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

Kaplan-Meier child survival analysis according to baseline maternal CD4+ count (above or below 350/mm³).

<p>Kaplan-Meier child survival analysis according to baseline maternal CD4+ count (above or below 350/mm³).</p

Retention in Care of Adult HIV Patients Initiating Antiretroviral Therapy in Tigray, Ethiopia: A Prospective Observational Cohort Study

<div><p>Introduction</p><p>Although Ethiopia has been scaling up the antiretroviral therapy (ART) services, low retention in care of patients remains one of the main obstacles to treatment success. We report data on retention in care and its associated determinants in Tigray, Ethiopia.</p><p>Methods</p><p>We used data from the CASA project, a prospective observational and multi-site study of a cohort of HIV-infected patients who initiated ART for the first time in Tigray. Four participating health facilities (HFs) located in the South of Tigray were considered for this study. Patients were followed for one year after ART initiation. The main outcome measure was represented by the current retention in care, defined as the proportion of patients who were alive and receiving ART at the same HF one year after ART initiation. Patients who started ART between January 1, 2013 and December 31, 2013 were included in this analysis. Patients were followed for one year after ART initiation. The determinants of retention were analysed using univariate and multivariate Cox Proportional Hazards model with robust sandwich estimates to account for within HF correlation.</p><p>Results</p><p>The four participating HFs in Tigray were able to retain overall 85.1% of their patients after one year from starting ART. Loss to follow-up (5.5%) and transfers to other HF (6.6) were the main determinant of attrition. A multivariate analysis shows that the factors significantly associated with retention were the type of HF, gender and active TB. Alamata health center was the HF with the highest attrition rate (HR 2.99, 95% CI: 2.77–3.23). Active TB (HR 1.72, 95% CI: 1.23–2.41) and gender (HR 1.64, 95% CI: 1.10–2.56) were also significantly associated with attrition.</p><p>Conclusions</p><p>Although Ethiopia has significantly improved access to the ART program, achieving and maintaining a satisfactory long-term retention rate is a future goal. This is difficult because of different retention rates among HFs. Moreover specific interventions should be directed to people of different sex to improve retention in care in male population.</p></div

Cohort profile.

<p>Cohort profile.</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

Treatment outcomes of HIV+ patients one year after ART initiation, year 2013/2014

<p>Treatment outcomes of HIV+ patients one year after ART initiation, year 2013/2014</p

The flowchart of the clinical trial.

<p>Experimental design of the study.</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