HIV‐1–Specific Cytotoxic T Lymphocytes and Breast Milk HIV‐1 Transmission

John‐Stewart, Grace; Mbori‐Ngacha, Dorothy; Payne, Barbara Lohman; Farquhar, Carey; Richardson, Barbra A.; Emery, Sandra; Otieno, Phelgona; Obimbo, Elizabeth; Dong, Tao; Slyker, Jennifer A.; Nduati, Ruth; Overbaugh, Julie; Rowland‐Jones, Sarah

doi:10.1086/597120

Cited by 50 publications

(64 citation statements)

References 37 publications

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“…We identified singleton and first-born twin infants who were confirmed to be HIV-uninfected at birth from a previously accrued cohort of HIV-infected mothers and their infants, details of which have been published previously 12–14 . Briefly, HIV-infected women were enrolled during pregnancy between 1999–2002 in Nairobi, Kenya and followed until one year postpartum.…”

Section: Methodsmentioning

confidence: 99%

Breastfeeding Is Associated with Decreased Risk of Hospitalization among HIV-Exposed, Uninfected Kenyan Infants

et al. 2015

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Background HIV-exposed uninfected (HEU) infants are a growing population in sub-Saharan Africa, with higher morbidity and mortality than HIV-unexposed infants. HEU infants may experience increased morbidity due to breastfeeding avoidance. Objective We sought to describe the burden and identify predictors of hospitalization among HEU infants in the first year of life. Methods Using a retrospective cohort of HIV-infected mothers and their HEU infants in Nairobi, Kenya, we identified infants who were HIV-uninfected at birth and were followed monthly until last negative HIV test, death, loss to follow-up or study exit at one year of age. Incidence, timing and reason for hospitalization was assessed overall as well as stratified by feeding method. Predictors of first infectious disease hospitalization were identified using competing risk regression, with HIV acquisition and death as competing risks. Results Among 388 infants, 113 hospitalizations were reported [35/100 infant-years, 95% confidence interval (CI) 29–42]. Ninety hospitalizations were due to one or more infectious diseases [26/100 infant-years, 95%CI 21–32], primarily pneumonia (n=40), gastroenteritis (n=17) and sepsis (n=14). Breastfeeding was associated with decreased risk of infectious disease hospitalization [SHR=0.39 (95%CI 0.24–0.64)], as was time-updated nutritional status [SHR=0.73 (95%CI 0.61–0.89)]. Incidence of infectious disease hospitalization among formula-fed infants was 51/100 child-years (95%CI 37–70) compared to 19/100 child-years (95%CI 14–25) among breastfed infants. Conclusion Among HEU infants, breastfeeding and nutritional status were associated with reduced hospitalization during the first year of life.

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Section: Methodsmentioning

confidence: 99%

Breastfeeding Is Associated with Decreased Risk of Hospitalization among HIV-Exposed, Uninfected Kenyan Infants

et al. 2015

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“…138,139,146 -148 CD8 + T-cell responses have been detected in infants exposed to HIV-1-infected maternal milk, including some who did not become infected. 149,150 Initial findings were, recently, confirmed in a large prospective cohort study, 151 showing IFN-responses to HIV-1 peptides in 47 % of exposed uninfected infants during the first year of life. It is not clear whether such responses are protective or merely an indicator of exposure to defective virus or virus that is restricted in replication to mucosal or peripheral lymphoid tissues, as suggested by primate models.…”

Section: Breast-feedingmentioning

confidence: 81%

An African perspective on mucosal immunity and HIV-1

et al. 2009

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HIV prevention mandates an understanding of the mechanisms of mucosal immunity with attention to some unique features of the epidemic and mucosal environment in the developing world. An effective vaccine will have to induce mucosal protection against a highly diverse virus, which is equipped with a number of immune evasion strategies. Its development will require assessment of mucosal immune responses, and it will have to protect a mucosal environment where inflammation and altered immune responses are common because of the presence of other mucosal infections, such as sexually transmitted infections and parasites, and where nutritional status may also be compromised. Ideally, not only prevention methods would protect adults but also provide cover against gastrointestinal transmission through maternal milk. Prevention might also be complemented by microbicides and circumcision, two alternative approaches to mucosal protection. It seems unlikely that a single solution will work in all instances and intervention might have to act at multiple levels and be tailored to local circumstances. We review here some of the mucosal events associated with HIV infection that are most relevant in an African setting.

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“…This study used specimens from an MTCT cohort collected between 1999 and 2005 in Nairobi, Kenya, as described previously [21,22]. Women were recruited during pregnancy, provided written informed consent for participation and storage of specimens, and received zidovudine (ZDV) prophylaxis for preventing MTCT [23].…”

Section: Methodsmentioning

confidence: 99%

“…Infants were diagnosed with HIV-1 infection as previously described [21]. Briefly, an infant was considered HIV-1 infected if either HIV-1gag DNA was detected from blood spotted onto filter papers by PCR [25] or HIV-1 RNA was detected in plasma with the Gen-Probe HIV-1 Viral Load Assay (Gen-Probe Inc, San Diego, California, USA) [26].…”

Section: Methodsmentioning

confidence: 99%

Natural killer cell and T-cell subset distributions and activation influence susceptibility to perinatal HIV-1 infection

Gasper

Kunwar

Itaya

et al. 2014

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Objective To determine neonatal immunologic factors that correlate with mother-to-child-transmission of HIV-1. Design This case–control study compared cord blood natural killer (NK) and T-cell populations of HIV-1 exposed infants who subsequently acquired infection by 1 month (cases) to those who remained uninfected by 1 year of life (controls). Control specimens were selected by proportional match on maternal viral load. Methods Cryopreserved cord blood mononuclear cells (CBMCs) were thawed and stained for multiparameter flow cytometry to detect NK and T-cell subsets and activation status. CBMCs were also used in a viral suppression assay to evaluate NK cell inhibition of HIV-1 replication in autologous CD4+ T cells. Results Cord blood from cases contained a skewed NK cell repertoire characterized by an increased proportion of CD16−CD56+ NK cells. In addition, cases displayed less-activated CD16−CD56+ NK cells and CD8+ T cells, based on HLA-DR+CD38+ costaining. NK cell suppression of HIV-1 replication ex vivo correlated with the proportion of acutely activated CD68+CD16−CD56+ NK cells. Finally, we detected a higher proportion of CD27−CD45RA− effector memory CD4+ and CD8+ T cells in cord blood from cases compared with controls. Conclusion When controlled for maternal viral load, cord blood from infants who acquired HIV-1 had a higher proportion of CD16−CD56+ NK cells, lower NK cell activation and higher levels of mature T cells (potential HIV-1 targets) than control infants who remained uninfected. Our data provide evidence that infant HIV-1 acquisition may be influenced by both innate and adaptive immune cell phenotypes and activation status.

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HIV‐1–Specific Cytotoxic T Lymphocytes and Breast Milk HIV‐1 Transmission

Cited by 50 publications

References 37 publications

Breastfeeding Is Associated with Decreased Risk of Hospitalization among HIV-Exposed, Uninfected Kenyan Infants

Breastfeeding Is Associated with Decreased Risk of Hospitalization among HIV-Exposed, Uninfected Kenyan Infants

An African perspective on mucosal immunity and HIV-1

Natural killer cell and T-cell subset distributions and activation influence susceptibility to perinatal HIV-1 infection

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