Project Details

HIV infection in utero and risk of primary KSHV infection in a Kenyan infant prospective cohort

Katherine Sabourin, PhD

Summary

BACKGROUND: Kaposi’s sarcoma (KS), a common pediatric cancer in sub-Saharan Africa with low survival, is associated with earlier Kaposi’s sarcoma-associated herpesvirus (KSHV) infection. HIV exposure in utero is associated with reduced transplacental antibody transfer, a child’s initial defense against infection, and poor childhood health outcomes. GAP: Whether HIV exposure in utero affects anti-KSHV antibody transplacental transfer, subsequent loss of maternally acquired antibodies, and susceptibility to childhood KSHV seroconversion is unknown. HYPOTHESIS: HIV exposure in utero will lead to reduced anti-KSHV antibody transplacental transfer, larger declines in maternally acquired anti-KSHV antibodies in children, and earlier ages of child KSHV seroconversion. METHODS: A prospective cohort of 227 Kenyan mother-child pairs were enrolled. Children born to HIV-positive women were considered HIV exposed in utero. Cord and maternal blood at delivery and child venous blood at ages 6, 12, 18, and 24 months were tested for anti-KSHV antibodies by multiplex immunoassay to 20 KSHV antigens. Multiple linear regression was used to model associations between in utero HIV exposure and anti-KSHV antibody transplacental transfer (defined as cord-to-maternal antibody ratios). Linear mixed effects models were used to identify associations between in utero HIV exposure and decline of maternally acquired anti-KSHV antibodies. Cox proportional hazards were used to model associations between in utero HIV exposure and age of child KSHV seroconversion, defined as first detection of anti-KSHV antibodies. All models will be adjusted for relevant confounders. RESULTS: HIV exposure in utero was significantly associated with decreased transplacental transfer of antibodies against all KSHV antigens explored and with lower cord blood levels for eight antigens. No significant association was seen in changes of anti-KSHV antibody levels from birth to age six-months nor with six-month levels in children by their mother’s HIV status, except for ORF50. KSHV seroconversion occurred in a large proportion of children (74% by age 24 months) but neither overall KSHV seroconversion not time to KSHV seroconversion differed in children exposed or unexposed to HIV in utero. IMPACT: Maternal HIV infection during pregnancy led to reduction in a child’s initial KSHV antibody levels but did not affect age of infection. Elucidating the relationship between HIV and KSHV in sub-Saharan Africa, where both viruses are prevalent, will identify high risk populations and direct future research on KSHV and HIV prevention, vaccination, and treatment in children.

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