The Prognostic Value of Cellular and Serologic Markers in Infection with Human Immunodeficiency Virus Type 1

Abstract

We evaluated three cellular and five serologic markers that are affected by infection with the human immunodeficiency virus type 1 (HIV-1) for their ability to predict the progression to clinical acquired immunodeficiency syndrome (AIDS). The cellular markers were the number of CD4+ T cells, the number of CD8+ T cells, and the ratio of CD4+ T cells to CD8+ T cells. The serologic markers were the serum levels of neopterin (a product of stimulated macrophages), beta 2-microglobulin, soluble interleukin-2 receptors, IgA, and HIV p24 antigen. We evaluated the usefulness of these measures as markers of the progression to AIDS prospectively, over four years, in a cohort of 395 HIV-seropositive homosexual men who were initially free of AIDS. CD4+ T cells (expressed as an absolute number, a percentage of lymphocytes, or a ratio of CD4+ to CD8+ T cells) were the best single predictor of the progression to AIDS, but the serum neopterin and beta 2-microglobulin levels each had nearly as much predictive power. The neopterin level appeared to be a slightly better predictor than the beta 2-microglobulin level. The levels of IgA, interleukin-2 receptors, and p24 antigen had less predictive value. A stepwise multivariate analysis indicated that the best predictors, in descending order, were CD4+ T cells (the percentage of lymphocytes or the CD4+: CD8+ ratio), the serum level of neopterin or beta 2-microglobulin, the level of IgA, that of interleukin-2 receptors, and that of p24 antigen. The last three markers had little additional predictive power beyond that of the first two. We conclude that of the eight markers studied, progression to AIDS was predicted most accurately by the level of CD4+ T cells in combination with the serum level of either neopterin or beta 2-microglobulin. At least one of these two serum markers, which reflect immune activation, should be used along with measurement of CD4+ T cells in disease-classification schemes and in the evaluation of responses to therapy.

Neopterin and other indicators of HIV progression in Zambian adults

“…The predictive value of B2M for HIV progression and mortality might differ between study populations. It has been strongly correlated with the risk of progression to AIDS in homosexual men (18) but not in intravenous drug users (19). In Gambian and Rwandan patients B2M predicted death (10,16).…”

Reduced naive and increased activated CD4 and CD8 cells in healthy adult Ethiopians compared with their Dutch counterparts

“…Loss of CD4 þ T cells is known to be the hallmark of HIV infection and it is a well accepted laboratory marker of HIV disease progression [6,7]. Also, changes in other T cell subsets have been implicated in HIV þ persons from studies in Europe and North America: expansion of CD8 þ T cells [8], loss of naive CD8 þ T cells, increase of both CD4 þ and CD8 þ T cell memory subsets [9,10] and increased activated CD4 þ and CD8 þ T cell subsets [11][12][13][14][15][16].…”

Association between insulin resistance, body mass and neopterin concentrations

“…In humans, elevations of neopterin in serum and urine have been found in viral infections including human immunodeficiency virus type 1, various malignant disorders, autoimmune diseases and during allograft rejection episodes [5][6][7][8][9][10]. Significant associations between enhanced neopterin and IFN-g production have been obtained also in patients [11], and monitoring of neopterin concentrations has turned out to be a sensitive and useful marker to estimate the activation of Th1-cells [6].…”