Dataset Information

Effect of Zinc Supplementation vs Placebo on Mortality Risk and HIV Disease Progression Among HIV-Positive Adults With Heavy Alcohol Use: A Randomized Clinical Trial.

ABSTRACT: Importance:Zinc supplementation can reduce alcohol-related microbial translocation and inflammation. Objective:To assess whether zinc supplementation reduces markers of mortality and risk of cardiovascular disease, reduces levels of inflammation and microbial translocation, and slows HIV disease progression in people with heavy alcohol use who are living with HIV/AIDS. Design, Setting, and Participants:This study is a double-blinded placebo-controlled randomized clinical trial of zinc supplementation among participants recruited from 2013 to 2015. Participants were recruited from HIV and addiction clinical and nonclinical care sites in St Petersburg, Russia. Participants were adults (aged 18-70 years) with documented HIV infection who were antiretroviral therapy-naive at baseline and had past 30-day heavy alcohol consumption. Data analysis was performed from February 2017 to February 2020. Intervention:Pharmacy-grade zinc gluconate supplementation (15 mg for men and 12 mg for women, taken daily by mouth for 18 months) was compared with a placebo. Main Outcomes and Measures:The primary outcome was mortality risk measured as a change in Veterans Aging Cohort Study (VACS) Index score between baseline and 18 months. The VACS Index scores range from 0 to 164, with higher scores indicating higher mortality risk. Secondary outcomes were change in CD4 cell count between baseline and 18 months, the assessment of cardiovascular disease risk (Reynolds Risk Score, which ranges from 0% to 100%, with higher scores indicating higher risk), and changes in inflammatory or microbial translocation biomarkers at 18 months. Adjusted linear regression analyses were performed. Results:A total of 254 participants (184 men [72%]; mean [SD] age, 34 [6] years) were enrolled in the trial; 126 were randomized to receive zinc, and 128 were randomized to receive placebo. Participants had high CD4 cell counts (mean [SD], 521 [292] cells/mm3), and 188 (74%) reported heavy drinking in the past week. In the main analyses, zinc supplementation did not affect changes in the VACS Index score at 18 months (change for zinc, mean [SD], 0.49 [14.6]; median [interquartile range], 0.0 [-7.0 to 6.0]; change for placebo, mean [SD], 5.5 [17.2]; median [interquartile range], 6.0 [-6.0 to 14.0]; adjusted mean difference [AMD], -4.68; 95% CI,?-9.62 to 0.25; P?=?.06) or any secondary outcomes, including change in CD4 cell count (AMD, 41.8 cells/mm3; 95% CI,?-20.3 to 103.8 cells/mm3; P?=?.19), Reynolds Risk Score (AMD, -0.014; 95% CI,?-0.167 to 0.139; P?=?.85), interleukin-6 level (AMD, -0.13 pg/mL; 95% CI,?-0.38 to 0.11 pg/mL; P?=?.30), dimerized plasmin fragment D level (AMD, -0.21 ?g/mL fibrinogen equivalent units; 95% CI,?-0.48 to 0.07 ?g/mL fibrinogen equivalent units; P?=?.14), soluble CD14 level (AMD, -38.01 ng/mL; 95% CI,?-166.90 to 90.88 ng/mL; P?=?.56), intestinal fatty acid binding protein level (AMD, 0.08 pg/mL; 95% CI,?-0.07 to 0.22 pg/mL; P?=?.32), and lipopolysaccharide binding protein level (AMD, -0.09 ng/mL; 95% CI,?-0.23 to 0.06 ng/mL; P?=?.24). In the per-protocol analyses, zinc supplementation statistically significantly affected changes in the VACS Index score at 18 months (AMD, -7.49; 95% CI,?-13.74 to -1.23; P?=?.02); however, the adherence rate to zinc supplementation was 51%. Conclusions and Relevance:Zinc supplementation did not reduce mortality risk, CD4 cell counts, cardiovascular disease risk, and levels of inflammation or microbial translocation in people with heavy alcohol use who are living with HIV/AIDS. Zinc supplementation did not change the VACS Index score but may have been limited by low adherence. Trial Registration:ClinicalTrials.gov Identifier: NCT01934803.

SUBMITTER: Freiberg MS

PROVIDER: S-EPMC7210486 | biostudies-literature | 2020 May

REPOSITORIES: biostudies-literature

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Effect of Zinc Supplementation vs Placebo on Mortality Risk and HIV Disease Progression Among HIV-Positive Adults With Heavy Alcohol Use: A Randomized Clinical Trial.

Freiberg Matthew S MS Cheng Debbie M DM Gnatienko Natalia N Blokhina Elena E Coleman Sharon M SM Doyle Margaret F MF Yaroslavtseva Tatiana T Bridden Carly C So-Armah Kaku K Tracy Russell R Bryant Kendall K Lioznov Dmitry D Krupitsky Evgeny E Samet Jeffrey H JH

JAMA network open 20200501 5

<h4>Importance</h4>Zinc supplementation can reduce alcohol-related microbial translocation and inflammation.<h4>Objective</h4>To assess whether zinc supplementation reduces markers of mortality and risk of cardiovascular disease, reduces levels of inflammation and microbial translocation, and slows HIV disease progression in people with heavy alcohol use who are living with HIV/AIDS.<h4>Design, setting, and participants</h4>This study is a double-blinded placebo-controlled randomized clinical tr ...[more]

PMID: 32383748

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Project description:BackgroundZinc supplementation can reduce subsequent morbidity in children recovering from diarrhoea and respiratory illness in developing countries. However, whether routine supplementation would decrease morbidity and mortality in populations with zinc deficiency is unclear. We assessed the effect of daily zinc supplementation on children in southern Nepal.MethodsWe did a community-based, cluster-randomised, double-masked, placebo-controlled, 2x2 factorial trial in children aged 1-35 months. Treatment groups were placebo, iron and folic acid, zinc, and iron and folic acid with zinc, with daily doses of 12.5 mg iron, 50 microg folic acid, and 10 mg zinc. Study staff gave children tablets on 2 days each week and left tablets with caregivers for other days. All children received vitamin A supplementation twice per year. Results of the iron arm of the trial have been reported previously. Between October, 2001, and January, 2006, 41,276 children were enrolled into the placebo (n=20,308) or zinc (n=20,968) groups and were followed-up for 60,636.3 person-years. The primary outcome was child mortality, and analyses were by intention to treat. Daily reports of signs and symptoms of common morbidities in stratified random subsamples of children were assessed every week for 12 months. This study is registered at ClinicalTrials.gov, number NCT00109551.Findings2505 children refused to continue the trial and 3219 children were lost to follow-up. There was no significant difference in mortality between the zinc and placebo groups (316 vs 333 deaths; hazard ratio 0.92, 95% CI 0.75-1.12). Zinc had no effect on mortality in children younger than 12 months (181 vs 168 deaths; 1.04, 0.83-1.31); mortality was lower, but not statistically significantly so, in older children receiving zinc (135 vs 165; 0.80, 0.60-1.06). The frequency and duration of diarrhoea, persistent diarrhoea, dysentery, and acute lower respiratory infections did not differ between the groups.InterpretationTotal mortality of children receiving zinc supplementation was not significantly different from that of children receiving placebo. Further data are needed from other populations with endemic zinc deficiency to confirm the potential age-specific effects reported in this study.

Project description:Large randomized trials have previously shown that high-dose micronutrient supplementation can increase CD4 counts and reduce human immunodeficiency virus (HIV) disease progression and mortality among individuals not receiving highly active antiretroviral therapy (HAART); however, the safety and efficacy of such supplementation has not been established in the context of HAART.To test the hypothesis that high-dose multivitamin supplementation vs standard-dose multivitamin supplementation decreases the risk of HIV disease progression or death and improves immunological, virological, and nutritional parameters in patients with HIV initiating HAART.A randomized, double-blind, controlled trial of high-dose vs standard-dose multivitamin supplementation for 24 months in 3418 patients with HIV initiating HAART between November 2006 and November 2008 in 7 clinics in Dar es Salaam, Tanzania. INTERVENTION The provision of daily oral supplements of vitamin B complex, vitamin C, and vitamin E at high levels or standard levels of the recommended dietary allowance.The composite of HIV disease progression or death from any cause.The study was stopped early in March 2009 because of evidence of increased levels of alanine transaminase (ALT) in patients receiving the high-dose multivitamin supplement. At the time of stopping, 3418 patients were enrolled (median follow-up, 15 months), and there were 2374 HIV disease progression events and 453 observed deaths (2460 total combined events). Compared with standard-dose multivitamin supplementation, high-dose supplementation did not reduce the risk of HIV disease progression or death. The absolute risk of HIV progression or death was 72% in the high-dose group vs 72% in the standard-dose group (risk ratio [RR], 1.00; 95% CI, 0.96-1.04). High-dose supplementation had no effect on CD4 count, plasma viral load, body mass index, or hemoglobin level concentration, but increased the risk of ALT elevations (1239 events per 1215 person-years vs 879 events per 1236 person-years; RR, 1.44; 95% CI, 1.11-1.87) vs standard-dose supplementation. CONCLUSION In adults receiving HAART, use of high-dose multivitamin supplements compared with standard-dose multivitamin supplements did not result in a decrease in HIV disease progression or death but may have resulted in an increase in ALT levels.Clinicaltrials.gov Identifier: NCT00383669.

Project description:High average daily consumption of alcohol has been associated with elevated mortality risk, but more moderate consumption, relative to abstinence, has been associated with reduced mortality risk. However, average daily consumption can be complicated to assess, limiting its usefulness in both research and clinical practice. There are also concerns that average consumption fails to capture the risk associated with certain drinking patterns, such as heavy episodic drinking. This study assessed mortality associated with drinking pattern, operationalized as the frequency of both heavy and nonheavy drinking occasions.Data from the 1997 to 2001 administrations of the National Health Interview Survey (NHIS; n = 111,511) were paired with the current release of the NHIS Linked Mortality Files, which provided mortality follow-up data through the end of 2006. We estimated the impact of drinking pattern on all-cause mortality, operationalized as the frequency of heavy (5+ drinks) and nonheavy (<5 drinks) drinking occasions. Other covariates in the model included survey wave, sex, age, race/ethnicity, ratio of family income to poverty threshold, educational attainment, body mass index, and smoking status.Over a third of past-year drinkers reported heavy drinking. Mortality risk increased steadily as heavy drinking frequency increased; daily heavy drinkers exhibited an almost 2-fold risk of death compared with abstainers (p < 0.001). Regular nonheavy drinking was associated with decreased mortality, similar to the "J-shaped curve" highlighted in past research on alcohol mortality; this potential protective effect peaked around 2 nonheavy occasions per week.Any heavy drinking likely elevates mortality risk, and substantial health benefits could be realized by reducing heavy drinking occasions or limiting overall drinking. Heavy and nonheavy drinking frequencies are valid targets for clinical screening and could be helpful in assessing risk and promoting less harmful drinking behavior.

Project description:BACKGROUND:Although it has been purported that HIV-positive individuals may experience a greater degree of intoxication than HIV-negative individuals following acute alcohol consumption, no research to date has empirically tested this supposition. The present investigation entailed a randomized controlled experiment to identify whether the administration of a weight-specified dose of alcohol would lead to differential blood alcohol concentrations (BACs) among HIV-positive versus HIV-negative men. METHODS:In a specialized barroom laboratory, 143 men (n = 76 HIV-positive and n = 67 HIV-negative; mean age = 42.9) consumed beverages based on a formulation of 0.7 g alcohol/kg body weight over a 15-minute time frame. BAC was assessed via breathalyzer at 2 set time points (10 and 13 minutes postconsumption) and then periodically until detoxification (BAC < 0.040%). Primary outcomes included (i) area under the curve (AUC), calculated based on all of one's BAC readings, (ii) "BAC-EXP," defined as one's BAC reading 13 minutes postconsumption, and (iii) BAC-PEAK, defined as one's highest recorded BAC reading. RESULTS:Contrary to predictions, AUC (t(141) = 2.23, p = 0.027), BAC-EXP (t(141) = 2.68, p = 0.008), and BAC-PEAK (t(141) = 2.29, p = 0.023) were significantly lower among HIV-positive versus HIV-negative participants. These effects were sustained in multivariable models controlling for age, race, and AUDIT-based hazardous drinking classification. Among the HIV-positive sample, outcomes did not significantly differ based on HIV viral load detectability, antiretroviral therapy (ART) status, or ART adherence. CONCLUSIONS:The administration of a controlled, weight-specified dose of alcohol led to lower BACs among HIV-positive versus HIV-negative participants. These differences might derive from decreased body fat percentage and delayed gastric emptying associated with HIV seropositivity; however, additional research is necessary to verify these mechanisms. Unique alcohol dosing formulas based on HIV serostatus may be required in future alcohol administration experiments involving HIV-positive samples.

Dataset Information

Effect of Zinc Supplementation vs Placebo on Mortality Risk and HIV Disease Progression Among HIV-Positive Adults With Heavy Alcohol Use: A Randomized Clinical Trial.

Publications

Effect of Zinc Supplementation vs Placebo on Mortality Risk and HIV Disease Progression Among HIV-Positive Adults With Heavy Alcohol Use: A Randomized Clinical Trial.

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