title: Maternal plasma and breastmilk viral loads are associated with HIV-1-specific cellular immune responses among HIV-1-exposed, uninfected infants in Kenya.
abstract: Infants exposed to maternal HIV-1 provide an opportunity to assess correlates of HIV-1-specific interferon (IFN)-γ responses and may be informative in the development of HIV-1 vaccines. HIV-1-infected women with CD4 counts 200-500 cells/mm(3) were randomized to short-course zidovudine/nevirapine (ZDV/NVP) or highly active anti-retroviral therapy (HAART) between 2003 and 2005. Maternal plasma and breastmilk HIV-1 RNA and DNA were quantified during the first 6-12 months postpartum. HIV-1 gag peptide-stimulated enzyme-linked immunospot (ELISPOT) assays were conducted in HIV-1-exposed, uninfected infants (EU), and correlates were determined using regression and generalized estimating equations. Among 47 EU infants, 21 (45%) had ≥1 positive ELISPOT result during follow-up. Infants had a median response magnitude of 177 HIV-1-specific spot-forming units (SFU)/106 peripheral blood mononuclear cells (PBMC) [interquartile range (IQR)=117-287] directed against 2 (IQR = 1-3) gag peptide pools. The prevalence and magnitude of responses did not differ by maternal anti-retroviral (ARV) randomization arm. Maternal plasma HIV-1 RNA levels during pregnancy (P=0.009) and breastmilk HIV-1 DNA levels at 1 month (P=0.02) were associated with a higher magnitude of infant HIV-1-specific ELISPOT responses at 1 month postpartum. During follow-up, concurrent breastmilk HIV-1 RNA and DNA (cell-free virus and cell-associated virus, respectively) each were associated positively with magnitude of infant HIV-1-specific responses (P=0.01). Our data demonstrate the importance of antigenic exposure on the induction of infant HIV-1-specific cellular immune responses in the absence of infection.
authors: Department of Epidemiology, University of Washington, Seattle, WA, USA.
authors: A Y
authors: AY
authors: Liu
authors: Department of Medicine, University of Washington, Seattle, WA, USA.|Department of Global Health, University of Washington, Seattle, WA, USA.|Department of Biostatistics, University of Washington, Seattle, WA, USA.
authors: B
authors: B
authors: Lohman-Payne
authors: Department of Epidemiology, University of Washington, Seattle, WA, USA.|Department of Medicine, University of Washington, Seattle, WA, USA.|Department of Global Health, University of Washington, Seattle, WA, USA.
authors: M H
authors: MH
authors: Chung
authors: Department of Obstetrics and Gynaecology, University of Nairobi, Nairobi, Kenya.
authors: J
authors: J
authors: Kiarie
authors: Department of Biostatistics, University of Washington, Seattle, WA, USA.
authors: J
authors: J
authors: Kinuthia
authors: Department of Global Health, University of Washington, Seattle, WA, USA.
authors: J
authors: J
authors: Slyker
authors: Department of Global Health, University of Washington, Seattle, WA, USA.|Department of Paediatrics, University of Nairobi, Nairobi, Kenya.|Departments of Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
authors: B
authors: B
authors: Richardson
authors: Departments of Human Biology, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
authors: D
authors: D
authors: Lehman
authors: Department of Epidemiology, University of Washington, Seattle, WA, USA.|Department of Medicine, University of Washington, Seattle, WA, USA.|Department of Global Health, University of Washington, Seattle, WA, USA.
authors: C
authors: C
authors: Farquhar
authors: Department of Epidemiology, University of Washington, Seattle, WA, USA.|Department of Medicine, University of Washington, Seattle, WA, USA.|Department of Global Health, University of Washington, Seattle, WA, USA.
authors: G
authors: G
authors: John-Stewart
mesh_terms: D000328:Adult; D019380:Anti-HIV Agents / Q000627:therapeutic use; D023241:Antiretroviral Therapy, Highly Active; D018791:CD4 Lymphocyte Count; D005260:Female; D015658:HIV Infections / Q000188:drug therapy / Q000276:immunology* / Q000378:metabolism / Q000821:virology*; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D007111:Immunity, Cellular; D007223:Infant; D007231:Infant, Newborn; D007371:Interferon-gamma / Q000097:blood; D007630:Kenya; D008895:Milk, Human / Q000821:virology*; D011247:Pregnancy; D019562:Viral Load; D055815:Young Adult
chemical_list: D019380:Anti-HIV Agents; D007371:Interferon-gamma
keywords: HIV-1-EU; interferon gamma; paediatric immunity
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