Effects of Intermittent IL-2 Alone or with Peri-Cycle Antiretroviral Therapy in Early HIV Infection: The STALWART Study

The Study of Aldesleukin with and without antiretroviral therapy (STALWART) evaluated whether intermittent interleukin-2 (IL-2) alone or with antiretroviral therapy (ART) around IL-2 cycles increased CD4+ counts compared to no therapy

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

Track D Social Science, Human Rights and Political Science

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/138414/1/jia218442.pd

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

RÉTINITE À CYTOMÉGALOVIRUS CHEZ LES PATIENTS SOUS THÉRAPIE ANTIRÉTROVIRALE HAUTEMENT ACTIVE (HAART)

L’infection à cytomégalovirus (CMV) représente l’infection opportuniste la plus fréquente et la plus grave qui survient au cours de la phase tardive de l’infection rétrovirale. L’atteinte rétinienne est de loin la plus fréquente des localisations. Depuis l’introduction de la trithérapie antirétrovirale hautement active en 1996, l’incidence de la rétinite à CMV a diminué de plus de 80%. L’utilisation du Ganciclovir par voie générale a largement amélioré le pronostic vital et fonctionnel de ces patients.Le but du travail est de rapporter les données épidémiologiques, cliniques et thérapeutiques de notre série, ainsi qu’une revue détaillée des protocoles thérapeutiques récemment adoptés dans la littérature.Matériel et méthodes : Etude rétrospective non comparative d’une série de cas menée au service des maladies infectieuses du CHU Ibn Rochd et au service d’ophtalmologie adulte de l’hôpital 20 Août 1953. L’étude a inclus 9 patients VIH positifs, présentantune rétinite à cytomégalovirus confirmée par l’aspect clinique des lésions rétiniennes, la sérologie CMV (Ig M, Ig G) et la recherche positive du CMV par la technique d’amplification génique (PCR) dans le sang. Le traitement d’attaque à base de Ganciclovir par voie intraveineuse à la dose de 10mg/kg/j pendant 21 jours en association avec la trithérapie antirétrovirale hautement active a été instauré chez tous les patients suivi d’un traitement d’entretien.Résultats : L’âge moyen des patients était de 35,4 ans. L’acuité visuelle initiale était inférieure à 1/10 chez 7 patients. L’atteinte rétinienne était unilatérale chez tous les patients. Le taux moyen initial de CD4 + était de 40 cellules/mm3. L’évolution était favorable chez 67% des cas (6 patients) avec une amélioration de l’acuité visuelle finale, une diminution de l’inflammation vitréenne et la cicatrisation des lésions rétiniennes. Trois patients sont décédés au cours du traitement.Discussion : Dans notre série, le taux de guérison après traitement intraveineux de Ganciclovir seul était de 67% ce qui rejoint les données de la littérature. Le Ganciclovir par voie intraveineuse est actuellement la molécule de référence dans le traitement des rétinites à CMV. Il permet d’arrêter la progression de l’infection, de diminuer le risque de récidive et de bilatéralisation. Plusieurs études randomisées ont évalué les implants intravitréens de Ganciclovir, ces derniers semblent offrir une bonne compliance et un contrôle satisfaisant des récidives à long terme.Conclusion : La rétinite à CMV est la principale cause de la baisse sévère de l’acuité visuelle chez les patients au stade SIDA maladie. Son pronostic a été largement amélioré par l’association de la trithérapie antirétrovirale hautement active et du Ganciclovir