IMMUNE RECOVERY OF HIV-1 INFECTED PATIENTS TREATED WITH HIGHLY ACTIVE ANTIRETROVIRAL THERAPY FOR TWO YEARS

THESIS.R. A. M. B. Almeida submitted this dissertation for his Masters in Tropical Diseases at Botucatu School of Medicine, São Paulo State University, UNESP, Botucatu, São Paulo, Brasil, 2003.

Advisor: Professor Domingos Alves Meira

ABSTRACT. A progressive and pronounced immune system dysfunction is the hallmark of HIV infection. Clinical evaluation, CD4⁺ T lymphocyte counts, and plasma viral load (VL) are the main parameters to evaluate this dysfunction. Highly active antiretroviral therapy (HAART) has dramatically improved life quality and decreased death rate, resulting from the interaction between lower HIV-1 replication and immune system recovery. However, this recovery is slow, variable, and partial indicating the need for markers that may reflect it not only quantitatively but also qualitatively. The objective of this study was to use three additional markers: serum cytokine levels (ELISA) and CD45RA/CD45RO cell counts (flow cytometry). Thirty-seven HIV-1 infected individuals and 49 normal blood donors (control group) were studied. The HIV-1 infected individuals were divided into three groups: Group 1 - individuals before HAART treatment; Group 2 - individuals were receiving treatment for 5 to 7 months, with predominant association of non-nucleoside reverse transcriptase inhibitors (NNRTI); and Group 3 - individuals were using HAART for at least two years, with predominant association of protease inhibitors (PI). This group showed the best performance. This can be explained as follows: all individuals were asymptomatic, with higher numbers of peripheral total lymphocyte counts and a significant increase in CD4⁺ T lymphocyte counts, but lower than normal levels; they showed predominantly undetectable viral load; low TNF-a, still higher than the controls; INF-g higher than the non-treated and equal to those under treatment for 5 to 7 months; IL-2 higher than the non-treated and equal to those under treatment for 5 to 7 months and controls; IL-10 and IL-4 statistically higher than the controls and equal to the non-treated and those under treatment for 5 to 7 months; mature 0 cytokine profile different from the non-treated (type 2 profile); CD45RA cell counts higher than the non-treated and equal to the controls; and CD45RO cell counts higher than the non-treated and controls. We may suggest that the best immune recovery can be attributed to a longer treatment and protease inhibitor activity. Correlation between variable pairs suggested that serum cytokines, especially IL-2 and INF-g, viral load determination, and CD45RA/CD45RO cell counts were important surrogate markers of HIV-1 infected individuals with HAART. These observations suggest that further studies should be performed with these variables, including a larger number of patients and longer treatment period.

KEYWORDS: AIDS, immune recovery, antiretrovirals, cytokines, CD45RA, CD45RO.

CORRESPONDENCE TO: Ricardo Augusto Monteiro de Barros Almeida, Departamento de Doenças Tropicais e Diagnóstico por Imagem, Faculdade de Medicina de Botucatu, UNESP, Distrito de Rubião Junior, s/n, 18618-000, Botucatu, São Paulo, Brasil. Phone: 55 14 3811 6212. E-mail: ralmeida@fmb.unesp.br