Mutations at codons 54 and 82 of HIV protease predict virological response of HIV-infected children on salvage lopinavir/ritonavir therapy.
BACKGROUND
Lopinavir/ritonavir is a protease inhibitor (PI) that has shown great effectiveness as salvage therapy in PI-experienced HIV-infected children.


OBJECTIVE
To study whether mutations in the HIV-1 protease gene can reliably predict virological responses to salvage therapy with lopinavir/ritonavir in HIV-infected children.


METHODS
We carried out a prospective study in 56 HIV-infected children. PI-associated resistance mutations were determined by genotypic testing and were scored according to the IAS-USA guidelines 2005.


RESULTS
Children with a 'lopinavir mutation score' (LMS) > or = 6 had a negative association for achieving viral load (VL) control [undetectable viral load (uVL) < or = 400 copies/mL] and maintaining uVL for at least 6 months. Moreover, children with protease-associated mutations (PRAMs) > or = 2 had a negative association for achieving VL control but not for maintaining uVL for at least 6 months. The relative proportion (RP) to uVL was 0.32 (CI95%: 0.16; 0.33; P = 0.002) in children with I54V (46% of total) and 0.48 (CI95%: 0.24; 0.97; P = 0.041) in children with V82A/F (52% of total). Children with I54V and V82A/F had higher prevalence of lopinavir-associated resistance mutations and showed RP of 0.36 (CI95%: 0.17; 0.76; P = 0.007) for achieving uVL.


CONCLUSIONS
LMS and PRAMs in HIV-infected children were associated with virological failure in pre-treated HIV-infected children on salvage therapy with lopinavir/ritonavir. Moreover, I54V and V82A/F led to the poorest virological response.
Luis Jiménez
José
J
Laboratory of Immunobiología-Molecular, Hospital General Universitario Gregorio Marañón, Madrid, Spain.
Resino
Salvador
S
Martinez-Colom
Alberto
A
Bellón
Jose Ma
JM
Angeles Muñoz-Fernández
Ma
M
D000293:Adolescent; D019380:Anti-HIV Agents / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D023241:Antiretroviral Therapy, Highly Active; D002648:Child; D002675:Child, Preschool; D024882:Drug Resistance, Viral / Q000235:genetics*; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000821:virology; D016333:HIV Protease / Q000235:genetics*; D015497:HIV-1 / Q000187:drug effects / Q000235:genetics; D006801:Humans; D007223:Infant; D061466:Lopinavir; D008297:Male; D009154:Mutation; D011379:Prognosis; D011446:Prospective Studies; D011744:Pyrimidinones / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D019438:Ritonavir / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D016879:Salvage Therapy; D019562:Viral Load
D019380:Anti-HIV Agents; D011744:Pyrimidinones; D061466:Lopinavir; D016333:HIV Protease; D019438:Ritonavir