Long-term effects of highly active antiretroviral therapy in pretreated, vertically HIV type 1-infected children: 6 years of follow-up.
BACKGROUND
Several studies of children with human immunodeficiency virus (HIV) type 1 infection have demonstrated sustained increases in CD4+ cell count, even when virological failure has occurred after receipt of highly active antiretroviral therapy (HAART), but these studies were of limited duration. Moreover, the CD4+ cell count threshold at which antiretroviral treatment should be initiated is still unsettled. The aim of this study was to define the long-term impact of HAART on CD4+ cell percentage and viral load according to CD4+ cell percentages before HAART was initiated.


METHODS
We conducted a retrospective study of 113 pretreated HIV-1-infected children stratified by pre-HAART CD4+ cell percentage (<5%, 5%-15%, 15%-25%, and >25%). The inclusion criteria were as follows: initiating HAART with a protease inhibitor, having 6 years of follow-up after starting HAART, having a CD4+ cell count or viral load recorded before initiation of HAART, and having received mono- or dual-nucleoside therapy before starting HAART.


RESULTS
During the first 2 years of HAART, HIV-1-infected children experienced a significant increase in CD4+ cell percentage and a decrease in viral load (P<.05). During their last 4 years of receiving HAART, we found a significant decrease in viral load but not an increase in CD4+ cell percentage, because the CD4+ cell percentage reached a plateau after the second year of HAART. Moreover, children with CD4+ cell percentages of <5% at baseline did not achieve CD4+ cell percentages of >25% after 6 years of HAART. Children with CD4+ cell percentages of 5%-25% at baseline had a strong negative association with achieving CD4+ cell percentages of >30% for at least 6 and 12 months but not with achieving CD4+ cell percentages of >30% for at least 24 months.


CONCLUSIONS
Long-term HAART allowed for restoration of CD4+ cell counts and control of viral loads in HIV-1-infected children. However, initiating HAART after severe immunosuppression has occurred is detrimental for the restoration of the CD4+ cell count.
Resino
Salvador
S
Laboratorio de Inmuno-Biología Molecular, Hospital General Universitario Gregorio Marañón, Madrid, Spain. sresino.hgugm@salud.madrid.org
Resino
Rosa
R
Micheloud
Dariela
D
Gurbindo Gutiérrez
Dolores
D
Léon
Juan Antonio
JA
Ramos
José Tomás
JT
Ciria
Luis
L
de José
Isabel
I
Mellado
José
J
Muñoz-Fernández
Angeles
A
D023241:Antiretroviral Therapy, Highly Active / Q000009:adverse effects; D018791:CD4 Lymphocyte Count; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D005260:Female; D005500:Follow-Up Studies; D015658:HIV Infections / Q000188:drug therapy* / Q000276:immunology / Q000635:transmission*; D015497:HIV-1; D006801:Humans; D018445:Infectious Disease Transmission, Vertical; D008297:Male; D012189:Retrospective Studies; D013030:Spain / Q000453:epidemiology; D019562:Viral Load