Antiretroviral treatment failure, drug resistance, and subtype diversity in the only pediatric HIV clinic in Rhode Island

Abstract

Background: Drug resistance development in the human immunodeficiency virus (HIV)-infected pediatric population in the United States can impact long-term antiretroviral therapy (ART) efficacy. Limited formularies and adherence constraints in children jeopardize lifelong-needed ART.

Methods: We examined treatment failure, drug resistance, and their correlates in ART-naive and ART-experienced children attending the pediatric HIV clinic in Rhode Island between 1991 and 2012. Pol sequences were obtained for phylogenetic, subtype, and resistance analyses. Associations between selected covariates and virologic failure and resistance were evaluated using generalized additive models and Fisher exact tests.

Results: Data were available for all 56 clinic-attending children. At diagnosis, 33% were aged <1 year, 31% aged 1-4 years, and 37% aged ≥ 5 years; 54% were male, 73% black or Hispanic, 55% US-born, 20% refugees, and 64% perinatally infected. Of 44 ART-experienced children, 57% had virologic failure, most never virologically suppressed. Failure was associated with missed appointments (P = .05) and missed doses (P < .01). Of 40 children with available genotypes, 35% were infected with non-B subtypes; 6% of ART-naive children had resistance; and 73% of ART-experienced children had ≥ 1 major mutation: (16% conferring triple-class, 47% dual-class, and 37% single-class resistance). An epidemiologically confirmed resistance transmission from a perinatally infected teenage male to a newly infected teenage female was demonstrated.

Conclusions: We report high HIV type 1 diversity, extensive drug resistance among ART-experienced children, and horizontal transmission of resistance in the Rh ode Island pediatric HIV clinic. As HIV-infected children mature into adulthood, close monitoring of ART, adherence, and diagnosis disclosure are essential to optimize patient care.

Keywords: HIV; antiretroviral resistance; pediatrics; subtype.

Figure 1.

Phylogenetic tree of 40 pediatric patients with available sequences. The figure demonstrates a maximum likelihood tree of children's available pol sequences (ID 1–40) and reference sequences. Branch bootstrap supports of >70% (1000 replicates) are shown to the left of the supported nodes, and HIV-1 subtype categories to the right of the brackets. Subtype reference sequences (GenBank accession numbers) included subtype A (DQ676872), subtype B (K03455), subtype C (U52953), circulating recombinant form (CRF) 02_AG (AY271690), CRF06_CPX (AF064699), and CRF24_BG (AY900574). The tree was rooted with the Group M ancestral sequence (www.lanl.gov). Asterisks (*) denote clusters with confirmed epidemiologic linkages. Abbreviation: HIV, human immunodeficiency virus.

Figure 2.

Treatment response groups (Gp) at the time of genotyping. Bar graph of treatment response groups according to viral load status and trajectories (as defined in the figure key and in “Methods” section). The bar height is determined by the percentage of children in a specific group. Numbers of each group are shown on top of each bar.