Avaliação dos metabólitos do óxido nítrico na infecção pelo HIV e impacto da terapia antirretroviral sobre as concentrações séricas de nitrito/nitrato

Abstract

The Acquired Immunodeficiency Syndrome (AIDS) is a disease of infectious origin, caused by the human immunodeficiency virus (HIV). The virus infects primarily helper T CD4+ lymphocytes, generating a severe immunosuppression and increased susceptibility to infections. Highly active antiretroviral therapy (HAART) significantly reduces viral load and restores the immune system. The infection requires monitoring throughout life and compliance failures and adverse effects of the medication are factors limiting treatment. The reasons for these effects appear to be multifactorial and between them are metabolic disorders, toxicity of antiretroviral drugs and the impact of viral replication, resulting in an increase of non-AIDS-related diseases, subclinical atherosclerosis and endothelial dysfunction. It is known that the endothelium plays a central role in maintaining vascular health. HIV-positive patients have impaired endothelial function and one of the major causes of morbidity and premature mortality are cardiovascular complications. In this context it was demonstrated that the loss of endothelial cells in vivo and in vitro, may involve the formation of reactive nitrogen species (RNS) and alter the bioavailability of nitric oxide (NO). Many regulatory mechanisms of the cardiovascular system have the involvement of NO, including vascular tone, vascular structure and cell-cell interactions in blood vessels. Studies have been conducted to elucidate the role of NO in vascular diseases. But there are few reports on the levels of this marker in HIV positive patients. Thus, the main objective of this study was to investigated the levels of nitrite/nitrate (NOx) in HIV-infected patients and verified whether the levels of this marker would alter with HAART. One hundred forty-seven volunteers were included in this case-control study. The subjects were divided into two groups: HIV-infected patients (n=101) and healthy subjects (n=46).Then, the HIV-infected patients were divided into two groups: HIV-infected patients on highly active antiretroviral therapy (HAART) (n=83) and HIV-infected patients without HAART (n=18). It was demonstrated that HIV-infected patients had significantly lower NOx levels [62.4 (28.4-116.0) μmol/L] than healthy individuals [86.8 (56.1-137.5) μmol/L]. Additionally, it was also found significantly lower NOx levels among treated [60.8 (27.9-105.4) μmol/L] compared to untreated patients [127.0 (36.2-277.1) μmol/L]. The findings suggest that these changes may be an important mechanism that predisposes patients to have a cardiovascular outcome and thus, the maintenance of these levels within the normal range may be a therapeutic strategy to reduce cardiovascular disease.