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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.

Given international interest in "treatment as prevention" (TasP) and the pertinence of optimizing antiretroviral treatment (ART) regimens for TasP, 19 French HIV experts were interviewed on their criteria for ART if used specifically for prevention with HIV-positive persons. Through content analysis of the interview material, nine criteria were identified. The most endorsed criteria, collectively, suggest a choice of treatment based on "minimal interference" where negative impacts of ART are minimized and ease of treatment integration maximized in the lives of people living with HIV/AIDS (PLHIV) for both the short and long term. These criteria were the tolerance, side effects, and/or toxicity profile of ART, simplicity (e.g., of treatment schedule, dosage form) and the individualization of treatment (e.g., adapted to lifestyle). While virologic efficacy (i.e., a durable, undetectable viral load) was also deemed important, several experts specified that it was virtually assured with current treatments. To a much lesser extent, experts endorsed diffusion of ART into the genital compartments, a strong genetic barrier (against resistance), validated treatments (as opposed to new classes of ART), a rapid reduction in HIV viral load, and treatment cost. Pharmacologically, minimal interference calls for further improvements in the tolerance, side effects and toxicity profile of ART and in the simplicity of ART administration. Clinically, it means avoiding a one-size-fits-all approach to ART in TasP and engagement with and of PLHIV in ART selection and side effects management. Strategically, it emphasises keeping the health and quality of life of PLHIV at the forefront of a TasP-oriented public health intervention.

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.

The decision by blood agencies in many developed countries to defer the donation of blood by men who have sex with men was justified when it was first implemented, in 1983, given that there was no effective mechanism to screen for HIV infection until screening for HIV antibodies became available in

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.

We investigated the effect of dyslipidemia associated with highly active antiretroviral therapy on cardiovascular risk and life expectancy among patients who had the human immunodeficiency virus. Dyslipidemia estimates were based on results from a phase 2 randomized trial that compared lipid changes after 32 weeks of therapy with atazanavir with those with nelfinavir (each in combination with stavudine and lamivudine). The resultant increased coronary risk was estimated using Framingham risk equations, and change in life expectancy (after adjustment for mortality due to human immunodeficiency virus) was based on the cardiovascular life expectancy model, which is based on a published Markov's model. Levels of total cholesterol and low-density lipoprotein cholesterol increased significantly more among patients who used nelfinavir (+24% and +28%) than among those who used atazanavir (+4% and +1%). This dyslipidemia increased the risk of coronary disease by 50% over 10 years. The absence of dyslipidemia was estimated to preserve life expectancy 0.15 to 1.53 additional years depending on a patient's age, gender, and other risk factors. There are increasing reports of dyslipidemia and cardiovascular events associated with highly active antiretroviral therapy. Significant increases in blood lipid levels observed with some protease inhibitors are associated with an increase in calculated 10-year coronary risk. Accordingly, minimizing dyslipidemia associated with highly active antiretroviral therapy may preserve life expectancy among adults who have the human immunodeficiency virus.

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

Errors occurred in Table 2. The correct values for the last row IL-6 (pg/ml) in Table 2 are incorrect. The correct values are: ST : 1.94±0.81, ART-Naive: 3.61±0.71, EC: 1.37±0.30, HS: 1.26±0.27, p value: 0.0089

To evaluate the nursing care needs of patients admitted to the hospital for complications of AIDS, we compared the estimated nursing care requirements of AIDS patients with non-AIDS patients at the...

This review of the human immunodeficiency virus (HIV) epidemic shows that HIV has had and will have a major impact on dentistry, just as it has had on so many other aspects of medical practice and society. These areas include the prevention of HIV transmission in the dental care workplace, the early and safe care and treatment of those who are infected, and the protection of those who are vulnerable or made more vulnerable because of HIV infection. To do this, the dental professional must be educated about HIV and its diseases, their treatment, and what must be done to prevent HIV transmission. Early recognition and treatment of HIV-related oral diseases have become the norms of practice today. Although more and more dentists face potential exposure to HIV, excellent dental care can be provided while minimizing this risk.

The growing importance of and demand for human immunodeficiency virus (HIV) antibody testing [ 1 ] and the complex medical, psychological, ethical and social issues this testing raises [2] require physicians to be prepared to counsel their patients about HIV infection and antibody testing. Since medical literature contains little in the way of specific guidelines for counselling and education relating to HIV antibody testing, this book has been prepared to provide physicians and other health care professionals with this information. It discusses the serologic tests, requirements for testing, pretest and post-test procedures, and relevant Canadian Medical Association policies [ 31.

Provision of nourishment to terminally ill patients has been a controversial topic in clinical medicine. Determination of the limits of palliative care requires an understanding of the disease process, as well as the boundaries of patient self-determination. With the advent of living wills, the determination of the patient to limit care, including nutrition support, has become socially acceptable. Difficulties arise when there are differences of opinion between the caregiver and the patient. The solutions to these conflicts are often decided in the courtroom, as demonstrated by the Cruzan and Quinlan cases. Living wills are often written to prevent unnecessary financial burdens in hopeless situations. As well, financial considerations influence the decisions made by caregivers in providing care to terminally ill patients. The following case report illustrates the conflict between patient self-determination and limitation of care for financial reasons. The use of substituted judgment within the Canadian health care system and the role of team meetings to resolve ethical decisions are discussed.

Cold stress by increasing circulating catecholamines may sensitize blood platelets to aggregate and release their constituents. This study investigates the effect of cold stress on the release of the platelet-specific protein beta-thromboglobulin into the coronary venous blood of 12 subjects with atherosclerotic coronary artery disease (CAD) and 7 subjects with angiographically normal coronary arteries (NCA). Cold pressor stress caused a greater increase in systolic arterial pressure in patients with CAD than in subjects with NCA (p less than 0.05). There was no significant difference between the platelet counts in the arterial or coronary venous blood either before or during cold stress. Arterial beta-thromboglobulin was higher in the group with CAD (77 +/- 18 ng/ml) than in subjects with NCA (49 +/- 12 ng/ml, p less than 0.01). Although there was no arteriovenous difference of beta-thromboglobulin at rest in either group, during cold stress, coronary venous beta-thromboglobulin increased in both the NCA (53 +/- 16 to 95 +/- 26 ng/ml, p less than 0.05) and CAD groups (76 +/- 13 to 117 +/- 53 ng/ml, p less than 0.025) despite no change in arterial beta-thromboglobulin. Release of beta-thromboglobulin, although not related to the presence of angiographic arterial disease, correlated with the systolic arterial pressure during cold stress (r = 0.66) and inversely with the platelet's ability to generate cyclic adenosine monophosphate (r = 0.69). The release of platelet constituents in the coronary circulation is provoked by cold stress and may play a role in stress-induced acute coronary occlusion in patients with atherosclerotic disease and in those with apparently normal vessels.

To determine if vesicular rosettes (VR), tubuloreticular structures (TRS), and "test-tube and ring-shaped forms" (TRF) are characteristic ultrastructural features of the syndromes of acquired immune deficiency (AIDS) or of unexplained persistent lymphadenopathy (PLS), the authors studied lymph nodes from nine patients with PLS, two patients with AIDS, and seven controls by electron microscopy. An average of 122 lymphocytes per case were photographed. VR were present in only 0.37% of lymphocytes in 4 of 11 index cases and were mimicked by grouped vesicles and degenerating multivesicular bodies (MVB). TRS were found in 10 of 11 index cases, compared with only one of seven controls (P less than 0.01). In the index cases, they were more frequent in AIDS (mean 21%) than in PLS lymphocytes (mean 4%) (P less than 0.05). MVB were found in all index cases and five of seven controls and were more frequent in index lymphocytes (mean 19%) than in controls (mean 5%) (P less than 0.01). TRF were found in one Haitian male with AIDS, where they were present in 4% of lymphocytes. VR are infrequent and indistinct. MVB probably reflect the reactivity of the lymphocytes. TRF is not a feature of PLS. The authors conclude that there are no pathognomonic ultrastructural markers of AIDS or PLS but that TRS are characteristic of both syndromes and occur frequently enough to be supportive to the diagnosis of AIDS and PLS.

The article addresses some of the issues raised in federal correctional institutions by the generation and communication of personal medical information pertaining the HIV infection. It examines, first, whether medical information pertaining to federal inmates — information considered confidential between medical staff and an inmate — can be disclosed absent the inmate's consent. It then examines what conditions or criteria determine whether or not such disclosure is ethically and legally justifiable, and if disclosure is justified, what conditions apply to its disclosure. Finally, specific situations in which a claim for disclosure may arise are examined. The article concludes that in federal correctional institutions, the disclosure of personal medical information absent consent of the person is seldom justifiable. In most situations, such disclosure is unnecessary and even appears to be counterproductive or harmful. Measures that can be undertaken to prevent exposure to and infection with HIV have to be undertaken regardless of whether an inmate or staff member is or is not known, to staff, wardens, or inmates, to be infected with HIV.

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