CROI 2015 Program and Abstracts

Abstract Listing

Poster Abstracts

Conclusions: In this large cohort of children from sub-Saharan Africa, only half initiated ART and 35% died or were lost before starting ART. Among those who started ART and had 5 years of follow-up, many achieved immune recovery which was associated with younger age, higher CD4 and D4T-based ART regimen at ART initiation. These findings are in keeping with previously reported study cohorts and represent important data on children enrolled in routine service programs in resource limited settings. 915 Antiretroviral Therapy in Severely Malnourished, HIV-Infected Children in Asia David C. Boettiger 1 ; Linda Aurpibul 2 ; Dina Muktiarti 3 ; Siew Fong 4 ; Pagakrong Lumbiganon 5 ; SaphonnVonthanak 6 ; NguyenVan Lam 7 ; Rawiwan Hansudewechakul 8 ; Azar Kariminia 1 On behalf ofTREAT Asia Pediatric HIV Observational Database 1 University of New South Wales, Sydney, Australia; 2 Chiang Mai University, Chiang Mai, Thailand; 3 Cipto Mangunkusumo General Hospital, Jakarta, Indonesia; 4 Hospital Likas, Kota Kinabalu, Malaysia; 5 Khon Kaen University, Khon Kaen, Thailand; 6 National Centre for HIV/AIDS Dermatology and STDs, Phnom Penh, Cambodia; 7 National Hospital of Pediatrics, Hanoi, Viet Nam; 8 Chiangrai Prachanukroh Hospital, Chiang Rai, Thailand Background: In HIV-infected children with severe malnutrition (SM), guidelines recommend that antiretroviral therapy (ART) is initiated soon after SM stabilization but information on ART use in this population is lacking. We evaluated growth, CD4% recovery, toxicity-associated ART modification and death in children with SM at ART initiation. Methods: Children enrolled in the TREAT Asia Pediatric HIV Observational Database who initiated ART with a weight-for-height z-score (WFH)<-3 if aged 6-60 months or body mass index-for-age z-score (BFA)<-3 if aged 61 months-14 years were included. Generalized estimating equations were used to investigate poor growth response (weight-for-age z-score<-3) and poor immune response (CD4%<25), and competing risk regression was used to analyze mortality and toxicity-associated treatment modification. Results: The SM definition was met by 310 (12%) of 2559 children starting ART with height and weight data available. Median age was 6.6 years, 60%were male, and median WFH/BFA was -3.8. Most initiated stavudine (64%) or zidovudine-based (30%) therapy. Periods of ART start were 2003-06 (45%), 2007-10 (44%) and 2011-13 (11%). Mean weight- for-age z-score increased on ART from -5.8 at initiation to -3.6 after 6 months, -2.9 after 12 months, -2.5 after 24 months, and -2.5 after 36 months. Age 61 months-14 years (OR 2.4 vs. 6-60 months, 95%CI 1.6-3.5, p<0.01) and prior tuberculosis diagnosis (OR 1.6 vs. none, 95%CI 1.1-2.4, p=0.03) predicted poor growth response. Mean CD4% increased on ART from 7.7 at baseline to 14.7 after 6 months, 20.2 after 12 months, 25.1 after 24 months, and 26.6 after 36 months. Poor immune response was associated with baseline CD4% (OR 10.9 for <10 vs. ≥ 10, 95%CI 6.4-18.7, p<0.01), age (OR 2.13 for 61 months-14 years vs. 6-60 months, 95%CI 1.4-3.2, p<0.01) and male sex (OR 1.5, 95%CI 1.0-2.2, p<0.05). Forty three deaths occurred at a rate of 3.0 per 100 patient-years. Lower baseline WFH/BFA (HR 3.5 for <-4.5 vs. -3.5 to <-3.0, 95%CI 1.4-8.6, p<0.01) predicted mortality (Figure 1). Twenty toxicity-associated ART modifications occurred at a rate of 2.6 per 100 patient-years and rates did not differ by baseline WFH/BFA strata (p=0.88).

Poster Abstracts

Conclusions: HIV-infected children with SM experienced rapid growth and immune recovery after starting ART, particularly when started at a young age. ART initiation at a less pronounced stage of SM increased survival but this did not appear to be due to more ART toxicity in children with lower WFH/BFA. 916 Pubertal Development in HIV-Infected African Children on First-Line Antiretroviral Therapy

Mutsa F. Bwakura Dangarembizi On behalf of the ARROWTrialTeam University of Zimbabwe, College of Health Sciences, Harare, Zimbabwe

Background: HIV has been associated with pubertal delay but data on the impact of initiating combination ART in older childhood are limited, particularly in sub-Saharan Africa. Methods: In the ARROW trial in Uganda/Zimbabwe, puberty was assessed by Tanner staging of genitalia (G1=prepubertal to G5=adult) in males, or breasts (B1 to B5) in females every 24 weeks from age 10 years; menarche every 12 weeks and height every 4-6 weeks. Age at attaining different Tanner stages was estimated using normal interval regression, considering the following predictors using multivariable regression: centre, initial ART regimen, CD4/no CD4 monitoring; age, CD4, WHO stage, height/BMI-for-age at ART initiation; and change in height/BMI-for-age during the first 6 months on ART. Growth was estimated using multi-level models with child-specific intercepts and trajectories. Results: 582 children were included: median age at ART initiation was 9.4 years (IQR 7.8,11.3); median CD4 was 234 cells/mm 3 (IQR 102,349). At the first assessment, the majority (80.2%) were in Tanner stage 1; median follow-up with staging was 2.8 years. There was a strong delaying effect of older age at ART initiation on age at attaining all Tanner stages (p<0.05) and menarche (p=0.02); but being one year older at ART initiation had different impacts on pubertal delay depending on the specific age at ART initiation (i.e. effects were non-linear; Figure). For example, a boy initiating ART aged 9 would expect to reach G2/G3/G4/G5 at age 13.4/14.0/14.4/16.7 years compared to 13.3/14.8/15.7/16.4 if initiating aged 11. Similarly a girl initiating aged 9 would expect to reach B2/B3/B4/B5 aged 11.8/12.7/13.7/14.7 compared to 12.3/13.6/14.5/15.7 aged 11. In boys, the delaying effect generally attenuated with older age. There were additional pubertal delays associated with greater pre-ART impairments in height-for-age Z-score (p<0.05) and BMI-for-age in girls (p<0.05). There was no evidence that pre-ART immune suppression independently delayed puberty or menarche. However, older children/adolescents had significant growth spurts in intermediate Tanner stages, and height continued to increase significantly even in Tanner stage 5 (p<0.01).

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CROI 2015