CROI 2017 Abstract e-Book

Abstract eBook

Poster and Themed Discussion Abstracts

Poster and Themed Discussion Abstracts

785 B-CELL SUBSETS PROFILE AND VACCINE RESPONSE IN HIV-EXPOSED UNINFECTED (HEU) CHILDREN Laurence Raymond Marchand 1 , Catherine Gravel 1 , Armelle Le Campion 2 , Marc Boucher 2 , Normand Lapointe 2 , Valerie Lamarre 2 , Fatima Kakkar 2 , Helene C. Cote 3 , Hugo Soudeyns 1 , for the CIHRTeam on Cellular Aging and HIV Comorbidities inWomen and Children (CARMA) 1 CHU Sainte Justine, Montreal, Canada, 2 Univ of Montreal, Montreal, Canada, 3 Univ of British Columbia, Vancouver, Canada Background: HEU children present with a higher incidence of morbidity and mortality in early life. There is evidence that some HEU children exhibit immunologic abnormalities involving the B cell compartment that could be related to in utero and/or perinatal exposure to HIV and/or combination antiretroviral therapy (cART). Here, longitudinal profiling of B cell subsets, naïve-memory differentiation, and vaccine responses was performed during the 1st year of life in HEU children. Methods: HEU children (n=60) from the CMIS Cohort were stratified based on whether maternal HIV-1 viral load (VL) throughout pregnancy was detectable or not (≥40 vs. <40 copies/ml). All received cART (AZT/3TC) from 12h after birth until week 6. Blood mononuclear cells were isolated at birth (cord blood), 6, and 12 months of age. CD19 B cell subsets (naïve; transitional T1 and T2/T3; classical memory; activated memory; atypical memory; plasmablasts) were characterized by flow cytometry based on the expression of CD10, CD20, CD21, CD27 and IgM. Vaccine responses were tested with fluorescent tetanus toxoid C fragment (TTCF) oligomers. Results: At birth, HEU infants born to mothers whose VL in pregnancy was ≥40 copies/ml had or tended to have a lower frequency of transitional T1 B cells (p=0.042) and a higher frequency of plasmablasts (p=0.066). At 12 months of age, they showed a higher frequencies of naïve B cells (p=0.012) and transitional T2/T3 B cells (p=0.016) and they had higher levels of non-class switched B cells in classical memory (p=0.022), activated memory (p=0.009) and atypical memory (p=0.057) subsets compared to HEU born to mothers with VL <40 copies/ml. No significant differences were noted in the frequency of any TTCF-specific B cell subsets between the 2 groups. Conclusion: Our results suggest an early maturation of the B cell compartment in infants born to mothers with detectable VL in pregnancy, with delayed development of antigen- experienced B cells and disturbances in class switching at 12 months of age. These differences in distribution of B cell subsets are analogous to those recently reported in HIV- infected children, compatible with effects induced by HIV exposure. Reassuringly, the presence of equal levels of TTCF-specific B cells in HEU children from both groups suggests and vaccine efficacy in the context of differential exposure to maternal viral load. 786 INFLAMMATORY RESPONSES ASSOCIATED WITH CMV AND MATERNAL HIV IN ZIMBABWEAN INFANTS Ceri Evans 1 , Bernard Chasekwa 2 , Sandra Rukobo 2 , Margaret Ghova 2 , Kuda Mutasa 2 , Robert Ntozini 2 , Jean Humphrey 2 , Andrew Prendergast 1 1 Queen Mary Univ of London, London, UK, 2 Zvitambo Inst for Maternal and Child Hlth Rsr, Harare, Zimbabwe Background: Previously identified abnormalities in HIV-exposed uninfected (HEU) infants include elevated immune activation. The causes are uncertain, but may be related to maternal HIV viremia, maternal immunosuppression, or increased acquisition of infections such as cytomegalovirus (CMV). We compared the effect of HIV exposure and CMV acquisition on infant inflammatory responses. Methods: Mother-infant pairs were recruited at birth to the ZVITAMBO trial before the availability of antiretroviral therapy in Zimbabwe. CMV and C-reactive protein (CRP) were measured at 6 weeks of age in cryopreserved plasma using real-time PCR and ELISA, respectively. Results: 231 HEU infants and 100 HIV-unexposed infants were included. HEU and HIV-unexposed infants had a similarly high prevalence of CMV acquisition at 6 weeks of age (83.1% vs. 74.0%, respectively; P=0.13), but HEU infants had significantly higher CMV viral loads (P=0.005). HEU infants had higher CRP concentrations than HIV-unexposed infants at 6 weeks (median 0.43mg/L vs. 0.20mg/L; P<0.0001). There was no significant association between CRP and CMV DNAemia in HIV-unexposed infants. By contrast, in HEU infants, CMV DNAemia was associated with increased CRP; this association persisted after adjusting for maternal CD4 count, but was no longer present after adjusting for maternal HIV viral load. There were no associations between CMV viral load and infant CRP, maternal HIV viral load or maternal CD4 count (all P>0.05). Conclusion: CMV acquisition was high in Zimbabwean infants irrespective of HIV exposure status. However, HEU infants had higher CMV viral loads which may suggest a failure to control viral infections. Compared to HIV-unexposed infants, HEU infants had more inflammation by 6 weeks of age. CMV DNAemia was associated with elevated CRP in HEU infants but not in HIV-exposed infants; this association appeared to be driven by more advanced disease in the mothers of CMV+ compared to CMV- HEU infants. In HEU infants, maternal HIV viremia had a greater influence on infant inflammation than maternal immunosuppression, highlighting the importance of rapid HIV viral load suppression in pregnant women to improve outcomes even in uninfected infants. 787 MATERNAL ART ASSOCIATED WITH IMPROVED PROTECTIVE TRANSPLACENTAL ANTIBODY TRANSFER Scott Dryden-Peterson 1 , Elize de Bruyn 2 , Gloria Mayondi 3 , Betsy Kammerer 4 , Jean Leidner 5 , Roger L. Shapiro 6 , Haruna Jibril 7 , Shabir Madhi 2 , Shahin Lockman 6

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