Background In human immunodeficiency virus (HIV)–positive adults, low CD4 cell counts despite fully suppressed HIV-1 RNA on antiretroviral therapy (ART) have been associated with increased risk of morbidity and mortality. We assessed the prevalence and outcomes of poor immune response (PIR) in children receiving suppressive ART. Methods Sixteen cohorts from the European Pregnancy and Paediatric HIV Cohort Collaboration (EPPICC) contributed data. Children <18 years at ART initiation, with sustained viral suppression (VS) (≤400 copies/mL) for ≥1 year were included. The prevalence of PIR (defined as World Health Organization advanced/severe immunosuppression for age) at 1 year of VS was described. Factors associated with PIR were assessed using logistic regression. Rates of acquired immunodeficiency syndrome (AIDS) or death on suppressive ART were calculated by PIR status. Results Of 2318 children included, median age was 6.4 years and 68% had advanced/severe immunosuppression at ART initiation. At 1 year of VS, 12% had PIR. In multivariable analysis, PIR was associated with older age and worse immunological stage at ART start, hepatitis B coinfection, and residing in Thailand (all P ≤ .03). Rates of AIDS/death (95% confidence interval) per 100 000 person-years were 1052 (547, 2022) among PIR versus 261 (166, 409) among immune responders; rate ratio of 4.04 (1.83, 8.92; P < .001). Conclusions One in eight children in our cohort experienced PIR despite sustained VS. While the overall rate of AIDS/death was low, children with PIR had a 4-fold increase in risk of event as compared with immune responders.
The aim of the study was to explore factors associated with CD4 percentage (CD4%) reconstitution following treatment interruptions (TIs) of antiretroviral therapy (ART). MethodsData from paediatric HIV-infected cohorts across 17 countries in Europe and Thailand were pooled. Children on combination ART (cART; at least three drugs from at least two classes) for > 6 months before TI of ≥ 30 days while aged < 18 years were included. CD4% at restart of ART (r-ART) and in the long term (up to 24 months after r-ART) following the first TI was modelled using asymptotic regression. ResultsIn 779 children with at least one TI, the median age at first TI was 10.1 [interquartile range (IQR) 6.4, 13.6] years and the mean CD4% was 27.3% [standard deviation (SD) 11.0%]; the median TI duration was 9.0 (IQR 3.5, 22.5) months. In regression analysis, the mean CD4% was 19.2% [95% confidence interval (CI) 18.3, 20.1%] at r-ART, and 27.1% (26.2, 27.9%) in the long term, with half this increase in the first 6 months. r-ART and long-term CD4% values were highest in female patients and in children aged < 3 years at the start of TI. Long-term CD4% was highest in those with a TI lasting 1 to <3 months, those with r-ART after year 2000 and those with a CD4% nadir ≥ 25% (all P < 0.001). The effect of CD4% nadir during the TI differed significantly (P = 0.038) by viral suppression at the start of the TI; in children with CD4% nadir < 15% during TI, recovery was better in those virally suppressed prior to the TI; viral suppression was not associated with recovery in children with CD4% nadir ≥ 25%. ConclusionsAfter restart of ART following TI, most children reconstituted well immunologically. Nevertheless, several factors predicted better immunological reconstitution, including younger age and higher nadir CD4% during TI.Parameters were estimated using multilevel asymptotic regression models. The intercept represents the CD4% at restart of ART, with b representing the difference in mean CD4% in patients with specific characteristics and the reference group. Similarly, the asymptote represents the longer term CD4% (up to 24 months after restart) and b represents longer term differences in mean CD4%. C is a rate parameter; negative values indicate a slower increase in CD4% and positive values indicate a faster increase. The intercept, asymptote and C constants represent the mean CD4% at restart and in the long term and the rate parameter for patients in the reference groups. Time to half the total CD4% recovery can be estimated as In(2)/c. CI, confidence interval; VL, viral load.
RiassuntoRaccogliendo dati relativi ad una popolazione di oltre 10.000 bambini, a partire dal 1985, il Registro Italiano per l'infezione da HIV in pediatria ha la finalità di studiare gli aspetti epidemiologici, clinici e immunologici dell'infezione da HIV in età pediatrica. Esso consente, pertanto, la valutazione prospettica della trasmissione verticale dell'infezione attraverso l'esame di dati riguardati le caratteristiche di madri infette, di bambini esposti al virus in utero o peripartum che abbiano o non abbiano contratto l'infezione e delle strategie di prevenzione e trattamento attuate negli anni. L'utilizzo dei dati del Registro è pertanto utile per la comprensione del fenomeno e la verifica dei comportamenti concretamente attuati dai pediatri italiani "sul campo", valutando le possibili discordanze con i comportamenti indicati dalle raccomandazioni delle linee guida esistenti e dai risultati di trials clinici. Tali dati permettono poi di individuare popolazioni "fragili", quali i bambini nati in Italia Abstract The Italian Register for HIV infection in children collected
We report the case of a perinatally HIV-1-infected child, previously immunologically unresponsive to antiretroviral treatments (including the highly active antiretroviral therapy), who instead developed a vigorous and long-lasting immune response after the highly active antiretroviral therapy was associated with antineoplastic chemotherapy undertaken for a B-cell non-Hodgkin bone lymphoma.
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