CROI 2016 Abstract eBook

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Poster Abstracts

standards for birth and postnatal measures respectively, with correction for prematurity. Mixed effects linear models were used to examine the association between duration of in utero TDF exposure and infant LAZ over time. Results: In 464 mother-infant pairs (median CD4 at ART initiation, 346 cells/µL), the median duration of TDF exposure was 16.7 wks (interquartile range 11-22) with 31%, 44% and 25% of infants exposed to <12, 12-22 and >22 wks of TDF respectively. Longer duration of TDF exposure in utero was associated with higher maternal socioeconomic status (SES) but not with baseline maternal age, CD4 cell count or HIV viral load. Infants with >22 wks of exposure were breastfed for shorter than those with 12-22 and <12 wks exposure (median duration 3, 5 and 6 months respectively). Median LAZ were slightly higher than the expected mean at birth, and slightly below thereafter, but did not vary by duration of TDF exposure at any time point (Figure). In the final model predicting LAZ over time, maternal height was strongly associated with LAZ (β=0.02 per cm increment, 95% confidence interval, CI: 0.01,0.04), but there was no association with duration of TDF exposure in utero: β for >22 vs <12 wks, 0.11 (95% CI: -0.25,0.47); β for 12-22 vs <12 wks, -0.03 (95% CI:

-0.28,0.22). Results were unchanged after adjustment for breastfeeding duration, maternal CD4 cell count, HIV viral load and SES. Conclusions: These data find no evidence for an association between duration of TDF exposure in utero and linear growth in infancy.

809 Severe Respiratory Infections in HIV-Exposed Uninfected Infants: Serologic Analysis AdrianaWeinberg 1 ; Marissa Mussi-Pinhata 2 ; QiluYu 3 ; Rachel Cohen 3 ;Volia Almeida 2 ; Fabiana Amaral 2 ; Laura Freimanis 3 ; Jennifer S. Read 4 ; George K. Siberry 5 ; for the NISDI, LILAC and CIRAI StudyTeams 1 Univ of Colorado, Denver, CO, USA; 2 Univ of Sao Paulo, Sao Paulo, Brazil; 3 Westat, Inc., Rockville, MD, USA; 4 Univ of California San Francisco, San Francisco, CA, USA; 5 Eunice Kennedy Shriver NICHD, Bethesda, MD, USA Background: HIV-exposed uninfected (HEU) infants have increased rates of severe lower respiratory tract infection (LRTI), sepsis, hospitalization and death. We examined the incidence of LRTI in HEU according to maternal antibody transfer and infant antibody production. Methods: We enrolled 247 HEU and 88 HIV-unexposed uninfected (HUU) Brazilian infant/mother pairs, including 107 HEU and 16 HUU with LRTI in the first 6 months of life. Antibodies to the following agents were measured by ELISA: respiratory syncytial virus (RSV) and pneumococcus (PNC) 1, 5, 6, 14 in mothers (delivery) and infants (0, 6 months); influenza A (Flu) and parainfluenza viruses (PIV) 1, 2, 3 (infants 0, 6 months); tetanus toxoid (infants 6 months). Results: Compared to HUU, HEU infants had lower antibody levels at birth for all respiratory agents (p<0.0001), although maternal antibodies to PNC and RSV did not differ by HIV status. Transplacental transfer of maternal antibodies was lower for RSV in HEU vs. HUU (mean±SD ratios=1.3±3.5 vs. 1.8±0.8; p=0.05). Infant: mother PNC antibody ratios were <1 in both HEU and HUU, but the differences between HEU and HUU were not statistically significant. Compared to mothers of LRTI-, those of LRTI+ HEU had higher antibody levels to PNC 1 and 6 and those of LRTI+ HUU to PNC 5 and 14 (p≤0.04). Flu, PIV, RSV and PNC antibodies at birth were similar in LRTI+ vs. LRTI- HEU or HUU, except for higher PNC 5 and 14 levels in LRTI+ vs. LRTI- HUU (p≤0.05). At 6 months, HEU and HUU had similar antibody responses to tetanus vaccine regardless of LRTI status. After controlling for birth levels, HEU had lower RSV (p<0.001), higher PIV 1, 2, 3 (p≤0.001) and similar Flu antibodies (p=0.11) compared with HUU at 6 months. At 6 months, LRTI+ HEU had higher anti-RSV antibody levels (p=0.08) and rates of seroconversion to ≥1, 2 or 3 paramyxoviruses (p=0.05, 0.02 and 0.06, respectively) than LRTI- HEU. Conclusions: The incidence of LRTI in HEU infants correlated with the frequency of paramyxovirus infections, but not with low levels of transferred maternal antibodies or with infant failure to make antibodies in response to infections or vaccines. The higher maternal PNC antibody levels in LRTI+ vs. LRTI- infants suggested that mothers of LRTI+ infants had higher rates of PNC infection and/or carriage increasing infant exposure to PNC and possibly contributing to LRTI morbidity. Collectively, our data suggest that environmental factors and innate and/or cell-mediated immune defects predispose HEU to LRTI. 810 Similar HIV Protection From ZDV vs NVP Prophylaxis in Formula-Fed Infants in Botswana Kathleen Powis 1 ; Shahin Lockman 2 ; Gbolahan Ajibola 3 ; Kara Bennett 4 ; Jean Leidner 5 ; Michael Hughes 6 ; Sikhulile Moyo 3 ; Erik vanWidenfelt 3 ; Joseph Makhema 3 ; Roger L. Shapiro 6 1 Massachusetts General Hosp, Boston, MA, USA; 2 Brigham and Women’s Hosp, Harvard Med Sch, Boston, MA, USA; 3 Botswana Harvard AIDS Inst Partnership, Gaborone, Botswana; 4 Bennett Statistical Consulting, Inc., Ballston Lake, NY, USA; 5 Goodtables Consulting, Oklahoma, OK, USA; 6 Harvard Sch of PH, Boston, MA, USA Background: The World Health Organization recommends that HIV-exposed formula fed infants receive prophylactic zidovudine (ZDV) or nevirapine (NVP) from birth for 4-6 weeks for prevention of mother-to-child HIV transmission (PMTCT). No studies have evaluated the health consequences of ZDV vs NVP prophylaxis in formula fed HIV-exposed infants. Methods: We analyzed data from the Mpepu study in Botswana, which evaluated infant cotrimoxazole vs. placebo among HIV exposed uninfected (HEU) children. Infant post- exposure prophylaxis for PMTCT changed during the course of the study: single dose of NVP (sdNVP) followed by ZDV was used fromMay 2011-Jan 2013, and either this regimen or extended NVP (without ZDV) was used after Jan 2013. Mpepu data for formula-fed, full-term (≥37 weeks gestation) infants without growth restriction (birthweight ≥ 2500 grams) were included to reduce study-specific sources of bias, and analyses were limited to those initiating ZDV or NVP ≤ 72 hours from birth with a documented ZDV or NVP 25-35 day course. Incidence of intrapartummother-to-child HIV transmission (MTCT) and first occurrence of anemia or neutropenia in the first 6 months of life using Division of AIDS grade 3 and 4 criteria were compared using Fisher’s exact tests. Results: Of 3164 infants born in the Mpepu Study, 1365 (43%) met inclusion criteria: 687 (50%) received ZDV (86% of ZDV-treated infants were born prior to 2013) and 678 (50%) received NVP. The most common reasons for infant exclusion included AZT or NVP prophylaxis variation, preterm or growth restricted infants, and breastfeeding. Most mothers received 3-drug antiretroviral treatment (ART) in pregnancy (74% in the ZDV group, and 95% in the NVP group). Of 1362 infants with documented negative HIV DNA PCR prior to a 2nd PCR test between 14 to 34 days of life, 4 infants were confirmed HIV-infected on their 2nd HIV DNA PCR test: 2 (0.3%) of ZDV recipients and 2 (0.3%) of NVP recipients (p=1.0). Anemia occurred in 19 (2.8%) ZDV recipients vs 13 (1.9%) NVP recipients (p=0.37), and neutropenia occurred in 32 (4.7%) ZDV recipients vs 25 (3.7%) NVP recipients (p=0.41).

Poster Abstracts

338

CROI 2016