Early multitherapy including a protease inhibitor for human immunodeficiency virus type 1-infected infants

Faye, Albert; Bertone, Catherine; Teglas, Jean Paul; Chaix, Marie Laure; Douard, Danielle; Firtion, Ghislaine; Thuret, Isabelle; Dollfus, Catherine; Monpoux, Fabrice; Floch, Corinne; Nicolas, J; Vilmer, E; Rouzioux, Christine; Mayaux, Marie Jeanne; Blanche, Stéphane

doi:10.1097/00006454-200206000-00008

Cited by 55 publications

(29 citation statements)

References 21 publications

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“…For instance, in studies where children were treated with different protease inhibitor-containing regimens (indinavir, nelfinavir, or ritonavir) or NNRTIs such as nevirapine or efavirenz, between 11% and 64% of the patients achieved HIV-1 RNA load suppression below the level of detection during follow-up. 5,[11][12][13][14][15] Thus, our finding of complete viral suppression after 1 year of treatment for more than half of the children is consistent with what others have reported. 12,13 In contrast, pediatric CD4 ϩ T cell counts generally increase uniformly and rapidly, regardless of virologic response.…”

Section: Art and Drug Resistance Predictors In Côte D'ivoire 915supporting

confidence: 91%

Virologic and Immunologic Response to Antiretroviral Therapy and Predictors of HIV Type 1 Drug Resistance in Children Receiving Treatment in Abidjan, Côte d'Ivoire

Adjé-Touré

Hanson

Talla-Nzussouo

et al. 2008

AIDS Research and Human Retroviruses

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We describe changes in HIV-1 viral load, CD4+ T cell percentage, and incidence of drug resistance and factors associated with drug resistance for 134 children receiving antiretroviral therapy (ART) for approximately 1 year in Abidjan. Between August 1998 and September 2003, ART was initiated for 395 HIV-infected children ages 0-15 years in the Côte d'Ivoire national drug access initiative. All 1-year samples with detectable HIV RNA >1000 copies/ml were tested for HIV-1 drug resistance and changes in viral load and CD4+ T cell counts were also determined. At treatment initiation, 80% of children had CD4+ T cell percentages <15% and a median viral RNA load of 5.6 log copies/ml. The median age at treatment initiation was 7 years with only 25% of patients less than 4 years of age. Of the 134 children receiving therapy, 72 (54%) had undetectable viral load. The estimated 1-year viral load decline was 1.9 log10 copies/ml and the CD4+ T cell percentage increase was 10.9%. The estimated 1-year cumulative probability for developing any class of drug resistance was 0.44 (95% CI, 0.35, 0.53). In a multivariate analysis, the magnitude of virologic response to therapy was inversely associated with development of drug resistance. Children with less CD4+ T cell rise from baseline values and the use of dual therapy were also associated with the development of drug resistance. Guidelines are needed for the treatment of pediatric HIV infection in Africa in order to minimize the occurrence of drug resistance and enhance better virologic, immunologic, and clinical outcomes.

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Section: Art and Drug Resistance Predictors In Côte D'ivoire 915supporting

confidence: 91%

Virologic and Immunologic Response to Antiretroviral Therapy and Predictors of HIV Type 1 Drug Resistance in Children Receiving Treatment in Abidjan, Côte d'Ivoire

Adjé-Touré

Hanson

Talla-Nzussouo

et al. 2008

AIDS Research and Human Retroviruses

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“…Drug resistance was observed in most viremic children (82%) as described in treated HIV adults experiencing virologic failure in the USA and West Europe studied at the same year period [Tamalet et al, 2003;Richman et al, 2004]. Randomized trials and observational studies in children also described a high prevalence of resistance to any drug, increasing with the number of prior ART received [Eshleman et al, 2001;Faye et al, 2002;Mullen et al, 2002;Aboulker et al, 2004].…”

Section: Discussionmentioning

confidence: 99%

Prevalence and risk factors associated with antiretroviral resistance in HIV‐1‐infected children

Delaugerre

Warszawski

Chaix

et al. 2007

Journal of Medical Virology

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In the USA and West Europe, nearly 80% of HIV-1-infected adults, experiencing virologic failure, harbored virus strain resistant to at least one antiretroviral drug. Limited data are available on antiretroviral drug resistance in pediatric HIV infection. The aims of this study were to analyze prevalence of HIV-1 drug resistance and to identify risk factors associated with resistance in this population. Prevalence of genotypic resistance was estimated retrospectively in treated children who experienced virologic failure (with HIV-1-RNA > 500 copies/ml) followed in Necker hospital between 2001 and 2003. Among 119 children with resistance testing, prevalence of resistance to any drug was 82.4%. Resistance ranged from 76.5% to nucleoside reverse transcriptase inhibitor (NRTI), to 48.7% to non-nucleoside reverse transcriptase inhibitor (NNRTI) and 42.9% to protease inhibitor (PI). Resistance to at least one drug of two classes and three classes (triple resistance) was 31.9 and 26.9%, respectively. Resistance was not associated with geographic origin, HIV-1 subtype, and CDC status. In multivariate analysis, resistance to any drug remained associated independently with current low viral load and high lifetime number of past PI. Triple resistance was independently associated with the high lifetime number of past PI and with gender, particularly among children aged 11 years old or more with a prevalence seven times higher in boys than in girls. In conclusion, antiretroviral resistance is common among treated HIV-1-infected children and prevalence was similar with those observed in adult population in the same year period. However, adolescent boys seem to be at greater risk.

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“…In addition, it is well established that viremia set points in children are higher than adults, and achieving undetectable viremia in perinatally infected subjects is only 56% after 12 mo (33) and 52% and 18% successful after 12 and 24 mo of treatment, respectively (34), which is much lower than adults. Pediatric subjects on combination ART have been reported to reach undetectable levels of viremia Ͻ400 and Ͻ50 copies HIV-1 RNA/mL by median of 4 and 20 wk, respectively (35).…”

Section: Discussionmentioning

confidence: 99%

Pediatric HIV-1–Specific Cytotoxic T-Lymphocyte Responses Suggesting Ongoing Viral Replication Despite Combination Antiretroviral Therapy

et al. 2007

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Human immunodeficiency virus-1 (HIV-1)-specific cytotoxic T-lymphocyte (CTL) responses are common in infected adults and usually exhibit rapid decay after combination antiretroviral therapy (ART). CTLs develop later in the first year of life, and the fate of HIV-1-specific responses in perinatally infected children after ART is less well described. HIV-1-specific CTL responses were measured in 17 perinatally infected children and adolescents (ages 3-20 y) receiving combination ART. Seven had prolonged viral suppression (Ͻ400 copies/mL) for 2.5-5.3 y and 10 had persistent viremia (median, 77,550 copies/mL). HIV-1-specific CTL responses were tested by interferon (IFN)-␥ enzyme-linked immunospot (ELISpot) assays using 53 overlapping peptide pools spanning the entire HIV-1 proteome. HIV-1-specific CTL responses were detected in 14 of 17 individuals. Responses to one to four viral proteins were found in eight of 10 individuals with persistent viremia and six of seven with prolonged viral suppression. The magnitude and breadth of CTL responses were similar between groups. HIV-1-specific CTL responses were present in the majority of perinatally infected subjects, irrespective of viremia at evaluation. Because ART-treated infected adults usually have rapid decay of responses, these data suggest viral replication below the limits of detection is more persistent in combination ART-treated perinatally infected pediatric subjects. The long-term clinical implications of these findings remain to be determined. (Pediatr Res 61: 692-697, 2007)

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Early multitherapy including a protease inhibitor for human immunodeficiency virus type 1-infected infants

Cited by 55 publications

References 21 publications

Virologic and Immunologic Response to Antiretroviral Therapy and Predictors of HIV Type 1 Drug Resistance in Children Receiving Treatment in Abidjan, Côte d'Ivoire

Virologic and Immunologic Response to Antiretroviral Therapy and Predictors of HIV Type 1 Drug Resistance in Children Receiving Treatment in Abidjan, Côte d'Ivoire

Prevalence and risk factors associated with antiretroviral resistance in HIV‐1‐infected children

Pediatric HIV-1–Specific Cytotoxic T-Lymphocyte Responses Suggesting Ongoing Viral Replication Despite Combination Antiretroviral Therapy

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