CROI 2018 Abstract eBook

Abstract eBook

Poster Abstracts

873 INFLAMMATION, CMV AND THE GROWTH HORMONE AXIS IN HIV- EXPOSED UNINFECTED INFANTS Ceri Evans 1 , Bernard Chasekwa 1 , Sandra Rukobo 1 , Margaret Ghova 1 , Kuda Mutasa 1 , Robert Ntozini 1 , Jean Humphrey 2 , Andrew Prendergast 3 1 Zvitambo Institute for Maternal and Child Health Research, Harare, Zimbabwe, 2 The Johns Hopkins University, Baltimore, MD, USA, 3 Queen Mary University of London, London, UK Background: Stunting (linear growth failure) is of considerable global health importance because it contributes to ±15% of under-5 mortality, impairs neurodevelopment, and reduces economic productivity in adulthood. HIV- exposed uninfected (HEU) infants have more stunting than HIV-unexposed infants, but the causes are uncertain. The growth hormone axis is an important regulator of infant growth through hepatic synthesis of insulin-like growth factor 1 (IGF-1), and may be disrupted by chronic inflammation and acute infections. We hypothesized that inflammation and viral infections disrupt the growth hormone axis in HEU infants, and contribute to linear growth impairment. Methods: This study used data and stored plasma samples from 243 HEU infants and 100 HIV-unexposed infants recruited to the ZVITAMBO trial in Zimbabwe prior to ART availability. Length was measured at birth, 6 weeks, 3 months and 6 months of age and converted into length-for-age Z-scores (LAZ). Plasma IGF-1, C-reactive protein (CRP) and cytomegalovirus (CMV) viremia were measured at 6 weeks of age by ELISA (IGF-1, CRP) and real-time quantitative DNA PCR (CMV). Unpaired t-tests were used to compare continuous variables and linear regression models were used to determine associations between variables. Results: Mean IGF-1 concentrations at 6 weeks were significantly lower in HEU compared to HIV-unexposed infants (29.5 vs. 32.6ng/mL; P=0.01). IGF-1 concentrations at 6 weeks were positively correlated with LAZ at 6 weeks, 3 months and 6 months of age, and negatively correlated with CRP (β= -0.84; P=0.03). HEU and HIV-unexposed infants had a similarly high prevalence of CMV viremia at 6 weeks of age (81.4% vs. 74%; P=0.14), but HEU infants had higher mean CMV viral loads (P=0.005). Among infants with CMV viremia, CMV viral loads were inversely associated with IGF-1 concentrations in HEU infants (β= -1.16; P=0.008) but not in HIV-unexposed infants (β = 0.21; P=0.83). Conclusion: IGF-1 at 6 weeks was associated with subsequent linear growth through 6 months of age. Increased inflammation was associated with lower IGF-1 concentrations, meaning the pro-inflammatory state of HEU infants may be one driver of growth impairment. An inverse relationship between CMV viral load and IGF-1 in HEU infants, but not in HIV-unexposed infants, is consistent with previous findings that suggest poorer handling of viral infections in HEU infants. Targeted interventions for HEU infants may be necessary to reduce stunting and its associated negative effects. 874 METABOLIC OUTCOMES IN OBESE HIV-EXPOSED UNINFECTED CHILDREN: COMPARISON WITH NHANES Jennifer Jao 1 , Denise Jacobson 2 , Wendy Yu 2 , Matthew McKenna 2 , William Borkowsky 3 , Mitchell Geffner 4 , Rohan Hazra 5 , Brad Karalius 2 , Elizabeth J. McFarland 6 , Kunjal Patel 2 , Paige L. Williams 2 , Tracie Miller 7 1 Icahn School of Medicine at Mt Sinai, New York, NY, USA, 2 Harvard University, Cambridge, MA, USA, 3 New York University, New York City, NY, USA, 4 University of Southern California, Los Angeles, CA, USA, 5 NIH, Rockville, MD, USA, 6 University of Colorado Denver, Denver, CO, USA, 7 University of Miami, Miami, FL, USA Background: Metabolic perturbations related to obesity in HIV-exposed uninfected (HEU) children may differ from that in the general obese pediatric population due to in utero HIV/antiretroviral (ARV) exposure. Methods: This study compared metabolic parameters in obese non-pregnant HEU youth enrolled in the Pediatric HIV/AIDS Cohort (PHACS) Surveillance Monitoring of ART Toxicities (SMARTT) study with obese youth from the U.S. general population enrolled in the National Health and Nutrition Examination Survey (NHANES). Obesity was defined as a body mass index (BMI)>95%ile for age and sex. Binary outcomes were systolic and diastolic hypertension (HTN) [blood pressure (BP) z score ≥90%ile for age, sex, and height], total cholesterol (TC) >200 mg/dL, high-density lipoprotein-C (HDL) <35 mg/dL, low-density lipoprotein-C (LDL) >130 mg/dL, triglycerides (TG) >150 mg/dL, and Homeostatic Model Assessment-Insulin Resistance (HOMA) >4. Because NHANES obtains metabolic measures only within certain age groups, 3 analytic samples were created: 1) TC and HDL (≥6 year), 2) systolic and diastolic BP (≥8 year), and 3) LDL, TG, and HOMA (≥12 year). For each group, up to 3 NHANES

that vaccine co-administration can interfere with elicited immune responses, it is important to evaluate how a potential pediatric HIV vaccine would fit into the current infant immunization schedule. In addition, the impact of maternal antibodies on infant HIV vaccine-elicited response is unknown. The goals of this study were to compare antibody responses to common pediatric vaccines in infant HIV vaccinees and placebo recipients and to evaluate whether maternal antibodies interfere with infant HIV vaccine-elicited antibody responses. Methods: We developed a pediatric vaccine multiplex assay (PVMA) to measure antibodies against common infant vaccines (HepB, DTaP, rubella, HiB) using minimal sample volume. To verify the PVMA, antibody concentrations in 50 plasma samples determined by PVMA and ELISA were compared. The PVMA was used to measure antibodies in participants from PACTG 230/326 HIV vaccine trials (n=129). To assess the effect of maternal HIV-specific antibodies on HIV vaccine responses, we used a multiplex assay to measure and compare the magnitude of gp120, V1V2, and V3-specific antibodies in vaccine recipients at birth (maternally acquired) and at two post-immunization time points. Results: Antibody concentrations determined by PVMA and ELISA strongly correlated (r>0.85 for each antigen) and the PVMA demonstrated a high degree of sensitivity and specificity. There was no significant difference in pediatric vaccine antibody concentrations between infant vaccine and placebo recipients (p>0.05). Additionally, there was no correlation between V3 (r=-0.13, p=0.41) or V1V2-specific antibodies (r=0.17, p=0.26) at birth and at peak immunogenicity. Though gp120-specific antibodies at birth and at peak immunogenicity were weakly correlated (r=0.33, p=0.03), likely due to the persistence of maternal antibodies, this correlation was no longer observed 6 months post peak immunogenicity (r=-0.10, p=0.50). Conclusion: Application of the PVMA to PACTG 230/326 cohorts suggests that there was no interference between the HIV vaccine and other vaccines administered during infancy, supporting the potential to include an HIV vaccine in the infant immunization schedule. We also found no evidence that maternal antibodies interfere with infant HIV vaccine responses. Similar investigations in future trials will inform pediatric HIV vaccine timing and efficacy. 872 GROWTH AND BONE MINERAL ACCRETION IN UGANDAN INFANTS EXPOSED TO MATERNAL HIV AND ART Florence Nabwire 1 , Ann Prentice 1 , MatthewM. Hamill 1 , Adeodata Kekitiinwa 2 , Josaphat Byamugisha 3 , Mary G. Fowler 4 , Gail R. Goldberg 1 1 MRC Elsie Widdowson Laboratory, Cambridge, UK, 2 Baylor College of Medicine Children’s Foundation, Kampala, Uganda, 3 Makerere University, Kampala, Uganda, 4 Johns Hopkins Hospital, Baltimore, MD, USA Background: Initiation of ART in HIV-infected adults is associated with a 2-6% decrease in bone mineral (BM) regardless of ART regimen. Maternal ART may perturb BMmobilisation in the mother during pregnancy and lactation, and/or may directly act on the baby’s bone leading to compromised growth/ BM accretion . Lower BM in American and African newborns has been reported following exposure to maternal TDF-based ART. However, there are limited data on infant BM accretion following both in-utero and postpartum exposure to maternal option B+ ART. We compared infant growth and bone mineral accretion between HIV/ART exposed (HEI) and HIV-unexposed infants (HUI). Methods: HIV-positive (on TDF-3TC-EFV previously ART naïve) and HIV- negative pregnant women were recruited in Kampala, Uganda; and their babies (82 HEI and 72 HUI) were followed at 2 (PP2) and 14 wks of age (PP14). Infant whole body (WB) and lumbar spine (LS) BM content (BMC) was measured by DXA at PP2 and PP14. Body weight (Wt) and length (Lt) were measured and Z-scores generated based on WHO 2006 growth standards. BMC was adjusted for bone area, Wt and Lt. The primary outcome was the difference between the groups in % change (± SE) in infant WB BMC between PP2 and PP14. Results: Mean gestation was 40.9±1.8 wks and not significantly different between groups. By PP14, the mean duration of exposure to ART was 29.3±5.1 wks. Maternal adherence to ART was >95% and median CD4 count was 403 (IQR 290-528) at PP14. More HEI were exclusively breastfed (EBF) (PP2 82.9% v 58.7%; PP14 86.7% v 66.2%, both p<0.05); showing that the BM accretion was appropriate for achieved infant size. In contrast, HEI had a greater increase in LS BMC (29.5±1.7% v 24.4±1.7%, p<0.05), a difference which remained after size-adjustment (11.4±5.4% v 6.5±5.8%, p<0.05. Conclusion: These data have shown early slower growth and whole body BM accretion in HEI whose mothers were on option B+ ART compared to HUI in the first 3 mo of life. It is important to determine longer-term infant growth and bone outcomes following exposure to maternal ART in early life.

Poster Abstracts

CROI 2018 331