Christiana Smith1, Natasha O Moraka2,3, Maryanne Ibrahim4, Sikhulile Moyo2,5, Gloria Mayondi2, Betsy Kammerer6,7, Jean Leidner8, Simani Gaseitsiwe2,5, Shaobing Li1, Roger Shapiro2,5,7,9, Shahin Lockman2,5,7,10, Adriana Weinberg1. 1. University of Colorado School of Medicine, Denver, Colorado, USA. 2. Botswana Harvard AIDS Institute Partnership, Gaborone, Botswana. 3. Stellenbosch University, Stellenbosch, South Africa. 4. Baylor College of Medicine, Houston, Texas, USA. 5. Harvard T.H. Chan School of Public Health, Boston, Massachusetts, USA. 6. Boston Children's Hospital, Boston, Massachusetts, USA. 7. Harvard Medical School, Boston, Massachusetts, USA. 8. Goodtables Data Consulting, Norman, Oklahoma, USA. 9. Beth Israel Deaconess Medical Center, Boston, Massachusetts, USA. 10. Brigham and Women's Hospital, Boston, Massachusetts, USA.
Abstract
BACKGROUND: Human immunodeficiency virus (HIV)-exposed, uninfected (HEU) infants experience high rates of infectious morbidity. We hypothesized that early cytomegalovirus (CMV) infection was associated with increased hospitalization rates and decreased vaccine responses in HEU compared with HIV-unexposed (HUU) infants. METHODS: Among infants enrolled in the Tshipidi study in Botswana, we determined CMV infection status by 6 months of age and compared hospitalization rates and responses to tetanus and Bacille Calmette-Guérin vaccines among HEU and HUU vaccinees. RESULTS: Fifteen of 226 (6.6%) HEU infants and 17 (19.3%) of 88 HUU infants were CMV-infected by 6 months. The HEU infants were approximately 3 times as likely to be hospitalized compared with HUU infants (P = .02). The HEU peripheral blood cells produced less interleukin (IL)-2 (P = .004), but similar amounts of interferon-γ, after stimulation with tetanus toxoid. Antitetanus immunoglobulin G titers were similar between groups. Cellular responses to purified protein derivative stimulation did not differ between groups. Maternal receipt of 3-drug antiretroviral therapy compared with zidovudine was associated with increased IL-2 expression after tetanus toxoid stimulation. The infants' CMV infection status was not associated with clinical or vaccine response outcomes. CONCLUSIONS: We observed that increased rates of hospitalization and decreased memory T-cell responses to tetanus vaccine were associated with HIV exposure and incomplete treatment of maternal HIV infection, but not early CMV infection.
BACKGROUND: Human immunodeficiency virus (HIV)-exposed, uninfected (HEU) infants experience high rates of infectious morbidity. We hypothesized that early cytomegalovirus (CMV) infection was associated with increased hospitalization rates and decreased vaccine responses in HEU compared with HIV-unexposed (HUU) infants. METHODS: Among infants enrolled in the Tshipidi study in Botswana, we determined CMV infection status by 6 months of age and compared hospitalization rates and responses to tetanus and Bacille Calmette-Guérin vaccines among HEU and HUU vaccinees. RESULTS: Fifteen of 226 (6.6%) HEU infants and 17 (19.3%) of 88 HUU infants were CMV-infected by 6 months. The HEU infants were approximately 3 times as likely to be hospitalized compared with HUU infants (P = .02). The HEU peripheral blood cells produced less interleukin (IL)-2 (P = .004), but similar amounts of interferon-γ, after stimulation with tetanus toxoid. Antitetanus immunoglobulin G titers were similar between groups. Cellular responses to purified protein derivative stimulation did not differ between groups. Maternal receipt of 3-drug antiretroviral therapy compared with zidovudine was associated with increased IL-2 expression after tetanus toxoid stimulation. The infants' CMV infection status was not associated with clinical or vaccine response outcomes. CONCLUSIONS: We observed that increased rates of hospitalization and decreased memory T-cell responses to tetanus vaccine were associated with HIV exposure and incomplete treatment of maternal HIV infection, but not early CMV infection.
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