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In JoVE (1)
Other Publications (5)
Articles by Esther Merlini in JoVE
JoVE Clinical and Translational Medicine
Sequencing of Bacterial Microflora in Peripheral Blood: our Experience with HIV-infected Patients
Our experiment will show how to perform a sequencing analysis of bacterial species translocating in peripheral blood of HIV positive patients.
Other articles by Esther Merlini on PubMed
CD8+ Hyperactivation and Senescence Correlate with Early Carotid Intima-media Thickness in HIV+ Patients with No Cardiovascular Disease
Increased Bone Marrow Interleukin-7 (IL-7)/IL-7R Levels but Reduced IL-7 Responsiveness in HIV-positive Patients Lacking CD4+ Gain on Antiviral Therapy
The bone marrow (BM) cytokine milieu might substantially affect T-lymphocyte homeostasis in HIV-positive individuals. Interleukin-7 (IL-7) is a bone marrow-derived cytokine regulating T-cell homeostasis through a CD4+-driven feedback loop. CD4+ T-lymphopenia is associated with increased free IL-7 levels and reduced IL-7R expression/function, which are only partially reverted by highly active antiretroviral therapy (HAART). We investigated the BM production, peripheral expression and signaling (pStat5+ and Bcl-2+ CD4+/CD8+ T cells) of IL-7/IL-7Rα in 30 HAART-treated HIV-positive patients who did not experience CD4+ recovery (CD4+ ≤200/µl) and who had different levels of HIV viremia; these patients included 18 immunological nonresponders (INRs; HIV-RNA≤50), 12 complete failures (CFs; HIV-RNA>1000), and 23 HIV-seronegative subjects.
Evidence for Polymicrobic Flora Translocating in Peripheral Blood of HIV-infected Patients with Poor Immune Response to Antiretroviral Therapy
In advanced HIV infection, the homeostatic balance between gastrointestinal indigenous bacteria and gut immunity fails and microbes are able to overcome the intestinal barrier and gain the systemic circulation. Because microbial translocation is not fully controlled by antiviral therapy and is associated with inefficient CD4+ reconstitution, we investigated the profile of translocating bacteria in peripheral blood of 44 HIV-infected patients starting therapy with advanced CD4+ T-lymphopenia and displaying poor CD4+ recovery on virologically suppressive HAART. According to CD4+ reconstitution at 12-months HAART, patients were considered Partial Immunological Responders, PIRs (CD4+≥250/µl, n = 29) and Immunological non Responders, INRs (CD4+<200/µl, n = 15)). We show that PIRs and INRs present similarly elevated plasma levels of lipopolysaccharide (LPS) and its ligand sCD14 that were not lowered by virologically suppressive therapy. Bacterial 16S rRNA gene amplification and sequencing resulted in a highly polymicrobic peripheral blood microbiota both prior and after 12-month HAART. Several differences in bacterial composition were shown between patients' groups, mainly the lack of probiotic Lactobacillaceae both prior and after therapy in INRs. Failure to control microbial translocation on HAART is associated with a polymicrobic flora circulating in peripheral blood that is not substantially modified by therapy.
Microbial Translocation Predicts Disease Progression of HIV-infected Antiretroviral-naive Patients with High CD4+ Cell Count
We investigated the significance of microbial translocation measured on average 3 years after HIV seroconversion in driving disease progression in HIV untreated patients with high CD4(+) cell count.
Reduced Central Memory CD4+ T Cells and Increased T-Cell Activation Characterise Treatment-Naive Patients Newly Diagnosed at Late Stage of HIV Infection
Objectives. We investigated immune phenotypes of HIV+ patients who present late, considering late presenters (LPs, CD4+ < 350/μL and/or AIDS), advanced HIV disease (AHD, CD4+ < 200/μL and/or AIDS), and AIDS presenters (AIDS-defining condition at presentation, independently from CD4+). Methods. Patients newly diagnosed with HIV at our clinic between 2007-2011 were enrolled. Mann-Whitney/Chi-squared tests and logistic regression were used for statistics. Results. 275 patients were newly diagnosed with HIV between January/2007-March/2011. 130 (47%) were LPs, 79 (29%) showed AHD, and 49 (18%) were AIDS presenters. LP, AHD, and AIDS presenters were older and more frequently heterosexuals. Higher CD8+%, lower CD127+CD4+%, higher CD95+CD8+%, CD38+CD8+%, and CD45R0+CD38+CD8+% characterized LP/AHD/AIDS presentation. In multivariate analysis, older age, heterosexuality, higher CD8+%, and lower CD127+CD4+% were confirmed associated with LP/AHD. Lower CD4+ and higher CD38+CD8+% resulted independently associated with AIDS presentation. Conclusions. CD127 downregulation and immune activation characterize HIV+ patients presenting late and would be studied as additional markers of late presentation.
