Journal Article

Mutations at codons 54 and 82 of HIV protease predict virological response of HIV-infected children on salvage lopinavir/ritonavir therapy

José Luis Jimeénez, Salvador Resino, Alberto Martinez-Colom, José Mª Bellón and Mª Ángeles Muñoz-Fernández

in Journal of Antimicrobial Chemotherapy

Published on behalf of British Society for Antimicrobial Chemotherapy

Volume 56, issue 6, pages 1081-1086
Published in print December 2005 | ISSN: 0305-7453
Published online September 2005 | e-ISSN: 1460-2091 | DOI: http://dx.doi.org/10.1093/jac/dki356
Mutations at codons 54 and 82 of HIV protease predict virological response of HIV-infected children on salvage lopinavir/ritonavir therapy

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  • Medical Oncology
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Background: Lopinavir/ritonavir is a protease inhibitor (PI) that has shown great effectiveness as salvage therapy in PI-experienced HIV-infected children.

Objectives: 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.

Patients and 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) ≥6 had a negative association for achieving viral load (VL) control [undetectable viral load (uVL) ≤400 copies/mL] and maintaining uVL for at least 6 months. Moreover, children with protease-associated mutations (PRAMs) ≥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.

Keywords: HIV-1; viral load; salvage therapy; resistance

Journal Article.  3156 words.  Illustrated.

Subjects: Medical Oncology ; Critical Care

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