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Virological phenotype switches under salvage therapy with lopinavirritonavir in heavily pretreated HIV-1 vertically infected children

Galán, Isabel; Jiménez, José L; González-Rivera, Milagros; De José, Ma Isabela; Navarro, Ma Luisa; Ramos, José Tb; Mellado, Ma Joséc; Gurbindo, Ma Dolores; Ma Bellón, José; Resino, Salvador; Cabrero, Estherd; Muñoz-Fernández, Ma Angeles

Clinical Science

Objective: To investigate the effects of salvage therapy with lopinavir–ritonavir on HIV-1 phenotype in heavily antiretroviral experienced HIV-infected children.

Design: Twenty antiretroviral experienced HIV-infected children were studied during a mean of time of 16.1 months from initiation of the treatment with lopinavir–ritonavir.

Methods: Besides CD4 T cells, viral load and clinical status, we analyzed 91 serial viral isolates to study the phenotype, and biological clones derived from co-cultivation techniques.

Results: We observed an increase in CD4 T cells, a statistically significant decrease in viral load and clinical benefits from 3 months after treatment. Ninety per cent of children had SI/X4 bulk isolates in peripheral blood mononuclear cells at study entry. The viral phenotype changed to non syncitium-inducing (NSI)/R5 in 94% of the children after a mean of 5.7 months (95% confidence interval, 2.1–9.3 months) of salvage therapy. The remaining 10% of children had NSI/R5 isolates at entry and at all follow-up study. Similar results were found at the clonal level. Thus, at study entry in PBMC of three children with bulk syncitium-inducing (SI) phenotype, we recovered 65 biologic clones, 56 being SI and nine NSI. After salvage therapy bulk isolates changed to NSI and of 40 biologic clones recovered only five were SI and the rest were NSI.

Conclusions: Our data suggest that lopinavir–ritonavir salvage therapy led not only to a viral load decrease but also to a phenotypic change. X4 virus appeared to be preferentially suppressed. Shifts in co-receptor usage may thereby contribute to the clinical efficacy of anti-HIV drugs in vertically infected infants.

From the Laboratorio de Inmuno-Biología Molecular and Servicio de Pediatría, Hospital General Universitario ‘Gregorio Marañón', aServicio de Infecciosos Infantil, Hospital Universitario ‘La Paz', bServicio de Infecciosos Infantil, Hospital Universitario ‘12 de Octubre', cServicio de Pediatría, Hospital Carlos III, dAbbot Laboratorios on behalf of he Spanish Pediatric Collaborative Group on HIV-infection in children, Madrid, Spain.

Correspondence to A. Muñoz-Fernández, Laboratorio de Inmuno-Biología Molecular, Hospital General Universitario ‘Gregorio Marañón', C/Doctor Esquerdo 46, 28007 Madrid, Spain.

Received: 5 February 2002; revised: 11 February 2003; accepted: 12 March 2003.

© 2004 Lippincott Williams & Wilkins, Inc.