CROI 2018 Abstract eBook

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Poster Abstracts

869 DECREASED DIARRHEAL AND RESPIRATORY DISEASE IN HEUS FOLLOWING RV AND PCV VACCINATION

Gbolahan Ajibola 1 , Kara Bennett 2 , Kathleen M. Powis 3 , Michael D. Hughes 4 , Jean Leidner 5 , Samuel W. Kgole 1 , Kerapetse Botebele 1 , Oganne Batlang 1 , Chipo Petlo 6 , Mompati O. Mmalane 1 , Joseph Makhema 1 , Shahin Lockman 7 , Roger L. Shapiro 4 1 Botswana Harvard AIDS Institute Partnership, Gabarone, Botswana, 2 Bennett Statistical Consulting, Inc, New York, NY, USA, 3 Massachusetts General Hospital, Boston, MA, USA, 4 Harvard University, Cambridge, MA, USA, 5 Goodtables Data Consulting, Norman, OK, USA, 6 Ministry of Health, Gaborone, Botswana, 7 Brigham and Women’s Hospital, Boston, MA, USA Background: Rotavirus vaccine (RV) and pneumococcal vaccine (PCV) decrease diarrheal and respiratory disease incidence and severity, but their impact has not been studied among HIV-exposed uninfected (HEU) children. We assessed the impact of the introduction of RV and PCV vaccination among HEU children in Botswana. Methods: We recorded RV and PCV vaccination history in HEU infants enrolled 2011-2015 in a double-blind, randomized placebo-controlled trial that studied the effect of cotrimoxazole (CTX) on mortality in HEU children at 3 sites in Botswana. We categorized infants into those enrolled before or after the Botswana government’s simultaneous April 2012 introduction of RV and PCV (given at 2, 3 and 4 months of age). We then compared grade 3 or 4 diarrhea and pneumonia diagnoses, hospitalizations, and deaths from the time of randomization to CTX/placebo (14-34 days) through the 12 months study visit (365 + 45days) by vaccine era (before or after April 2012). Kaplan-Meier survival estimates were used to estimate the cumulative incidence of events in the two study eras. Results: Of 2848 HEU children included in this analysis, 687 (24%) were born in the pre-vaccine era and 2161 (76%) were born in the vaccine era; 49 (7%) children in the pre-vaccine era received either RV or PCV vaccine and 184 (9%) children in the vaccine era did not receive either vaccine. The estimated proportion with a grade 3 or 4 diagnosis of diarrhea by age 12 months was 17.2% in the pre-vaccine era and 7.8% in the vaccine era (difference -9.4%, 95% CI -12·5, -6·3%). The estimated proportion with a grade 3 or 4 diagnosis of pneumonia by age 12 months was 4.7% in the pre-vaccination era and 2.1% in the vaccination era (difference -2.6%, 95% CI -4.3 to -0.9%). A significant difference was also observed for the composite endpoint of hospitalization or death from diarrhea or pneumonia, with estimated proportions of 10.7% in the pre-vaccination era and 7.2% in the vaccination era (difference -3.5%, CI -6.1, -1.0%) (Figure). Differences between eras for all events varied significantly among the three sites (diarrhea p<0.001, pneumonia: p=0.10, hospitalization or death for reason of diarrhea or pneumonia p=0.03). Conclusion: Although temporal confounding cannot be excluded, significant declines in the burden of diarrheal and respiratory illness were observed among HEU children in a large clinical trial in Botswana following the introduction of RV and PCV vaccines, particularly at the most rural study location.

870 PERSISTENT B CELL DEFICIENCY IN HIV-EXPOSED UNINFECTED INFANTS FOLLOWING IMMUNIZATION Liane S. Sadder 1 , Li Yin 2 , Kai-Fen Chang 2 , Bernard Fischer 1 , Maureen Goodenow 3 , John W. Sleasman 1 1 Duke University, Durham, NC, USA, 2 NIH, Bethesda, MD, USA, 3 NIH, Rockville, MD, USA Background: HIV-exposed uninfected (EU) infants are candidates for HIV vaccine trials. However, it is unclear if EU infants have similar immune responses when compared to unexposed healthy infants (HI). Methods: Longitudinal assessment of vaccine responses and plasma biomarkers associated with B cell responses in a cohort of 48 breastfed (BF) or formula fed (FF) HI were compared to 10 EU infants. Comparisons among groups for vaccination titers to B. pertussis, H. flu, Hep B, and tetanus measured in cord blood samples (CB), 6, and 12 months of age by ELISA. Plasma biomarkers included APRIL, BAFF, sCD163, sCD40L, and IL-10 measured by multiplex ELISA and IgA levels by nephelometry. Statistical comparisons among and within groups used a t test. Regression analysis assessed relationship between vaccine responses and plasma cytokine levels in HI and EU infants. Results: Post vaccination titers to B. pertussis and tetanus were lower at birth in EU infants as compared to HI (2394 and 6019 U/ml, p= 0.0006, and 99.8 and 383.8 p=0.004, respectively). However, EU infants had higher tetanus titers at 6 and 12 months and higher pertussis titers at 12 months. In contrast, Hep B titers were significantly lower in EU infants compared to HI. Within all groups, CB levels of APRIL, BAFF, sCD40L, and IL-10 were elevated and declined at 6 and 12 months. BAFF levels were lower in EU infants compared to HI in CB, 6 and 12 months (1626, 342, 305 pg/ml vs 7599, 1045, 862 pg/ml, p<0.05). There were no significant differences between EU infants and HI for APRIL, sCD163, sCD40L, IL-10, and IgA. Linear regression analysis showed a negative correlation between CB and 6 month B. pertussis titers in HI (rho= -0.75, p=0.0009) but not in EU infants. There was a strong positive correlation between both APRIL and sCD40L to B. pertussis, tetanus, H flu, and Hep B titers at 12 months in HI (rho > 0.51, p <0.05). However, with the exception of tetanus (rho= 0.73, p= 0.01) this correlation was not evident in EU infants. Conclusion: Lower CB vaccine titers in EU infants reflects HIV-associated maternal immune suppression. However, while EU infants’ vaccine responses are more robust for tetanus and B. pertussis, subtle immune defects were revealed in pro-inflammatory pathways involving BAFF, APRIL and sCD40L. These results indicate persistent B cell developmental defects in EU infants, which may have implications for HIV vaccine trials in this population. 871 INFANT HIV VACCINATION: RELATIONSHIP TO CHILDHOOD VACCINES AND MATERNAL ANTIBODIES Hannah Itell 1 , Erin McGuire 1 , Meng Chen 1 , Petronella Muresan 2 , Sallie Permar 1 , Genevieve Fouda 1 1 Duke Human Vaccine Institute, Durham, NC, USA, 2 Harvard University, Boston, MA, USA Background: A pediatric HIV vaccine may be critical to eliminating the 150,000 pediatric HIV infections that occur annually. As previous research has shown

Poster Abstracts

CROI 2018 330