Impact of highly active anti-retroviral therapy (HAART) on cytokine production and monocyte subsets in HIV-infected patients

Abstract

SUMMARYHIV infection is associated with cytokine production by monocytes and expansion of a monocyte subset that expresses high levels of CD16. Our study was designed to investigate the effects of anti-retroviral therapies on these immune parameters. Four groups of HIV 1 patients were included in the study. The first group comprised drug-naive patients (n 20); the second included patients who received two inhibitors of HIV reverse transcriptase (n 45); the third group received a therapy combining these two inhibitors and one inhibitor of HIV protease (HAART) (n 35); the fourth consisted of patients who had stopped their treatment (n 20). The release of inflammatory cytokines (tumour necrosis factor, IL-1b , IL-6) and immunoregulatory cytokines such as IL-10 by monocytes was determined by ELISA. The monocyte subsets expressing low or high levels of CD16 were studied by flow cytometry. Monocytes from patients naive of treatment released higher amounts of inflammatory cytokines and IL-10 than HIV 2 individuals. Each anti-retroviral therapy restored a normal pattern of cytokine secretion. Nevertheless, the release of cytokines increased again after the arrest of the treatment. The expansion of the monocyte subset that expresses high levels of CD16 was significantly decreased by HAART but not by the treatment including two inhibitors of reverse transcriptase. These results suggest that only HAART controls monocyte activation in the treatment of HIV infection.

A non-specific biomarker of disease activity in HIV/AIDS patients from resource-limited environments

“…In contrast, the levels of the anti-inflammatory cytokine, IL-4, were not significantly different between the HAART and HAART-naïve groups (Table 2). These results, which demonstrated a down-regulation of neopterin and therefore in inflammatory activity upon treatment with highly active antiretroviral treatment are in agreement with that of Amirayan-Chevillard et al 14 . Amirayan-Chevillard et al further showed that neopterin levels again increase with cessation of antiretroviral treatment 14 , a finding that implies neopterin to be a useful marker of the efficacy of HAART and perhaps for the assessment of patient compliance.…”

Anaemia in HIV-Positive Patients in Relation to Immune Status of the Disease - A Hospital Based Study

“…ART was found to be associated with lower prevalence of anaemia and severe anaemia in all Categories. Inflammatory cytokines such as tumor necrosis factor (TNF)-α have been implicated in the suppression of erythropoiesis 16,17 , and HAART appears to reduce the expression of TNF-α by monocytes. 18 HAART has been shown to reduce diarrheal disease and enteric infections such as microsporidiosis and cryptosporidiosis.…”

Macrophage/Microglial Accumulation and Proliferating Cell Nuclear Antigen Expression in the Central Nervous System in Human Immunodeficiency Virus Encephalopathy

“…This conclusion is further supported by the response of patients with HIVD to highly active anti-retroviral therapy, in which pharmacotherapeutics poorly penetrate the blood brain barrier, 1,42,43 with the concomitant reduction in circulating CD16ϩ MPs. 44 Additional studies will be necessary to elucidate the mechanisms involved in PCNA expression observed in cells of the CNS, particularly the monocyte/macrophage, and the potential role of cytokines and/or viral proteins in promoting up-regulation of this antigen. Furthermore, monocyte/macrophage trafficking studies will be needed to help identify alterations in homeostatic parameters contributing to the accumulation of MPs in the CNS in HIVE.…”