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

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 nonprogressor 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 (Th[2]) 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 (Th[1]) 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 profilemay provide valuable predictors of subsequent fall in CD4+ cell value. (author’s)