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Witness for the prosecution: Maria MontroniStructured treatment interruption (STI) has been considered among the possible therapeutic options for multidrug experienced HIV-infected individuals facing virological failure, since early studies suggested the possibility of viral reversion from drug-resistant mutated species to drug-sensitive wild-type virus following the release of drug pressure. However, the persistence of mutated viral populations during STI has been observed. The lack of detection of resistance mutations in plasma is mainly due to the low sensitivity of the currently available genotypic resistance testing, which is unable to detect resistant less fit virus masked by overwhelming re-emerged wild-type quasi-species. Restarting antiretroviral therapy (ART) is frequently followed by the reappearance of resistant virus, as well as by disease progression. STI should be applied with extreme caution in multidrug experienced HIV-infected individuals with virological failure. Use of genotype resistance testing in this particular setting, although useful in controlled clinical trials, should be considered of little help in clinical practice. Witness for the defence: Antonella D'Arminio MonforteThe rationale for salvage STI has been elucidated. Data from observational and randomized studies have been revised, and the following conclusions in defence of salvage STI are: in more than 60% of patients undergoing salvage STI for at least 3 months there is a reversion of drug-associated mutations. Concurrently, increases in HIV-RNA and decreases in CD4 cells occur. Few clinical events have been reported in patients with CD4 counts of < 200 cells/mm3. New resistance-driven salvage regimens, including at least 1 new drug, result in good virological outcome in a short-term follow-up. Warnings are related to possible clinical progression and to the course of the infection in reservoirs. Randomized studies are required to elucidate these findings. [ABSTRACT FROM AUTHOR]

The first report of the antiviral activity of (+)-sattabacin against varicella-zoster virus (VZV) is described. Our results show that (+)-sattabacin potently inhibits the growth of VZV at concentrations in the range of other drugs commonly prescribed for VZV infection. Experiments detailing the synthesis of (+)-sattabacin, quantification of cytotoxicity and gene expression data in human fibroblast cells are also presented. Gene expression data was obtained through microarray analysis from human fibroblast cells exposed to sattabacin in order to identify a possible mechanism by which (+)-sattabacin inhibits VZV replication., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

Objective: To address the mechanisms of the thrombocytopoietic dysfunction that may follow HIV infection and to compare peripheral blood and bone marrow as sources of CD34 progenitor cells in HIV-infected patients., Methods: The study used CD34 progenitor cells from 20 previously untreated HIV-infected individuals, 20 HIV-infected individuals treated with antiretroviral therapy and a control group of 20 HIV-uninfected healthy individuals to examine in-vitro megakaryocytopoiesis. There were no hematological abnormalities at baseline in the study groups. CD34 progenitor cells derived from peripheral blood and bone marrow were purified and cultured in medium containing thrombopoietin, interleukin-3, and interleukin-6. HIV-1 plasma viral load was determined by b-DNA technique. Expression of receptors for thrombopoietin, interleukin-3, and interleukin-6 was assessed on CD34 cells by flow cytometry, and numbers of receptors per single cell were calculated by Quanticalc software., Results: Growth of megakaryocytopoietic colony-forming units (CFU-MK) were impaired in untreated HIV-infected individuals despite normal platelet counts. Viral load levels inversely correlate with CFU-MK growth and platelet counts. Antiretroviral drug-treated individuals showed normal megakaryocyte development. Similar results were obtained whether the CD34 progenitor cells derived from peripheral blood or bone marrow., Conclusions: These findings suggest that megakaryocyte differentiation is impaired before the onset of overt thrombocytopenia in HIV-infected patients and provide evidence for a direct link between viral replication and perturbed megakaryocytopoiesis, which appears to be prevented and/or restored by antiretroviral therapy. The results indicate that peripheral blood represents a suitable source of CD34 hematopoietic progenitors for studies of megakaryocytopoiesis in HIV disease.

Cryopreservation of isolated peripheral blood mononuclear cells (PBMCs) for phenotypic and functional analyses is considered a standard procedure in order to minimize operator-dependent inter-assay variability and to optimize the use of available resources. However, only few and somewhat conflicting data are presently available on the effects of cryopreservation on PBMCs, especially in samples from HIV-infected patients in which assessment of lymphocyte phenotype and function is of the outmost importance. In this study, we compared fresh versus frozen/thawed (F/T) samples isolated from 19 healthy individuals and 21 HIV-infected patients, showing that cryopreservation induces: (i) a profound decrease of CD62L expression, with a consequent significant decline of the calculated proportions of "naïve" (CD45RA+CD62L+) and "central memory" (CD45RO+CD62L+) T cells; (ii) an increase of the calculated proportions of "effector" CD8+ T cells (CD45RA+CD62L- and CD45RO+CD62L-) in the healthy subjects, while no changes were observed in the HIV-infected group; (iii) a significant decline of CC chemokine receptor 5 (CCR5) expression; (iv) a loss of proliferative responses to some HIV antigens (i.e. p24) and recall antigens [cytomegalovirus (CMV) and Influenza] in HIV-infected patients. We thus conclude that cryopreservation induces a consistent set of changes in PBMCs from both healthy and HIV-infected individuals, and that certain immunological studies of HIV-infected patients (i.e. studies of immune reconstitution following antiretroviral therapy in HIV-infected patients or studies of HIV-infectivity in vitro using CCR5-tropic strains) should be performed on fresh samples.

Highly active antiretroviral therapy (HAART) improves the immunodeficiency of HIV-infected individuals. In this report we show that HAART increases both naive (CD45RA+CD62L+) and central memory (CD45RO+CD62L+) CD4 lymphocytes. On CD8 lymphocytes, HAART induces an increase of naive cells associated with a consistent decrease of effector cells (CD45 RO+CD62L-). No specific differences in phenotypic changes were observed with different HAART regimens, suggesting that, once viral suppression is achieved, the pharmacological class of antiretroviral drugs does not affect immune reconstitution.