Pascale Leclercq

Change in transaminases in hepatitis C virus- and HIV-coinfected patients after highly active antiretroviral therapy : Differences between complete and partial virologic responders?

Patients with HIV and hepatitis C virus (HCV) coinfection have more severe hepatitis-related disease than do patients with HCV infection alone. Highly active antiretroviral therapy (HAART) with protease inhibitor appears to restore pathogen-specific immune responses, especially in patients with persistent undetectable HIV viral load. To evaluate the potent impact of immune restoration induced by HAART on the course of HCV-related disease, HCV viremia and levels of transaminases were compared between two groups of patients: 10 HIV/HCV-coinfected patients with persistently undetectable HIV viremia (group A) and 12 HIV/HCV-coinfected patients with persistent detectable HIV viremia. No difference was detected in HCV viral load in either group. An increase in transaminases was found only in patients with persistent undetectable HIV viral load, which was correlated with the increase in CD8+ T cells. This may suggest that the restoration of CD8+ T cell cytotoxicity could lead to an enhancement of hepatitis C-related disease in HCV/HIV-coinfected patients receiving HAART.

Human herpesvirus 8 and Epstein Barr-virus in a cutaneous B-cell lymphoma and a malignant cell line established from the blood of an AIDS patient.

Human Herpesvirus 8 (HHV-8) has been consistently associated with Primary Effusion Lymphoma (PEL or body-cavity-based lymphoma) but not with other lymphomas. This paper reports on an AIDS patient without obvious malignant effusion in body cavities but with a cutaneous lymphoma where HHV-8 and Epstein-Barr virus (EBV) were detected by PCR and electron microscopy. Both viruses were also detected in all the cells of a malignant cell line (BBG1) established from the patients peripheral blood mononuclear cells. As in PEL and PEL-derived cell lines, both the tumor and the lines lacked B-antigen expression in immunological studies but were of the same B origin as shown by clonal immunoglobulin gene rearrangements. In contrast to other co-infected cell lines, BBG1 and subclones spontaneously expressed the HHV-8 lytic antigens p40, p27, p60 and the EBV transforming latent antigen EBNA2. These data suggest that the clinical and biological features of HHV-8-and EBV-associated lymphomas could be wider than has been described to date in PEL particularly with the in vivo presence of circulating malignant dually-infected cells engaged in a spontaneous HHV-8 lytic infection.

Performance of an antigen-antibody combined assay for hepatitis C virus testing without venipuncture.

BACKGROUND Hepatitis C virus (HCV) is underdiagnosed and therefore increasing the opportunities for HCV testing without venipuncture may be useful. OBJECTIVES We evaluated the analytical performance of a modified, commercially available, combined HCV antigen-antibody assay (cEIA) (Monolisa(®) HCV-Ag-Ab-ULTRA) and a commercially available point-of-care (POC) device (OraQuick(®) HCV) on fingerstick blood (FSB) and oral mucosal transudate (OMT). STUDY DESIGN FSB, OMT and serum samples were collected from 113 cases of HCV-antibody-positive patients and 88 HCV-antibody-negative controls. The HCV-antibody-positive group included 63 patients with quantifiable HCV-RNA (56%) and 17 HIV/HCV co-infected patients (15%). FSB and OMT specimens were collected as dried blood spots (DBSs) or with the OraSure collection system, before testing with cEIA. RESULTS With FSB specimens, the cEIA and the POC device exhibited 100% specificity and 98.2% and 97.4% sensitivity, respectively. The specificity of the cEIA in FSB sharply decreased if stored 3days at room temperature. With OMT specimens, the cEIA sensitivity (71.7%) and specificity (94.3%) were significantly lower than the performance of OraQuick(®) HCV (sensitivity, 94.6%; specificity, 100%). The optical densities obtained with the cEIA in FSB and OMT were lower in HIV/HCV co-infected patients compared with HCV monoinfected patients. CONCLUSION The cEIA using FSB specimens collected on DBSs preserved in appropriate storage conditions was a reliable alternative, equivalent to the POC assay, for HCV testing without venipuncture. The cEIA was not adapted for HCV testing on OMT.

Infection par le virus de l’immunodéficience humaine et diabète : vécu et qualité de vie des patients confrontés à deux maladies chroniques

OBJECTIVES Diabetes mellitus is frequently associated with HIV infection but theres only limited evidence regarding the control and impact of this co-morbidity. This study aimed to estimate the prevalence of diabetes, compliance with treatment, perception and quality of life of HIV patients with diabetes. METHODS We conducted a cross-sectional study among patients treated for diabetes and registered in the DMI2 databasis in a French university hospital in January 2010. Clinical assessment and follow-up data were collected using chart review and self-administered questionnaires. Quality of life (MOS SF-12) and compliance with treatment (simplified medication adherence questionnaire) were assessed using validated scales. RESULTS The prevalence of treated diabetes mellitus was 3.9% (29/748, 95% confidence interval, 2.6% to 5.5%). Among these 29 HIV diabetic patients, 93% had a virologic control of HIV infection while only 22% had well-controlled diabetes. Ninety-six percent of patients were scared to die from HIV-which was rated as the main pathology-compared with 71% of patients for diabetes. The mean score for physical quality of life was 43.1 (13.2), which was lower than estimates for overall population. Non-compliance with treatment was reported for 35% of patients. DISCUSSION Although anti-retroviral treatments turned HIV infection into a chronic disease, patient perception was not altered. This study shows a better control of HIV infection than diabetes. We have to find out ways (e.g. patient education programs, annual multidisciplinary consultation...) to give the patient a global feel for his health thereby improving prognosis and quality of life.

Reconstitution immunitaire et infections à mycobactéries sous traitement antirétroviral : Étude rétrospective de 6 observations

Resume Introduction Peu apres l’introduction d’un traitement anti-retroviral hautement actif (Haart), quelques patients ont une deterioration de leur etat clinique due a la reconstitution de leur systeme immunitaire. Les mycobacteries sont les principaux agents compliquant cette periode de reconstitution immunitaire. Observations Nous avons observe 6 sujets, sur une file active de 650 patients suivis par an, ayant developpe ou aggrave une infection a mycobacteries apres introduction d’une therapie Haart. Les manifestations cliniques les plus frequentes etaient : adenopathies (4/6), hyperthermie (3/6), douleur thoracique (2/6), abces (2/6), degradation neurologique (1/6). Discussion Apres une reactivation ou une aggravation tuberculeuse a l’instauration d’une therapie Haart, il faut poursuivre ce traitement, instaurer ou continuer la therapie antituberculeuse, evaluer le recours aux corticoides. Il est necessaire de chercher de facon active les infections opportunistes pouvant se reactiver avant d’instaurer un traitement de type Haart chez des patients au stade sida.INTRODUCTION Soon after starting highly active antiretroviral therapy (HAART), some patients experience clinical deterioration due to the reactivation of their immune system. Mycobacteria are the principal agents complicating this immune reconstitution period. CASES A retrospective examination of patients with mycobacterial disease before or shortly after beginning HAART at Grenoble University Hospital from January 2001 through July 2004 identified six subjects (among 650 outpatients per year) with a new or aggravated mycobacterial disease after starting HAART. Clinical manifestations were: adenopathy (4/6), hyperthermia (3/6), thoracic pain (2/6), abscess (2/6), and neurological deterioration (1/6). DISCUSSION Severely immunosuppressed patients who begin HAART may reactivate or aggravate a mycobacterial disease such as tuberculosis. In such cases, current recommendations call for continuing HAART, beginning or continuing the antimycobacterial therapy, and considering corticosteroids on a case-by-case basis. For patients with AIDS, opportunistic infections that might be reactivated should be actively sought before HAART.

Ultradeep sequencing of B and non-B HIV-1 subtypes: Viral diversity and drug resistance mutations before and after one month of antiretroviral therapy in naive patients

BACKGROUND Ultradeep pyrosequencing technologies permit an assessment of the genetic diversity and the presence and frequency of minority variants in a viral population. The effect of these parameters on the outcome of highly active antiretroviral therapy (HAART) in HIV-infected patients is poorly understood. OBJECTIVES The present study used the pyrosequencing Roche 454 prototype assay to determine whether antiretroviral efficacy is correlated with viral diversity and minority drug resistance mutations in HIV-infected treatment-naive patients and to compare assay performance in B and non-B subtypes. STUDY DESIGN The study included 30 HIV-1 infected naive patients (20 with subtype non-B and 10 with subtype B). Ultradeep pyrosequencing of protease and reverse transcriptase genes was performed at baseline and 1 month after HAART initiation. Plasma HIV VL was measured at 0 and after 1, 3, and 6 months of HAART. RESULTS Pre-HAART minority drug resistance mutations were observed to NRTI in 4 patients, to NNRTI in 6 patients, and to PI in 1 patient; there was no difference in HAART-induced VL decay between patients. Pre-HAART diversity was significantly correlated with the time elapsed since HIV-1 infection diagnosis, but not with the subtype, VL, or CD4 count. Patients with an undetectable VL after 3 months of HAART had a higher pre-HAART diversity. Pre- and post-HAART diversities were not statistically different. There was no difference in assay performance between subtype B and non-B. CONCLUSIONS A high pre-HAART viral diversity might have a positive effect on the outcome of HAART. Pre-therapeutic minority drug resistance mutations are uncommon in naive patients.

Influence of the First Consultation on Adherence to Antiretroviral Therapy for HIV-infected Patients.

Background: Physician attitude influences the way patients cope with diagnosis and therapy in chronic severe diseases such as cancer. Previous studies showed that such an effect exists in HIV care; it is likely that it begins with the first contact with a physician. Objective: We aimed to explore in HIV-infected persons their perception of the first consultation they had with an HIV specialist (PFC-H), and whether this perception correlates with adherence to antiretroviral therapy. Method: The study was conducted in Grenoble University Hospital, France, a tertiary care center. Every antiretroviral-experienced patient was asked to freely complete a self-reported, anonymous questionnaire concerning retrospective PFC-H, present adherence (Morisky scale), and present perceptions and beliefs about medicine (BMQ scale). Results: One hundred and fifty-one questionnaires were available for evaluation. PFC-H score and adherence were correlated, independently from age, gender, and numbers of pill(s) and of pill intake(s) per day. BMQ score also correlated with adherence; structural equation analysis suggested that the effect of PFC-H on adherence is mediated by positive beliefs. Conclusion: These results suggest that for HIV-infected persons, the perceptions remaining from the first consultation with an HIV specialist physician influence important issues such as adherence and perception about medicine. Physicians must be aware of this potentially long-lasting effect.