CROI 2018 Abstract eBook

Abstract eBook

Poster Abstracts

Results: Eleven children were enrolled (four female), with median (IQR) age 15.0 (12.8-28.1) months and weight 9.8 (8.4-10.7) kg. LPV doses ranged from 20.0-23.5 mg/kg/8 h. Four children (36%) had Cmin<1mg/L, the median AUC was 48.7mg*h/L (5.6-70.2). Children who received doses below the median (21.5mg/kg) were significantly more likely to have low Cmin values (p=0.006). There was no association between AUC-8h and age, sex, weight, or weight- for-height z-score. AUC-8h and total LPV dose exhibited a positive trend in association (p=0.08). No significant ALT elevation occurred. Conclusion: In this small cohort 8-hourly LPV/r dosing was safe and appeared to perform better than the current double-dose q12h strategy, but further adjustment of the 8-hourly LPV/r-4:1 dose is needed to optimize this strategy. 839 TUBERCULOSIS DISEASE AND ISONIAZID USE IN SOUTH AFRICAN CHILDREN LIVING WITH HIV Gloria E. Anyalechi 1 , Chloe A. Teasdale 2 , Emilia M. Rivadeneira 1 , Rommel Bain 1 , Gurpreet Kindra 3 , Mary Mogashoa 3 , Stephen M. Arpadi 2 , Elaine J. Abrams 2 1 CDC, Atlanta, GA, USA, 2 ICAP at Columbia University, New York, NY, USA, 3 US CDC Pretoria, Pretoria, South Africa Background: Tuberculosis (TB) is a major cause of morbidity and mortality for children living with HIV (CLHIV). In 2016, South Africa had an estimated 33,000 TB cases in children < 15 years but no data for TB in CLHIV. Although World Health Organization (WHO) and South African guidelines recommend isoniazid preventive therapy (IPT) in HIV, uptake of this effective intervention has been poor. We describe factors associated with TB prevalence among HIV-infected children 0-12 years in a cohort eligible for antiretroviral therapy (ART) in South Africa and examine IPT use among enrolled children. Methods: From 2012-2014 HIV-infected children receiving care at five facilities in Eastern Cape Province were enrolled into a prospective cohort at ART eligibility based on South African 2010 and 2013 guidelines. Children were defined to have TB at cohort enrollment if a caregiver reported TB or TB was recorded in the medical record 90 days before or after enrollment. IPT as of enrollment was defined for children with an IPT start date recorded in the medical record prior to or on the enrollment date. Factors associated with TB at enrollment were assessed using logistic regression with generalized estimating equation adjusted odds ratios (aOR) and 95% confidence intervals (CI) to account for facility clustering. Results: Of 397 enrolled children, 106 (26.7%) had TB disease at enrollment including; twenty-four (16.2%) infants < 1 year; 37 (30.8%) children 1-< 5 years; and 45 (34.9%) children 5-12 years. In multivariable analyses, including sex, CD4 count, and history of TB as known risk factors, only older age (5-12 years vs. <1 year) (aOR 3.2 [1.0-9.7]) and weight for age z-score < 2 standard deviations below the mean (aOR 1.7 [1.0-2.8]) were significantly associated with TB at enrollment. Among 362 children with available IPT data, 31 (8.6%) were documented to have ever received IPT. Of 26 (83.9%) children with known IPT start date, 19 (73.1%) received IPT prior to, or on the date of enrollment at a median of 7 days (range: 0-723) before enrollment. Conclusion: Among these HIV-infected South African children eligible for ART, 27% had TB while less than 10%were documented to have ever received IPT. Children 5-12 years old, and those with moderate malnutrition were more likely to have TB. Preventing, diagnosing, and treating TB must be prioritized for vulnerable populations in South African HIV programs particularly older and malnourished children. 840 TEMPORAL TRENDS IN GLOBAL PEDIATRIC COTRIMOXAZOLE USE AND IMPACT ON MORTALITY David C. Boettiger 1 , Matthew Law 1 , Annette H. Sohn 2 , Mary-Ann Davies 3 , Kara K. Wools-Kaloustian 4 , Valériane Leroy 5 , Marcel Yotebieng 6 , Michael J. Vinikoor 7 , Rachel Vreeman 4 , Andrew Edmonds 8 , Azar Kariminia 1 1 Kirby Institute, Sydney, NSW, Australia, 2 TREAT Asia, amfAR, Bangkok, Thailand, 3 University of Cape Town, Cape Town, South Africa, 4 Indiana University, Indianapolis, IN, USA, 5 INSERM, Toulouse, France, 6 The Ohio State University, Columbus, OH, USA, 7 Centre for Infectious Disease Research in Zambia, Lusaka, Zambia, 8 University of North Carolina Chapel Hill, Chapel Hill, NC, USA Background: Cotrimoxazole (CTX) is recommended for all children recently diagnosed with HIV in order to prevent pneumocystis pneumonia. Although it improves survival in HIV-infected children, the impact of CTX on mortality in those without severe immune deficiency is unclear. We evaluated temporal trends in CTX use at antiretroviral therapy (ART) initiation and mortality rates while on CTX in the absence of severe immune deficiency.

Methods: Pediatric data collected between 1 Jan 2006 and 31 Mar 2016 in the International Epidemiology Databases to Evaluate AIDS global cohort consortiumwere analyzed from regions that routinely report information on CTX use (East, West, Central, and Southern Africa, Asia-Pacific). All 24 countries included are considered low- or middle-income by World Bank criteria. Severe immune deficiency was defined by the age-specific CD4 thresholds in the 2006 WHO ART guidelines. Logistic regression was used to evaluate factors associated with using CTX at ART initiation. Competing risk regression was used to assess factors associated with mortality. Sensitivity analyses used multiple imputation to account for missing data. Results: A total of 54,113 children aged 1 month to 15 years were included. Median age at ART initiation was 5.7 years and 51%were female. CTX use increased from 67% in 2006 to a peak of 86% in 2010 and then declined to 49% in 2015/16. The proportion of children with severe immune deficiency dropped from 70% in 2006 to 43% in 2015/16 (figure). In our adjusted analysis, age (odds ratio [OR] 1.2 for <1 year vs. 1 to <5 years, 95% confidence interval [CI] 1.1-1.3), anemia (OR 1.1, 95%CI 1.0-1.2), severe immune deficiency (OR 1.3, 95%CI 1.2-1.3), height-for-age z-score (OR 1.2 for <-3 vs. >-2, 95%CI 1.1-1.2), year of ART initiation (OR 2.8 for 2010 vs. 2006, 95%CI 2.5-3.1 and OR 0.7 for 2015/16 vs. 2006, 95%CI 0.6-0.8) and region (OR 9.0 for East vs. Southern Africa, 95%CI 8.2-9.9) were associated with CTX use. The rate of death in children without severe immune deficiency was 0.5 per 100 person-years and did not differ with CTX use (adjusted hazard ratio 1.0 for non-users versus users, 95%CI 0.8-1.3). Sensitivity analyses yielded similar results. Conclusion: Recent declines in pediatric CTX use coincide with declines in the proportion of children starting ART with severe immune deficiency. CTX did not improve survival among children without severe immune deficiency although use was not randomized and unmeasured confounders cannot be excluded.

Poster Abstracts

841 PHARMACOKINETICS AND SAFETY OF LOPINAVIR/RITONAVIR SOLUTION IN HIV-INFECTED NEWBORNS Adrie Bekker 1 , Nathan Hanan 2 , Mae Cababasay 3 , Jiajia Wang 3 , Firdose Nakwa 4 , Elizabeth Smith 5 , Jack Moye 6 , Avy Violari 4 , Mark Cotton 1 , Lubbe Wiesner 7 , Jennifer Norman 7 , Barend Fourie 1 , Edmund V. Capparelli 2 , Mark Mirochnick 8 1 Stellenbosch University, Cape Town, South Africa, 2 University of California San Diego, La Jolla, CA, USA, 3 Harvard University, Cambridge, MA, USA, 4 University of the Witwatersrand, Johannesburg, South Africa, 5 DAIDS, NIAID, Bethesda, MD, USA, 6 NIH, Bethesda, MD, USA, 7 University of Cape Town, Cape Town, South Africa, 8 Boston University, Boston, MA, USA Background: Reports of life-threatening cardiac, metabolic, renal and CNS dysfunction in newborns receiving lopinavir/ritonavir (LPV/r) in the first weeks of life have led to a recommendation that LPV/r should not be used in newborns <2 weeks postnatal and <42 weeks postconceptional age. Due to limited treatment options, however, clinicians may initiate LPV/r in newborns if benefit outweighs risk. Data on pharmacokinetics (PK) and safety of LPV/r in newborns are few. Methods: IMPAACT P1106 is a multi-arm Phase IV study of PK/safety in newborns on antiretroviral and antituberculosis medicines received for clinical care at two South African sites. HIV-infected newborns in whom LPV/r was

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