Metabolic disease in HIV infection Lake, Jordan E, MD; Currier, Judith S, Prof
The Lancet infectious diseases,
11/2013, Volume:
13, Issue:
11
Journal Article
Peer reviewed
Summary The treatment of metabolic disease is becoming an increasingly important component of the long-term management of patients with well controlled HIV on antiretroviral therapy (ART). Metabolic ...diseases probably develop at the intersection of traditional risk factors (such as obesity, tobacco use, and genetic predisposition) and HIV-specific and ART-specific contributors (including chronic inflammation and immune activation). This Review discusses present knowledge on adipose tissue dysfunction, insulin–glucose homoeostasis, lipid disturbances, and cardiovascular disease risk in people with HIV on ART. Although new antiretroviral drugs are believed to induce fewer short-term metabolic perturbations than do older drugs, the long-term effects of these drugs are not fully understood. Additionally, patients remain at increased risk of cardiovascular disease and other metabolic comorbidities. Research and treatment should focus on selection of ART that is both virologically effective and has minimum metabolic effects, minimisation of traditional risk factors for metabolic disease, and development of novel therapies to treat metabolic disease in patients with HIV, including use of anti-inflammatory and immunomodulatory drugs.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Background Persistent immune activation and inflammation in virologically suppressed human immunodeficiency virus (HIV) infection are linked to excess cardiovascular risk. Objective To evaluate ...atorvastatin as a strategy to reduce cardiovascular risk. Methods A5275 was a multicenter, prospective, randomized, double-blind, placebo-controlled, cross-over pilot study of atorvastatin (10 mg/day for 4 weeks then 20 mg/day for 16 weeks) with a planned enrollment of 97 HIV-infected participants ≥18 years old, receiving boosted protease inhibitor–based antiretroviral therapy for ≥6 months, with plasma HIV-1 RNAs below limits of quantification ≥180 days, and fasting low-density lipoprotein (LDL) cholesterol ≥70 and <130 mg/dL. Primary endpoints were differences of changes (week 44–week 24–week 20–baseline) in CD4+ and CD8+ T-lymphocyte activation (% CD38+ /DR+ ) and plasma levels of IL-6 and D-dimer. Arms were compared using the Wilcoxon rank-sum tests and also summarized changes pre-to-post atorvastatin treatment. Analyses were as-treated. Results Ninety-eight participants were enrolled at 31 U S sites and 73 completed study treatment. Atorvastatin treatment did not decrease T-lymphocyte or monocyte activation, circulating biomarker levels (interleukin-6, D-dimer, soluble CD14, soluble CD163, monocyte chemoattractant protein-1, interferon-gamma–induced protein-10, high-sensitivity C-reactive protein, CD40L, and P-selectin) or white blood cell Krüppel-like Factor 2/4 messenger RNA levels. Pre-to-post atorvastatin reductions in calculated LDL (−38%), oxidized-LDL (−33%), and lipoprotein-associated phospholipase A2 (−31%) were significant ( P < .01). Conclusion In virologically suppressed individuals with HIV infection, atorvastatin did not significantly decrease levels of soluble or cellular biomarkers of immune activation and inflammation but resulted in robust reductions in LDL cholesterol, oxLDL, and lipoprotein-associated phospholipase A2 , biomarkers associated with cardiovascular risk.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
Transgender women's (TW) social networks may facilitate HIV prevention information dissemination and normative reinforcement. We conducted a qualitative study of social networks among 20 TW ...affiliated with 3 “casas trans” (houses shared among TW) in Lima, Peru, using diffusion of innovations theory to investigate community-level HIV prevention norms. Participants completed demographic questionnaires, social network interviews, and semistructured in-depth interviews. Median age was 26 and all participants engaged in sex work. Interviews revealed high HIV prevention knowledge and positive attitudes, but low engagement in HIV prevention. Respondents primarily discussed HIV prevention with other TW. Network members’ opinions about pre-exposure prophylaxis (PrEP) frequently influenced respondents’ personal beliefs, including mistrust of healthcare personnel, concern that PrEP efficacy was unproven, fear of adverse effects, and frustration regarding difficulty accessing PrEP. Patterns of influence in TW networks may be leveraged to improve uptake of HIV prevention tools, including PrEP.
BACKGROUNDGonorrhea (Neisseria gonorrhoeae GC) and chlamydia (Chlamydia trachomatis CT) disproportionately affect men who have sex with men (MSM), and public health implications vary by anatomic site ...and bacterial agent. Urethral and rectal GC and CT can increase risk of HIV transmission, whereas pharyngeal GC may be a reservoir for antimicrobial resistance. To define screening priorities in Latin America, we compare differences in the prevalence and correlates of urethral, pharyngeal, and rectal GC and CT among MSM in Peru.
METHODSA cross-sectional sample of 787 MSM from Lima was screened between 2012 and 2014. We described prevalence of urethral, pharyngeal, and rectal GC and CT infection and conducted bivariate analyses of associations with social, behavioral, and biological characteristics. Poisson regression analyses assessed the correlates of each infection at each anatomic site.
RESULTSThe most commonly symptomatic infection (urethral GC; 42.1%) was the least prevalent (2.4%). The most prevalent infections were rectal CT (15.8%) and pharyngeal GC (9.9%). Rectal CT was the least commonly symptomatic (2.4%) infection, and was associated with younger age (adjusted prevalence ratio 95% confidence interval, 0.96 0.94–0.98), HIV infection (1.46 1.06–2.02), and pasivo (receptive; 3.59 1.62–7.95) and moderno (versatile; 2.63 1.23–5.60) sexual roles.
CONCLUSIONSResults highlight limitations of current syndromic screening strategies for sexually transmitted diseases in Peru, wherein urethral CT and rectal GC and CT may be missed due to their frequently asymptomatic presentations. Successful management of GC and CT infections among MSM in low-resource settings requires differentiating between bacterial agent, symptomatic presentation, associated risk factors, and public health implications of untreated infection at different anatomic sites.
Non-antiviral therapeutic options are required for the treatment of hospitalised patients with COVID-19. CD24Fc is an immunomodulator with potential to reduce the exaggerated inflammatory response to ...tissue injuries. We aimed to evaluate the safety and efficacy of CD24Fc in hospitalised adults with COVID-19 receiving oxygen support.
We conducted a randomised, double-blind, placebo-controlled, phase 3 study at nine medical centres in the USA. Hospitalised patients (age ≥18 years) with confirmed SARS-CoV-2 infection who were receiving oxygen support and standard of care were randomly assigned (1:1) by site-stratified block randomisation to receive a single intravenous infusion of CD24Fc 480 mg or placebo. The study funder, investigators, and patients were masked to treatment group assignment. The primary endpoint was time to clinical improvement over 28 days, defined as time that elapsed between a baseline National Institute of Allergy and Infectious Diseases ordinal scale score of 2–4 and reaching a score of 5 or higher or hospital discharge. The prespecified primary interim analysis was done when 146 participants reached the time to clinical improvement endpoint. Efficacy was assessed in the intention-to-treat population. Safety was assessed in the as-treated population. This study is registered with ClinicalTrials.gov, NCT04317040.
Between April 24 and Sept 22, 2020, 243 hospitalised patients were assessed for eligibility and 234 were enrolled and randomly assigned to receive CD24Fc (n=116) or placebo (n=118). The prespecified interim analysis was done when 146 participants reached the time to clinical improvement endpoint among 197 randomised participants. In the interim analysis, the 28-day clinical improvement rate was 82% (81 of 99) for CD24Fc versus 66% (65 of 98) for placebo; median time to clinical improvement was 6·0 days (95% CI 5·0–8·0) in the CD24Fc group versus 10·0 days (7·0–15·0) in the placebo group (hazard ratio HR 1·61, 95% CI 1·16–2·23; log-rank p=0·0028, which crossed the prespecified efficacy boundary α=0·0147). 37 participants were randomly assigned after the interim analysis data cutoff date; among the 234 randomised participants, median time to clinical improvement was 6·0 days (95% CI 5·0–9·0) in the CD24Fc group versus 10·5 days (7·0–15·0) in the placebo group (HR 1·40, 95% CI 1·02–1·92; log-rank p=0·037). The proportion of participants with disease progression within 28 days was 19% (22 of 116) in the CD24Fc group versus 31% (36 of 118) in the placebo group (HR 0·56, 95% CI 0·33–0·95; unadjusted p=0·031). The incidences of adverse events and serious adverse events were similar in both groups. No treatment-related adverse events were observed.
CD24Fc is generally well tolerated and accelerates clinical improvement of hospitalised patients with COVID-19 who are receiving oxygen support. These data suggest that targeting inflammation in response to tissue injuries might provide a therapeutic option for patients hospitalised with COVID-19.
Merck & Co, National Cancer Institute, OncoImmune.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
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