Long-term safety and effectiveness of ritonavir, nelfinavir, and lopinavir/ritonavir in antiretroviral-experienced HIV-infected children.
OBJECTIVE
To evaluate the long-term safety and effectiveness of ritonavir, nelfinavir, and lopinavir/ritonavir in antiretroviral-experienced, initially protease inhibitor (PI)-naive, human immunodeficiency virus (HIV)-1-infected children.


METHODS
HIV-1-infected children enrolled in the Swiss Mother and Child HIV Cohort Study were eligible for this observational cohort study if they received at least 1 PI of interest between March 1996 and October 2003: ritonavir, nelfinavir, or lopinavir/ritonavir. Data regarding demographics, clinical disease and antiretroviral treatment history, HIV-1 RNA copies/mL, CD4 T-cell counts [absolute (cells/microL) and percentages (%)], adverse events, clinical laboratory values, reasons for discontinuation of PIs, and concomitant medications were extracted from the database for PI-naive (first-line) and PI-experienced (second- or higher-line) PI use.


RESULTS
The total duration of ritonavir, nelfinavir, and lopinavir/ritonavir use for 133 HIV-1-infected children was 163.8, 235.0, and 46.1 patient-years, respectively. In an on-treatment analysis, first-line therapy with any of the PIs significantly reduced HIV-1 concentrations and increased CD4 T-cell counts and percentages from baseline throughout the 288-week study (P <or= 0.05) for ritonavir and nelfinavir and throughout 84 weeks of use for lopinavir/ritonavir, which was introduced into treatment more recently. All PIs investigated were most effective in PI-naive children. Thirteen PI-associated toxicities occurred requiring treatment changes or interruptions (neurologic symptoms, n = 2; pancreatitis, n = 1; allergic reactions, n = 4; visual symptoms, n = 3; and hyperlipidemia, n = 3).


CONCLUSIONS
Long-term PI-based therapy seems to be safe and to result in durable virologic and immunologic effectiveness in HIV-1-infected antiretroviral-experienced children.
Rudin
Christoph
C
Division of Infectious Diseases, University Children's Hospital, Basel, Switzerland. christoph.rudin@unibas.ch
Burri
Marcus
M
Shen
Yang
Y
Rode
Richard
R
Nadal
David
D
D000293:Adolescent; D018791:CD4 Lymphocyte Count; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000276:immunology / Q000821:virology; D017320:HIV Protease Inhibitors / Q000009:adverse effects* / Q000627:therapeutic use*; D015497:HIV-1; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008137:Longitudinal Studies; D061466:Lopinavir; D008297:Male; D019888:Nelfinavir / Q000009:adverse effects* / Q000627:therapeutic use*; D011247:Pregnancy; D011744:Pyrimidinones / Q000009:adverse effects* / Q000627:therapeutic use*; D019438:Ritonavir / Q000009:adverse effects* / Q000627:therapeutic use*; D013557:Switzerland; D016896:Treatment Outcome; D019562:Viral Load; D028761:Withholding Treatment
D017320:HIV Protease Inhibitors; D011744:Pyrimidinones; D061466:Lopinavir; D019888:Nelfinavir; D019438:Ritonavir