Hearing Measures in Children Perinatally HIV-exposed and Uninfected in the PHACS SMARTT Study

Abstract

Background: Few studies have evaluated the ototoxic effects of in utero antiretroviral (ARV) exposure on hearing in children HIV-exposed uninfected (CHEU). Concerns have been identified for some ARVs: tenofovir disoproxil fumarate (TDF), emtricitabine (FTC), lamivudine (3TC), zidovudine (ZDV) and atazanavir (ATV). The aims are to describe hearing outcomes in 5-year-old CHEU in the Surveillance Monitoring for Antiretroviral Therapy Toxicities study and evaluate their association with in utero ARV exposures.

Methods: Hearing evaluations including pure-tone thresholds and distortion product otoacoustic emissions (DPOAEs) were completed in CHEU at 5 years. Log-binomial regression models were fit to assess associations of maternal ARV exposures with risk of sensorineural hearing loss (SNHL) and incomplete DPOAE responses.

Results: Among 1078 CHEU, 13% had SNHL. Among those exposed to <13 weeks gestation, there was 28% higher risk (95% confidence interval: -37% to 158%) of SNHL with TDF/FTC with ATV and 38% lower risk (95% confidence interval: -68% to 19%) with ZDV/3TC without ATV than for regimens containing TDF/FTC without ATV. There was a higher risk of incomplete DPOAE responses for ZDV/3TC without ATV and a lower risk for TDF/FTC with ATV. For CHEU with first ARV exposure at 13-26 weeks gestation, those exposed to TDF/FTC with ATV or ZDV/3TC without ATV had a lower risk for SNHL compared with TDF/FTC without ATV. Despite nontrivial relative risks, all confidence intervals were wide.

Conclusions: While SNHL was relatively common, there were no consistent associations between in utero ARV exposure and SNHL or incomplete DPOAEs. Further research is needed on ARV exposures and other hearing measures in CHEU.

Keywords: HIV; antiretroviral; children; hearing; in utero.