HIV Drug Resistance Among Children Initiating First-Line Antiretroviral Treatment in Uganda

Abstract

Background: There are limited data on primary human immunodeficiency virus drug resistance (HIVDR) in pediatric populations. This study aimed to assess the prevalence of primary HIVDR and associated risk factors among children initiating first-line antiretroviral therapy (ART) in Uganda.Methods: At three Ugandan clinics, children (age <12 years) requiring ART were recruited between January 2010 and August 2011. Before starting ART, blood was collected for viral load and pol gene sequencing. Drug resistance mutations were determined using the 2010 International AIDS Society–USA mutation list. Risk factors for HIVDR were assessed with multivariate regression analysis.Results: Three hundred nineteen HIV-infected children with a median age of 4.9 years were enrolled. Sequencing was successful in 279 children (87.5%). HIVDR was present in 10% of all children and 15.2% of children <3 years. Nucleoside reverse transcriptase inhibitors (NRTIs), non-NRTI (NNRTI), and dual-class resistance was present in 5.7%, 7.5%, and 3.2%, respectively. HIVDR occurred in 35.7% of prevention of mother-to-child transmission (PMTCT)–exposed children, 15.6% in children with unknown PMTCT history, and 7.7% among antiretroviral-naive children. History of PMTCT exposure [adjusted odds ratio (AOR): 2.6, 95% CI: 1.3–5.1] or unknown PMTCT status (AOR: 3.8, 95% CI: 1.1–13.5), low CD4 (AOR: 2.2, 95% CI: 1.3–3.6), current breastfeeding (AOR: 7.4, 95% CI: 2.6–21), and current maternal ART use (AOR: 6.4, 95% CI: 3.4–11.9) emerged as risk factors for primary HIVDR in multivariate analysis.Conclusion: Pretreatment HIVDR is high, especially in children with PMTCT exposure. Protease inhibitor (PI)–based regimens are advocated by the World Health Organization, but availability in children is limited. Children with (unknown) PMTCT exposure, low CD4 count, current breastfeeding, or maternal ART need to be prioritized to receive PI-based regimens.

HIV drug resistance in infants increases with changing prevention of mother-to-child transmission regimens

“…Among 2014 samples with available clinical information, infants with PMTCT exposure had a higher prevalence and significantly stronger drug resistance than those without, which is consistent with other studies from the region [14, 17] . However, we did not find a correlation between age and prevalence of drug resistance [14] .…”

“…However, we did not find a correlation between age and prevalence of drug resistance [14] . As in prior studies, some children with no reported PMTCT exposure still had resistance, indicating a direct transmission of resistant viruses from mother to child had occurred [14, 17] . We were unable to determine if resistance originated in the mother or arose de novo in the infant.…”

Pretreatment HIV drug resistance results in virological failure and accumulation of additional resistance mutations in Ugandan children

“…Study methods of this cohort have previously been described in detail. 12 We enrolled HIV-infected children aged ≤12 years from January 2010 to August 2011. For this analysis, participants starting on first-line ART were included and followed up for 24 months.…”

“… 11 Our group has previously shown high rates of HIV drug resistance among children initiating ART in Uganda. 12 …”

Prevalencia de resistencia a los anti-retrovirales en niños y adolescentes uruguayos infectados con el virus de la inmunodeficiencia humana en el Centro de Referencia VIH-SIDA. Centro Hospitalario Pereira Rossell. Montevideo-Uruguay

“…La prevalencia total de mutaciones de resistencia (28,6%) y la de resistencias primarias (11,1%) en la población analizada es similar a la descrita en la región y en el mundo, pero fue más elevada en los casos de resistencia secundaria (60%) 23,[31][32][33][34][35][36][37] .…”