15 research outputs found
Circulating microRNAs in sera correlate with soluble biomarkers of immune activation but do not predict mortality in ART treated individuals with HIV-1 infection: A case control study
Introduction: The use of anti-retroviral therapy (ART) has dramatically reduced HIV-1 associated morbidity and mortality. However, HIV-1 infected individuals have increased rates of morbidity and mortality compared to the non-HIV-1 infected population and this appears to be related to end-organ diseases collectively referred to as Serious Non-AIDS Events (SNAEs). Circulating miRNAs are reported as promising biomarkers for a number of human disease conditions including those that constitute SNAEs. Our study sought to investigate the potential of selected miRNAs in predicting mortality in HIV-1 infected ART treated individuals. Materials and Methods: A set of miRNAs was chosen based on published associations with human disease conditions that constitute SNAEs. This case: control study compared 126 cases (individuals who died whilst on therapy), and 247 matched controls (individuals who remained alive). Cases and controls were ART treated participants of two pivotal HIV-1 trials. The relative abundance of each miRNA in serum was measured, by RTqPCR. Associations with mortality (all-cause, cardiovascular and malignancy) were assessed by logistic regression analysis. Correlations between miRNAs and CD4+ T cell count, hs-CRP, IL-6 and D-dimer were also assessed. Results: None of the selected miRNAs was associated with all-cause, cardiovascular or malignancy mortality. The levels of three miRNAs (miRs -21, -122 and -200a) correlated with IL-6 while miR-21 also correlated with D-dimer. Additionally, the abundance of miRs -31, -150 and -223, correlated with baseline CD4+ T cell count while the same three miRNAs plus miR- 145 correlated with nadir CD4+ T cell count. Discussion: No associations with mortality were found with any circulating miRNA studied. These results cast doubt onto the effectiveness of circulating miRNA as early predictors of mortality or the major underlying diseases that contribute to mortality in participants treated for HIV-1 infection
Development and Validation of a Risk Score for Chronic Kidney Disease in HIV Infection Using Prospective Cohort Data from the D:A:D Study
Ristola M. on työryhmien DAD Study Grp ; Royal Free Hosp Clin Cohort ; INSIGHT Study Grp ; SMART Study Grp ; ESPRIT Study Grp jäsen.Background Chronic kidney disease (CKD) is a major health issue for HIV-positive individuals, associated with increased morbidity and mortality. Development and implementation of a risk score model for CKD would allow comparison of the risks and benefits of adding potentially nephrotoxic antiretrovirals to a treatment regimen and would identify those at greatest risk of CKD. The aims of this study were to develop a simple, externally validated, and widely applicable long-term risk score model for CKD in HIV-positive individuals that can guide decision making in clinical practice. Methods and Findings A total of 17,954 HIV-positive individuals from the Data Collection on Adverse Events of Anti-HIV Drugs (D:A:D) study with >= 3 estimated glomerular filtration rate (eGFR) values after 1 January 2004 were included. Baseline was defined as the first eGFR > 60 ml/min/1.73 m2 after 1 January 2004; individuals with exposure to tenofovir, atazanavir, atazanavir/ritonavir, lopinavir/ritonavir, other boosted protease inhibitors before baseline were excluded. CKD was defined as confirmed (>3 mo apart) eGFR In the D:A:D study, 641 individuals developed CKD during 103,185 person-years of follow-up (PYFU; incidence 6.2/1,000 PYFU, 95% CI 5.7-6.7; median follow-up 6.1 y, range 0.3-9.1 y). Older age, intravenous drug use, hepatitis C coinfection, lower baseline eGFR, female gender, lower CD4 count nadir, hypertension, diabetes, and cardiovascular disease (CVD) predicted CKD. The adjusted incidence rate ratios of these nine categorical variables were scaled and summed to create the risk score. The median risk score at baseline was -2 (interquartile range -4 to 2). There was a 1: 393 chance of developing CKD in the next 5 y in the low risk group (risk score = 5, 505 events), respectively. Number needed to harm (NNTH) at 5 y when starting unboosted atazanavir or lopinavir/ritonavir among those with a low risk score was 1,702 (95% CI 1,166-3,367); NNTH was 202 (95% CI 159-278) and 21 (95% CI 19-23), respectively, for those with a medium and high risk score. NNTH was 739 (95% CI 506-1462), 88 (95% CI 69-121), and 9 (95% CI 8-10) for those with a low, medium, and high risk score, respectively, starting tenofovir, atazanavir/ritonavir, or another boosted protease inhibitor. The Royal Free Hospital Clinic Cohort included 2,548 individuals, of whom 94 individuals developed CKD (3.7%) during 18,376 PYFU (median follow-up 7.4 y, range 0.3-12.7 y). Of 2,013 individuals included from the SMART/ESPRIT control arms, 32 individuals developed CKD (1.6%) during 8,452 PYFU (median follow-up 4.1 y, range 0.6-8.1 y). External validation showed that the risk score predicted well in these cohorts. Limitations of this study included limited data on race and no information on proteinuria. Conclusions Both traditional and HIV-related risk factors were predictive of CKD. These factors were used to develop a risk score for CKD in HIV infection, externally validated, that has direct clinical relevance for patients and clinicians to weigh the benefits of certain antiretrovirals against the risk of CKD and to identify those at greatest risk of CKD.Peer reviewe
Association of CD209L tandem repeats polymorphism with susceptibility to human immunodeficiency virus-1 infection, disease progression, and treatment outcomes: a Moroccan cohort study
AbstractIn order to investigate the association between length variation of the CD209L neck region and human immunodeficiency virus (HIV)-1 susceptibility, disease progression, and treatment response outcomes, we genotyped 139 HIV-1-seropositive and 109 seronegative individuals. The heterozygous genotype 6/5 showed a significant increased risk of HIV-1 infection (OR 3.03, 95% CI 0.99–9.33, p 0.046). Moreover, after highly active antiretroviral therapy (HAART), HIV-1-seropositive individuals carrying the 6/5, 7/5 and 7/7 genotypes and alleles 5, 6 and 7 showed good CD4+ T-cell recovery. In addition, individuals with the 7/5, 6/6 and 7/7 genotypes showed a significant decrease in viral load during the treatment period as compared with baseline (p < 0.05). Interestingly, we found that alleles 4 and 6 were associated with protection against AIDS progression. D209L variation may influence susceptibility to HIV-1, response to treatment, and disease progression
Parasitoses opportunistes digestives chez les adultes infectés par le VIH : Aspects épidémiologiques Opportunistic digestive parasitic infections in adults infected with HIV: epidemiological expression
Introduction :Les parasitoses digestives opportunistes restent les principaux agents responsables de diarrhées chez les patients infectés par le VIH/Sida. Ce sont des infections classant Sida.le but de travail était de déterminer la fréquence des parasitoses digestives opportunistes chez les patients infectés par le VIHMatériels et méthodes :Etude retroprospective descriptive de 20 mois déroulée dans le service de maladies infectieuses de casablanca. Ont été inclus tous les patients infectés par le VIH et présentant une parasitose digestive opportuniste confirmée à l’EPS.Résultats :Nous avons colligé 70 patients. L’âge moyen était de 37 ans. La médiane de lymphocytes CD4 était de 62celellule/mm³. Les parasitoses opportunistes digestives étaient révélatrices de l’infection à VIH dans 54 cas (77%) et dans 16 cas (23%) elles sont survenues au décours d’un échec thérapeutique. Tous les patients présentaient des diarrhées liquidiennes. Ces agents parasitaires opportunistes étaient isolés seuls dans 56 cas dont 28 cas de Cryptosporidiose (40%), 22 cas de microsporidiose (31%), 4 cas d’Isospora belli (6%) et 2 cas de cyclosporose (3%). Elles étaient associées dans 14 cas dont 13 cas de Cryptosporidiose + Microsporidiose (18,57%) et 1 cas de Cryptosporidiose + Isosporose (1,43%). Sous HARRT, 86% des patients ont bien évolué (n=60) et nous avons enregistré 14% de décès (n=10).Conclusion :Les parasitoses digestives opportunistes restent fréquentes dans notre contexte à cause du diagnostic tardif du VIH/SIDA. Le dépistage précoce du VIH permettra de les prévenir