Correlation of Viral Load and CD8 T-Lymphocytes with Development of Neurological Manifestations in Vertically HIV-1-Infected Infants. A Prospective Longitudinal Study

Abstract

To assess the predictive power of immunological and virological markers for the development of neurological syndromes, 39 HIV-1-infected infants with a mean age of 4.05+/-0.5 months and without neurological manifestations at enrolment were studied. They had neither been previously treated with antiretroviral therapy, nor had their mothers been given such treatment during pregnancy. They were routinely assessed for signs of neurological impairment during follow-up (19.54+/-3.37 months). Cox regression analysis was used to evaluate the risk of appearance of neurological signs, associated to viral load and T-lymphocyte subsets. A HR > 1 for viral load, and <1 for CD8+, but not for CD4+T-lymphocyte percentage, was observed, indicating that higher viral load and lower CD8+ T-lymphocytes percentages are risk factors for developing neurological signs. By applying the Kaplan-Meier method we found that infants with viral load > 5 1og10 copies/ ml or <20% CD8+T lymphocyte had higher relative risk for developing neurological impairment than those with these two parameters below or above these values, respectively. Finally, CD8+ T lymphocyte had a stronger prognostic value to predict neurological manifestations than viral load. Our data strongly suggest that in the early postnatal period viral load and CD8+ percentages are useful markers in predicting neurological impairment. To our knowledge, this is the first time that CD8+ T-lymphocyte levels are related to development of neurological disorders in AIDS.

Low Blood CD8+ T-Lymphocytes and High Circulating Monocytes Are Predictors of HIV-1-Associated Progressive Encephalopathy in Children

“…1 We previously demonstrated in a prospective study that CD8 ϩ T-lymphocyte counts in the first months of life were significantly associated with the risk for emergence of neurologic signs defining probable PE (cognitive deterioration, cerebral atrophy, progressive motor dysfunction, gait disorder, reflex http://www.pediatrics.org/cgi/content/full/111/2/e168 e173 disturbances, abnormal muscle tone, and HIV-1 encephalitis. 15 Of note, there were not differences in confounding factors, particularly equal number of patients exposed to drugs in utero. The most striking result is that among all of the immunologic and virologic variables assessed in this observational study, the only significant difference during the first months of life and before the onset of PE are the CD8 ϩ T-lymphocytes.…”

“…More important, CD8 ϩ T-lymphocytes were a predictive marker for PE independent of the CD4 ϩ Tlymphocyte and viral load (VL). 15 Here, we sought to determine in an observational study whether any immunologic (CD4 ϩ and CD8 ϩ T-lymphocyte counts, monocyte counts) or virologic (VL, biological characteristics of viral isolates) marker might be predictive of PE and whether any particular marker may be involved in the timing of clinical onset of PE. To evaluate this hypothesis, we initially examined the occurrence of PE in a cohort of vertically HIV-1-infected children.…”

Incidence and prevalence of HIV encephalopathy in children with HIV infection receiving highly active anti-retroviral therapy (HAART)

“…22 Gurbindo et al, on the other hand, reported that both VL and lymphocyte count (CD8 more than CD4) were predictive of progression of neurologic impairment. 23 A Spanish study spanning 1984 to 2000 found that only CD8 level in the first month of life was predictive of progression to PHE. 24 The authors speculated that increased CD8 trafficking through the blood-brain barrier could lead to the development of PHE.…”

Neurological and developmental effects of HIV and AIDS in children and adolescents

“…This manifestation has not been reported in young children. The risk of clinical HIV encephalopathy increases with very early age of infection and with high viral loads [Gurbindo et al, 1999]. In vertically transmitted HIV, advanced maternal disease is a risk for encephalopathy in the infant, probably due to high maternal viral loads.…”