CROI 2018 Abstract eBook

Abstract eBook

Poster Abstracts

as infants aged <3 months, ‘late diagnosis’ as infants aged ≥3 months. Within ‘late diagnosis,’ ‘late presenters’ had no PCR test <3 months of age. Results: Between 2010-2015, 83 318 (3.5%) of 2 372 064 HIV PCR tests performed were positive. After de-duplication, 71 878 (4.3%) infants were diagnosed with HIV out of 1 674 535 infants tested. Among HIV infected infants, 26 808 (37.3%) and 35 393 (49.2%) tested positive aged <2 and <3 months respectively. Among the 36 485 infants who tested positive ≥3 months of age only 4 513 (12.4%) had a previous negative result at <3 months, indicative of postnatal transmission. The majority of late diagnosis, 31 972 (44.5%), was due to late presenters. Between 2010-2015, the annual number of late presenters decreased from 8 352 to 4 080 (53.8%-37.4% of positives) and confirmed postnatal infections increased from 175 to 862 infants (1.1%-7.9% of positives). Conclusion: Late presentation for first PCR test declined over time yet, despite high EID coverage, accounted for more than a third of infections in 2015 suggesting poor access to care among HIV-infected mother-infant pairs. Late presenters likely represent different modes of transmission and threaten efforts to eliminate MTCT.

and higher pre-transmission plasma nAb activity against heterologous envs (p = 0.03). TM as compared to NTM also had higher neutralization responses against autologous strains although this difference was not statistically significant (p = 0.39). Infants born to mothers with greater pre-transmission neutralizing breadth and potency had a 3.4-fold greater likelihood of having a grade 4 serious adverse event or death over follow-up (p = 0.03). A subset of maternal breast milk (n = 10) demonstrated neutralization BP scores that were on average 3-fold lower than maternal plasma but significantly correlated with both infant plasma IgG (r = 0.82, p = 0.006) with a trend towards correlation with maternal plasma (r = 0.61, p = 0.07). Conclusion: These results imply that pre-existing anti-HIV-1 nAb activity present in exposed infants does not prevent breast milk HIV transmission. Pre- existing high maternal neutralizing breadth and potency associated with both a higher frequency of breast milk transmission and subsequent infant morbidity. These results have implications for vaccine and passive immunization strategies for infected mothers targeted at preventing MTCT. 828 ROLE OF REGULATORY T CELLS IN MOTHER TO CHILD TRANSMISSION OF HIV Peter A. Kessler , Surinder P. Gill, Chris C. Ibegbu Emory University, Atlanta, GA, USA Background: Mother-to-child transmission of HIV-1 occurs in a minority of HIV-infected mother-infant pairs, even without any interventions. The mechanisms that protect the majority of HIV-exposed infants from infection are unclear. T regulatory cells (Treg) have important immunomodulatory functions, but their role in the fetus as well as in mother-to-child transmission of HIV is under-studied. Methods: We studied available cryopreserved peripheral blood mononuclear cells from HIV-exposed infants from the Breastfeeding, Antiretrovirals and Nutrition (BAN) Study cohort in Malawi: 64 infants were HIV-uninfected and 28 infants were HIV-infected at birth. We quantified the frequency of Treg cells (CD4+CD25+FoxP3+), and activated CD4+ and CD8+ T cells (CD38+HLADR+) by flow cytometry at birth, 6 weeks and 6, 9 and 12 months of age. Descriptive statistics were performed to describe the distributions of these lymphocyte markers according to HIV infection status; and Student’s t tests and Wilcoxon- Rank Sum tests to perform comparisons between HIV- infected and uninfected infants. Results: T cell activation increased rapidly in the first 6 weeks of life, more pronounced on CD8+ T cells; a further increase in activation was observed at the time of weaning from breastfeeding at 6 months of age. In contrast, the frequency of Treg was stable over the first 6 weeks of life (median, 0.5%), slightly decreased between 6 weeks and 6 months (median at 6 months, 0.3%) and then slightly increased between 6 months (time of weaning) and 12 months of age (median, 0.45%). HIV-infected infants had significantly higher frequencies of activated T cells than uninfected infants (P<0.01), as expected. At the time of birth, HIV-exposed uninfected infants had higher levels of Treg, compared to infants infected in utero (Figure, P=0.03). Among infants with negative HIV tests at birth, Treg % tended to be higher in those who were HIV- infected by 6 months of life, compared with those who remained uninfected (median, 1.25% vs. 0.55%). Conclusion: This study provides evidence that Treg may play a role in preventing mother-to-child transmission of HIV, and perhaps even delaying detection of HIV infection in the infant, likely by suppressing immune activation in the fetus and infant. Better characterization of the role of Treg in fetal and neonatal immunity may provide a valuable complementary approach to achieve eradication of mother-to-child transmission of HIV.

Poster Abstracts

827 MATERNAL ANTI-HIV-1 NAB RESPONSE ASSOCIATES WITH TRANSMISSION AND INFANT MORBIDITY

Melissa Ghulam-Smith 1 , Alex Olson 1 , Laura F. White 1 , Charles Chasela 2 , Sascha Ellington 3 , Athena Kourtis 3 , Denise Jamieson 3 , Gerald Tegha 4 , Charles van der Horst 5 , Manish Sagar 1 1 Boston University, Boston, MA, USA, 2 University of the Witwatersrand, Johannesburg, South Africa, 3 CDC, Atlanta, GA, USA, 4 University of North Carolina Project–Malawi, Lilongwe, Malawi, 5 University of North Carolina Chapel Hill, Chapel Hill, NC, USA Background: In sub-Saharan Africa, mother-to-child transmission (MTCT) of HIV-1 through breast milk may be prevented by passive immunization with neutralizing antibodies (nAbs). Currently, there are conflicting results about the ability of nAbs to halt MTCT and their impact on infant outcomes. Methods: Breast milk and plasma collected prior to transmission frommother- infant pairs (MIPs) (n = 21) was compared to matched samples from 2 different non-transmitting mother (NTM) and HIV-exposed uninfected (HEU) infant pairs (n = 42). Matching was based on maternal CD4 and virus level, and duration of time from birth to sample collection. Neutralization was assessed against both a pool of full-length envelopes (envs) isolated frommaternal plasma using area under the curve and a global panel of reference envs (n=11) using a breadth-potency (BP) score, consisting of the average of log normalized % neutralization. Groups were compared using generalized estimating equations, Wilcoxon rank sum tests, and Kaplan Meier statistics. Results: HEU infants, compared to those that eventually acquired infection, did not possess higher nAb responses against both the heterologous envs (p = 0.46) or their mothers’ viral variants (p = 0.45). Transmitting mothers (TM) plasma as compared to NTM, however, had a unique neutralization fingerprint (p = 0.03)

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