Evaluation of several serum interleukins as markers for treatment effectiveness in naïve HIV infected patients: A pilot study.

Cristian Jianu,Sorana D Bolboacă,Corina Itu-Mureşan,Mihaela Elena Jianu,Cristina Drugan,Irina Filipescu,Ioana Iulia Morar,Adriana Violeta Topan,Cristian Apetrei

doi:10.1371/journal.pone.0260007

Abstract

In this observational pilot study, we investigated the impact of Dolutegravir, Raltegravir, Elvitegravir (Integrase Strand Transfer Inhibitors, INSTIs), or boosted Darunavir (a Protease Inhibitor, PI) in combination with two nucleoside reverstranscriptase inhibitors (Emtricitabine/Tenofovir disoproxil or Lamivudine/Tenofovir disoproxil, NRTI) on four interleukins (IL-4, IL-10, IL-13, and IL-21) as immune activation markers in naïve HIV(Human Immunodeficiency Virus)-infected patients during the first six months of combined standard-of-care antiretroviral therapy (cART). Newly diagnosed with HIV-infected subjects and without any disease that could affect the immune activation markers were evaluated. The patients’ physicians recommended the cART as standard-of-care and the ILs were measured before cART and six months of cART. The levels of CD4+ T-cells count and CD4+/CD8+ ratio significantly increased at six months (P-value<0.02) regardless of the drugs, INSTIs or PI. However, a CD4+/CD8+ >1 was observed in 25% of patients treated with Raltegravir and half of those treated with Dolutegravir. At six months of cART, viral load was detectable in only 6/31 individuals. IL-21 had an undetectable level in 30/31 patients after six months of cART. Our results suggest the potency in restoring immune markers in HIV-infected patients with all investigated drugs. Dolutegravir showed a tendency to statistically significant changes in IL-4 and IL-10. A clinical trial with random allocation of medication and an extensive follow-up is needed to replicate this research and validate the usefulness of evaluated ILs as markers of cART effectiveness.

Highlights

Infection with human immunodeficiency virus (HIV) is an important public health problem all over the world
Our pilot study found that IL-13 levels were undetectable for 2/4 of patients treated with Dolutegravir and all patients treated with Elvitegravir (Table 5)
Our study suggests a potency in restoring immune markers in HIV-infected patients with all investigated drugs

Summary

Introduction

Infection with human immunodeficiency virus (HIV) is an important public health problem all over the world. Manifestations, and the infected persons can spread the virus unwittingly This issue affects public health policies and represents the main barrier to HIV pandemic control. A chronic inflammatory response characteristic to HIV infection is seen in the absence of an efficient viral response and elimination of the virus. This chronic inflammation is associated with functional changes of immune cells [15], a decrease in antiviral response [16], failure of immune reconstruction under cART [17], and organ damage [18]. The immune activation mechanism in HIV infection is explained by persistent viral replication, loss of the gut mucosa’s integrity, and increased proinflammatory cytokines. Our pilot observational study aimed to investigate the effects of standard-of-care cART on four markers of immune activation, namely IL-4, IL-10, IL-13, and IL-21 evaluated before and at six- months of cART

Study design and data sources

Results

Discussion

Conclusions