Effects of Anti-Retroviral Therapy on Baseline Serum Interleukin-18 levels in HIV-I Infected Patients Relative to Viral Suppression and CD4+ Gain: a prospective pilot study

Abstract

Background In HIV infection, dysregulation of cytokines, including interleukin 18 (IL-18), has been linked to poor clinical outcomes in studies mainly conducted in resource-rich countries. This phenomenon has not been well-studied in resource-limited settings where outcomes could be confounded by exposure to endemic infections and genetic factors. Objectives Therefore, the influence of immunological and virological status of HIV-infected, antiretroviral therapy (ART)-naïve patients on serum IL-18 levels at baseline (pretreatment) and 24 weeks following initiation of combination ART (cART24) in a resource-limited setting was investigated. Methods Using the cross-sectional and longitudinal mixed method design, a total of Forty-four (44) newly diagnosed consenting HIV patients were consecutively recruited during routine clinic visits at the Nasara Treatment & Care Centre of the Ahmadu Bello University Teaching Hospital (ABUTH), Zaria, Nigeria between December 2016 to January 2018, and followed up for 24 weeks on initiation of first-line cART. Results Serum IL-18 concentrations, CD4+ T-cell counts (CD4+) counts, and HIV1 RNA levels were determined at baseline and cART24. There was little CD4 + count gain in both <200 and ≥ 200 cell/mm 3 subgroups despite the high proportion of subjects having virological suppression (n = 35, [80%]) at cART24. However, at cART24 there was a more than a threefold decrease in the level of IL-18 concentration compared to baseline in patients with <200 cells/mm 3 and a significant decrease in the median plasma IL-18 concentration in patients with HIV1 RNA <1000 cp/mL at cART24. A multivariate logistic regression model shows IL-18 intermediate quartile to be more related to immunological poor gain as compared to the highest quartile. Conclusion Our study found high baseline and significantly low levels of IL-18 at cART24 in virologically suppressed subjects but not among virological non-suppressed responders despite comparable IL-18 levels by CD4+ T cell count strata at cART24. These findings have implications for risk stratification and treatment outcomes in HIV-positive persons.

Prevalence of Cytopenia and its Correlation with Immunosuppression in Naïve HIV-1 Infected Patients Initiating First-Line Antiretroviral Therapy: A Pilot Study

“…This finding diverges from studies elsewhere that reported profound resolution of cytopenia following ART treatment [ 21 27 33 ]. Despite previous indications that retroviral therapy is associated with reduced cytopenia incidence and severity due to ART-related attenuation of disease progression, as measured by CD4+ T cell count [ 26 ], our findings reveal a limited correlation of cART24 with decreased HGB concentration in participants with CD4+ T cell counts <200 cells/mm 3 . Notably, HGB concentration, the diagnostic marker for anemia, exhibited a robust negative correlation among participants with CD4+ T-lymphocyte counts above 200 cells/mm 3 , potentially linked to the use of integrase enzyme inhibitor, DTG.…”

“…In 2018, the WHO recommended transitioning to DTG-based antiretroviral therapy due to compelling evidence showcasing its rapid reduction of HIV viremia. However, this rapid viral reduction itself poses an independent risk factor for the development of immune reconstitution inflammatory syndrome (IRIS), characterized by paradoxical inadequate immune function recovery [ 34 35 ], as also suggested in our previous reports [ 25 26 ]. Furthermore, DTG triggers cell shrinkage and phospholipid scrambling of the erythrocyte cell membrane, a phenomenon known as eryptosis [ 34 ].…”

“…The correlation between increases in CD4+ T cell counts following cART and undetectable plasma HIV-1 RNA levels has been highlighted [ 22 32 ]. However, our earlier analysis of CD4+ T cell counts and viral load suggested a discordant response [ 26 ], where despite achieving a median viral load below the detection threshold of <50 copies/mL post-cART treatment, the median CD4+ T-lymphocyte counts failed to surpass pre-treatment baselines (CD4+ T cell count increase >50 cells/mm 3 ) after six months of highly effective antiretroviral therapy, as recommended by regulatory authorities [ 26 ].…”

“…Baseline haematological and CD4+ T lymphocyte counts were assessed, followed by evaluations at 24 weeks post-commencement of combined antiretroviral therapy (cART24). Detailed socio-demographic characteristics and HIV diagnosis information have been previously documented in our earlier studies [ 25 26 ]. All participants received dolutegravir/lamivudine/tenofovir (DTG/3TC/TDF), a fixed-dose combination antiretroviral medication, in line with the 2019 WHO recommendation for first-line treatment in adults.…”

“…Haematological parameters were assessed using the Mindray 3200 Auto Haematology Analyzer (Shenzhen Mindray Bio-Medical, Shenzhen, China). The techniques employed for HIV diagnosis, viral load measurement, and CD4+ T cell count determination have been elaborated in previous publications [ 25 26 ].…”