efavirenz--emtricitabine--tenofovir-disoproxil-fumarate-drug-combination and Inflammation

BIT225 is a first-in-class inhibitor of human immunodeficiency virus (HIV) type 1 Vpu. A phase II trial enrolled 36 HIV-1-infected, treatment-naive participants in Thailand to receive standard-of-care antiretroviral therapy (ART), tenofovir disoproxil fumarate/emtricitabine/efavirenz (Atripla), with 100 or 200 mg of BIT225 or placebo (daily) for 12 weeks. Combined treatment with BIT225 and ART was found to be generally safe and well tolerated, with antiviral efficacy comparable to that of ART alone. The secondary end point-soluble CD163, a marker of monocyte/macrophage inflammation-was noted to be significantly decreased in the BIT225 arm. Plasma-derived activated CD4+ and CD8+ T cells, natural killer cells, and interleukin 21 were increased in those treated with BIT225. These findings are consistent with inhibition of the known effects of HIV Vpu and may reflect clinically important modulation of inflammatory and immune function. Further clinical study is planned to both confirm and extend these important findings in treatment-naive, and treatment-experienced individuals. Clinical Trials Registration. Australian New Zealand Clinical Trials Registry (Universal Trial Number U1111-1191-2194).

Topics: Anti-HIV Agents; Australia; CD4-Positive T-Lymphocytes; CD8-Positive T-Lymphocytes; Drug Therapy, Combination; Efavirenz, Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination; Guanidines; HIV Infections; HIV-1; Human Immunodeficiency Virus Proteins; Humans; Inflammation; Pyrazoles; Thailand; Viral Regulatory and Accessory Proteins; Viroporin Proteins

We performed a randomized controlled trial in 30 HIV-infected participants to either continue tenofovir/emtricitabine/efavirenz (Continuation Group) or switch to tenofovir/emtricitabine/raltegravir (Switch Group) for 24 weeks. There were no significant differences in the changes in flow-mediated dilation, 25(OH) vitamin D, or parathyroid hormone levels. Total cholesterol, high sensitivity C-reactive protein, serum alkaline phosphatase, sCD14 levels, and renal function significantly declined in the Switch Group compared with the Continuation Group; however, sCD163 levels significantly increased in the Switch Group. These findings suggest that raltegravir is not inherently more beneficial to endothelial function compared with efavirenz but may impact renal function and monocyte activation.

Topics: Adenine; Adult; Alkaline Phosphatase; Anti-HIV Agents; Biomarkers; Bone and Bones; C-Reactive Protein; Cholesterol; Deoxycytidine; Drug Combinations; Efavirenz, Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination; Endothelium, Vascular; Female; HIV Infections; Humans; Indiana; Inflammation; Male; Organophosphonates; Oxazines; Pyrrolidinones; Raltegravir Potassium; Renal Insufficiency; Treatment Outcome; Viral Load