Imbalance of naive and memory T lymphocytes with sustained high cellular activation during the first year of life from uninfected children born to HIV-1-infected mothers on HAART

The immune consequences of in utero HIV exposure to uninfected children whose mothers were submitted to highly active antiretroviral therapy (HAART) during gestation are not well defined. We evaluated 45 HIV-exposed uninfected (ENI) neonates and 45 healthy unexposed control (CT) neonates. All HIV-infected mothers received HAART during pregnancy, and the viral load at delivery was <50 copies/mL for 56.8 percent. Twenty-three ENI neonates were further evaluated after 12 months and compared to 23 unexposed healthy age-matched infants. Immunophenotyping was performed by flow cytometry in cord and peripheral blood. Cord blood lymphocyte numbers did not differ between groups. However, ENI neonates had a lower percentage of naive T cells than CT neonates (CD4+, 76.6 vs 83.1 percent, P < 0.001; CD8+, 70.9 vs 79.6 percent, P = 0.003) and higher percentages of central memory T cells than CT neonates (CD4+, 13.9 vs 8.7 percent, P < 0.001; CD8+, 8.6 vs 4.8 percent, P = 0.001). CD38 mean fluorescence intensity of T cells was higher in ENI neonates (CD4+, 62.2 vs 52.1, P = 0.007; CD8+, 47.7 vs 35.3, P < 0.001). At 12 months, ENI infants still had higher mean fluorescence intensity of CD38 on T cells (CD4+, 34.2 vs 23.3, P < 0.001; CD8+, 26.8 vs 19.4, P = 0.035). Despite effective maternal virologic control at delivery, HIV-exposed uninfected children were born with lower levels of naive T cells. Immune activation was present at birth and remained until at least 12 months of age, suggesting that in utero exposure to HIV causes subtle immune abnormalities.

The mortality of infants and children born to HIV-infected mothers.

A retrospective study was made on seventy-one infants and children born to HIV-1 infected mothers, who admitted and expired at Department of Pediatrics, Siriraj Hospital from September 1991 to August 1995. Sixty-three were diagnosed to be HIV infected and 8 were undetermined. In the group of undetermined HIV-infection, the causes of death included sepsis, prematurity, pneumonia and congenital heart disease. Among the 63 of HIV-infected group, 25 (40%) died before age 6 months, 36 (57%) and diarrhea 29 (46%). Other causes of death included gastrointestinal heamorrhage, congestive heart failure, candida esophagitis, wasting syndrome and liver failure. P.carinii was identified in 5 cases (12.2%) among the group of children who died with pneumonia. Of 36 children who died with sepsis, the etiologic agent were confirmed by blood culture 29 (80.5%). A single pathogen was isolated in 18 cases (62%) whereas multiple pathogens were isolated in 10 cases (38%) and only 1 yielded Candida albican. Gram-positive bacteria was identified in 11 cases (38%) which 8 cases (73%) of S.aureus were the most common isolated bacteria. Gram negative bacteria were confirmed in 22 cases (62%) of which 7 cases (32%) of salmonella species were the most frequent isolated bacteria. In the group of children who died of diarrhea, the causative agents wee identified in 12 cases (43%) by which 8 cases (66%) of cryptosporidium and 6 cases (50%) of salmonella species were the most common isolated pathogens. Among the 63 of HIV-infected children, 20 (32%) were the first admitted group and pneumonia 17 (85%) was found to be the most common cause of death.