CROI 2016 Abstract eBook

Abstract Listing

Poster Abstracts

Conclusions: Among formula fed infants in the Mpepu Study, an infant prophylactic regimen of either sdNVP/ZDV or NVP were similarly efficacious in achieving low peripartum transmission in the setting of extensive maternal ART use through delivery. Infant ZDV vs. NVP did not result in significant differences in hematologic events in the first 6 months of life. 811 Risk of Cancer in Children Exposed to Didanosine in Utero Mira Hleyhel 1 ; Stéphanie Goujon 2 ; RolandTubiana 3 ; Catherine Dollfus 4 ; Albert Faye 5 ; Laurent Mandelbrot 6 ; Jacqueline Clavel 2 ; JosianeWarszawski 1 ; Stéphane Blanche 7 ; for the ANRS CO1/CO11-EPF French Perinatal Cohort Study Group 1 CESP, INSERM U1018, Le Kremlin-Bicêtre, France; 2 INSERM, UMR 1153, Villejuif, France; 3 Sorbonne Univs, Paris, France; 4 Hosp Trousseau, Assistance Publique-Hôpitaux de Paris, Paris, France; 5 Univ Diderot Paris 7, Sorbonne Paris-Cité, Paris, France; 6 Hosp Louis Mourier, Colombes, France; 7 Hosp Necker Enfants Malades, Paris, France Background: Antiretroviral treatment during pregnancy has been effective in reducing perinatal HIV transmission. Some nucleos(t)ide reverse transcriptase inhibitors (NRTIs) display genotoxicity in vitro so we evaluated the incidence of cancer among children exposed to NRTIs in utero between 1990 and 2014 in the ANRS French Perinatal Cohort (EPF). Methods: We updated the evaluation of cancer incidence among children exposed to NRTIs in the cohort by cross checking with the French national cancer registry. Associations between cancer risk and exposure to the various NRTIs were evaluated by univariate survival analysis and Cox proportional hazard models. Standardized incidence ratios (SIR) were used to compare risks with those for the general population. Results: Twenty-one cancers were identified in 15,163 children (median age: 9.9 years [interquartile range (IQR): 5.8-14.2]) exposed to at least one NRTI in utero between 1990 and 2014. Five children were exposed to zidovudine monotherapy, and 15 to various combinations, seven including didanosine. Didanosine was included in only 10% of the prescriptions but was associated with one third of the cancers. Compared with the 2281 children exposed to zidovudine monotherapy, the risk of cancer was higher in the 1461 children exposed to combinations including didanosine (adjusted HR = 3.0 [0.9-9.8]), but similar for all other NRTI combinations. The risk was specifically higher in children exposed during the first trimester, than never exposed, to didanosine (HR=5.5 [2.1-14.4]); it was not significantly associated with second or third trimester exposure to didanosine (HR=1.6 [0.2-12.2]). Overall, the total number of cases was not significantly different from that expected for the general population (SIR = 0.8 [0.47-1.24]), but among those exposed to didanosine it was twice that expected (SIR = 2.5 [1.01-5.19]). Three cases of pineoblastoma, a very rare cancer, were observed, whereas 0.03 were expected; two of these cases were associated with didanosine exposure. Conclusions: There are strong arguments to suggest that didanosine displays transplacental oncogenicity. Although these findings cannot be extrapolated to other NRTIs, they stress the need for comprehensive evaluation of the transplacental genotoxicity of this class of antiretrovirals. 812 Elevated Mitochondrial DNA Content in HIV-Exposed Uninfected ChildrenWith Autism Matthew Budd 1 ; Lindy Samson 2 ; Jennifer Bowes 2 ; Kristina Calli 1 ; Suzanne Lewis 1 ; Hélène Côté 1 ; Jason Brophy 2 ; for the CIHRTeam in Cellular Aging and HIV Comorbidities inWomen and Children (CARMA) 1 Univ of British Columbia, Vancouver, BC, Canada; 2 Children’s Hosp of Eastern Ontario, Ottawa, ON, Canada Background: Recently, a Canadian pediatric HIV program reported a high prevalence of autism spectrum disorder (ASD) among HIV-exposed uninfected (HEU) children. Many of these children are enrolled in the prospective Children & Women AntiRetrovirals & Markers of Aging (CARMA) cohort. Of all 296 HEU children in CARMA, 16 have a diagnosis of ASD. Four more are strongly suspected and are undergoing formal assessments. This represents an ASD prevalence (5.4%) >4-fold higher than the North American population estimate of 1.47%. In addition to genetic predisposition, it is postulated that ASD may also be associated with maternal infections in pregnancy and mitochondrial dysfunction. Increased blood mitochondrial DNA (mtDNA) content, which may indicate mitochondrial dysfunction, has been observed in HEU children with perinatal exposure to combination antiretroviral therapy (cART). This study analysed mtDNA content in HEU children with and without ASD, as well as HIV-unexposed uninfected (HUU) children with and without ASD. Methods: CARMA HEU children with confirmed ASD (HEU+ASD, n=16) aged 2-16 years were matched 1:3 on age, sex, and ethnicity with CARMA HEU children without ASD (n=48); and 1:3 on age and sex with HUU children with ASD taking part in the BC Autism Spectrum Interdisciplinary Research (ASPIRE) program (n=48). A fourth group included HUU anonymous controls (n=48) age- and sex-matched 3:1 to the HEU+ASD group, and 10 age- and sex-matched ASPIRE controls (n=58 HUUs total). Leukocyte mtDNA content (mtDNA/nDNA ratio) was measured via monochrome multiplex qPCR, and specimens were randomized and blinded to account for inter-assay variability. Comparisons between groups were performed using the Mann-Whitney U test or unpaired t-test. Results: Among the 16 HEU+ASD children, 15 had received approximately 6 weeks of AZT prophylaxis and 13 were exposed to cART in utero . Between-group comparisons are shown in Figure 1. Conclusions: HEU children have significantly elevated blood mtDNA levels compared to HUU controls, and HEU+ASD children have higher mtDNA than all other groups. It is unclear if this effect is modulated by exposure to cART or HIV. This finding is consistent with previous studies in younger HEU children, which suggested the increase may be a compensatory mechanism in response to mitochondrial dysfunction. This study suggests an association between mtDNA and both HEU and ASD status which may be cumulative and could help to explain the observed high ASD prevalence among HEU children.

Poster Abstracts

339

CROI 2016