Perception of PrEP-related stigma in PrEP users: Results from the ANRS-PREVENIR cohort.

INTRODUCTION: Since the advent of HIV pre-exposure prophylaxis (PrEP), stigma has been shown to be a major barrier to its uptake and adherence. It is therefore essential to define the proportion of users who consider that PrEP can negatively impact their image and the factors associated with this perception. METHOD: We performed a multivariable logistic regression on data from the 2567 participants in the ANRS-PREVENIR study who answered the outcome question. RESULTS: Almost one-third of the sample (comprising mostly cisgender men who have sex with men [94.3%]) considered that taking PrEP could give others a negative image of them. Younger participants (adjusted odds ratio [aOR] 0.98; 95% confidence interval [CI] 0.97-0.99) and more psychologically vulnerable participants (i.e., lower self-esteem score [aOR 0.98; 95% CI 0.96-0.99] and higher depression score [aOR 1.02; 95% CI 1.00-1.03]) were also more likely to have this perception. In contrast, participants encouraged to take PrEP by their main partner (aOR 0.67; 95% CI 0.51-0.88) and friends (aOR 0.79; 95% CI 0.66-0.95), and those who protected themselves more because they had knowledge of their most recent sexual partner's HIV status (aOR 0.83; 95% CI 0.69-0.99) and systematic use of PrEP and/or condoms during intercourse in the previous 3 months (aOR 0.80; 95% CI 0.67-0.96) were less likely to have this perception. DISCUSSION: Given the strong interrelation between stigmatization (real or perceived), risky behaviours and adherence, our results emphasize the need for HIV prevention campaigns to promote a positive image of PrEP users. They also show that stigmatization and its effects need to be fully considered to improve HIV prevention offers to current and potential PrEP users who are most likely to be psychologically vulnerable.

A Randomized Placebo-Controlled Efficacy Study of a Prime Boost Therapeutic Vaccination Strategy in HIV-1-Infected Individuals: VRI02 ANRS 149 LIGHT Phase II Trial.

In this placebo-controlled phase II randomized clinical trial, 103 human immunodeficiency virus type 1 (HIV-1)-infected patients under cART (combined antiretroviral treatment) were randomized 2:1 to receive either 3 doses of DNA GTU-MultiHIV B (coding for Rev, Nef, Tat, Gag, and gp160) at week 0 (W0), W4, and W12, followed by 2 doses of LIPO-5 vaccine containing long peptides from Gag, Pol, and Nef at W20 and W24, or placebo. Analytical treatment interruption (ATI) was performed between W36 to W48. At W28, vaccinees experienced an increase in functional CD4+ T-cell responses (P < 0.001 for each cytokine compared to W0) measured, predominantly against Gag and Pol/Env, and an increase in HIV-specific CD8+ T cells producing interleukin 2 (IL-2) and tumor necrosis factor alpha (TNF-α) (P = 0.001 and 0.013, respectively), predominantly against Pol/Env and Nef. However, analysis of T-cell subsets by mass cytometry in a subpopulation showed an increase in the W28/W0 ratio for memory CD8+ T cells coexpressing exhaustion and senescence markers such as PD-1/TIGIT (P = 0.004) and CD27/CD57 (P = 0.044) in vaccinees compared to the placebo group. During ATI, all patients experienced viral rebound, with the maximum observed HIV RNA level at W42 (median, 4.63 log10 copies [cp]/ml; interquartile range [IQR], 4.00 to 5.09), without any difference between arms. No patient resumed cART for CD4 cell count drop. Globally, the vaccine strategy was safe. However, a secondary HIV transmission during ATI was observed. These data show that the prime-boost combination of DNA and LIPO-5 vaccines elicited broad and polyfunctional T cells. The contrast between the quality of immune responses and the lack of potent viral control underscores the need for combined immunomodulatory strategies. (This study has been registered at ClinicalTrials.gov under registration no. NCT01492985.)IMPORTANCE In this placebo-controlled phase II randomized clinical trial, we evaluated the safety and immunogenicity of a therapeutic prime-boost vaccine strategy using a recombinant DNA vaccine (GTU-MultiHIV B clade) followed by a boost vaccination with a lipopeptide vaccine (HIV-LIPO-5) in HIV-infected patients on combined antiretroviral therapy. We show here that this prime-boost strategy is well tolerated, consistently with previous studies in HIV-1-infected individuals and healthy volunteers who received each vaccine component individually. Compared to the placebo group, vaccinees elicited strong and polyfunctional HIV-specific CD4+ and CD8+ T-cell responses. However, these immune responses presented some qualitative defects and were not able to control viremia following antiretroviral treatment interruption, as no difference in HIV viral rebound was observed in the vaccine and placebo groups. Several lessons were learned from these results, pointing out the urgent need to combine vaccine strategies with other immune-based interventions.

[Pneumocystis jirovecii and quantitative PCR: Pneumonia or colonization?] / Pneumocytis jirovecii et PCR quantitative : pneumonie ou colonisation à Pneumocystis jirovecii ?

BACKGROUND: Quantitative PCR to detect Pneumocystis jirovecii (Pj) is a new tool for the diagnosis of Pneumocystis jirovecii pneumonia (PJP). The yield of this technique, in cases of low fungal burden, when the standard technique using immunofluorescence (IF) is negative, needs to be evaluated. METHODS: We retrospectively reviewed the charts of all patients with a positive PCR but negative IF test (PCR+/IF-) in bronchoalveolar lavage (BAL) fluid performed over one year. We used an algorithm based on underlying immunosuppression, clinical picture, thoracic CT scan appearances, existence of an alternative diagnosis and the patient's outcome on treatment. Using this, each case was classified as probable PJP, possible PJP or colonization. RESULTS: Among the 416 BAL performed, 48 (12%) were PCR+/IF- and 43 patients were analyzed. Patients were mostly male (56%) with a median age of 60 years. Thirty-five (84%) were immunocompromised: 4 (9%) HIV-infected patients, 26 (60%) with hematologic or solid organ cancer, 3 (7%) were renal transplant recipients. Seven (16%) were classified as probable PPJ and 9 (21%) as possible PJP. Patients with a probable or possible PJP were more frequently admitted to the ICU (P<0.02) and had higher risk of death (P<0.01) when compared to those with colonization. Median PCR levels were very low and were not different between PJP or colonized patients (P=0.23). CONCLUSIONS: Among patients with a positive Pj PCR in BAL but with negative IF, only 37% had probable or possible PJP and PCR could not discriminate PJP from colonization.

Factors associated with tuberculosis-associated haemophagocytic syndrome: a multicentre case-control study.

SETTING: Tuberculosis (TB) is a potential trigger of haemophagocytic syndrome (HS) but little is known about the features of TB-associated HS.OBJECTIVE: To assess the risk factors associated with HS in patients with TB.DESIGN: We performed a multicentre case-control study assessing the medical records of adult patients diagnosed with proven TB with (TB/HS+) or without (TB/HS-) associated HS.RESULTS: Twenty-one patients with TB/HS+ (24% women, median age, 37 years [IQR 30-48]) were included in the study. Eleven patients (52%) were infected with human immunodeficiency virus and seven patients (33%) were immunocompromised due to other reasons. TB was disseminated in 17 patients (81%). Compared with 50 control TB patients (TB/HS-), patients with TB/HS+ were more likely to be immunocompromised (86% vs. 18%; P < 0.001) and to present with disseminated TB (80% vs. 12%; P < 0.001). The outcome was poorer in patients with TB/HS+, with a higher admission rate to intensive care (71% vs. 0%; P < 0.001) and a higher risk of death (38% vs. 7%; P = 0.005).CONCLUSION: TB/HS+ occurred more likely in immunocompromised patients and severely impaired the prognosis of TB. Further studies are needed to devise therapeutic strategies for patients with TB/HS+.

HIV preexposure prophylaxis: An essential, safe and effective prevention tool for sexual health.

Preexposure prophylaxis of HIV with antiretroviral drugs is a prevention tool available in France since 2016, combined with the prevention methods already used (condoms, post-exposure treatment, rapid treatment of diagnosed HIV infections, etc.). It is targeted at populations at high risk of HIV infection, especially men who have sex with men, for whom traditional prevention methods are insufficient. We collected clinical research data, which resulted in the launch of preexposure prophylaxis in the United States and then elsewhere in the world, safety, tolerability and cost data, as well as ongoing research data (new molecules/methods of administration). We also provided an update of its use in France.

Incidence, risk factors, and outcome of multidrug-resistant Acinetobacter baumannii acquisition during an outbreak in a burns unit.

BACKGROUND: Multidrug-resistant Acinetobacter baumannii (MR-AB) can cause outbreaks in a burns unit. AIM: To study the incidence, risk factors and outcome of MR-AB colonization during an outbreak. METHODS: A prospective study was conducted from April to November 2014 in a burns unit in Paris. Weekly surveillance cultures of patients and their environment were performed. MR-AB acquisition, discharge, or death without MR-AB colonization were considered as competing events. To identify risk factors for colonization, baseline characteristics and time-dependent variables were investigated in univariate and multivariate analyses using Cox models. MR-AB strains were genotypically compared using multi-locus sequence typing. FINDINGS: Eighty-six patients were admitted in the burns unit during the study period. Among 77 patients without MR-AB colonization at admission, 25 (32%) acquired MR-AB with a cumulative incidence of 30% at 28 days (95% CI: 20-40). Median time to MR-AB acquisition was 13 days (range: 5-34). In multivariate analysis, risk factors for MR-AB acquisition were ≥2 skin graft procedures performed [hazard ratio (HR): 2.97; 95% confidence interval (CI): 1.10-8.00; P = 0.032] and antibiotic therapy during hospitalization (HR: 4.42; 95% CI: 1.19-16.4; P = 0.026). A major sequence type of MR-AB (ST2) was found in 94% and 92% of patients and environmental strains, respectively, with all strains harbouring the blaOXA-23 gene. MR-AB colonization increased length of hospitalization (HR: 0.32; 95% CI: 0.17-0.58; P = 0.0002) by a median of 12 days. CONCLUSION: A high incidence of MR-AB acquisition was seen during this outbreak with most strains from patients and their environment belonging to single sequence type. MR-AB colonization was associated with more skin graft procedures, antibiotic use, and prolonged hospitalization.

Cytochrome 2B6 polymorphism and efavirenz-induced central nervous system symptoms : a substudy of the ANRS ALIZE trial.

OBJECTIVES: Single nucleotide polymorphisms in the cytochrome P450 (CYP) 2B6 gene have been associated with high interindividual variation in efavirenz pharmacokinetics. However, clinical data on the relationship of CYP2B6 polymorphisms with the occurrence of efavirenz-induced central nervous system (CNS) symptoms are limited. METHODS: We analysed four polymorphisms in the CYP2B6 (516 G>T), CYP3A5 (6986 A>G) and ATP-binding cassette, sub-family B, member 1 (ABCB1) (2677 G>T/A and 3435 C>T) genes in HIV-infected adults virologically suppressed on a protease inhibitor-based regimen who switched to a regimen containing emtricitabine, didanosine and efavirenz in the setting of the ANRS ALIZE trial. Kaplan-Meier methods and Cox regression analysis were used to investigate their association with efavirenz plasma levels and CNS events up to 48 months after switching. RESULTS: In total, 191 patients with a median age of 41 years, who were 87% male and 85% Caucasian, were enrolled in the study. Variant allelic frequencies were 0.49, 0.93, 0.59 and 0.63 for CYP2B6 516, CYP3A5 392, ABCB1 2677 and ABCB1 3435, respectively. The median efavirenz plasma concentration (MEPC) was 2.2 mg/L [interquartile range (IQR) 1.7-2.8 mg/L] and was significantly higher in patients with the deficient CYP2B6 516T. Overall, 242 CNS events were reported in 104 individuals (54%). No correlation was found between MEPC and CNS events. The occurrence of a first CNS event was lower in patients with the CYP2B6 516 G/G genotype vs. CYP2B6 516 T genotypes [50% (IQR: 40-60%) vs. 66% (IQR: 56-75%), respectively; P = 0.02]. In an adjusted Cox regression model, there was a tendency towards a higher risk of a first CNS event among carriers of the variant CYP2B6 516 T allele (relative risk 1.4 [95% CI, 0.99-2.1]; P?=?.06), compared with noncarriers. CONCLUSIONS: The deficient CYP2B6 516 T allele is associated with higher efavirenz plasma drug levels and more frequent CNS-related symptoms.

Five cases of acute Zika virus infection in French women of reproductive age returning from Central and South America.

INTRODUCTION: The favorable season for Aedes albopictus circulation has started in Europe and may lead to autochthonous transmission of Zika virus. Health care providers should be familiar with evocative clinical presentations and able to give updated information to women of reproductive age infected by Zika virus. OBSERVATIONS: We report five laboratory-confirmed Zika virus infections imported to metropolitan France from Central and South America between January and April, 2016. The five young women were not connected and not pregnant; common presentation combined a rash with persistent arthralgia. Zika virus was identified by RT-PCR from serum or urines, between two and eight days after the onset of the symptoms. CONCLUSION: As the duration of potential materno-foetal infectivity is still unknown, we were unable to answer with certitude to the patients' questions about the time interval to respect before attempting a pregnancy: one of them became pregnant one month after the diagnosis.

Pre-exposure prophylaxis: a useful tool to prevent human immunodeficiency virus infection?

The aim of preventive measures against human immunodeficiency virus (HIV) is to reduce the incidence of HIV infection in the general population and in high-risk groups, such as men having sex with men (MSM), and to reduce the risk that a given individual will contract or spread the virus. Male and female condoms, post-exposure prophylaxis and circumcision are preventive methods currently recognized or promoted worldwide. Although modest success has been reported in a phase-III vaccine trial, other methods are being evaluated, such as vaginal and rectal microbicides, and pre-exposure prophylaxis (PrEP). Herein, we discuss results from prevention trials, especially those focusing on PrEP and particularly on recent results from 'on-demand' PrEP regimens. The efficacy of PrEP (rates of 0%-86%) is strongly correlated with adherence and plasma concentrations of antiretrovirals. Adverse events are rare. Selection of emtricitabine-resistant strains is mainly reported in individuals with an undiagnosed HIV infection using PrEP. PrEP is now strongly recommended in WHO prevention programmes for individuals at substantial risk for HIV with a view to controlling this epidemic by 2030.

Oclusión de rama arterial retiniana en un paciente con ojo único. Abordaje mediante láser Nd: YAG / Branch retinal artery occlusion in a patient with one eye. Laser Nd: YAG approach

CASO CLÍNICO: Varón de 82 años que acude de urgencia al servicio de oftalmología por disminución súbita e indolora de la agudeza visual de su ojo izquierdo (OI), fue diagnosticado de una oclusión de rama arterial retiniana(ORAR) con émbolo visible. En 2012 padeció de una oclusión de arteria central retiniana (OACR) en el ojo derecho (OD). Se realizó embólisis con láser Nd:YAG en el OI, recuperando completamente el flujo arterial retiniano y mejorando el campo visual sin complicaciones secundarias. Conclusiones: La embólisis mediante láser Nd:YAG debe ser considerada en pacientes con ORAR con émbolo visible. Los riesgos y beneficios deben ser evaluados y comparados con la posible pérdida de agudeza visual, y otras complicaciones producidas por la oclusión arterial

CLINICAL CASE: An 82-year-old man was admitted to the emergency department complaining of a sudden painless visual loss in his left eye (OS). He was diagnosed with branch retinal artery occlusion (BRAO) with a visible embolus. In 2012, he had a central artery occlusion (CRAO) in his right eye (OD). An embolysis with Nd:YAG laser was attempted, the retinal arterial blood flow was restored completely and the visual field was improved, with no secondary complications. CONCLUSIONS: Nd:YAG laser embolysis is a treatment to be considered in patients with BRAO with a visible embolus. The risks and benefits of the procedure should be evaluated, comparing it with possible permanent loss of visual acuity and other vascular complications caused by BRAO

Usefulness of daily surveillance blood cultures in allogeneic hematopoietic stem cell transplant recipients on steroids: a 1-year prospective study.

BACKGROUND: Bloodstream infections (BSI) are frequent and potentially severe complications in allogeneic hematopoietic stem cell transplant (AHSCT) recipients. In patients on steroids, surveillance blood cultures (SBCs) are routinely performed to detect asymptomatic BSI but their usefulness remains controversial. METHODS: We performed a 1-year, observational, prospective, single-center study to assess the utility of daily SBCs in AHSCT recipients on steroids and a case-control study to identify risk factors associated with positive SBCs. All blood cultures (BCs) obtained from adults hospitalized in the HSCT unit were prospectively studied throughout 1 year. Characteristics, treatments, and outcome of patients were retrieved from medical charts. RESULTS: A total of 3594 BCs were obtained in 177 patients, including 1450 SBCs in 82 AHSCT recipients on steroids. In 33 patients, 103 SBCs (7%) were positive. Low-virulence bacteria were identified in 74% of episodes. When analyzing first episode of positive SBCs (28 patients), 6 (21%) true BSI were identified. CONCLUSIONS: Patients with positive SBCs were receiving antibiotic treatment less frequently at the time of SBCs (P < 0.001) and had more frequently BCs obtained through central venous access (P < 0.04) when compared to patients with negative SBCs. Daily SBCs in AHSCT recipients on steroids only rarely identify BSI and clear benefit for patients could not be demonstrated.

Diversity and combinations of infectious agents in 38 adults with an infection-triggered reactive haemophagocytic syndrome: a multicenter study.

Reactive haemophagocytic syndrome (HS) is a rare condition that occurs in patients with infections, haematological malignancies or autoimmune diseases. Although various microorganisms are thought to trigger HS, most of the literature data on this topic have been gathered in single-centre case series. Here, we sought to characterize infectious triggers in a large, multicentre cohort of patients with HS. Patients were included in the present study if HS was solely due to one or more infections. Detailed microbiological data were recorded. Of the 162 patients with HS in the cohort, 40 (25%) had at least one infection and 38 of the latter (including 14 women, 36.8%) were included. The median age was 46 years. Seven patients were presumed to be immunocompetent (18.4%), whereas 19 patients (50%) were infected with human immunodeficiency virus and 12 patients (31.6%) were immunocompromised for other reasons. Twenty-seven patients (71.1%) had a single infection, whereas six (15.8%) and five (13.1%) patients had, respectively, two and three concomitant infections. We observed pyogenic bacterial infections (n = 7), tuberculosis (n = 10), non-tuberculous mycobacteriosis (n = 3), viral infections (n = 17: 11 cytomegalovirus, three Epstein-Barr virus, two human herpesvirus 8, one herpes simplex virus 2), parasitic infections (n = 8: four disseminated toxoplasmosis, one leishmaniasis, three malaria), fungal infections (n = 5: four pulmonary pneumocystosis and one candidaemia). Eighteen patients (47.4%) received corticosteroids and/or etoposide. Twelve patients died (31.6%). All multiple infections and all deaths occurred in immunocompromised patients. When compared with patients suffering from malignancy-associated HS, patients with infection-triggered HS were younger and more likely to be immunocompromised, and had a better outcome.

Prevalence, risk factors, and impact on clinical outcome of extended-spectrum beta-lactamase-producing Escherichia coli bacteraemia: a five-year study.

BACKGROUND: The impact of extended-spectrum beta-lactamase (ESBL)-producing Escherichia coli (ESBL-EC) bacteraemia on outcome remains controversial. METHODS: A retrospective analysis of the prevalence, risk factors, clinical features, and outcomes of all ESBL-EC bacteraemia in one French hospital over a 5-year period was performed. A case-control study was undertaken: cases had at least one ESBL-EC bacteraemia and controls a positive non-ESBL-EC bacteraemia. RESULTS: The prevalence of ESBL-EC bacteraemia increased from 5.2% of all positive E. coli blood cultures in 2005 to 13.5% in 2009 (p<0.003). CTX-M represented 70% of ESBL-EC bacteraemia strains, and strains were not clonally related. On adjusted analysis, the only significant risk factor for ESBL-EC bacteraemia was a previous ESBL-EC colonization (odds ratio 11.3, 95% confidence interval 1.2-107; p=0.003). Initial antimicrobial therapy was less frequently adequate in the ESBL-EC group (48% vs. 85%; p=0.003). The presence of ESBL-EC bacteraemia was not associated with a longer hospital stay (p=0.088). Day 30 mortality was high, but not significantly different in the two groups (30% vs. 27%; p=0. 82). CONCLUSION: The prevalence of ESBL-EC bacteraemia has been increasing dramatically. Previous colonization with ESBL-EC was a strong risk factor for ESBL-EC bacteraemia. More inadequate initial antimicrobial therapy was noted in the ESBL-EC group, but mortality and length of hospital stay were not significantly different from those of patients with non-ESBL-EC bacteraemia.

La membrane amniótica en oftalmología: del recubrimiento - injerto a la ingeniería tisular. Artículo de revisión / The amniotic membrane in ophthalmology: from the coating- graft to the tisualr engineering, revies article

El trasplante de la membrana amniótica sigue siendo un método efectivo en un gran número de patologías de la superficie ocular. Sus innumerables propiedades antiinflamatoria, anticicatricial, estimuladora de la proliferación del epitelio corneal,junto con las constantes mejoras en cuanto a los métodos de obtención, preparación, conservación y a la aparición de nuevas técnicas y dispositivos para su implantación, han permitido una mejoría substancial en los resultados obtenidos y una ampliación de sus aplicaciones. Así, la membrana amniótica se ha convertido en un elemento esencial tanto para la cirugía ocular como para la ingeniería tisular aplicada en la Oftalmología (AU)

The amniotic membrane transplantation continues to be an effective method in a large number of ocular surface pathologies. Its numerous properties anti-inflammatory, anti-cicatricial, corneal epithelium proliferation stimulatin, together with the continuous improvements in relation to obtaining, preparation and conservation methods and to the development of new techniques and devices for its implantation, have allowed not only substantial improvements in the results obtained but also the extension of its application in Ophthalmology. Therefore the amniotic membrane has become an essential element both for ocular surgery and applied tissue engineering in Ophthalmology (AU)

Breakthrough invasive fungal disease in patients receiving posaconazole primary prophylaxis: a 4-year study.

Posaconazole (PSC) is currently recommended as primary prophylaxis in neutropenic patients with acute myeloid leukaemia (AML) and in allogenic haematopoietic stem cell transplantation (AHSCT) recipients with graft-versus-host disease (GVHD). Studies focusing on breakthrough invasive fungal disease (IFD) upon PSC prophylaxis show disparate results. In order to evaluate the incidence of IFD in patients on PSC prophylaxis and identify IFD risk factors, we carried out a retrospective study of all consecutive patients on PP from January 2007 to December 2010 in our hospital. Breakthrough IFDs were identified from the database of the central pharmacy and the French administrative database (PMSI), registering final medical diagnoses of hospitalized patients. Medical data were reviewed to study proven or probable IFD, according to EORTC/MSG definition. PSC plasma concentrations (PPC) were also retrieved. Poisson models were used for statistical analysis. Two hundred and seventy-nine patients received PSC prophylaxis for a median duration of 1.4 months (range 0.2-17.9). Proven (n=6) or probable (n=3) IFDs were diagnosed in nine cases (3.2%). IFD incidence rate per 100 person-month was 1.65 (95% CI, 0.79-2.97). IFDs were candidaemia (Candida glabrata, n=2), pulmonary invasive aspergillosis (n=3), disseminated fusariosis (n=2) and pulmonary mucormycosis (n=2). Seven deaths were reported, directly related to IFD in three patients (33.3%). First dosage of PPC under 0.3 mg/L was the single significant risk factor for IFD (RR, 7.77; 95% CI, 1.30-46.5; p 0.025). Breakthrough IFD in patients receiving PSC prophylaxis is rare but associated with a poor outcome. Low PSC plasma concentrations are associated with an increased risk of IFD.

Acute enteritis associated with Coxsackievirus A19 in a kidney transplant patient.

Diarrhea is a frequent complication after kidney transplantation, with an incidence rate between 22% and 51%. In many cases, the cause remains unknown. We describe here the first case, to our knowledge, of persistent diarrhea associated with Coxsackievirus A19 (CVA19) in a kidney transplant recipient. The patient was a 46-year-old man who received a deceased-donor kidney. He experienced delayed graft function because of donor kidney donation after circulatory determination of death. Maintenance immunosuppression consisted of low-dose cyclosporine, high-dose mycophenolate mofetil (MMF) (3 g/day), and prednisone (10 mg/day). He had severe diarrhea for 2 weeks associated with acute renal failure. No pathogens were found in the stool cultures. Enterovirus detection was positive by real-time polymerase chain reaction, and sequence analysis found CVA19 (from Enterovirus C group). Area under the curve of MMF was 48 mg.h/L. Because of the persistence of diarrhea, MMF was stopped and replaced by azathioprine. The diarrhea disappeared, but serum creatinine did not return to baseline. CVA19 rarely causes gastroenteritis. This case illustrates that MMF is not always the direct cause of diarrhea, and that new clinical infectious diseases will be detected with the expansion of molecular-based DNA diagnostics.

Lymphoma and Epstein-Barr virus DNA in blood during interleukin-2 therapy in antiretroviral-naïve HIV-1-infected patients: a substudy of the ANRS 119 trial.

OBJECTIVES: Interleukin-2 (IL-2) therapy increased CD4 cell counts and delayed antiretroviral therapy (ART) initiation in HIV-infected patients in the Agence Nationale de Recherche sur le SIDA et les Hépatites Virales (ANRS) 119 trial. However, four cases of lymphoma were reported. Epstein-Barr virus (EBV) replication is associated with an increased risk of lymphoma in immunocompromised patients. We assessed whether IL-2 had an impact on EBV replication and the development of lymphoma. METHODS: A total of 130 ART-naïve patients were randomized to receive IL-2 therapy (n = 66) or no treatment (n = 64). Clinical data for patients with lymphomas were reviewed and tumours assessed for evidence of EBV infection and CD25 (the IL-2 receptor) expression. EBV DNA levels were measured in whole blood and plasma in both arms using real-time polymerase chain reaction (PCR), up to 48 weeks after baseline (BL). RESULTS: Four lymphomas occurred, a median of 61 weeks [range 40-94 weeks] after randomization at a median CD4 cell count of 396 cells/µL (IQR 234-536 cells/µL). In the IL-2 arm, two patients developed EBV-positive Hodgkin's lymphoma, and one developed EBV-negative Burkitt-type lymphoma. One patient in the control group developed EBV-positive non-Hodgkin's lymphoma. CD25 was negative in all cases. Among the 41 of 55 (control arm) and 44 of 58 (IL-2 arm) patients with detectable EBV DNA in whole blood at both BL and week 48, the median change in EBV DNA between BL and week 48 was +0.04 log10 copies/ml in both arms (P = 0.7). In plasma, EBV was detected at least once in 22 of 52 controls and 21 of 54 IL-2-treated patients (P = 0.8). CONCLUSIONS: IL-2 therapy had no significant effect on EBV replication over 48 weeks in these ART-naïve patients. The occurrence of lymphomas did not seem to be associated with IL-2 therapy.