interleukin-8 and efavirenz

Persistent immune activation and inflammation are lying behind HIV-infection even in the setting of ART mediated viral suppression. The purpose of this study is to define the in vivo effect of two first-line ART regimens on certain inflammatory mediators in male HIV patients.. Male, naive, HIV-infected volunteers were assigned either to tenofovir-DF/emtricitabine/efavirenz (Group_T) or abacavir/lamivudine/efavirenz (Group_A). Platelet Activating Factor (PAF) levels and metabolic enzymes together with HIV-implicated cytokines (IL-1beta, IL-6, IL-8, IL-10, IL-12p70, TNFa) and VEGF were determined for a 12-month period. Differences within each group were determined by non-parametric Friedman and Wilcoxon test, while the differences between the groups were checked by ANOVA repeated measures.. Both ART regimens present pronounced effect on inflammatory mediators, resulting in decreased PAF levels and Lipoprotein-associated phospholipase A2 (Lp-PLA2) activity for tenofovir-containing regimen and same as baseline PAF levels with a peak though at the 3rd month as well as elevated Lp-PLA2 activity for abacavir-containing regimen.. Studies regarding the effect of first-line ART regimens on inflammation may be beneficial in preventing chronic morbidities during HIV-treatment. From this point of view, the present study suggests an anti-inflammatory effect of tenofovir-containing ART, while the temporary increase of PAF levels in abacavir-containing ART may be the link between the reported cardiovascular risk and abacavir administration.

Topics: Adenine; Adult; Alkynes; Animals; Anti-HIV Agents; Benzoxazines; Cyclopropanes; HIV Infections; Humans; Interleukin-10; Interleukin-6; Interleukin-8; Lamivudine; Male; Middle Aged; Organophosphonates; Platelet Activating Factor; Tenofovir; Tumor Necrosis Factor-alpha

CCL2 (MCP-1) is a proinflammatory chemokine induced in HIV-1 infection. We have previously demonstrated a significant correlation of CCL2 gene expression with HIV-1 viremia. In this study we investigated the effect of prednisolone on CCL2 gene expression and viral load in an HIV-1-infected patient receiving high-dose prednisolone for severe uveitis. We observed a >1 log reduction of HIV-1 viral load, associated with more than hundred fold reduction of CCL2 expression at day 3 of prednisolone treatment. In vitro HIV-1 infection of PBMC demonstrated reduced HIV-1 replication in the presence of prednisolone. Flow cytometric analysis revealed 50% reduction of LTR driven GFP activity by prednisolone in GHOST cells. These findings indicate that prednisolone suppresses both HIV-1 viral load and CCL2 mRNA expression, an association which might be exploited for future anti-inflammatory therapeutic strategies in HIV-1 infection.

Topics: Alkynes; Anti-HIV Agents; Anti-Inflammatory Agents; Benzoxazines; Chemokine CCL2; Cyclopropanes; Drug Resistance, Viral; Flow Cytometry; Gene Expression; HIV Infections; HIV-1; Humans; In Vitro Techniques; Interleukin-8; Lamivudine; Male; Prednisolone; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; Tumor Necrosis Factor-alpha; Uveitis; Viral Load; Viremia; Zidovudine