Search

Objective: The risk of virologic failure and selection of resistant strains remains a challenge in HIV-1 perinatally infected children. HIV-1 coreceptor usage was determined in HAART-failing children followed in Necker Hospital (Paris, France) in order to estimate the proportion of these patients who may benefit from CCR5-antagonists therapy., Methods: HIV-1 coreceptor usage was determined with the SVM(Geno2pheno10%) algorithm in 51 children with virologic failure after a median treatment exposure of 7.8 years., Results: CXCR4-tropic strains were found in 31.4% of the patients. CXCR4 usage was associated with high HIV-1 DNA (P=0.01), old age (P=0.02), long ART cumulative exposure (P=0.006), and previous exposure to high number of different drugs (P=0.03) and ART combinations (P=0.03) in univariate analysis. Selection of resistant viruses and current exposure to a darunavir-based HAART tended to be more frequent in the CXCR4 group compared with the children infected with CCR5-tropic strains (P=0.06). In multivariate analysis, CXCR4 usage was exclusively correlated with HIV-1 DNA (P=0.03), which accurately reflects the cumulative exposure to viral replication over the whole duration of HIV infection., Conclusion: Two-thirds of HAART-failing children could benefit from CCR5 antagonists-based strategies, even in case of triple-class virologic failure. Such therapy should be discussed more appropriately at early stages of infection, when CCR5-tropic strains are most frequently isolated. However, before considering such strategies, further studies are needed to evaluate the efficacy and the tolerability of CCR5 antagonists in this pediatric population., (© 2012 Wolters Kluwer Health | Lippincott Williams & Wilkins)

Background: Lopinavir/ritonavir (LPV/r) is now the protease inhibitor regimen of choice in the first-line antiretroviral therapy for children <6 years of age., Methods: We included all the human immunodeficiency virus (HIV) type 1-infected highly active antiretroviral therapy (HAART)-naive children who started an LPV/r-based regimen between 2000 and 2009 at the Necker Hospital (Paris, France). Virologic failure (VF) was defined as an HIV-RNA ≥50 copies/mL. Resistance genotypic test was performed in case of VF., Results: A total of 43 children were included at a median age of 4.8 years (1.8-8.0). Median level of HIV RNA and percentage of CD4 cell count was 5.5 log₁₀ copies/mL (4.6-6) and 15% (8-27.5), respectively. HAART included LPV/r and 2 nucleoside reverse-transcriptase inhibitors, mainly lamivudine (3TC), zidovudine, and/or abacavir. The median follow-up period was 36 months (18-72). Less than 50 copies/mL of HIV RNA was observed in 46%, 67%, and 70% of the children at months 6, 9, and 12, respectively. In all, 20 children (46.5%) experienced a VF. The risk factors of primary VF were a young age and a low socioeconomic status. The genotypic resistance test, performed for 18 of 20 children with VF, revealed 1 LPV/r-resistant virus and protease inhibitor-related major mutations without LPV/r resistance in 2 other children. Of the 18 children with VF, 15 received a 3TC-based HAART: 12 of 15 (80%) harbored a 3TC-resistant virus. No virus resistant to zidovudine or abacavir was found., Conclusion: In all, 70% of HAART-naive children had virologic success at month 12. The selection of LPV-resistant strains was a rare event. A high rate of selection of 3TC-mutations strengthens the recommendation to prefer a first-line 3TC-sparing regimen, particularly for children with risk factors of poor adherence.

Pediatric HIV-1 infections are still being diagnosed in France, despite the efficacy of prophylactic treatment to prevent mother-to-child transmission. To describe the characteristics and mode of infection of these children, we retrospectively analysed data of 59 children diagnosed with the HIV-1 infection between January 2000 and June 2005 in a Parisian university hospital. Twenty of these children had been born in France, and none had received appropriate prophylaxis (insufficient, not taken or given too late). Six received no preventive treatment due to failures in screening: three mothers were HIV-seronegative at the start of pregnancy and no test was carried out for the other three. At diagnosis, four had a severe immune deficiency (CD4 cells <15%). The 39 children born abroad were diagnosed at a median age of 3 years (range: 3 months-16 years), sometimes several years after their arrival in France. The clinical, virological and immunological status of these children was poorer than that of the children born in France: 18 had less than 15% CD4 cells. In contrast, the response to treatment of the children born in France was not as good as that of the children born abroad. The HIV-1 screening and prevention programme for pregnant women could be improved. Some children infected following the failure of prevention are at high risk of subsequent treatment failure. HIV-1 infection should be taken into consideration in children born in countries with a high prevalence of HIV, even if they have been living in France for several years and present no symptoms.