Pathogenesis and immune responses in HIV-l infected infants and children

Abstract

There are limited reports on HIV-l RNA load, CD4 T-Iymphocyte counts, anti-HIV-l antibody responses and age in relation to disease progression in HIV-1 infected untreated children in Africa. Understanding these parameters and their relationship to disease progression may help in determining the best way to implement antiviral therapy in these children. This study describes the HIV-1 load, CD4 T-Iymphocyte count, anti-HIV antibody responses and age in relation to disease progression in untreated perinatally HIV- 1 infected children in Kenya. Serial blood samples were obtained from 51 perinatally HIV- 1 infected orphaned children at the Nyumbani Hospice for HIV-1 infected orphans. Five millilitres of blood from each patient was used for both plasma and peripheral blood mononuclear cell (PBMC) preparations. During pregnancy none of the infants mothers received anti-HIV therapy. HIV-1 RNA load was assayed by reverse transcriptase polymerase chain reaction (RT- PCR) using commercial HIV-l Amplicor 1.5. CD4+ T-Iymphocyte counts were enumerated by fluorescence activated cell counter. Anti-HIV-l antibody responses were determined by limiting dilution Enzyme linked immunosor6ant assays (ELISA). HIV-l infection was confirmed by PCR and western blot. Disease progression was correlated with HIV-l RNA load, T-Iymphocyte counts, anti-HIV-l antibody responses and age. The children were between one and fifteen years old. Infants and children with rapid diseases· progression had higher HIV-1 RNA load (mean 391307 HIV-l RNA copies/ml for those below 6 years and 338748 HIV-l RNA copies/ml for those above 6 years), normal or low CD4 T-Iymphocyte counts (619 and 465 mean CD4+ cells/]..il for children below and above 6 years old respectively) and normal, low or no anti-HIV antibodies compared to those with slow disease progression who had low HIV-1 RNA load (23995 and 27921mean copies/ml for those below and above 6 years respectively), high CD4 T-Iymphocyte counts (851 and 1044 mean CD4+ cells/ul for children below and above 6 years respectively) and normal or high antibody titres. Very young children with high viral load, low CD4 T-lymphocytes and normal or low anti-HIV antibodies died rapidly compared to older children with similar clinical conditions. This data suggests that children with no anti-HIV-1 antibodies were severely immunosuppressed as they were unable to mount an effective anti-HIV antibody response. This data further suggests that younger children with high HIV load, low CD4 Tlymphocyte counts and normal or no anti-HIV antibody response are at a greater risk for rapid disease progression than older ones with similar parameters. Consequently, younger children should be considered for immediate anti-HIV treatment.