Incidence and predictors of antiretroviral resistance in perinatally HIV-1 infected children and adolescents

German A Contreras; Cynthia S Bell; Gabriela Del Bianco; Norma Pérez; Laura Benjamins; Matthew T Kleinosky; Gilhen Rodriguez; James R Murphy; Gloria P Heresi

doi:10.1016/j.jinf.2015.12.005

Incidence and predictors of antiretroviral resistance in perinatally HIV-1 infected children and adolescents

J Infect. 2016 Mar;72(3):353-61. doi: 10.1016/j.jinf.2015.12.005. Epub 2015 Dec 19.

Authors

German A Contreras¹, Cynthia S Bell², Gabriela Del Bianco³, Norma Pérez³, Laura Benjamins⁴, Matthew T Kleinosky³, Gilhen Rodriguez³, James R Murphy³, Gloria P Heresi³

Affiliations

¹ Division of Pediatric Infectious Diseases, Department of Pediatrics, University of Texas UTHealth, 6431 Fannin Street, MSB 3.002 Houston, TX 77030, USA; Molecular Genetics and Antimicrobial Resistance Unit, Universidad El Bosque, Bogotá, Colombia Av. Cra 9 No. 131 A - 02. Electronic address: German.Contreras@uth.tmc.edu.
² Division of Pediatric Nephrology, Department of Pediatrics, University of Texas UTHealth, 6431 Fannin, MSB 3.121 Houston, TX 77030, USA.
³ Division of Pediatric Infectious Diseases, Department of Pediatrics, University of Texas UTHealth, 6431 Fannin Street, MSB 3.002 Houston, TX 77030, USA.
⁴ Adolescent Division, Department of Pediatrics, University of Texas UTHealth, 6431 Fannin Street, MSB 3.002 Houston, TX 77030, USA.

PMID: 26711193
DOI: 10.1016/j.jinf.2015.12.005

Abstract

Objectives: Individuals with perinatally acquired HIV infection have benefited from antiretroviral therapy. However, they often have complex patterns of major resistance mutations that limit the effectiveness of available antiretroviral medications. Knowledge of incidence rates of major antiretroviral resistance mutations should provide a benchmark enabling comparisons of different HIV care delivery modalities.

Methods: We test the hypothesis that incidence rate of major antiretroviral resistance mutations will decline with improvement in HIV care between 1998 and 2009 to NRTI, NNRTI, PI and triple class resistance in perinatally HIV infected individuals. Logistic regression is used to evaluate predictors of single and triple class resistance.

Results: Sixty-six individuals are included from a total population of 97 perinatally HIV infected individuals. The incidence rate of NRTI, NNRTI, PI and triple class resistance decreases with decreasing age in parallel with the introduction of new HIV treatment regimens. The youngest children (born 2000-2007) are free of triple class resistance. Mono-therapy associates with major resistance mutations to NRTI (OR 8.7, CI 1.5-50.9, P 0.02); NNRTI exposure associates with major resistance mutations to NNRTI (OR 24.4, CI 5.7-104.5, P 0.01) and triple class resistance (OR 10.7, CI 1.8-67.1, P 0.01). Cumulative viral load is an important predictor of PI resistance (OR 4.0, CI 1.3-12.3, P 0.02).

Conclusions: There is a progressive decrease in the incidence rate of major resistance mutations to antiretroviral drugs and triple class resistance from the oldest to the youngest birth cohort; where adolescents have the highest risk of harboring resistant viruses. The incidence rate of major antiretroviral resistance mutations provides a benchmark for the comparative measurement of effectiveness of different HIV care delivery modalities.

Keywords: Adolescents; Antiretroviral resistance; Cumulative viral load; HIV; Incidence rate.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adolescent
Anti-HIV Agents / pharmacology*
Anti-HIV Agents / therapeutic use*
Child
Drug Resistance, Viral*
Female
HIV Infections / drug therapy*
HIV Infections / epidemiology
HIV Infections / virology*
HIV-1 / drug effects*
Humans
Incidence
Male
Retrospective Studies

Substances

Anti-HIV Agents