Recovery of the Immune System With Antiretroviral Therapy

Powderly, William G.; Landay, Alan; Lederman, Michael M.

doi:10.1001/jama.280.1.72

Cited by 207 publications

(113 citation statements)

References 49 publications

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“…In line with previous observations (41)(42)(43), ART induced a rapid suppression of viral replication. Despite this, CD38 expression on PB CD8þ T-cells and monocytes from HIV-1þ patients remained significantly increased, even after one year of ART, independent of their initial PB CD4þ T-cell counts.…”

Section: Discussionsupporting

confidence: 92%

Relationship between CD38 expression on peripheral blood T‐cells and monocytes, and response to antiretroviral therapy: A one‐year longitudinal study of a cohort of chronically infected ART‐naive HIV‐1+ patients

Almeida

Cordero

Almeida

et al. 2006

Cytometry Part B Clinical

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Background: HIV-1 infection has been associated with high expression of CD38 on peripheral blood (PB) CD81 and CD41 T-cells, which has been related with poor prognosis in untreated HIV-11 patients. In turn, CD38 expression on PB monocytes from HIV-11 individuals and its behavior after starting antiretroviral therapy (ART) have been poorly studied.Methods: CD38 expression on PB CD81 and CD41 T-lymphocytes and monocytes was prospectively analyzed in 30 ART-naive HIV-11 patients, using a quantitative multiparameter flow cytometry approach. Patients were tested prior to therapy, and at weeks 12, 14, 18, 112, and 152 after ART.Results: Prior to ART, CD38 expression was significantly increased on PB CD81 and CD41 T-cells and monocytes; despite a significant decrease after ART, CD38 expression remained abnormally high on PB CD81 T-cells and monocytes, even after one year of therapy, in the absence of detectable plasma viral load. The ART-induced early changes on CD38 expression by PB T-cells and monocytes differed among the cell subsets analyzed and patient groups, probably reflecting an interaction between the direct effects of therapy and a redistribution of the PB compartments of T-cells and monocytes. Hierarchical clustering analysis showed that the overall pattern of changes in CD38 expression observed early after starting ART was predictive of a better response to therapy, not only for PB CD81 T-cells, but also for CD41 T-cells and monocytes. Accordingly, those HIV-11 patients, who experienced a more pronounced increase in CD38 expression on both PB CD41 T-cells and monocytes after 2 weeks of ART, showed a more rapid viral clearance, which might reflect decreased HIV-1 replication in lymph nodes and other tissues, and a partial restoration of hematopoiesis.Conclusions: Combined quantitative measurement of CD38 expression on PB monocytes, and CD81 and CD41 T-cells is a more useful tool for monitoring HIV-11 patients under ART, rather than quantitation of CD38 expression on PB CD81 T-lymphocytes alone. q

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Section: Discussionsupporting

confidence: 92%

Relationship between CD38 expression on peripheral blood T‐cells and monocytes, and response to antiretroviral therapy: A one‐year longitudinal study of a cohort of chronically infected ART‐naive HIV‐1+ patients

Almeida

Cordero

Almeida

et al. 2006

Cytometry Part B Clinical

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“…IPA, characterized by hyphal invasion and destruction of pulmonary tissue, is a leading cause of attributable mortality among patients with hematologic malignancies (4) and aplastic anemia (5) and among solid organ transplant recipients (6). Aspergillosis has recently surfaced as a frequent complication in critically ill neonates (7) and in patients with advanced HIV infection (8), although the highly active anti-retroviral therapy has dramatically reduced the risk of opportunistic infections in the latter (9).…”

Section: T Cell Vaccination In Mice Withmentioning

confidence: 99%

T Cell Vaccination in Mice with Invasive Pulmonary Aspergillosis

Cenci

Mencacci

Bacci

et al. 2000

The Journal of Immunology

202

166

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Aspergillus fumigatus, an opportunistic fungal pathogen, is responsible for multiple airway diseases of an allergic and a nonallergic nature. In a murine model of invasive pulmonary aspergillosis, resistance is associated with a decreased lung inflammatory pathology and the occurrence of an IL-12-dependent Th1-type reactivity that are both impaired by IL-4. In the present study we assess the ability of Aspergillus crude culture filtrate Ags and the recombinant allergen Asp f 2 to induce protective antifungal responses in mice with invasive pulmonary aspergillosis. Similar to what occurred upon nasal exposure to viable A. fumigatus conidia, treatment of immunocompetent mice with Aspergillus crude culture filtrate Ags resulted in the development of local and peripheral protective Th1 memory responses, mediated by Ag-specific CD4+ T cells producing IFN-γ and IL-2 capable of conferring protection upon adoptive transfer to naive recipients. Protective Th1 responses could not be observed in mice deficient of IFN-γ or IL-12 and did not occur in response to Asp f 2, which, on the contrary, elicited high level production of inhibitory IL-4. The results show that Ags of Aspergillus exist with the ability to induce both Th1- and Th2-type reactivity during infection, a finding that suggests a possible mechanism through which potentially protective immune responses are inhibited in mice with the infection. However, the occurrence of Th1-mediated resistance upon vaccination with Aspergillus crude culture filtrate Ags, suggests the existence of fungal Ags useful as a candidate vaccine against invasive pulmonary aspergillosis.

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“…Initiation of ART is usually accompanied by substantial decreases in HIV-1 viral load and increases in CD4 ϩ T-lymphocyte counts (21,22). Studies with long-term survivors and with subjects treated during acute infection show that vigorous HIV-1-specific cytotoxic T-lymphocyte (CTL) responses and strong HIV-1-specific TH1 responses correlate with long-term control of viral replication in the absence of therapy, resulting in prolonged, symptom-free survival (17,19,23,24,30).…”

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confidence: 99%