Disease progression markers during asymptomatic phase of HIV-1 infected children with unimpaired CD4+ cell values: evaluation of repeat CD4+ cell evaluation vs. other immunological parameters.

Abstract

The availability of a marker that could predict the course of disease progression in HIV-infected individuals would be of considerable relevance during the asymptomatic stage in order to undertake timely prophylactic measures. A prospective study was undertaken in a group of 42 children suffering from thalassemia major with HIV-1 infection to assess the status of immune parameters, such as peripheral CD4+ T lymphocyte (CD4+ cell) percentage, delayed type of hypersensitivity (DTH) response to recall antigens, detection rate and levels of p24 antigen, and levels of beta-2 microglobulin and cytokines in serum. All were assessed at an interval of 2 years during the asymptomatic period, (baseline and follow-up assessments) in relation to the development of AIDS defining illness within a follow-up period of 3 years. No difference could be observed in the mean CD4+ cell percentage at baseline between those who progressed subsequently to develop AIDS within the follow-up period (progressors) and those who did not (non-progressors). However, at the point of follow-up assessment the progressor group showed significantly lower CD4+ cell percentage compared to the non-progressor group (33 +/- 4.9 vs. 22 +/- 5.6; p < 0.05), although in the progressor group there was no correlation of the baseline and follow-up CD4+ cell percentage with the duration of the AIDS-free interval. However, in the progressor group there was a strong negative correlation between the rate of decline in CD4+ cell percentage and subsequent duration of the AIDS-free interval (r = -0.859). Analysis of additional immune parameters at baseline revealed that the progressor group, despite having CD4+ cell values comparable to non-progressors, showed impaired DTH response (number and total induration of positive responses being 2.0 +/- 1.23 and 6.2 +/- 1.4 in the former group vs. 3.2 +/- 0.76 and 12.6 +/- 3.80 in the later group; p < 0.05 for both the parameters), and elevated levels (mg/l) of serum beta-2 microglobulin (2.92 +/- 0.89 vs. 1.38 +/- 0.43; p < 0.05). The serum cytokine profile at baseline in the progressor group showed a T helper type-2 (Th2) dominant pattern, i.e. elevation of interleukin-4 (IL-4) and interleukin-10 (IL-10) levels with decreased levels of interleukin-2 (IL-2) and gamma interferon (gamma-IFN) compared to the non-progressor group that showed a T helper type-1 (Th1) dominant profile, i.e., elevation of IL-1 and gamma-IFN level with decreased levels of IL-4 and IL-10 (p < 0.05 for all four cytokines). The present study points out that rate of decline rather than single point of assessment of CD4+ cell values is a more reliable predictor for disease progression in HIV-1 infected children. In addition, parameters such as DTH response, serum levels of beta-2 microglobulin and serum cytokine profile, may provide valuable predictors of subsequent fall in CD4+ cell value.