Analysis of the gut microbiota in alopecia areata: identification of bacterial biomarkers.

BACKGROUND: Alopecia areata is a T-cell-mediated autoimmune disease with an unknown etiopathogenesis. Gut microbiota has been revealed as a key modulator of systemic immunity. OBJECTIVE: To determine whether patients affected by alopecia universalis present differences in gut bacteria composition compared with healthy controls and investigate possible bacterial biomarkers of the disease. METHODS: We conducted a cross-sectional study that involved 15 patients affected by alopecia universalis and 15 controls. Gut microbiome of the study subjects was analysed by sequencing the 16SrRNA of stool samples. We searched for bacterial biomarkers of alopecia universalis using the linear discriminant analysis effect size (LEFse) tool. RESULTS: In total, 30 study subjects (46.6% female; mean [SD] age, 40.1 [9.8] years) were enrolled. Neither alpha (Shannon diversity index 5.31 ± 0.43 vs. 5.03 ± 0.43, P 0.1) or beta diversity (ADONIS P value: 0.35) of gut microbiota showed statistically significant differences between cases and controls. In patients affected with alopecia, we found an enriched presence (LDA SCORE > 2) of Holdemania filiformis, Erysipelotrichacea, Lachnospiraceae, Parabacteroides johnsonii, Clostridiales vadin BB60 group, Bacteroides eggerthii and Parabacteroides distasonis. A predictive model based on the number of bacterial counts of Parabacteroides distasonis and Clostridiales vadin BB60 group correctly predicted disease status in 80% of patients (AUC 0.804 (0.633-0.976), P 0.004). CONCLUSION: Alopecia universalis does not seem to affect broadly gut microbiota structure. Bacterial biomarkers found associated with the disease (Holdemania filiformis, Erysipelotrichacea, Lachnospiraceae, Parabacteroides johnsonii, Eggerthellaceae, Clostridiales vadin BB60 group, Bacteroides eggerthii and Parabacteroides distasonis) should be further studied as they could be involved in its pathophysiology or be used as diagnostic tools.

Evaluation of kidney function in HIV-infected patients receiving an antiretroviral regimen containing one or two inhibitors of the tubular secretion of creatinine.

OBJECTIVES: The aim of this study was to determine the evolution of renal function in patients receiving one or two inhibitors, according to different baseline factors. Some antiretroviral drugs such as rilpivirine (RPV), dolutegravir (DTG), or cobicistat (COBI), interact with the tubular secretion of creatinine, but there are no data about their impact in renal function evaluation in patients with renal disease or when these drugs are used concomitantly. METHODS: A prospective cohort study was carried out in HIV-infected patients who switched to a dual regimen including DTG, RPV or darunavir/COBI, separately or in combination. The primary endpoint was the evolution of the serum creatinine-based estimated glomerular filtration rate (eGFR-scr). A control group not receiving any transporter inhibitor was included. RESULTS: A total of 288 patients on different dual regimens were included (DTG + RPV, 92; DTG + darunavir/COBI, 23; DTG, 26; COBI, 19; control group, 128). In patients receiving two transporter inhibitors, eGFR-scr decreased by a mean of -8.4 mL/min/1.73 m2 , similar to that observed with the separate use of DTG or COBI (mean of both groups, -8.6 mL/min/1.73 m2 ), while eGFR-scr improved in the control group. Similar evolution of proteinuria and tubular dysfunction was observed in all the groups, and there were no significant changes in the cystatin C-based eGFR. Mean eGFR-scr change inversely correlated with baseline eGFR-scr value (r = -0.39; P < 0.01), with a lower eGFR-scr decrease in patients with chronic kidney disease. CONCLUSIONS: Similar eGFR-scr decreases were observed in patients using different antiretroviral drugs inhibiting the tubular transport of creatinine, separately or in combination, with no alterations in proteinuria or cystatin C-based eGFR. The lack of additional changes when the drugs were used in combination, and the lower impact in cases of previous chronic kidney disease, suggest that there are compensatory mechanisms for creatinine secretion.

Decreasing prevalence of HCV coinfection in all risk groups for HIV infection between 2004 and 2011 in Spain.

While hepatitis C virus (HCV) infection seems to be expanding among HIV-infected men who have sex with men (MSM), the rate of coinfection in intravenous drug users (IDU) is assumed to remain constant. We evaluated the serial prevalence of HIV/HCV coinfection across all risk groups for HIV infection in Spain. We used data from 7045 subjects included in the multicentre, prospective Spanish Cohort of Adult HIV-infected Patients (CoRIS) between 2004 and 2011. We analysed risk factors for HIV/HCV coinfection by logistic regression analyses. The prevalence of HIV/HCV coinfection decreased from 25.3% (95% CI, 23.1-27.5) in 2004-2005 to 8.2% (95% CI, 6.9-9.5) in 2010-2011. This trend was consistently observed from 2004 to 2011 among all risk groups: IDU, 92.4% to 81.4%; MSM, 4.7% to 2.6%; heterosexual men, 13.0-8.9%; and heterosexual women, 14.5-4.0% (all P < 0.05). Strongest risk factors for HIV/HCV coinfection were IDU (OR, 54.9; 95% CI, 39.4-76.4), birth decade 1961-1970 (OR, 2.1; 95% CI, 1.1-3.7) and low educational level (OR, 2.4; 95% CI, 1.6-3.5). Hence, the prevalence of HIV/HCV coinfection decreased in Spain between 2004 and 2011. This decline was observed across all risk groups and is likely to be explained by a declining burden of HCV in the general population.

The CD4:CD8 ratio is associated with markers of age-associated disease in virally suppressed HIV-infected patients with immunological recovery.

OBJECTIVES: Inversion of the CD4:CD8 ratio (< 1) has been identified as a hallmark of inmmunosenescence and an independent predictor of mortality in the general population. We aimed to assess the association between the CD4:CD8 ratio and markers of age-associated disease in treated HIV-infected patients with good immunovirological response. METHODS: A cross-sectional analysis was conducted in 132 HIV-infected adults on antiretroviral therapy (ART), with plasma HIV RNA < 50 HIV-1 RNA copies/mL for at least 1 year, CD4 count > 350 cells/µL and age < 65 years. We analysed the associations between the CD4:CD8 ratio and subclinical atherosclerosis [assessed using carotid intima-media thickness (IMT)], arterial stiffness [assessed using the augmentation index (AIx)], the estimated glomerular filtration rate (eGFR), muscle wasting and sarcopenia [assessed using appendicular lean mass/height(2) (ALM) measured by dual-energy X-ray absorptiometry (DEXA)]. RESULTS: CD4:CD8 ratio inversion was associated with higher IMT, lower eGFR and lower ALM (all values P < 0.05), but not with AIx. In multivariate analyses adjusted for age, sex, hypertriglyceridaemia, tobacco use and cumulative ART exposure, inversion of the CD4:CD8 ratio was independently associated with higher IMT [odds ratio (OR) 2.9; 95% confidence interval (CI) 1.2-7.1], arterial stiffness (OR 4.8; 95% CI 1.0-23.5) and lower eGFR (OR 5.2; 95% CI 1.0-64.4), but not sarcopenia (OR 0.7; 95% CI 0.2-2.7). These associations persisted when models were applied to subjects with nadir CD4 counts > 200 cells/µL and those with CD4 counts > 500 cells/µL. CONCLUSIONS: The CD4:CD8 ratio in treated HIV-infected subjects with good immunovirological response is independently associated with markers of age-associated disease. Hence, it might be a clinically useful predictor of non-AIDS-defining conditions.

Smoking cessation in HIV patients: rate of success and associated factors.

BACKGROUND: Smoking is the modifiable cardiovascular (CV) risk factor that contributes most to causing premature CV disease. Prevalence of smoking in patients with HIV infection is double that of the general population. OBJECTIVES: To determine the rate of patients succeeding in quitting smoking after 12 months, factors associated with this success, and the characteristics of tobacco consumption and nicotine dependence. METHODS: Longitudinal descriptive study. Three hundred and sixty-eight HIV-infected patients were interviewed. Smokers in Prochaska's stage of action began a programme to quit smoking. We registered the variables related to tobacco consumption and the level of success of cessation. RESULTS: 63.9% of the patients were active smokers and 14% of them began the cessation programme. Average motivation for cessation was 7.8 +/- 1.4 (Richmond) and nicotine dependence rate 5.5 +/- 3.0 (Fagerström). After 1 year, 25% had quit smoking. Those patients who stopped smoking presented a higher motivation level (8.8 +/- 1.3 vs. 7.5 +/- 1.5, P=0.048). Cessation significantly reduced their CV risk at 12 months [2.5 [interquartile range (IQR) 2.0-5.2] vs. 1.7 [IQR 1.0-3.5], P=0.026]. CONCLUSIONS: The prevalence of smokers in our population of HIV-infected patients was 63.9%. Only 14% began a smoking cessation programme. Twelve months after a programme to quit smoking, cessation rate was 25%; this was influenced mostly by the level of motivation of the patient.

The effects of prebiotics on microbial dysbiosis, butyrate production and immunity in HIV-infected subjects.

Altered interactions between the gut mucosa and bacteria during HIV infection seem to contribute to chronic immune dysfunction. A deeper understanding of how nutritional interventions could ameliorate gut dysbiosis is needed. Forty-four subjects, including 12 HIV+ viremic untreated (VU) patients, 23 antiretroviral therapy-treated (ART+) virally suppressed patients (15 immunological responders and 8 non-responders) and 9 HIV- controls (HIV-), were blindly randomized to receive either prebiotics (scGOS/lcFOS/glutamine) or placebo (34/10) over 6 weeks in this pilot study. We assessed fecal microbiota composition using deep 16S rRNA gene sequencing and several immunological and genetic markers involved in HIV immunopathogenesis. The short dietary supplementation attenuated HIV-associated dysbiosis, which was most apparent in VU individuals but less so in ART+ subjects, whose gut microbiota was found more resilient. This compositional shift was not observed in the placebo arm. Significantly, declines in indirect markers of bacterial translocation and T-cell activation, improvement of thymic output, and changes in butyrate production were observed. Increases in the abundance of Faecalibacterium and Lachnospira strongly correlated with moderate but significant increases of butyrate production and amelioration of the inflammatory biomarkers soluble CD14 and high-sensitivity C-reactive protein, especially among VU. Hence, the bacterial butyrate synthesis pathway holds promise as a viable target for interventions.

Altered metabolism of gut microbiota contributes to chronic immune activation in HIV-infected individuals.

Altered interplay between gut mucosa and microbiota during treated HIV infection may possibly contribute to increased bacterial translocation and chronic immune activation, both of which are predictors of morbidity and mortality. Although a dysbiotic gut microbiota has recently been reported in HIV+ individuals, the metagenome gene pool associated with HIV infection remains unknown. The aim of this study is to characterize the functional gene content of gut microbiota in HIV+ patients and to define the metabolic pathways of this bacterial community, which is potentially associated with immune dysfunction. We determined systemic markers of innate and adaptive immunity in a cohort of HIV-infected individuals on successful antiretroviral therapy without comorbidities and in healthy non-HIV-infected subjects. Metagenome sequencing revealed an altered functional profile, with enrichment of the genes involved in various pathogenic processes, lipopolysaccharide biosynthesis, bacterial translocation, and other inflammatory pathways. In contrast, we observed depletion of genes involved in amino acid metabolism and energy processes. Bayesian networks showed significant interactions between the bacterial community, their altered metabolic pathways, and systemic markers of immune dysfunction. This study reveals altered metabolic activity of microbiota and provides novel insight into the potential host-microbiota interactions driving the sustained inflammatory state in successfully treated HIV-infected patients.

Development of tuberculosis in human immunodeficiency virus infected patients receiving antiretroviral therapy.

BACKGROUND: It is unclear whether optimal immunological recovery reduces the risk of tuberculosis (TB) in human immunodeficiency virus (HIV) infected patients receiving antiretroviral therapy (ART), in whom it is still significantly higher than in the general population. METHODS: Retrospective cohort study in ART-treated patients without a previous diagnosis of TB. TB was microbiologically proven. Multivariate analyses were performed to identify risk factors associated with TB. RESULTS: This study included 1824 patients; the median follow-up was 473 days. The median CD4 count was 207 cells/µl (90-363.8); 339 (18.6%) were tuberculin skin test positive. Increased CD4 count gain after ART initiation was a protective factor against active TB (per each 100 cells/µl increase, OR 0.683, 95%CI 0.522-0.894). Maximal protection was observed in patients reaching increments ⩾150 cells/µl after 12 months of ART (OR 0.29, 95%CI 0.11-0.8) or ⩾300 cells/µl after 24 months (OR 0.73, 95%CI 0.71-0.75). There was no association between achieving HIV RNA <50 copies/ml and risk of active TB (OR 1.43, 95%CI 0.68-2.49). CONCLUSIONS: The risk of TB in patients starting ART is reduced among those with better immunological response, and is unrelated to the virological response. Our results emphasise the need for adjunctive strategies in immunological non-responders to minimise any residual risk of TB.