Combined antiretroviral therapy reduces hyperimmunoglobulinemia in HIV-1 infected children

Objective: To evaluate the effect of combined antiretroviral therapy on serum immunoglobulin (Ig) levels in HIV-1 perinatally infected children. Methods: Data from 1250 children recorded by the Italian Register for HIV Infection in Children from 1985 to 2002 were analysed. Since Ig levels physiologically vary with age, differences at different age periods were evaluated as differences in z-scores calculated using means and standard deviations of normal population for each age period. Combined antiretroviral therapy has become widespread in Italy since 1996, thus differences in Ig z-scores between the periods 1985-1995 and 1996-2002 were analysed. Data according to type of therapeutic regimen were also analysed. Results: Between the two periods 1985-1995 and 1996-2002, significant (P < 0.0001) decreases in IgG (6.29 ± 4.72 versus 4.44 ± 4.33), IgM (9.25 ± 13.32 versus 5.61 ± 7.93), and IgA (10.25 ± 15.68 versus 6.48 ± 11.56) z-scores, together with a parallel significant (P < 0.0001) increase in CD4 T-lymphocyte percentages, were found. These decreases were confirmed regardless of whether the children were receiving intravenous Ig or not. Ig z-scores were significantly higher in children receiving mono-therapy than in those receiving double-combined therapy (IgC, P < 0.0001; IgM, P = 0.003; IgA, P = 0.031) and in the latter children than in those receiving three or more drugs (P < 0.0001 for all z-scores). Ig z-scores correlated inversely with CD4 T-lymphocyte percentages and, directly, with viral loads. Conclusions: Our data show that in HIV-1 infected children combined antiretroviral therapy leads to reduction of hyperimmunoglobulinemia which parallels restoration of CD4 T-lymphocyte percentage and viral load decrease, which it turn probably reflects improved B-lymphocyte functions. © 2004 Lippincott Williams & Wilkins

Virologic, immunologic and clinical benefits from early combined antiretroviral therapy in infants with perinatal HIV-1 infection

Objective: To investigate the impact of early versus deferred combined antiretroviraltreatment (ART) in asymptomatic or moderately symptomatic [Centers for DiseaseControl and Prevention (CDC) category N, A or B] infants with perinatal HIV-1infection.Methods: A multi-centre nationwide case–control study was conducted. Data from 30infants treated with combined ART with three or more drugs before 6 months of agewere compared with data from 103 infants starting ART with three or more drugs after 6months of age. The median follow-up time was 4.1 years (range, 1.0–6.5 years).Results: No difference was evident in the first available viral load and CD4T-lymphocyte percentage between the two groups of children. Early-treated infantsshowed significantly lower viral loads than infants receiving deferred treatment at all thefollow-up periods. A higher proportion of early-treated infants than infants receivingdeferred treatment (73.3% versus 30.1%; P < 0.0001) reached an undetectable viralload. Higher CD4 T-lymphocyte percentages were found in early-treated infants at 13–24 (P < 0.0001), 25–36 (P < 0.0001), and 37–48 (P ¼ 0.003) months of age. No earlytreatedinfant versus 20 of 103 (19.4%) infants receiving deferred ART (P ¼ 0.02)showed a CD4 T-lymphocyte percentage of less than 15% at one time point duringfollow-up. No CDC category A, B or C clinical event occurred in early-treated infantsover the follow-up period while 44 of 103 (42.7%) infants receiving deferred treatmentpresented a decline in the CDC category. Kaplan–Meier analyses revealed significantdifferences in CDC category A (P ¼ 0.0002), B (P ¼ 0.0003), and C (P ¼ 0.0018) eventfreesurvivals.Conclusion: The data suggest virologic, immunologic, and clinical benefits from earlyadministration of ART

Once versus twice daily administration of didanosine in children with symptomatic HIV-associated disease who were intolerant to or clinically deteriorated on zidovudine. The Italian Pediatric Collaborative Study Group on Didanosine.

The objective of this study was to compare the safety, tolerability and clinical response of once- versus twice-daily administration of didanosine given at a dosage of 270 mg/m2/day in children with symptomatic HIV-associated disease who were intolerant to or clinically deteriorated on zidovudine monotherapy. We carried out a randomized, open-label multicentre trial. Didanosine was supplied in buffered tablets, which could be chewed or dispersed in liquid. The children were recruited from 16 paediatric departments participating in the Italian Register for HIV Infection in Children. A total of 53 children (median age 5.5 years) started trial treatment; 26 were given didanosine twice daily and 27 once daily; 85% had AIDS and 98% had clinically deteriorated while on zidovudine therapy. Similar safety and tolerability results were demonstrated for the two schemes of therapy. A total of 11 children (20.7%) required discontinuation of didanosine for severe adverse events (five children (19.2%) in the twice-daily group; six children (22.2%) in the once-daily group, log-rank P = 0.81). Severe hepatic toxicity was uncommon (5.6%) while mild to moderate hepatic dysfunction was demonstrated in about 17% of the participants, without any difference between the two groups. Haematological toxicity was common (about 40% of the children, 11 in the twice- and 19 in the once-daily group) but never severe. Clinical pancreatitis and retinal lesions were never demonstrated. There was no significant difference in progression to death or to a new opportunistic infection between the two treatment regimens (log-rank P = 0.54). The modification of surrogate efficacy parameters during the study period was similar in the two groups. However, weight gain was poorer in children treated once daily. This study suggests that the safety and tolerability of 270 mg/m2/day of didanosine given once daily is substantially similar to that of the traditionally recommended schedule of two divided doses. Owing to the small sample and to the severity of the clinical condition of the children enrolled, no definite conclusions on the comparative efficacy of the two regimens can be drawn