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

Abstract

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.

Relationship between viral load and behavioral measures of adherence to antiretroviral therapy in children living with human immunodeficiency virus in Latin America

“…Although a participant might be adherent, their medications may not be taken as directed with respect to the timing of doses and timing of food consumption, which could reduce medication effectiveness (24). Children who have developed resistance would also not be expected to achieve viral suppression despite high levels of adherence; high prevalence of viral resistance has been identified in several cohorts of perinatally-infected children [38–40]. Finally, children have greater difficulty in achieving optimal viral suppression than adults, which has been attributed to higher baseline viral load and differences in viral dynamics (41).…”

Effect of HIV genotypic drug resistance testing on the management and clinical course of HIV-infected children and adolescents

“…6,7 In addition, children may have a more difficult time maintaining adherence to ARVs and thus maintaining adequate drug levels to prevent the development of virological failure and HIV drug resistance. 1,2,8 Determining the HIV genotypic or phenotypic resistance are frequently employed strategies to help guide the selection of ARVs for treatment naïve patients and for patients requiring adjustments in therapy as a result of inadequate virological response. 9 Both approaches have been shown to be beneficial in the care of HIV-infected adults, 9 but few studies have assessed their impact in the paediatric and adolescent population.…”

Rapid Development of Antiretroviral Drug Resistance Mutations in HIV-Infected Children Less Than Two Years of Age Initiating Protease Inhibitor-Based Therapy in South Africa

“…15 However, studies from both resource-rich and resource-limited settings suggest that antiretroviral-related resistance mutations develop in 44-94% of children failing PIbased ART, and many children develop multiclass drug resistance. [16][17][18][19][20] Antiretroviral resistance mutations that develop while on PI-based ART may lead to decreased susceptibility across many other PIs and limit future treatment options. 17,21 Historically, RTV-based regimens have been associated with suboptimal treatment responses, with only 36% of children achieving sustained virologic suppression in an early study.…”

“…[16][17][18][19][20] Antiretroviral resistance mutations that develop while on PI-based ART may lead to decreased susceptibility across many other PIs and limit future treatment options. 17,21 Historically, RTV-based regimens have been associated with suboptimal treatment responses, with only 36% of children achieving sustained virologic suppression in an early study. 22 Pediatric AIDS Clinical Trials Group investigations have shown that response to ritonavir-based therapy in NTRIexperienced but PI-naive children was robust initially, with 55% achieving virologic suppression by 12 weeks, but only 32% maintained virologic suppression at 48 weeks.…”