INTERFERON-GAMMA AND INTERLUKIN-10 DERANGEMENTS IN HIV-1 ANTIRETROVIRAL NON-ADHERENT PATIENTS ATTENDING SIAYA COUNTY REFERRAL HOSPITAL, KENYA

Abstract

Despite significant decline in HIV-1 infection rates from up-scaling of Anti-Retroviral Therapy (ART) accessibility, Kenya is among leading African countries in prevalence. Siaya County has the second-highest prevalence of HIV/AIDS in Kenya. During immune responses to infections, crucial cytokines such as Interferon-gamma (IFN-γ) and interleukin 10 (IL-10) are expressed by CD4+ T-cells. However, their production is dysregulated during HIV infection of these cells. Antiretroviral treatment (ART) aims to reduce viral load and restore balance within the immune system through normalizing IFN-γ levels alongside IL-10 levels while enabling stable CD4+ cell counts. Non-adherence inhibits this process impairing viral suppression that undermines restoration or maintenance of immunity equilibrium. Despite its importance, few studies have analyzed how ART non-adherence affects circulating cytokine levels like IFN-γ and IL-10. Therefore, we conducted a cross-sectional study involving 163 individuals who visited Siaya County Referral Hospital inclusive of ART-naive patients with or without HIV-infection living inside Western Province between October–December 2017. Our research aimed to determine whether there was any effect exerted on clinical therapy outcomes together with measuring changes made among participants' blood samples outlining differing adherence groups: those adherent wholly – ‘HIV1+, ART-adherent’ vs inadequately treated people - "HIV1 + , Art-nonadherent." HIV-1 status was determined by automated Abbott m2000 System, Viral load was measured using the COBAS® AmpliPrep/COBAS® TaqMan®, while CD4 count and cytokines measurement were done using BD PRESTO and Sandwiched ELISA respectively. The serum IFN-ɤ and IL-10 levels for HIV-1 -ve, HIV-1 [+] ART-naive, HIV-1 [+] ART-adherent, HIV-1 [+] ART-Non-adherent were: (5.73 vs. 5.89; 0.74 vs. 32.26; 2.55 vs. 14.9 and 0.98 vs. 26.73) pg/MmL. The CD4 T cell count was significantly lower in the HIV [+] ART-Naïve group (median, 395.9 IQR 349 copies per microliter of blood) as compared to HIV-1 negative (median 1407.4 IQR 1303 copies per microliter of blood), HIV [+] ART-Adherents, median, 575.4 IQR 374 copies per microliter of blood) and HIV [+] ART-Non-Adherents, median, 423.6, IQR, 252 copies per microliter of blood); P <0.001. Conversely, the viral load was higher in HIV [+] ART-Non-Adherents, median, 4.6, IQR 1.1 copies per microliter of blood), than HIV [+] ART-Adherents, median, 3.4, IQR 1.9 copies per microliter of blood) and HIV [+] ART-Naïve, median, 4.5, IQR, 1.6 copies per microliter of blood); P <0.001. Interleukin 10 (IL-10) levels correlated positively with viral load (ρ= 0.272; P=0.004) and inversely with CD4 T cell count (ρ= -0.627; P<0.0001) as well as BMI (ρ= -0.376; P<0.0001). Nevertheless, there was a negative correlation observed between IFN-γ and both viral load (ρ= -0.326; P<0.0001) and BMI (ρ= -0.342; P<0.0001). Conversely, a positive correlation was found between IFN-γ and CD4 T cell count (ρ= 0.619; P<0.0001). The current study has uncovered that the deficiency in compliance with highly active antiretroviral therapy (HAART) among HIV-1 infected patients is having a substantial impact on the quantities of pro-inflammatory and anti-inflammatory cytokines present within their blood. This discrepancy in cytokine balance could potentially disturb the sensitive equilibrium between these two conflicting factors. It is suggested that monitoring serum levels of IFN-γ and IL-10 may be an effective technique for tracking advancements made regarding HIV-1 infection management.