COMBINED THERAPY IN HUMAN IMMUNODEFICIENCY VIRUS-INFECTED CHILDREN - A 4-YEAR EXPERIENCE

From 1988 to 1991 the long-term efficacy of a combined therapy with a polyvalent immunoglobulin/cytomegalovirus (CMV) hyperimmunoglobulin, o ral low dose zidovudine, oral cotrimoxazole or inhaled pentamidine was investigated in three groups of human immunodeficiency virus (HIV)-in fected children. Group 1A consisted of three perinatally infected chil dren with a CD4 cell decrease of > 400 cells/mul per year. Group 1B we re 17 perinatally infected children with a CD4 cell decrease of < 400 cells/mul per year. Group 2 comprised eight haemophilic children infec ted by clotting factors. Despite combined therapy none of group 1A sur vived longer than 12 months showing a rapid loss of CD4 cell counts, p rogressive encephalopathy, wasting syndrome and severe bacterial, fung al and CMV reactivation. Under pure intravenous immunoglobulin (IVIG) therapy severe bacterial infections were seen in 1 of 12 children in g roup 1B. The majority of these patients showed increases or stabilisat ion of length and weight percentiles. In this group low dose zidovudin e therapy was of benefit in HIV-associated neurological symptoms. Neve rtheless combined therapy could not prevent further deterioration of C D4 cell counts. In group 2 severe bacterial infections were not seen u nder IVIG therapy. In this group a temporary increase (6 months) of CD 4 cell counts under IVIG/zidovudine combined therapy occurred. Pneumo cystis carinii pneumonia (PCP) prophylaxis with oral cotrimoxazole or inhaled pentamidine successfully prevented PCP in all three groups. Un der CMV hyperimmunoglobulins (n = 22), ten out of ten patients did not acquire primary CMV infection, whereas CMV reactivations mainly locat ed in the CNS could not be prevented in 5 of 12 patients. Our findings indicate that this combined therapy showed remarkable differences in therapeutic efficacy in children with different modes of HIV progressi on. These modes must be considered for correct timing, dosage and eval uation of therapeutic measures.