Patterns of HIV Resistance in Children Attending an Antiretroviral Clinic in Soweto, South Africa: A Case-Control Study

Abstract

Background: Exposure to suboptimal serum levels of antiretrovirals (ARVs) places resistance pressure on circulating human immunodeficiency virus (HIV), with consequent emergence of resistance. HIV resistance leads to treatment failure and adverse outcomes. We explored factors associated with the emergence of ARV resistance in children living with HIV (CLWH) attending a treatment clinic in Soweto. Methods: We reviewed the clinical and laboratory characteristics, and factors associated with ARV resistance in children aged 0 to 15 years of age that were treated at the clinic from 01 January 2011 through 31 December 2020. The Stanford HIV drug resistance database was used to identify HIV drug resistance mutations and generate resistance profiles. Characteristics of children that underwent drug resistance testing (DRT) were compared to those of children who remained virologically suppressed on fist-line ARVs. Results: During the study period, 7,029 children attended the clinic of which 425 (6.0%) underwent DRT (cases) and 953 (13.6%) remained suppressed on first-line ARVs (controls). The resistance dataset included 431 resistance tests that were done in 425 children and adolescents that were eligible for the study. Non-nucleoside reverse transcriptase inhibitor (NNRTI) mutations accounted for 50.8% of all mutations, followed by nucleoside reverse transcriptase inhibitor (NRTI) mutations (44.5%) and protease inhibitor (PI) mutations (4.6%). Cases were significantly older at ARV initiation (81.6 vs 45.2 months), had a higher prevalence of ever being diagnosed with tuberculosis (33.2% vs 27.4%), ever being orphaned (57.6% vs 50.6%) and ever experiencing severe acute malnutrition (SAM) (19.8% vs 11.7%). In all modelling approaches, SAM was consistently associated with ARV resistance adjusted odds ratios (aOR) ranging from 3.548 (95% confidence interval (CI) 1.979-6.359) to 6.383 (95% CI, 3.811-10.690)). Increasing baseline CD4 percentage was associated with significantly lower adjusted odds of case-status aOR ranging from 0.971 (95% CI, 0.953-0.989) to 0.951 (95% CI, 0.931-0.972)). Seventeen (5.6%) cases died, compared to two (0.3%) controls; P<0.001. Conclusions: Tenuous nutritional status was consistently and significantly associated with the requirement for DRT in this cohort of children and adolescents. Conversely, higher baseline CD4 percentage was associated with control status. Early ARV initiation, to preserve immunological status, and nutritional support throughout the course of clinic attendance may limit the emergence of drug resistance in CLWH.