Positive virological outcome after lopinavir/ritonavir salvage therapy in protease inhibitor-experienced HIV-1-infected children: a prospective cohort study.
BACKGROUND
Lopinavir/ritonavir has demonstrated antiviral activity in the HIV-infected patient.


OBJECTIVE
To analyse virological response to lopinavir/ritonavir therapy in previously protease inhibitor (PI)-experienced HIV-1-infected children.


METHODS
Sixty-seven HIV-1-children on lopinavir/ritonavir were studied in a multicentre prospective cohort observational study. The outcome variables were undetectable viral load (uVL; VL < or =400 copies/mL) and virological failure after uVL with a rebound of VL >400 copies/mL. VL and genotype of HIV-1-isolates were measured using standard assays.


RESULTS
83.5% of children had a 1 log10 VL decrease including 65.6% who reached uVL. Children with >2 changes of antiretroviral therapy (ART) or >5 drugs needed a median time of 3-4 months higher than children with < or =2 changes of ART or < or =5 drugs previous to lopinavir/ritonavir, to reach those values, and the relative proportions (RP) were 2.2 (P =0.038) and 1.9 (P=0.050), respectively. Children with CD4+>15% (P=0.122), VL < or =30,000 (P < 0.001) copies/mL, and age >12 years (P=0.096) achieved an earlier control of VL during the follow-up. The children with virological failure or rebound of VL had higher baseline VL and lower CD4+ T-lymphocytes/mm3 and had taken a greater number of drugs previous to lopinavir/ritonavir. HIV-children with a new nucleoside reverse transcriptase inhibitor (NRTI), or protease inhibitor (PI) or PI plus non-nucleoside reverse transcriptase inhibitors (NNRTI) in the current regimen had a better virological response than children without these new drugs. Also, children with <6 protease mutations had an RP of 2.31 of achieving uVL.


CONCLUSIONS
Highly active antiretroviral therapy (HAART) including lopinavir/ritonavir induces beneficial effects in terms of virological outcome responses, and it is an effective option for salvage therapy in PI-experienced HIV-1-infected children.
Laboratory of Immuno-Molecular Biology, Hospital Gregorio Marañón, Madrid, Spain.
Salvador
S
Resino
Jose Ma
JM
Bellón
José Tomás
JT
Ramos
Milagros
M
Gonzalez-Rivera
Ma Isabel
MI
de José
Ma Isabel
MI
González
Dolores
D
Gurbindo
Ma Jose
MJ
Mellado
Esther
E
Cabrero
Ma Angeles
MA
Muñoz-Fernández
D000163:Acquired Immunodeficiency Syndrome / Q000188:drug therapy* / Q000276:immunology / Q000821:virology; D023241:Antiretroviral Therapy, Highly Active; D018791:CD4 Lymphocyte Count; D015331:Cohort Studies; D004359:Drug Therapy, Combination; D015497:HIV-1; D006801:Humans; D061466:Lopinavir; D011446:Prospective Studies; D011744:Pyrimidinones / Q000008:administration & dosage* / Q000009:adverse effects; D019438:Ritonavir / Q000008:administration & dosage* / Q000009:adverse effects; D016879:Salvage Therapy
D011744:Pyrimidinones; D061466:Lopinavir; D019438:Ritonavir