Table_2_APOBEC3G/3A Expression in Human Immunodeficiency Virus Type 1-Infected Individuals Following Initiation of Antiretroviral Therapy Containing Cenicriviroc or Efavirenz.docx

<p>Apolipoprotein B mRNA editing enzyme catalytic polypeptide-like 3 (APOBEC3) family members are cytidine deaminases that play crucial roles in innate responses to retrovirus infection. The mechanisms by which some of these enzymes restrict human immunodeficiency virus type 1 (HIV-1) replication have been extensively investigated in vitro. However, little is known regarding how APOBEC3 proteins affect the pathogenesis of HIV-1 infection in vivo and how antiretroviral therapy influences their expression. In this work, a longitudinal analysis was performed to evaluate APOBEC3G/3A expression in peripheral blood mononuclear cells of antiretroviral-naive HIV-1-infected individuals treated with cenicriviroc (CVC) or efavirenz (EFV) at baseline and 4, 12, 24, and 48 weeks post-treatment follow-up. While APOBEC3G expression was unaffected by therapy, APOBEC3A levels increased in CVC but not EFV arm at week 48 of treatment. APOBEC3G expression correlated directly with CD4⁺ cell count and CD4⁺/CD8⁺ cell ratio, whereas APOBEC3A levels inversely correlated with plasma soluble CD14. These findings suggest that higher APOBEC3G/3A levels may be associated with protective effects against HIV-1 disease progression and chronic inflammation and warrant further studies.</p

Table_1_APOBEC3G/3A Expression in Human Immunodeficiency Virus Type 1-Infected Individuals Following Initiation of Antiretroviral Therapy Containing Cenicriviroc or Efavirenz.docx

<p>Apolipoprotein B mRNA editing enzyme catalytic polypeptide-like 3 (APOBEC3) family members are cytidine deaminases that play crucial roles in innate responses to retrovirus infection. The mechanisms by which some of these enzymes restrict human immunodeficiency virus type 1 (HIV-1) replication have been extensively investigated in vitro. However, little is known regarding how APOBEC3 proteins affect the pathogenesis of HIV-1 infection in vivo and how antiretroviral therapy influences their expression. In this work, a longitudinal analysis was performed to evaluate APOBEC3G/3A expression in peripheral blood mononuclear cells of antiretroviral-naive HIV-1-infected individuals treated with cenicriviroc (CVC) or efavirenz (EFV) at baseline and 4, 12, 24, and 48 weeks post-treatment follow-up. While APOBEC3G expression was unaffected by therapy, APOBEC3A levels increased in CVC but not EFV arm at week 48 of treatment. APOBEC3G expression correlated directly with CD4⁺ cell count and CD4⁺/CD8⁺ cell ratio, whereas APOBEC3A levels inversely correlated with plasma soluble CD14. These findings suggest that higher APOBEC3G/3A levels may be associated with protective effects against HIV-1 disease progression and chronic inflammation and warrant further studies.</p

Semiquantitative analyses of CD4+ and IL-17+ cells before (M0) and after (M8) cART.

<p>Slides of colon tissues were scored as “−” (less than 3 positive cells); “+” (3–10 positive cells); “++” (20–40 positive cells) and “+++” (more than 50 positive cells). <b>Bold:</b> samples in which both IL-17+ and CD4+ cells were increased at M8; Black: samples in which only IL-17+ cells were increased at M8; <b>Gray</b>: samples in which neither IL-17+ nor CD4+ cells were increased at M8.</p><p>Semiquantitative analyses of CD4+ and IL-17+ cells before (M0) and after (M8) cART.</p

The flowchart of the clinical trial.

<p>Experimental design of the study.</p

Effects of short-term cART on peripheral and intestinal CD4 T cell levels.

<p>Longitudinal assessment of CD4 T cells in peripheral blood (PB) and intestinal biopsy (IB) during eight months of cART treatment. The absolute number (<b>A</b>) and percentage (<b>B</b>) of PB CD4 T cells are shown before (M0) and after eight months (M8) of cART. Fold change over baseline (M0) of CD4 T cell absolute number (left) and percentage (right) is depicted in (<b>C</b>). Extent of intestinal CD4 T cells before (M0) and after (M8) cART (<b>D</b>). Positive correlation between the percentages of CD4 T cells in PB and IB atM0 (close circles) and M8 (open circles) (<b>E</b>).</p

Effects of short-term cART on microbial translocation and T cell activation/proliferation.

<p>Plasma levels of lipopolysaccharide (LPS), 16S rDNA and soluble CD14 (sCD14) before (M0) and after eight months (M8) of cART (<b>A</b>). LPS and sCD14 were measured by ELISA, while 16S rDNA by PCR. Percentages of activated (as determined by expression of CD38 and HLA-DR; left), and proliferating (as determined by expression of Ki-67) staining; right) CD4 and CD8 T cells (<b>B</b>).</p

Reconstitution of intestinal CD4 T cell inversely correlates with plasma LPS level.

<p>The reconstitution of the intestinal CD4 T cells, expressed as %M8 - %M0(Δ), inversely correlates with the reduction of plasma LPS, expressed as level at M8 - level M0 (Δ).</p

Characteristics of patient population.

<p>The characteristics of patient population at baseline including anagraphic data, transmission routes and CDC stages.</p><p>Characteristics of patient population.</p