CROI 2015 Program and Abstracts

Abstract Listing

Poster Abstracts

TUESDAY, FEBRUARY 24, 2015 Session P-U9 Poster Session

Poster Hall

2:30 pm– 4:00 pm Responses to Vaccines in Children 945 Sustained Responses to Measles Revaccination in HIV-Infected Children on ART in Kenya Laura Newman 1 ; Anne Njoroge 1 ; Bhavna Chohan 1 ; Amalia Magaret 1 ; Jonathan Gorstein 1 ; Julie M. Overbaugh 2 ; DaltonWamalwa 3 ; Elizabeth M. Obimbo 3 ; RuthW. Nduati 3 ; Carey Farquhar 1 1 University of Washington, Seattle, WA, US; 2 Fred Hutchinson Cancer Research Center, University of Washington, Seattle, WA, US; 3 University of Nairobi, Nairobi, Kenya Background: Despite recent advances in reducing measles incidence in Africa, a number of measles outbreaks have occurred in countries with high HIV prevalence. One hypothesis is that there is a growing population of measles-susceptible HIV-infected children. This study was conducted to determine the effectiveness of measles revaccination in HIV-infected children on ART. Methods: In this prospective cohort study, HIV-infected children 15 months to 12 years of age on ART in Nairobi, Kenya received an additional measles vaccine. Questionnaires, physical examinations, and blood draws were completed at enrollment, one, 12, and 24 months after measles revaccination. Measles antibody concentrations were determined by enzyme-linked immunosorbent assay (ELISA) at all time points. Results: Of 232 enrolled children, 228 (98%) had received at least 1 measles vaccine before 1 year of age. There were 123 (53%) males, median age was 7.5 years (interquartile range (IQR): 5.5–9.5), and median CD4%was 32 [IQR: 27–38]. All children were on ART, and median time on ART was 3.4 years (IQR: 1.8–4.9). At enrollment, 52 (23%) of 231 children had an HIV viral load ≥ 1,000 copies/mL. Before revaccination, 125 (54%) of 232 study participants had protective levels of measles antibody. Seropositivity was observed in 216/220 (98%) participants at one month post revaccination and 158/224 (70%) at 12 months post revaccination. Of the 187 participants with with currently completed laboratory results from 24 months post revaccination, 105 (58%) were seropositive. Seroconversion and sustained seropositivity among those seronegative at enrollment was 37% at 12 months post revaccination. In this group, children with an HIV viral load <50 copies/mL at enrollment were twice as likely to seroconvert at 12 months compared to those with an HIV viral load ≥ 1000 copies/mL (RR=2.04, 95% CI 1.01 – 4.10, p=0.047). A larger height-for-age z-score at enrollment was associated with seroconversion at 12 months (RR=1.24, 95% CI 1.04 – 1.48, p=0.016). Time on ART, age, gender, CD4%, and vitamin A status at enrollment were not significantly associated with seroconversion at 12 months. Conclusions: Measles revaccination conferred short-term sustained antibody response in HIV-infected children receiving ART, especially those who had suppressed levels of HIV virus and those with increased height-for-age z-score. Periodic measles revaccination of HIV-infected children on ART may be necessary to confer long-term immunologic memory. 946 T-Cell Anergy and Activation Are AssociatedWith Suboptimal Humoral Responses to Measles Revaccination in HIV-Infected Children on Antiretroviral Therapy in Nairobi, Kenya Matthew B. Buechler 1 ; Laura Newman 2 ; Bhavna Chohan 3 ; Anne Njorge 5 ; DaltonWamalwa 6 ; Carey Farquhar 3 1 University of Washington, Seattle, WA, US; 2 University of Washington, Seattle, WA, US; 3 University of Washington, Seattle, WA, US; 4 Fred Hutchinson Cancer Research Center, University of Washington, Seattle, WA, US; 5 Kenyatta National Hospital, Nairobi, Kenya; 6 University of Nairobi, Nairobi, Kenya Background: HIV-infected children are less capable of mounting and maintaining protective humoral responses to vaccination against measles compared to HIV-uninfected children. This poses a public health challenge in countries with high HIV burdens. Administration of antiretroviral therapy (ART) and revaccinating children against measles is one approach to increase measles immunity in HIV-infected children, yet it is not effective in all cases. Immune system anergy and activation during HIV infection are factors that could influence responses to measles revaccination. Methods: This work was nested within a larger study in which HIV-infected children on ART were revaccinated for measles when their CD4 + T cell frequency reached 15% of total T cells. During clinic visits at the time of revaccination, one month post-revaccination and one year post-revaccination, serumwas collected to assess levels of measles-specific IgG by ELISA and PBMC were collected. We examined PBMC from 20 participants who were measles seronegative (measles-specific IgG antibody titer <350 mIU/mL) at enrollment and developed detectable measles antibodies one month after revaccination. Of the twenty participants, ten children maintained measles antibodies one year after revaccination (responders) and ten children did not exhibit detectable measles antibodies one year after revaccination (non-responders). We utilized a flow cytometry-based approach to examine whether T cell anergy and activation were associated with the maintenance of measles-specific IgG antibodies generated in response to measles revaccination in cohort of HIV-infected children on ART in Nairobi, Kenya. T cells were identified as CD3 + CD4 + (CD4 + T cells) or CD3 + CD4 - (CD8 + T cells). T cells were identified as anergic by expression of PD1 and activated by coexpression of CD38 and HLADR. Results: Children who sustained measles-specific IgG for at least one year after revaccination displayed significantly lower PD1 surface expression on CD8 + T cells on a per-cell basis and exhibited less activated CD4 + T cells compared to those unable to maintain detectable measles-specific antibodies. Children in both groups were similar in age and sex, CD4 + T cell frequency, duration of ART treatment and HIV viral load at enrollment. Conclusions: These data suggest that aberrant T cell anergy and activation are associated with the impaired ability to sustain an antibody response to measles revaccination in HIV-infected children on ART.

Poster Abstracts

947 Molecular Profiles of CXCR5+ CD4 Memory T Cells AssociatedWith Flu Vaccine Response Lesley R. de Armas 1 ; Nicola Cotugno 1 ; Suresh Pallikkuth 1 ; Alberto Cagigi 3 ; Paolo Palma 2 ; Paolo Rossi 2 ; Savita Pahwa 1 1 University of Miami Miller School of Medicine, Miami, FL, US; 2 Children’s Hospital Bambino Gesu, Rome, Italy; 3 Children Hospital Bambino Gesu, Rome, Italy

Background: HIV-infected patients of all ages consistently underperform in flu vaccine efficacy. Peripheral T follicular helper (pTfh) cells, a subset of CD4 T cells which provide help to B cells for developing into Ab secreting cells, are characterized by (CXC) motif chemokine R5 (CXCR5) expression. We previously demonstrated functional impairment of this subset in adult HIV+ flu vaccine non-responders (NR) (Pallikkuth Blood 2012). Microarray data from a pediatric HIV-infected cohort receiving the 2009/10 pandemic influenza vaccine revealed upregulation of CXCR5 in whole blood of vaccine responders (R) compared to NR 4 weeks post-vaccination. We hypothesized that pTfh play a role in Ab responses to the flu vaccine and investigated whether defects in pTfh function could be identified prior to vaccination. Methods: Fluidigm BioMark RT-PCR was performed on pTfh cells from a cohort of virally suppressed, vertically infected HIV+ children who received the 2012 seasonal flu vaccine. PBMC from baseline (T0) were stimulated with H1N1 antigen (16h) and then sort-purified as 500 cell pools into PCR buffer. This technology allowed us to study a panel of 96 genes related to Tfh function, immune activation, TCR signaling, and co-stimulation/inhibition simultaneously in pTfh from R (n=7) and NR (n=9), compared to healthy controls (HC,

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CROI 2015