Human Immunodeficiency Virus Exposure but Not Early Cytomegalovirus Infection Is Associated With Increased Hospitalization and Decreased Memory T-Cell Responses to Tetanus Vaccine

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.

Premature skewing of T cell receptor clonality and delayed memory expansion in HIV-exposed infants

“…Although studies conducted before the wide adoption of perinatal ARV treatment reported heightened immune activation and/or exhaustion in iHEU 48 , 49 , more recent studies have shown reduced or impaired memory T cells among iHEU compared to iHUU 17 , 50 – 52 . Such T cell alterations were associated with poor responses to vaccines and/or increased hospitalisation 50 , 51 . Other viral infections occurring during pregnancy such as SARS-Cov2 have also been documented to alter infant immunity even in the absence of viral transmission 53 , 54 .…”

Cytomegalovirus as an Uninvited Guest in the Response to Vaccines in People Living with HIV

“…In infants with antenatal or postnatal CMV infection, studies have also evaluated the effect of CMV on response to vaccines, especially in poor-resource settings where the majority of children are infected before their first year of life [ 73 ]. CMV-induced alterations of immune response to measles and to a lesser extent to polio vaccines have been reported, whereas no difference in the response to Hib or tetanus vaccines were reported [ 74 , 75 ]. Interestingly, a study evaluating the immune response to oral polio vaccine in Zambian infants suggested a synergistic negative effect of HIV and CMV coinfection on the antibody response [ 76 ].…”

Вплив Герпесвірусної Інфекції На Показники Імунної Відповіді Дітей, Хворих На Ротавірусний Гастроентерит

“…Однак висновки дослідників відносно впливу герпесвірусної інфекції на імунну відповідь далеко не однозначні. На думку одних авторів, в інфікованих герпесвірусами осіб гальмується реакція імунної системи [6,7], натомість ряд інших дослідників схиляється до думки, що герпесвіруси навпаки мають імуномоделювальний ефект [4,8,9]. Суперечливість даних простежується в доступній літературі і стосовно реакції інтерлейкінів крові дітей, інфікованих і неінфікованих герпесвірусами [10,11].…”