Polysubstance use and adherence to antiretroviral treatment in the Miami Adult Studies on HIV (MASH) cohort.

Evidence for a relationship between polysubstance use, depression, and adherence to antiretroviral therapy (ART) is limited. The objectives of this study were to examine the associations of depression, illicit drug, and alcohol use with adherence to ART. People living with HIV (PLHIV) from the Miami Adult Studies on HIV cohort were asked about the number of doses of their ART medication missed to assess ART adherence. Harmful alcohol drinking was evaluated using the Alcohol Use Disorders Identification Test and illicit substance use assessed with self-report and urine screen. The Center for Epidemiologic Studies Depression Scale was used to assess depression symptoms. Of 391 PLHIV, 16.6% missed at least one dose (range:1-4) in the past four days. Cocaine/crack, opiate use, and depression were significantly independently associated with a greater mean number of doses missed. The mean number of doses missed was significantly greater among participants who used alcohol in combination with cocaine/crack, marijuana, and tobacco compared to non-users. In conclusion, polysubstance use increased the risk for poor ART adherence among PLHIV. The use of cocaine/crack or opiates individually and depressive symptoms also promote poor ART adherence. An integrated approach targeting substance disorders and depression may help achieve better ART adherence.

Role of Selenium in Viral Infections with a Major Focus on SARS-CoV-2.

Viral infections have afflicted human health and despite great advancements in scientific knowledge and technologies, continue to affect our society today. The current coronavirus (COVID-19) pandemic has put a spotlight on the need to review the evidence on the impact of nutritional strategies to maintain a healthy immune system, particularly in instances where there are limited therapeutic treatments. Selenium, an essential trace element in humans, has a long history of lowering the occurrence and severity of viral infections. Much of the benefits derived from selenium are due to its incorporation into selenocysteine, an important component of proteins known as selenoproteins. Viral infections are associated with an increase in reactive oxygen species and may result in oxidative stress. Studies suggest that selenium deficiency alters immune response and viral infection by increasing oxidative stress and the rate of mutations in the viral genome, leading to an increase in pathogenicity and damage to the host. This review examines viral infections, including the novel SARS-CoV-2, in the context of selenium, in order to inform potential nutritional strategies to maintain a healthy immune system.

Feeding modifications and additional primary caregiver support for infants exposed to Zika virus or diagnosed with congenital Zika syndrome: a rapid review of the evidence.

OBJECTIVE: Infants exposed to Zika virus (ZIKV) or diagnosed with congenital Zika syndrome (CZVS) may present dysphagia, regurgitation and other feeding difficulties. They may require special feeding practices to minimise the risk of mortality, morbidity and developmental problems. Improving knowledge, skills and behaviours of caregivers may preserve health, maximise development and promote quality of life among affected infants. We reviewed intervention studies of modified feeding practices and additional primary caregiver support to improve outcomes among infants 0 to 12 months of age exposed to ZIKV or diagnosed with CZVS. METHODS: Rapid review and meta-analysis. We searched PubMed/MEDLINE and contacted experts. The search is current to 18 July 2020. We planned a meta-analysis using fixed-effect models; if unfeasible, we intended to summarise studies narratively. We planned to assess risk of bias of included studies and quality of evidence using Cochrane guidance. RESULTS: We identified 42 records for title and abstract screening; 14 were eligible for full-text assessment. Among these, no intervention studies were found. Eight observational studies reported on the nutritional status, feeding practices and outcomes among infants affected by ZIKV or diagnosed with CZVS. They are presented and discussed to provide a basis for future research. CONCLUSIONS: While no intervention studies were found, evidence from eight observational studies highlights the need for early nutrition interventions and caregiver support among infants affected by ZIKV or diagnosed with CZSV. More research is needed to assess whether modifications of feeding practices and provision of additional primary caregiver support will impact outcomes of interest.

OBJECTIF: Les nourrissons exposés au virus Zika (VZIK) ou diagnostiqués avec le syndrome congénital Zika (SCZ) peuvent présenter une dysphagie, des régurgitations et d'autres difficultés d'alimentation. Ils peuvent nécessiter des pratiques alimentaires spéciales pour minimiser le risque de mortalité, de morbidité et de problèmes de développement. L'amélioration des connaissances, des compétences et des comportements des soignants peut préserver la santé, maximiser le développement et promouvoir la qualité de vie des nourrissons affectés. Nous avons examiné les études d'intervention sur les pratiques d'alimentation modifiées et le soutien additionnel aux principaux soignants pour améliorer les résultats chez les nourrissons de 0 à 12 mois exposés au VZIK ou diagnostiqués avec le SCZ. MÉTHODES: Revue rapide et méta-analyse. Nous avons effectué des recherches dans PubMed/MEDLINE et contacté des experts. La recherche a été mise à jour au 18 juillet 2020. Nous avons prévu une méta-analyse utilisant des modèles à effets fixes; si cela n'était pas réalisable, nous avions l'intention de résumer les études de manière narrative. Nous avons prévu d'évaluer le risque de biais des études incluses et la qualité des données en utilisant les directives Cochrane. RÉSULTATS: Nous avons identifié 42 reports pour la recherche des titres et des résumés; 14 étaient éligibles pour une évaluation en texte intégral. Parmi ceux-ci, aucune étude d'intervention n'a été trouvée. Huit études observationnelles ont rapporté sur l'état nutritionnel, les pratiques d'alimentation et les résultats chez les nourrissons atteints du VZIK ou diagnostiqués avec le SCZ. Elles sont présentées et discutées pour fournir une base pour les futures recherches. CONCLUSIONS: Bien qu'aucune étude d'intervention n'ait été trouvée, les données de huit études observationnelles mettent en évidence la nécessité d'interventions nutritionnelles précoces et de soutien des soignants des nourrissons atteints de VZIK ou diagnostiqués avec le SCZ. Des recherches supplémentaires sont nécessaires pour évaluer si les modifications des pratiques d'alimentation et la fourniture d'un soutien additionnel aux principaux soignants auront un impact sur les résultats d'intérêt.

Validation and Refinement of Noninvasive Methods to Assess Hepatic Fibrosis: Magnetic Resonance Elastography Versus Enhanced Liver Fibrosis Index.

BACKGROUND: Noninvasive fibrosis markers are routinely used in patients with liver disease. Magnetic resonance elastography (MRE) is recognized as a highly accurate methodology, but a reliable blood test for fibrosis would be useful. We examined performance characteristics of the Enhanced Liver Fibrosis (ELF) Index compared to MRE in a cohort including those with HCV, HIV, and HCV/HIV. METHODS: Subjects enrolled in the Miami Adult Studies on HIV (MASH) cohort underwent MRE and blood sampling. The ELF Index was scored and receiver-operator curves constructed to determine optimal cutoff levels relative to performance characteristics. Cytokine testing was performed to identify new markers to enhance noninvasive marker development. RESULTS: The ELF Index was determined in 459 subjects; more than half were male, non-white, and HIV-infected. MRE was obtained on a subset of 283 subjects and the group that had both studies served as the basis of the receiver-operator curve analysis. At an ELF Index of > 10.633, the area under the curve for cirrhosis (Metavir F4, MRE > 4.62 kPa) was 0.986 (95% CI 0.994-0.996; p < 0.001) with a specificity of 100%. For advanced fibrosis (Metavir F3/4), an ELF cutoff of 10 was associated with poor sensitivity but high specificity (98.9%, 95% CI 96.7-99.8%) with an AUC of 0.80 (95% CI 0.749-0.845). ELF Index performance characteristics exceeded FIB-4 performance. HCV and age were associated with increased fibrosis (p < 0.05) in a multivariable model. IP-10 was found to be a promising biomarker for improvement in noninvasive prediction algorithms. CONCLUSIONS: The ELF Index was a highly sensitive and specific marker of cirrhosis, even among HIV-infected individuals, when compared with MRE. IP-10 may be a biomarker that can enhance performance characteristics further, but additional validation is required.

Economic and Cardiometabolic Risk Factors Are Predictors of Lower Thyroid Stimulating Hormone (TSH) Levels in Hispanic/Latinx Adults with Euthyroidism-A Community-Based Study.

Thyroid hormone abnormalities are among the most common endocrine disorders comorbidly suffered alongside metabolic syndrome and type 2 diabetes mellitus (T2DM), and within the euthyroid range they may also impact other outcomes, such as mood disorders. This study aimed to observationally examine the relationship between TSH and social determinants of health and clinical measures in a euthyroid Hispanic/Latinx patient sample with a diagnosis of anxiety and/or depression disorders from a community health clinic. A needs assessment was completed using a random sample of 100 de-identified medical records of individuals who received free medical care, including mental health, at a community-based clinic. Those with low normal TSH (<2 mIU/L) compared with high normal TSH (≥2 mIU/L) had a greater odds of food insecurity (p = 0.016) and being at 100% of the federal poverty level (p = 0.015). The low normal TSH group had significantly higher fasting glucose (p = 0.046), hemoglobin A1c (p = 0.018), and total cholesterol (p = 0.034) compared with the high normal TSH group. In those with T2DM, individuals with low normal TSH had six-times greater odds of having high fasting glucose (p = 0.022) and high hemoglobin A1c (p = 0.029). These relationships warrant further study, to inform future public health policies and follow-up care for underserved and vulnerable communities.

Multiomic analysis reveals microbiome-related relationships between cocaine use and metabolites.

OBJECTIVE: Over 19 million individuals globally have a cocaine use disorder, a significant public health crisis. Cocaine has also been associated with a pro-inflammatory state and recently with imbalances in the intestinal microbiota as compared to nonuse. The objective of this pilot study was to characterize the gut microbiota and plasma metabolites in people with HIV (PWH) who use cocaine compared with those who do not. DESIGN: Cross-sectional study. METHODS: A pilot study in PWH was conducted on 25 cocaine users and 25 cocaine nonusers from the Miami Adult Studies on HIV cohort. Stool samples and blood plasma were collected. Bacterial composition was characterized using 16S rRNA sequencing. Metabolomics in plasma were determined using gas and liquid chromatography/mass spectrometry. RESULTS: The relative abundances of the Lachnopspira genus, Oscillospira genus, Bifidobacterium adolescentis species, and Euryarchaeota phylum were significantly higher in the cocaine- using PWH compared to cocaine-nonusing PWH. Cocaine-use was associated with higher levels of several metabolites: products of dopamine catabolism (3-methoxytyrosine and 3-methoxytyramine sulfate), phenylacetate, benzoate, butyrate, and butyrylglycine. CONCLUSIONS: Cocaine use was associated with higher abundances of taxa and metabolites known to be associated with pathogenic states that include gastrointestinal conditions. Understanding key intestinal bacterial functional pathways that are altered due to cocaine use in PWH will provide a better understanding of the relationships between the host intestinal microbiome and potentially provide novel treatments to improve health.

Presence of Ebola virus in breast milk and risk of mother-to-child transmission: synthesis of evidence.

To help inform global guidelines on infant feeding, this systematic review synthesizes evidence related to the presence of the Ebola virus (EBOV) in breast milk and its potential risk of viral transmission to the infant when breastfeeding. We relied on a comprehensive search strategy to identify studies including women with suspected, probable, or confirmed EBOV infection, intending to breastfeed or give breast milk to an infant. Our search identified 10,454 records, and after deduplication and screening, we assessed 148 full texts. We included eight studies reporting on 10 breastfeeding mothers and their children (one mother with twins), who provided breast milk samples for assessment. EBOV was detected via RT-PCR or viral culture in seven out of ten breast milk samples. Four out of the five-breastfed infants with EBOV-positive breast milk were found positive for EBOV infection, and all of these EBOV-positive infants died. Since previous reports have detected EBOV in tears, saliva, sweat, and contaminated surfaces, with the current evidence, it is not possible to conclude with certainty that breast milk was the main route of EBOV transmission.

The effect of micronutrient supplementation on active TB incidence early in HIV infection in Botswana.

BACKGROUND: Coinfection with active tuberculosis (TB) is one of the leading causes of death in people living with HIV (PLWH) in Africa. This investigation explores the role of micronutrient supplementation in preventing active TB in PLWH. METHODS: A randomized trial of nutritional supplementation was conducted among antiretroviral- naïve (without previous antiretroviral treatment [ART]) HIV-infected people in Botswana between 2004 and 2009. The study had a factorial design with four arms: the selenium (Se) alone arm, the multivitamins (MVT) alone arm that contained vitamin B complex and vitamins C and E, the combined Se+MVT group and the placebo group. Those participants with prior or current active TB were excluded, as were participants with advanced HIV disease (CD4 <250 cells/µL) or who had already qualified for ART. HIV-positive adults (N=878) were followed monthly for study pill dispensation, every 3 months for CD4 cell count and every 6 months for viral load during 24 months or until they were started on ART. RESULTS: The participants' characteristics were not significantly different among the four groups at baseline. Supplementation with Se alone (hazard ratio =0.20, 95% confidence interval: 0.04, 0.95, P=0.043) and the two combined SE groups (Se and Se+MVT) had significantly lower risk of developing incident TB disease compared with placebo in multivariate adjusted models (hazard ratio=0.32, 95% confidence interval: 0.11, 0.93, P=0.036). Multivitamins alone did not affect the incidence of TB. Isoniazid preventive therapy was received by 12.2% of participants, a rate that was not significantly different among the four study arms (P=0.122) and the newly diagnosed cases. CONCLUSION: Se supplementation, alone and with MVT, decreased the incidence of TB disease in PLWH who were ART-naïve. Supplementation with these micronutrients should be considered in HIV infection, prior to ART, in areas where TB and malnutrition are endemic.

Lower Plasma Zinc Levels in Hyperglycemic People Living with HIV in the MASH cohort.

BACKGROUND: Zinc deficiency is prevalent in HIV and hyperglycemic patients. Antiretroviral therapy (ART) is a treatment to control HIV progression; however it increases the risk for hyperglycemia. The objective of this study was to assess the plasma zinc levels in hyperglycemic people living with HIV (PLWH). METHODS: Secondary analysis was conducted on the data from the Miami Adult Studies in HIV (MASH) cohort in Florida. Patients were categorized into hyperglycemic group (fasting blood glucose ≥100 mg/dL) and normal group (<100 mg/dL). RESULTS: Plasma zinc status and CD4 levels were lower in the hyperglycemic group, however the difference was not significant. There was a greater percentage of plasma zinc deficiency in the hyperglycemic group (69%) compared to the normoglycemic group (64%). DISCUSSION: Although not statistically significant, related biomarkers such as plasma zinc levels and CD4 levels were lower in the hyperglycemic group. This may be due to the role zincplays in the immune system. Due to the fact that there was a higher percentage of plasma zinc deficiency in the hyperglycemic group (69%) compared to the normoglycemic group (64%), it is important to monitor and manage blood glucose levels to minimize complications. Our findings along with previous findings suggest that zinc supplementation may benefit hyperglycemic PLWH.

Cocaine Use and Liver Disease are Associated with All-Cause Mortality in the Miami Adult Studies in HIV (MASH) Cohort.

OBJECTIVE: Liver disease is a frequent cause of morbidity and mortality in HIV infection. We examined the relationship of cocaine use, liver disease progression and mortality in an HIV-infected cohort. METHODS: Consent was obtained from 487 HIV+ participants, a subset of the Miami Adult Studies on HIV (MASH) cohort. Participants were eligible if they were followed for at least two years, completed questionnaires on demographics and illicit drug use and had complete metabolic panels, CD4 cell counts and HIV-viral loads. FIB-4 was calculated and cut-off points were used for staging liver fibrosis. Death certificates were obtained. RESULTS: Participants were 65% men, 69% Black and 81% were on ART at recruitment. Cocaine was used by 32% of participants and 29% were HIV/HCV co-infected. Mean age was 46.9 ± 7.7 years, mean CD4 cell count was 501.9 ± 346.7 cells/µL and mean viral load was 2.75 ± 1.3 log10 copies/mL at baseline. During the follow-up, 27 patients died, with a mortality rate of 28.2/1000 person-year. Cocaine was used by 48% of those who died (specific mortality rate was 13/1000 person-year). Those who died were more likely to use cocaine (HR=3.8, P=0.006) and have more advanced liver fibrosis (HR=1.34, P<0.0001), adjusting for age, gender, CD4 cell count and HIV-viral load at baseline and over time. Among the HIV mono-infected participants, cocaine users were 5 times more likely to die (OR=5.09, P=0.006) than participants who did not use cocaine. CONCLUSION: Cocaine use and liver fibrosis are strong and independent predictors of mortality in HIV infected and HIV/HCV co-infected adults. Effective interventions to reduce cocaine use among people living with HIV (PHLW) are needed.

Recruitment, Follow-Up and Characteristics of HIV Infected Adults who Use Illicit Drugs in Southern Africa.

BACKGROUND: With one of the worst HIV prevalence rates in the world, Botswana has made great strides in addressing AIDS. Nevertheless, to fully contain the epidemic, outreach to marginalized groups, including illicit drug users, is critical. OBJECTIVE: To conduct targeted outreach within an intervention trial to recruit HIV-infected drug users and assess HIV disease and nutritional status. METHOD: Recruitment strategies included safeguarding confidentiality, involving ocal health-care professionals, advertising, and participation incentives. Urine toxicology, CD4 cell count, HIV viral load, blood chemistry, plasma micronutrients, dietary history, drug use and morbidity were assessed for two years. RESULTS: Targeted outreach identified 138 HIV-infected persons who used marijuana; 18.1% had CD4 cell counts ≤ 350 cells/µL and 39.9% had low BMI. Eligible marijuana users (N=52) had significantly lower BMI (21.8 3.7 vs. 24.3 ± 5.3 kg/m2, P=0.001), higher HIV viral load (4.36 ± 0.89 vs. 4.09 ± 0.89 log10, P=0.018), and higher kilocalorie intake (1924 ± 1055 vs. 1620 ± 926 Kcalories, P=0.025) than those who did not use marijuana (N=748) with similar CD4 cell count. Marijuana users ≥ 40 years old had more opportunistic diseases (P=0.020) than non-users of the same age. Benzodiazepine use was detected among 57 participants and they had higher BMI than marijuana users (24.4 ± 6.8 vs. 21.8 ± 3.7 kg/m2, P= 0.017). CONCLUSION: A population stigmatized by illicit drug use and HIV-infection can be brought into a clinical research setting in Africa. HIV-infected marijuana users were at a risk for higher HIV viral load, lower BMI and more comorbidities than nonusers. Outreach to this marginalized group is important for containing the HIV epidemic.

Effect of GSTM1-Polymorphism on Disease Progression and Oxidative Stress in HIV Infection: Modulation by HIV/HCV Co-Infection and Alcohol Consumption.

OBJECTIVE: To examine the effects of GSTM1 null-allele polymorphism on oxidative stress and disease progression in HIV infected and HIV/hepatitis C (HCV) co-infected adults. METHODS: HIV-infected and HIV/HCV co-infected participants aged 40-60 years old with CD4 cell count >350 cells/ µl, were recruited. GSTM1 genotype was determined by quantitative PCR. Oxidative stress (mitochondrial 8-oxo-2'-deoxyguanosine [8-oxo-dG], malondialdehyde [MDA], oxidized glutathione and Complexes I and IV), apoptosis and HIV disease (CD4 count and viral load) markers were measured. Gene copies were not quantified, thus the Hardy-Weinberg formula was not applicable. RESULTS: Of the 129 HIV-infected participants, 58 were HIV/HCV co-infected. GSTM1 occurred in 66% (62/94) in those of African descent, and 33% (11/33) of the Caucasians. Those with GSTM1 coding for the functional antioxidant enzyme Glutathione S-transferase (GST), had higher CD4 cell count (ß=3.48, p=0.034), lower HIV viral load (ß=-0.536, p=0.018), and lower mitochondrial 8-oxo-dG (ß=-0.28, p=0.03). ART reduced oxidative stress in the participants with the GSTM1 coding for the functional antioxidant enzyme. HIV/HCV co-infected participants with the GSTM1 coding for the functional antioxidant enzyme also had lower HIV viral load, lower 8-oxo-dG and lower rate of apoptosis, but also higher oxidized glutathione. Alcohol consumption was associated with lower HIV viral load but higher oxidized glutathione in those with the GSTM1 genotype coding for the functional antioxidant enzyme. CONCLUSION: The GSTM1 genotype coding for the functional antioxidant enzyme is associated with lower HIV disease severity, and with lower oxidative stress, compared to GSTM1 null-allele polymorphism. HCV co-infection and alcohol use may be associated with increased oxidative stress even in the presence of the GSTM1 coding for the functional antioxidant enzyme. The null-gene, on the contrary, appears to have a detrimental effect on immune function, viral load control, and antioxidant status, suggesting a potential benefit from antioxidants in HIV infected patients with the defective gene.