Pierre Sellier

Effect of a short-term HAART on SIV load in macaque tissues is dependent on time of initiation and antiviral diffusion

BackgroundHIV reservoirs are rapidly established after infection, and the effect of HAART initiated very early during acute infection on HIV reservoirs remains poorly documented, particularly in tissue known to actively replicate the virus. In this context, we used the model of experimental infection of macaques with pathogenic SIV to assess in different tissues: (i) the effect of a short term HAART initiated at different stages during acute infection on viral dissemination and replication, and (ii) the local concentration of antiviral drugs.ResultsHere, we show that early treatment with AZT/3TC/IDV initiated either within 4 hours after intravenous infection of macaques with SIVmac251 (as a post exposure prophylaxis) or before viremia peak (7 days post-infection [pi]), had a strong impact on SIV production and dissemination in all tissues but did not prevent infection. When treatment was initiated after the viremia peak (14 days pi) or during early chronic infection (150 days pi), significant viral replication persists in the peripheral lymph nodes and the spleen of treated macaques despite a strong effect of treatment on viremia and gut associated lymphoid tissues. In these animals, the level of virus persistence in tissues was inversely correlated with local concentrations of 3TC: high concentrations of 3TC were measured in the gut whereas low concentrations were observed in the secondary lymphoid tissues. IDV, like 3TC, showed much higher concentration in the colon than in the spleen. AZT concentration was below the quantification threshold in all tissues studied.ConclusionsOur results suggest that limited antiviral drug diffusion in secondary lymphoid tissues may allow persistent viral replication in these tissues and could represent an obstacle to HIV prevention and eradication.

Recurrent Subcutaneous Infection Due to Scopulariopsis brevicaulis in a Liver Transplant Recipient

We describe a case of recurrent Scopulariopsis brevicaulis subcutaneous infection, which occurred 6 years after the patient underwent liver transplantation. Combined surgery and long-term oral therapy with terbinafine resulted in a favorable outcome, although this is not the rule in the previously reported S. brevicaulis infections in immunocompromised patients.

Dynamics of viral replication in blood and lymphoid tissues during SIVmac251 infection of macaques

BackgroundExtensive studies of primary infection are crucial to our understanding of the course of HIV disease. In SIV-infected macaques, a model closely mimicking HIV pathogenesis, we used a combination of three markers -- viral RNA, 2LTR circles and viral DNA -- to evaluate viral replication and dissemination simultaneously in blood, secondary lymphoid tissues, and the gut during primary and chronic infections. Subsequent viral compartmentalization in the main target cells of the virus in peripheral blood during the chronic phase of infection was evaluated by cell sorting and viral quantification with the three markers studied.ResultsThe evolutions of viral RNA, 2LTR circles and DNA levels were correlated in a given tissue during primary and early chronic infection. The decrease in plasma viral load principally reflects a large decrease in viral replication in gut-associated lymphoid tissue (GALT), with viral RNA and DNA levels remaining stable in the spleen and peripheral lymph nodes. Later, during chronic infection, a progressive depletion of central memory CD4+ T cells from the peripheral blood was observed, accompanied by high levels of viral replication in the cells of this subtype. The virus was also found to replicate at this point in the infection in naive CD4+ T cells. Viral RNA was frequently detected in monocytes, but no SIV replication appeared to occur in these cells, as no viral DNA or 2LTR circles were detected.ConclusionWe demonstrated the persistence of viral replication and dissemination, mostly in secondary lymphoid tissues, during primary and early chronic infection. During chronic infection, the central memory CD4+ T cells were the major site of viral replication in peripheral blood, but viral replication also occurred in naive CD4+ T cells. The role of monocytes seemed to be limited to carrying the virus as a cargo because there was an observed lack of replication in these cells. These data may have important implications for the targeting of HIV treatment to these diverse compartments.

Description of liver disease in a cohort of HIV/HBV coinfected patients

BACKGROUND Factors associated with advanced liver disease have been incompletely explored in HIV/HBV coinfected patients. OBJECTIVES To describe liver-related morbidity, mortality, and related risk factors, in HIV/HBV coinfected patients. STUDY DESIGN We followed-up 107 consecutive HIV/HBV coinfected patients. Clinical, biological and virological data were collected every 3 months. Liver-related mortality and a composite score were used to define advanced liver disease. RESULTS The patients were mainly sub-Saharan Africans (61%) or Europeans (33%). Forty-four percent of patients had liver biopsy, 78% of patients received lamivudine. Advanced liver disease (ALD) was diagnosed in 19/107 patients during follow-up (mean 4.8 years): 10 extensive fibrosis, 5 cirrhosis, 3 hepatocellular carcinoma resulting from cirrhosis, and 1 fulminant hepatitis following lamivudine withdrawal. Eleven patients died, 4 from HBV-related liver disease. In univariate analysis, male gender, mean HIV and HBV viral loads, and raised AST/ALT transaminases were associated with increased risk of ALD. The strongest associations, in a multivariate model, were mean AST transaminase and cumulated time receiving lamivudine, with a favourable effect. 39% of patients with increased mean AST presented with ALD, versus 7% when normal mean AST (Relative Risk 5.5). CONCLUSIONS During HIV/HBV coinfection, transaminase levels are strongly associated with ALD. Normal mean AST has a high negative predictive value, contrary to previously reported data in HIV/HCV patients.

Comparative Evaluation of Adherence to Antiretroviral Therapy in Sub-Saharan African Native HIV-Infected Patients in France and Africa

Patients with human immunodeficiency virus (HIV) infection who were native to sub-Saharan Africa but lived in France were less adherent to antiretroviral therapy during a visit back to Africa, compared with their level of adherence in France. This was mainly related to self-perceived insufficient support from family members and/or fear of the consequences of disclosure of their HIV infection status to their family.

Central nervous system tuberculomas in 23 patients.

Abstract Central nervous system tuberculomas are rare and severe complications of tuberculosis. We performed a retrospective study of the clinical, biological, radiological, pathological, and therapeutic features of 23 patients. Almost all patients were from countries with a high prevalence of tuberculosis (22/23). Their mean age was 37.3 y; 43.5% had laboratory-proven meningitis and 17.4% had biopsy-proven tuberculomas. For most of the patients, the duration of treatment lasted 13–18 months. The disease was controlled without relapse in16 patients and 3 patients died. Diagnosis relies on magnetic resonance imaging and bacteriological specimens from all the involved sites. This study indicates that central nervous system tuberculomas occur in young patients from high risk countries. The anti-tuberculous drug regimen in this series was 2 months of isoniazid, rifampin, pyrazinamide and ethambutol, followed by at least 10 months of isoniazid and rifampin. Results did not contradict the use of a 12-month regimen as currently recommended.

Fatal interruption of a 3TC-containing regimen in a HIV-infected patient due to re-activation of chronic hepatitis B virus infection

PIERRE SELLIER, PHILIPPE CLEVENBERGH, MARIE-CHRISTINE MAZERON, DOMINIQUE CAZALS-HATEM, JOHN EVANS, JEANINE CERVONI, ESMA BADSI, MARC BENDENOUN, MYRIAM DIEMER, VALERIE VINCENT, CHARLES CAULIN and JEAN-FRANCOIS BERGMANN From the Service de Médecine Interne A, Hôpital Lariboisière, Paris, Service de Bactériologie-Virologie, Hôpital Lariboisière, Paris, Service d’Anatomie et Cytologie Pathologiques, Hôpital Beaujon, Clichy, and Département de Médecine, Hôpital Paul Brousse, Villejuif, France

Incidence d’atteinte hépatique avancée dans une cohorte de patients co-infectés VIH et hépatite B

ésultats.– Parmi une file active de plus de 4000 patients, 143 ont présenté un ancer, incluant 93 cancers non classant sida et 50 classant sida. L’âge moyen es patients était de 48,8 ans et 83 % étaient des hommes. Au diagnostic de ancer, 70 patients avaient un ARN VIH > 500 copies/ml et 43 patients un taux e lymphocytes CD4+ < 200 par millimètres cube, 111 patients étaient traités ar antirétroviraux. u total, 14 patients avaient au moins une ADNémie CMV détectable dans les ans précédant le diagnostic de cancer. Parmi ces 14 patients, 10 ont présenté un ancer classant sida et 4 un cancer non classant sida. Au diagnostic de cancer, 11 vaient un ARN VIH > 500 copies/ml et 9 un taux de CD4 < 200 par millimètres ube, 7 étaient sous traitement antirétroviral. onclusion.– Parmi les patients infectés par le VIH affectés d’un cancer classant u non classant, 10 % présentaient au moins une ADNémie CMV positive dans es 3 ans précédant le diagnostic. Ceux-ci semblaient plus immunodéprimés et vaient plus souvent un ARN VIH > 500 copies/ml que les patients n’ayant pas résenté d’ADNémie CMV positive. Une étude cas-témoin est actuellement enée pour identifier si la prévalence de l’ADNémie CMV chez les patients ffectés d’un cancer est différente de celle observée chez les patients infectés ar le VIH, indemnes de cancer.