Antiretroviral Treatment Failure, Drug Resistance, and Subtype Diversity in the Only Pediatric HIV Clinic in Rhode Island

Highly active antiretroviral therapy (HAART) decreases morbidity and mortality of human immunodeficiency virus type 1 (HIV-1)–infected children [1]. However, medication effectiveness can be hindered by development of drug resistance (DR) [2]. Consequently, US pediatric treatment guidelines recommend DR testing prior to treatment initiation and before antiretroviral therapy (ART) regimen change [3]. Younger children are at high risk of DR development due to high viral loads (VLs) [4], less robust immune responses [5], and accurate dosing challenges owing to formulary limitations, potentially leading to subtherapeutic drug concentrations [6]. Further limitations to ART success include adherence challenges related to complex psychosocial factors, such as lack of caregiver support, denial of HIV diagnosis, and disclosure [7]. The rate of new pediatric HIV infections in the United States is low (0.4 per 100 000 children aged <13 years) [8]; however, DR development can be a major concern in the already infected population that needs lifelong ART. Published data on transmitted DR (TDR) in US children are limited to 3 studies in infants (12%–24% TDR between 1998 and 2005 [9–11]) and 2 studies in adolescents (18% TDR in 2004 and 2014 [12, 13]). Even fewer data are available on DR in ART-experienced US children, including 1 study reporting DR in 61% of 18 adolescents from Pediatric AIDS Clinical Trials Group 381 [14]; 1 study on sexual risk behaviors of perinatally infected adolescents with DR in 81% of 37 youth [15]; and 1 study with DR in 65% of 47 perinatally infected children [16]. Sequences obtained for DR testing in routine care can be used for additional purposes such as subtype determination, which may impact DR development [17] and characterization of transmission networks. Despite reports of increasing HIV-1 diversity in US adults [18, 19], >90% of HIV-infected individuals in North America harbor subtype B [20]. Subtype diversity reports in US children vary, with 3%–17% carrying non-B subtypes [10, 11, 16], possibly due to geographic differences in immigration rates from higher-prevalence settings. Phylogenetic transmission networks analyses can provide information on common HIV sources (ie, mother-to-child transmission or sexual networks) [21]. Characterization of these networks is important for HIV transmission disruption; however, such analyses have been performed mostly in adults [22]. We characterized treatment failure, DR, subtype diversity, and molecular epidemiology, and examined their correlates and potential impact on patient care, in the pediatric HIV clinic in Rhode Island.