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Objectives Chloroquine (CQ), an anti-inflammatory drug, inhibits Toll-like receptor (TLR) signalling in plasmacytoid dendritic cells (pDCs) and may be beneficial for HIV-infected patients in whom immune activation persists despite effective antiretroviral therapy (ART). The effect of CQ on CD4 T-cell recovery and immune activation in immune nonresponding patients receiving successful ART was therefore studied. Methods Nineteen adults on ART with CD4 counts ≤ 350 cells/μL and undetectable viral load (VL) orally received CQ at 250 mg/day for 24 weeks. Side effects, CD4 and CD8 T-cell counts, VL, T-cell activation, pDC proportion and plasma inflammatory markers were assessed at baseline, at 24 weeks, and at 12 weeks after CQ discontinuation (clinicaltrial.org registration #NCT02004314). Results CQ was well tolerated and all patients maintained an undetectable VL. The absolute CD4 and CD8 T-cell counts and their percentages, the pDC proportion, T-cell activation, D-dimer and C-reactive protein (CRP) plasma levels and the kynurenine/tryptophan ratio did not change with CQ treatment. Among nine cytokines/chemokines measured, only levels of interferon (IFN)-α2 were significantly increased by CQ treatment. Conclusions CQ was well tolerated in patients with low CD4 T-cell counts despite long-term effective ART; however, 24 weeks of CQ treatment did not improved CD4 T-cell recovery, lymphoid and myeloid immune activation or inflammatory markers.

Early use of highly active antiretroviral treatment (ART) in people living with HIV for HIV prevention has gained legitimacy but remains controversial. Nineteen French HIV experts with diverse specializations (over half of whom were clinicians) were qualitatively interviewed on their views about ART irrespective of CD4 count of more than 500 cells/mm3for purposes of HIV prevention, which is not systematically recommended in France. Content analysis identified 2 broad categories: individual considerations (subcategories: patient health and well-being; patient preparedness and choice) and collective considerations (subcategories: HIV transmission risk; impact on the epidemic; cost). Uncertainty surrounded many experts’ considerations, and unity was lacking on key issues (eg, candidacy for early preventive treatment, expected clinical- and population-level effects). An umbrella theme labeled “Weighing the merits of early ART in the face of uncertainties” was identified. Our analyses raise doubts about the current acceptability of widespread implementation of early ART for HIV prevention in France.

After the introduction of effective combination antiretroviral therapy (cART), more than 50% of deaths among persons infected with human immunodeficiency virus (HIV) are from causes other than acquired immune deficiency syndrome (AIDS) [1]. Overall, liver-related death, mainly due to chronic infection with hepatitis C virus (HCV) or hepatitis B virus, represents the most frequent cause of non-AIDS-related death [2]. Human immunodeficiency virus mono-infected persons are also at risk for liver disease from multiple cofactors, including insulin resistance, long-term use of cART, and HIV hepatotoxicity [3, 4]. Hepatic steatosis is a common liver disease in Western countries associated with metabolic abnormalities [5, 6]. Cross-sectional studies reported it in up to 40% of HIV mono-infected patients [3]. Hepatic steatosis is the first pathophysiological step for nonalcoholic steatohepatitis (NASH), a progressive liver disease leading to cirrhosis and related complications [6]. Liver fibrosis is the hallmark of a progressive disease that can lead to cirrhosis, hepatic failure, and hepatocellular carcinoma (HCC) [7]. Liver fibrosis may be as frequent as 8% in HIV mono-infected patients [8]. Liver biopsy has long been the gold standard to assess hepatic steatosis and fibrosis. However, this procedure is invasive, costly, impractical as a screening tool, and prone to sampling error [9]. The burden of liver disease in HIV mono-infected persons may not be fully appreciated because of the drawbacks of liver biopsy and its underutilization. As such, data on incident hepatic steatosis and fibrosis and associated predictors in HIV mono-infection are lacking. Recently, noninvasive serum biomarkers have been implemented in place of liver biopsy. Validated fibrosis biomarkers include fibrosis-4 (FIB-4) index, based on aspartate aminotransferase (AST), alanine aminotransferase (ALT), platelets, and age, as well as AST-to-Platelet Ration Index (APRI) [10, 11]. These biomarkers are based on routine parameters and have been validated in the setting of HIV infection, where their accuracy to assess liver fibrosis ranges from 65% to 90% [7, 12]. Lee et al [13] have proposed an index named hepatic steatosis index (HSI), based on transaminases, body mass index (BMI), gender, and absence or presence of diabetes. This biomarker has been validated in more than 10 000 apparently healthy individuals, with a sensitivity of 93.1% and a specificity of 92.4% to diagnose hepatic steatosis when compared with ultrasound [13]. Most of the previous studies on hepatic steatosis and fibrosis in HIV mono-infected patients had a cross-sectional design, so they captured prevalence and associated risk factors at a single time point. Because hepatic steatosis and fibrosis are chronic processes, longitudinal studies are more suitable to capture dynamic changes. Moreover, no study has employed a simple serum biomarker to evaluate hepatic steatosis in HIV mono-infected patients. The aim of this study was to investigate incidence and predictors of hepatic steatosis and fibrosis in a large cohort of well characterized HIV mono-infected persons by using validated serum biomarkers. We also validated for the first time HSI versus liver ultrasound in the specific context of HIV mono-infection. To our knowledge, this is the first large-scale longitudinal study designed to investigate incident hepatic steatosis in HIV mono-infection.

Dendritic cells (DCs) modulate B-cell survival and differentiation, mainly through production of growth factors such as B lymphocyte stimulator (BLyS; also known as "B-cell factor belonging to the tumor necrosis factor family" [BAFF]). We have recently shown that, in human immunodeficiency virus (HIV)-infected individuals with rapid and those with classic disease progression, B-cell dysregulations were associated with increased BLyS expression in plasma and by blood myeloid DCs (mDCs), in contrast to aviremic HIV-infected individuals with slow disease progression (also known as "elite controllers"). In previous work with transgenic mice expressing HIV genes, B-cell dysregulations were concomitant with altered mDCs and dependent on HIV negative factor (Nef). We now report that HIV Nef is detected early after infection and despite successful therapy in plasma and BLyS-overexpressing blood mDCs of HIV-infected rapid and classic progressors, whereas it is low to undetectable in aviremic slow progressors. In vitro, HIV Nef drives monocyte-derived DCs toward BLyS overexpression through a process involving STAT1. Importantly, this is counteracted in the presence of all-trans retinoic acid. Nef thus contributes to high BLyS proinflammatory profiles in HIV-infected individuals.

Objectives To examine the relationship between levels of the T-cell regulatory cytokine interleukin-7 (IL-7) and CD4 cell counts during immune reconstitution and to assess its prognostic value in advanced HIV-1-infected patients receiving lopinavir/ritonavir-based therapy. Methods Thirty-six HIV-1-infected adults who completed 48 weeks of follow-up visits were included in this prospective study. Patients having failed two or more antiretroviral therapy regimens were treated with lopinavir/ritonavir-based therapy. An enzyme-linked immunosorbent assay was used to determine IL-7 plasma levels, flow cytometry was used to analyse cell surface antigens, and polymerase chain reaction was used to quantify plasma HIV-1. Results Pretreatment IL-7 levels were elevated in all patients (mean 11.0 pg/mL) and were negatively correlated with CD4 cell counts and age (r=−0.59, P

Background The level of HIV-1 integrated DNA in CD4 T cells was reported to predict the evolution of untreated HIV-1 infection independently of CD4 cell counts or plasma HIV-1 RNA levels. However, the relevance of reservoir level while on efficient antiretroviral therapy (ART) is still unknown. Objectives To evaluate factors that may contribute to the establishment and maintenance of HIV-1 reservoir size in ART-treated HIV-1-infected adults with complete suppression of viremia. Study design 35 subjects receiving ART with plasma HIV-1 RNA below the limit of detection for an average duration of 3.2 years were studied. A highly sensitive PCR was used to assess HIV-1 integrated DNA levels in sorted CD4 T cells. Results The mean HIV-1 integrated DNA was 300 ± 7 copies/10 6 CD4 cells (range 10–1408). In univariate analysis, the levels of HIV-1 proviral DNA appeared to be independent of duration of HIV-1-infection, duration on ART, time since HIV-1 viral load was undetectable, delay between HIV-1 infection and starting ART, or viral load before starting ART. Conversely, CD4 T cell nadir, CD4/CD8 ratio and, to lesser degree, CD4 T cell counts were inversely associated with HIV-1 proviral DNA levels. In multivariate analysis, only CD4 T cell nadir significantly predicted levels of HIV-1 proviral DNA ( P = 0.025). Conclusions CD4 T cell nadir strongly predicted reservoir size independently of other factors in HIV-1-infected adults with complete suppression of viremia. Collectively, these results indicate that the extent of CD4 T cell depletion before ART drives the size of the viral reservoir after prolonged therapy.

Antiretroviral-naive HIV-1-infected volunteers received zidovudine/lamivudine plus either lopinavir/ritonavir (n = 104) or efavirenz (n = 51). Lopinavir/ritonavir-treated subjects demonstrating 3 consecutive monthly HIV-1 RNA levels

Infection of a newly described human T lymphoid cell line, CEM-CL10, with three different variants of HIV-1 resulted in cytopathic effects followed by cell lysis. Following primary lytic infection, proviral DNA could not be detected by Southern blot analysis in the outgrowth of the surviving CEM-CL 10 cells 60 days after initial exposure to HIV-1. These surviving cells could be further grown as a separate line, derived from CEM-CL10, and were found to be resistant to subsequent infection by HIV-1. A marked decrease in CD4 antigen expression was observed in these latter cells but not of the CD3 and transferrin receptor antigens. This decline in cell surface CD4 expression was correlated with both an absence of specific CD4 mRNA and with changes in structure of the CD4 gene. Both the HIV-1-sensitive CEM-CL10 cell line and its CD4(-), HIV-1-resistant derivative line, will be made available to interested investigators.

Methods Plasma and Peripheral blood mononuclear cells (PBMCs) were longitudinally collected in 41 PHI patients (infection