Lopinavir/Ritonavir-based HAART at 12 Months Has a Potent and Durable
Antiretroviral Effect in Heavily Pretreated Children with Resistance
to 3 Drug Classes
Like many adults with HIV infection, many HIV-infected
children have already failed treatment with 2 or
even 3 classes of antiretrovirals.
Co-formulation of lopinavir with low dose ritonavir (Kaletra) exhibits a potent antiretroviral effect.
However, the data on HAART use in heavily pretreated children
are scarce.
The
current study evaluated the safety and effectiveness of combination
therapy including lopinavir/ritonavir in children with prior exposure to all
classes of oral antiretrovirals.
This
was an open label multicenter observational study, in which data were reviewed
according to a standardized protocol.
The
study population included all HIV-1-infected children with virologic failure (HIV-1 RNA >5000 copies/mL) followed in 12 Spanish hospitals for >12 months, experienced
with the 3 classes of oral antiretrovirals,
in whom a lopinavir/ritonavir-containing
regimen was started.
Results
By March 2003, 45 patients had been treated with lopinavir/ritonavir
for a median of 18 months (range, 3-28).
The median age at baseline
was 9.7 years (range, 4.3-17.1).
The median times of prior
treatment were 88 months (range, 31-145) with nucleoside reverse
transcription inhibitors and 42 months (range,
19-63) with protease
inhibitors.
Twenty-five patients were
classified as Centers for Disease Control and Prevention clinical
category C.
Median values for absolute
and percentage CD4 at baseline were 501and 19%, respectively,
and plasma HIV-RNA was 5.0 log10 copies/mL.
During follow-up, 11 (24%)
children switched from liquid to solid formulation.
At 48 weeks, the median
values for absolute and percentage CD4 increased by
199 cells/muL and 3%, respectively,
and median plasma viral load declined 1.75 log10 copies/mL.
Forty-two percent of children
achieved a plasma RNA of <400 copies/mL
(intent to treat analysis).
Baseline genotypic resistance
was available in 40 children.
Nonresponders had 7.0 +/- 1.6 protease inhibitor-associated mutations
at baseline compared with 4.8 +/- 1.7 in children achieving virologic suppression (P = 0.06).
Adverse events
were described in 18 children. Three children permanently discontinued
and 4 transiently withdrew lopinavir/ritonavir.
At 12 months, there were
mild but not significant increases in plasma
cholesterol and triglycerides.
Based
on the findings, the authors conclude, “Lopinavir/ritonavir
when given as part of salvage
regimen is well-tolerated, although switching to
pills is frequently required.”
“The
regimen has a potent and durable antiretroviral activity in most
heavily pretreated children, despite the presence of multiple
mutations to all classes of oral antiretrovirals.”
Hospital 12 Octubre, Madrid,
Spain; Hospital La Paz, Madrid, Spain;Hospital
Son Dureta, Palma de Mallorca, Spain;
Hospital San Joan de Deu, Barcelona,
Spain; Hospital Sant Joan, Alicante, Spain; Hospital
Carlos III, Madrid, Spain; Hospital del Mar, Barcelona Spain;
Hospital Gregorio Maranon, Madrid, Spain;
Hospital La Fe, Valencia, Spain; Hospital de Cruces, Bilbao,
Spain; and Abbott Laboratories, Madrid, Spain.
10/17/05
Reference
J T Ramos and others (Spanish Collaborative Group on
HIV Infection in Children). Safety and Antiviral Response at 12 Months of Lopinavir/Ritonavir
Therapy in Human Immunodeficiency Virus-1-Infected Children Experienced
With Three Classes of Antiretrovirals.
Pediatric Infectious
Diseases Journal 24(10):867-873.
October 2005.
