CROI 2016 Abstract eBook

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Poster Abstracts

813 ARV Risk for Speech and Language Impairments in HEU Children at 3 and 5 Years Mabel L. Rice 1 ; Jonathan S. Russell 2 ;Toni Frederick 3 ; Murli Purswani 4 ; Paige L.Williams 5 ; George K. Siberry 6 ; Sean M. Redmond 7 ; Howard J. Hoffman 8 ;Tzy-JyunYao 2 ; for the Pediatric HIV/AIDS Cohort Study (PHACS) 1 Univ of Kansas, Lawrence, KS, USA; 2 Harvard Univ, Boston, MA, USA; 3 Univ of Southern California, Los Angeles, CA, USA; 4 Albert Einstein Coll of Med, Bronx, NY, USA; 5 Harvard Sch of PH, Boston, MA, USA; 6 Eunice Kennedy Shriver NICHD, Bethesda, MD, USA; 7 Univ of Utah, Salt Lake City, UT, USA; 8 Natl Inst on Deafness and Other Communication Disorders, Bethesda, MD, USA Background: Perinatally HIV-exposed but uninfected (PHEU) children have elevated risk of late language emergence at age 1 year, with possible links to in utero antiretroviral (ARV) exposure. This study investigated possible risks, including ARV exposure, for speech impairments (SI) and language impairments (LI) in monolingual PHEU children in the important preschool period. This is the first study of SI in PHEU children and the first to examine LI among PHEU children in this age range. Methods: Speech and Language assessments were conducted as part of the PHACS Surveillance Monitoring of ART Toxicities (SMARTT) study at ages 3 (N= 238) and 5 (N = 465, of whom 145 were also tested at age 3) years. Domains of speech, overall language, vocabulary and grammar were assessed. SI/LI was defined as standardized score (SC) below the 15 th percentile and was subdivided into primary (PSI /PLI) (normal nonverbal IQ ≥85 without hearing loss) versus concomitant (CSI /CLI) (low nonverbal IQ or presence of hearing loss). Mean SCs among PHEU children were compared to population norms by t-test. Logistic regression models were used to estimate adjusted odds of SI and LI for different ARV exposures, controlling for confounding variables. Results: PHEU children had lower SCs compared to population norms (PN) at ages 3 for vocabulary (mean SC = 94.4, 95% CI: 92.4, 96.4; PN = 100) and 5 years for overall language (mSC = 90.4, CI: 89.1, 91.8; PN = 100), vocabulary (mSC = 9.4, CI: 9.2, 9.7; PN = 10) and grammar (mSC=8.4, CI: 8.1, 8.6; PN = 10), but did not underperform on the speech assessment at either age. Risk factors included male sex, black race, and other socioeconomic measures, although these varied somewhat by age group, primary vs. concomitant group, and by the particular speech or language measure. Adjusted logistic regression models revealed possible protective effects as well as increased risk for specific ARVs, including tenofovir at age 3 and both didanosine and zidovudine at age 5 (see table). Conclusions: In the preschool period, risk for LI was higher among older children. There was no indication of overall increased risk for SI. Outcomes with in utero ARV exposure depended on the child’s age, whether SI/LI was accompanied by other impairments (PSI/PLI vs CSI/CLI), and the dimensions of speech and language outcomes. Both protection and increased risk were seen with specific ARV exposures.

814 Longitudinal Evaluation of Language Impairment in Perinatally HIV Exposed Adolescents Sean M. Redmond 1 ;Tzy-JyunYao 2 ; Jonathan S. Russell 2 ; Mabel L. Rice 3 ; Howard J. Hoffman 4 ; George K. Siberry 5 ; Paige L.Williams 6 ; for the Pediatric HIV/AIDS Cohort Study (PHACS) Team. 1 Univ of Utah, Salt Lake City, UT, USA; 2 Harvard Univ, Boston, MA, USA; 3 Univ of Kansas, Lawrence, KS, USA; 4 Natl Inst on Deafness and Other Communication Disorders, Bethesda, MD, USA; 5 Eunice Kennedy Shriver NICHD, Bethesda, MD, USA; 6 Harvard Sch of PH, Boston, MA, USA Background: We previously documented a significantly higher prevalence (relative to comparable communities) of both primary language impairment (PLI) and language impairment concomitant with hearing/cognitive impairments (CLI) in perinatally HIV-infected (PHIV) and perinatally HIV-exposed uninfected (PHEU) participants (age range: 7-17y) from the Adolescent Master Protocol (AMP), a component of PHACS. This analysis describes longitudinal outcomes of this cohort to determine the persistence of PLI and CLI and associations with antiretroviral (ARV) treatment, disease status, and other risk factors. Methods: The Clinical Evaluation of Language Fundamentals (CELF-4) was repeated on AMP participants 18 months after their baseline assessment. General linear regression models were utilized to identify independent predictors of change in standardized score (SC). The sample was also split by baseline status to LI (SC<85) and no LI (SC≥85), and separate logistic regression analyses were used to identify factors associated with the resolution or development of LI. Results: Complete language data at both time points were available on 319 participants (mean baseline age=12y, 80% black, 9% Hispanic). Among these, 112 (35%) had LI at baseline. Overall, SCs for the study population were highly stable and changes were similar in PHIV (n=212) and PHEU (n=107) participants. Family history of language delays/ learning difficulties had a negative association with SC change after controlling for demographic and socioeconomic factors and baseline LI status (coefficient=-3.35, 95% CI: -5.83, -0.88). Among the PHIV group, being on combination antiretroviral treatment (cART) (4.50, CI: 0.31, 8.69) and high CD4 count (>350 cells/mm 3 ) (4.61, CI: 0.48, 8.74) at baseline were associated with a higher mean SC change. Over the follow-up period, initial LI was persistent in the majority of cases (78%) and 21 new cases of LI occurred (10%). No significant risk factors for either developing or resolving LI were found among combined PHIV and PHEU after adjusting for demographics and baseline SC. Among PHIV, not being on cART at baseline was associated with lower odds of LI resolution (adj. Odds Ratio<0.01, CI: <0.01, 0.61) after controlling for demographics and baseline SC Conclusions: Perinatally HIV exposed youth with LI are at risk for persistent LI, irrespective of infection status. Risk factors for declining scores included family history and–for PHIV–not receiving cART and low CD4 count. 815 Nevirapine (NVP) Concentrations in HIV-Infected Newborns Receiving Therapeutic Dosing Edmund Capparelli 1 ; Kenneth Maswabi 2 ; Steven Rossi 1 ; Muchaneta Bhondai 2 ; Sikhulile Moyo 2 ; Patrick Jean-Philippe 3 ; Michael Hughes 4 ; Mathias Lichterfeld 5 ; Daniel Kuritzkes 6 ; Roger L. Shapiro 4 1 Univ of California San Diego, San Diego, CA, USA; 2 Botswana Harvard AIDS Inst Partnership, Gaborone, Botswana; 3 Henry M. Jackson Fndn for the Advancement of Military Med, Inc, Rockville, MD, USA; 4 Harvard Sch of PH, Boston, MA, USA; 5 Ragon Inst of MGH, MIT, and Harvard, Cambridge, MA, USA; 6 Harvard Med Sch, Boston, MA, USA Background: Very early antiretroviral treatment (ART) initiation in HIV infected newborns may limit the seeding of viral reservoirs and maintain immune responses, but few antiretroviral agents are approved for use in newborns. Prophylactic NVP dosing is well established, but the appropriate NVP dose for treatment, which requires higher NVP levels than prophylaxis, is still unknown. While NVP is well absorbed in infants, its auto-induction, maturation and polymorphisms in its metabolism all complicate prediction of NVP treatment dosing in newborns. A very early treatment study in Botswana (BHP-074) was recently initiated using a NVP treatment dose of 6mg/kg BID for the first few weeks. Early objectives of this study are to determine NVP safety using 6mg/kg BID and if newborns achieve therapeutic levels with this dose. Methods: HIV-infected infants born at >35 weeks gestation and >2 kg were enrolled in the early treatment protocol and had pre-dose plasma pharmacokinetic (PK) samples collected at Weeks 1 and 2. Participants received NVP 6mg/kg BID in combination with lamivudine (3TC) 2mg/kg BID and zidovudine (ZDV) 4mg/kg BID until 2 weeks of age (or 40 weeks gestational age equivalent, whichever later). Samples were analyzed for NVP and 3TC by High Performance Liquid Chromatography (HPLC). Drug concentrations were

Poster Abstracts

340

CROI 2016