Viral load, CD4+ T-lymphocyte counts and antibody titres in HIV-1 infected untreated children in Kenya; implication for immunodeficiency and AIDS progression

Abstract

Background: There are limited reports on HIV-1 RNA load, CD4+ T-lymphocytes and antibody responses in relation to disease progression in HIV-1 infected untreated children in Africa.

Methods: To describe the relationships between these parameters, we conducted a longitudinal cohort study involving 51 perinatally HIV-1 infected children aged between 1 and 13 years. HIV status was determined by ELISA and confirmed by western blot and PCR. Antibodies were quantified by limiting dilution ELISA, plasma HIV-1 RNA load by RT-PCR and CD4+ T-lymphocytes by FACSCount.

Results: Asymptomatic and symptomatic disease had, respectively, a rise in median HIV-1 RNA load from 1,195 to 132,543 and from 42,962 to 1,109,281 copies/ml in children below 6 years. The increase in viral load was 10-fold higher for asymptomatic compared to other categories and 2-fold faster for children less than 6 years than those above. Similarly, symptomatic children below 6 years had initial median CD4+ T-lymphocyte counts of 647 (22%) cells/muL, declining to 378 (20%) while those above 6 years had initial values of below 335 (15%) but which increased to 428 (17%). Median viral load correlated significantly with median CD4+ T-lymphocyte percentage in children above 6 years (p=0.026) but not below.

Conclusions: Viral load is lower in older than younger children and correlates significantly with percentage CD4+ T-lymphocytes. Survival by HIV-1 infected children requires a competent immune response early in infection to counter the rapidly replicating virus. Interventions aimed at boosting the naïve immune system may prolong survival in these children.

Figure IA. Western Blot

Figure 1A shows Western blot profile for 3 initially antibody positive but later negative (lanes 1–3) and some selected antibody indeterminate (lanes 4–7) children. (++) strong positive; (+-) weak positive and (-) negative control serum

Figure IB

Figure 1B shows gag (upper panel) and pol (lower panel) proviral HIV-1 DNA nested PCR for children with indeterminate anti-HIV-1 antibodies and typical positive (lanes 1–10) or negative (lane 11) results. Column M shows the separation of a 100 base-pairs DNA ladder while + and - represents positive and negative control human DNA respectively.

Figure 2

Figure 2 is a bar graph showing median anti HIV-1 antibody titres against respective grouping categories. Antibody titres were measured over a 2-time point period separated by a 4-months interval and reported as reciprocal end-point titres. Data was acquired using Statistical Package for Social Scientists (SPSS) and graphs generated using Microsoft Excel. Log-transformed medians of grouped data were analysed as described under statistical methods' section.

Figure 3

Figure 3 is a profile (line) plot showing trends in median log transformed HIV-1 RNA (viral) load during infection for different categories or groups of children. Viral loads were measured over a 3-time point period separated by a 4-months interval and reported as medians of log-transformed HIV-1 RNA copies per millilitre plasma. Data was acquired using Statistical Package for Social Scientists (SPSS) and graphs generated using Microsoft Excel. Log-transformed medians of grouped data were analyzed as described under statistical methods' section.

Figure 4

Figure 4 is a profile (line) plot showing progression of CD4+T-lymphocyte percentage during infection. CD4+T-lymphocytes were measured over a 3-time point period separated by a 4-months interval and reported as median counts per microlitre blood or as percentage of total (CD3+) T-Lymphocytes for different categories. Data was acquired using Statistical Package for Social Scientists (SPSS) and graphs generated using Microsoft Excel. Analyses have been described under statistical methods' section.