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Objectives The objective of this study was to assess clinical and biological changes during intermittent ART (I-ART) started early, with significant time spent on versus off ART, which has never before been studied in ART-naive patients with high nadir and current CD4 cell count. Patients and methods ART-naive HIV-1-infected patients with baseline CD4 =500/mm³ and nadir CD4 ≥400/mm³ received 2 years of I-ART (6 month periods on once-daily boosted-PI-based ART, alternating with 6 month periods without ART) in a 2 year, Phase II, non-comparative multicentre trial. The trial is registered with ClinicalTrials.gov, number NCT 00820118. Results The CD4 cell count remained ≥500/mm³ at 2 years in all 44 patients included in the study. The mean 2 year count was higher than the mean count at baseline in 24 patients overall (55%; 95% CI 40%-69%) and in 20 (65%; 95% CI 48%-81%) of the 31 patients who fully adhered to the trial strategy. All but three of these latter patients had HIV-1 RNA concentrations below 50 copies/mL after each 6 month 'on' period. Only one strategy-related genotypic mutation (M184I) was detected. The HIV-1 DNA median load fluctuated, but it did not differ between month 0 and month 24 (2.8 versus 2.6 log10 copies/106 leucocytes, P=0.29). Biomarkers of inflammation and endothelial activation remained stable between month 0 and month 24. Naive CD4, CD8+CCR5+ and CD8+CD38+ T cell numbers tended to decline. One patient developed Burkitt's lymphoma and 12 patients reported sexually transmitted infections. Conclusions In patients with high nadir and current CD4 cell counts, 2 year I-ART maintained the CD4 cell count above 500/mm³, with no increase in the viral reservoir. Immune activation seems related to HIV replication, while inflammation seems to evolve independently and require specific attention. [ABSTRACT FROM AUTHOR]

Background: Human immunodeficiency virus (HIV) infection is associated with a high risk of classical Hodgkin's lymphoma (cHL) in the combined antiretroviral therapy (cART) era. Methods: We analyzed the characteristics and outcome of HIV-associated cHL diagnosed in the modern cART era. The French ANRS-CO16 Lymphovir cohort enrolled 159 HIV-positive patients with lymphoma, including 68 (43%) with cHL. HIV-HL patients were compared with a series of non-HV-infected patients consecutively diagnosed with HL. Results: Most patients (76%) had Ann-Arbor stages III-IV and 96% of patients were treated with ABVD. At diagnosis, median CD4 T-cell count was 387/µL and 94% of patients were treated with cART. All patients received cART after diagnosis. Five patients died from early progression (n = 2), sepsis (1) or after relapse (2). Two additional patients relapsed during follow-up. Two-year overall and progression free survivals (PFS) were 94% [95% CI, 89%, 100%] and 89% [82%, 97%], respectively. The only factor associated with progression or death was age with a relative risk of 8.1 [1.0; 67.0] above 45 years. The PFS of Lymphovir patients appeared similar to PFS of HIVnegative patients, 86% [82%, 90%], but patients with HIV infection displayed higher risk features than HIV-negative patients. Conclusions: Although high-risk features still predominate in HIV-HL, the prognosis of these patients, treated with cART and mainly ABVD, has markedly improved in the modern cART era and is now similar to non-HIV-infected patients. [ABSTRACT FROM AUTHOR]

Objectives To track changes in the V3 env region of HIV-1 quasispecies and determine virus coreceptor use in cell reservoirs of patients on long-term suppressive antiretroviral therapy (ART). Patients and methods Ten patients whose plasma viraemia had been suppressed for a median of 5.5 years were followed for 5 years. The V3 env regions of viruses in peripheral blood mononuclear cells were analysed by ultra-deep sequencing (UDS). HIV-1 tropism was predicted using the geno2pheno 5.75 algorithm and a phenotypic assay. Results The UDS and phenotypic assay data were concordant for predicting HIV-1 tropism. CXCR4-using viruses detected by UDS accounted for 14.7%–76.5% of the virus populations in samples from five patients at enrolment. Five patients harboured pure R5 virus populations and no X4 viruses emerged during the 5 years. The selection pressures estimated by the dN/dS ratio were acting on the V3 region to produce diversification of the quasispecies in CXCR4-infected patients and purification of the quasispecies in R5-infected patients on effective ART. Conclusions UDS showed that the virus quasispecies in cell reservoirs of patients on long-term suppressive ART continued to evolve. CXCR4-using variants became more diversified. Analysis of the selection pressures on the virus quasispecies could provide a clearer picture of virus persistence in patients on effective ART. [ABSTRACT FROM PUBLISHER]

Objectives R5 viruses have long been thought to account for almost all strains present in primary HIV-1 infections (PHIs), but recent studies using sensitive phenotypic assays have revealed that 3%–6.4% of subjects also harbour CXCR4-using viruses. Phenotypic assays provide only qualitative results: the presence or absence of CXCR4-using viruses. We have therefore used ultra-deep pyrosequencing (UDS) to determine the frequency of CXCR4-using viruses among HIV-1 quasispecies. Methods We first screened 200 patients for HIV-1 tropism using a sensitive phenotypic assay during PHI and identified 11 infected with an R5X4 dual/mixed (D/M) virus population. We then used UDS of the V3 env region with the geno2pheno algorithm (false positive rate = 5.75) to identify the HIV-1 quasispecies. Results CXCR4-using viruses were detected in all but 1 of the 11 patients by UDS, and accounted for 0.2%–100% of the virus populations. The frequency of CXCR4-using viruses was <20% in six subjects and 100% in four subjects. Virus populations containing 100% CXCR4-using variants during PHI persisted for at least 1–2 years after the acute phase. The CCR5 Δ32 heterozygous genotype was similarly prevalent in patients infected with D/M (27%) and R5 (15%) viruses. Conclusions UDS and the phenotype were concordant for determining HIV-1 coreceptor usage. UDS analysis indicated large differences in the percentage of CXCR4-using viruses in the HIV-1 quasispecies during PHI. Further studies should examine the impact of the proportion of CXCR4-using viruses on disease prognosis. [ABSTRACT FROM PUBLISHER]

Objectives Resistance of HIV-1 to CCR5 antagonists can occur without coreceptor switching by mutations in envelope glycoproteins that enable virus entry using the inhibitor-bound form of CCR5. We investigated whether mutations in the V3 region of HIV-1 from subjects naive to maraviroc could be associated with primary resistance to this drug. Methods The frequency of CCR5-tropic HIV-1 subtype B isolates harbouring putative V3 maraviroc resistance mutations was assessed among the HIV tropism database of Toulouse University Hospital, France. Phenotypic assessment of maraviroc susceptibility was performed for 14 isolates representative of the main mutation patterns and 14 controls. V3 mutations were reversed or introduced by site-directed mutagenesis. Results Ninety-three of 951 (9.8%) isolates harboured V3 mutations assumed to be associated with maraviroc resistance. Maraviroc completely blocked virus entry for all but 1 of the 14 isolates harbouring V3 mutations [IC50 8.6 nM; 95% CI (6.6–47.4)], as in the 14 control isolates [IC50 13.4 nM; 95% CI (7.7–50.3)] (P = 0.24). Primary resistance to maraviroc, with a plateau in entry inhibition, was found in one isolate (harbouring a 20F/21I genotype). Site-directed mutagenesis showed that V3 mutations are necessary but not sufficient to induce maraviroc resistance. Conclusions The impact of V3 mutations depended on the env context in which they occurred. Simple assessment of the V3 genotype thus cannot accurately predict maraviroc resistance. Rather, phenotypic assessment of virus particles expressing the envelope glycoprotein as a whole is required. This approach revealed that primary resistance of CCR5-tropic HIV-1 subtype B isolates to maraviroc seems uncommon. [ABSTRACT FROM PUBLISHER]

Kidney injury during HIV infection encompasses a wide variety of disorders, including acute interstitial nephritis. We report a case of acute granulomatous interstitial nephritis related to a mycobacterial-triggered immune reconstitution inflammatory syndrome (IRIS) in an HIV-infected patient. IRIS is an emerging health concern during HIV infection and should be considered in the diagnostic frame of acute renal failure during immune restoration. [ABSTRACT FROM AUTHOR]

Background The aim of our study was to determine whether HIV-1 DNA level before antiretroviral therapy (ART) was associated with short- and long-term virological and immunological responses. Methods Patients starting first-line protease inhibitor-containing regimens were enrolled in a prospective multicentre cohort in 1998–99. HIV-1 DNA was quantified using real-time PCR at baseline and after 1 year of ART. The association between HIV-1 DNA and virological and immunological responses after 1 and 7 years on ART was studied in multivariate regression models along with other biological and clinical variables. Virological failure (VF) at month 12 (M12) was defined as a plasma HIV-1 RNA >500 copies/mL. Time to death or two plasma HIV-1 RNA >500 copies/mL between M12 and M84 was studied for long-term VF. Results HIV-1 DNA levels were measured in 148 patients. The median baseline peripheral blood mononuclear cell (PBMC) HIV-1 DNA was 3.7 log10 copies/106 PBMCs. At M12, the median PBMC HIV-1 DNA was 2.99 log10 copies/106 PBMCs. The median decrease in PBMC HIV-1 DNA between M0 and M12 was −0.7 log10 copies/106 PBMCs. Higher baseline PBMC HIV-1 DNA and plasma HIV-1 RNA were independently associated with a higher risk of VF at M12. Only the baseline plasma HIV-1 RNA was independently associated with long-term virological response. The baseline CD4 cell count was the only parameter associated with short- and long-term immunological responses. Conclusions HIV-1 DNA impacted the virological response in our cohort. Further research is warranted to study the impact of HIV-1 DNA with currently recommended first-line cART. [ABSTRACT FROM PUBLISHER]

Anti-retroviral therapy partially restores the immune function of patients infected with human immunodeficiency virus, thereby drastically reducing morbidity and mortality. However, the clinical condition of a subset of patients on anti-retroviral therapy secondarily deteriorates due to an inflammatory process termed immune reconstitution inflammatory syndrome. This condition results from the restoration of the immune system that upon activation can be detrimental to the host. Among the various clinical manifestations, central nervous system involvement is associated with greater morbidity and mortality. This review covers the pathogenesis of this novel neuroinflammatory disease, including the nature of the provoking pathogens and the composition and specificity of the evoked immune responses. Our current perception of this neuroinflammatory disease supports therapeutic strategies aimed at modulating immune aggression without dampening the life-saving restoration of the immune response. [ABSTRACT FROM AUTHOR]

We analyzed the effect of age on highly active antiretroviral therapy efficacy and tolerance in 639 patients with human immunodeficiency virus (HIV) infection (99 of whom were aged >50 years, and 540 of whom were aged <50 years). Late testing, which was more frequent in the older age group, was the only independent factor associated with immunologic and clinical evolution of infection. Age >50 years was associated with earlier treatment discontinuation. [ABSTRACT FROM AUTHOR]

Reports on the case of a male expatriate with plasmodium falciparum whose neurologic side effects were successfully treated after exposure to two courses of artemether. Clinical manifestations; Result of the neurological examination.

We compared the ability of four newer β-lactam compounds to produce resistance in an experimental model of Enterobacter cloacae infection. Mice infected intraperitoneally developed resistance depending on antibiotic treatment and the dose given. Percentages of mice in which resistance was observedwere as follows: 100% after ceftriaxone (50 mg/kg, two doses); 87% after ceftriaxone (50 mg/kg, one dose); 35% after ceftriaxone (500 mg/kg, one dose); and 21% after carumonam (25 mg/kg, two doses). No resistance occurred after therapy with either BMY 28142(25 mg/kg, two doses) or Sch 34343 (50 mg/kg, two doses). Heterogeneous resistance to 13-lactams among the cells within a given Enterobacter population accounted for these differences. The minimal concentration inhibiting the growth of the preexisting resistant variants, together with the antibiotic concentrations obtained in the peritoneal fluid, were associated with further emergence of resistance in the mouse treated with this antibiotic. [ABSTRACT FROM PUBLISHER]

Summary: Febrile illness is a common cause of attendance at emergency departments. The purpose of this study was to describe infectious aetiologies of fever in a tropical setting. We prospectively included 1443 febrile patients, all French Guiana residents, who presented at Cayenne Hospital emergency department. This report will propose an overview of aetiologies of febrile illness in French Guiana, and tropical diseases such as malaria and arbovirus infections are discussed. Almost 30% of fevers remained unexplained. Further prospective multicentre studies are warranted to improve the diagnosis of overlooked pathogens in French Guiana. Such studies would lead to conclusions of specific interest in the travel medicine field. [Copyright &y& Elsevier]

An abstract of the article "Alveolar and Blood T Lymphocyte Profiles in Pneumocystis jirovecii Positive Patients: Effects of HIV Status," by Xavier Iriart and colleagues is presented.

Two black African immigrants, with no history of recent travel outside France, received a diagnosis of a malignant lymphoproliferative disorder and splenomegaly, and they subsequently underwent splenectomy. A few weeks after surgery, both patients experienced an acute episode of Plasmodium falciparum malaria, so the initial diagnosis was corrected retrospectively and changed to hyperreactive malarial splenomegaly. These cases illustrate the difficulty in distinguishing hyperreactive malarial splenomegaly from malignant lymphoproliferative disorders and therefore underline the role of the spleen in the immune system's defense against malaria. [ABSTRACT FROM AUTHOR]