extrinsic apoptosis pathway between IR and INR: (A)CASP3 (FC = 1.39; p = 0.047); (B)FAS (FC = -1.2; p = 0.638); (C)FASLG (FC = 1.94; p < 0.0001). The relative expression levels of these genes are depicted in scatter plots based on fold change values. The relative expression levels of these genes were analyzed using the 2^−ΔΔCq method and compared between groups with the Mann-Whitney test. The data are presented as the mean with the corresponding standard deviation