HIV‐1‐infected children on HAART: Immunologic features of three different levels of viral suppression

Abstract

Background: HIV-1-infected children show changes of blood lymphocyte subpopulations. We have, therefore, investigated how highly active anti-retroviral therapy (ART) alter these subsets. Blood samples were taken from 41 HIV-1-infected children on ART who were divided into groups showing good, partial and poor responses to ART on the basis of viral load (VL) measurement in blood. The observations were compared to those seen in 20 uninfected children.Methods: The samples were studied using 4-color flow cytometry for ''naïve'', central memory and effector memory cells as well as for CD38 expression as the sign of activation within both the CD4+ and the CD8+ T cell populations. HIV-1 infected children were also evaluated for the presence and the titers of antibodies induced by vaccination against childhood infections in our patients while on HAART.Results: Lymphocyte counts were lower in the \poor" viral load responding (VLR) group when compared with partial and good VLRs. Poor VLRs had lower total and naïve CD4+ T cell counts. HIV-1-infected children from all three groups had high CD8+ T cell counts. Central memory CD4+ and CD8+ T cell percentages were particularly low in the poor VLR group while in the poor VLR group the percentages of effector memory CD4+ and CD8+ T cells were higher when compared with the control group. Higher cellular activation of CD8+ T cells was observed in HIV-1-infected children, particularly when analyzed for the intensity of CD38 expression in the poor VLR group. CD5 expression on B cells was higher among all HIV-1-infected children. Antibodies to tetanus, diphtheria, measles, rubella, and hepatitis B were present in a large proportion of children but the titers were similarly low for all three groups of HIV-infected children.Conclusions: Children with different levels of viral response to HAART present immune phenotype characteristics that tend to place the children with partial and good virological responses into the same group. These children are still moderately deficient in their immune responses but show better recovery than seen with children in the poor VLR group. These observations indicate that the proportions of central memory cells among the CD4+ T cells and the intensity of the expression of CD38 activation antigen on CD8+ T cells provide more informative parameters for monitoring children on HAART than the absolute numbers of CD4+ and CD8+ T cells alone. q

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

“…ZaccarelliFilho et al (15) have also reported high basophil numbers in HIV-infected children. These cells are known to be elevated in conditions associated with Th2 responses (16).…”

Memory B Cell Function in HIV-Infected Children—Decreased Memory B Cells Despite ART

“…Three patients, in whom tetanus toxoid-specific proliferation was measured before booster vaccine, regained specific proliferation indicating an immune reconstitution through effective ART without any booster. Zaccarelli-Filho et al (38) also observed low levels of vaccine specific antibodies in HIV-infected children, whereas other authors also observed good revaccination results concerning tetanus (39), measles, mumps, and rubella (40) and other live attenuated vaccines (41)(42)(43)(44) in most children on ART.…”

Immune reconstitution and vaccination outcome in HIV-1 infected children

“…51 For tetanus and diphtheria toxoids, positive responses are indicated by ELISA with a minimal cut-off of 0.01 IU/mL with optimal levels of 0.1 IU/mL or by LPA with SI above 3. 52,53 numbers of functional memory B-cells in this population including HIV-1 specific responses. [36][37][38][39] However, currently HIV-1 infected children in developing countries do often have access to HAART late in childhood and receive some of the routine immunizations, i. e. against tuberculosis, poliomyelitis, diphtheria, tetanus and pertussis, within the first weeks of life before being treated, most likely, when ongoing HIV-1 replication reaches its highest level.…”

“…53 Duration of HAART has also been shown not to play a major role in relation to vaccine responses to tetanus toxoid. 59 However, we have shown that antibodies to tetanus toxoid remain high (to levels comparable to age-matched healthy individuals) for several years after DTP in children treated with HAART before 1 y of age compared with children also having Many studies on DTP (mostly analyzing immunity to tetanus toxoid) involving re-vaccination of children on HAART are available.…”

“…69 A cut-off of 10 mIU/mL measured by ELISA is indicative of a protective antibody response. 53 Untreated HIV-1 infected children produce lower antibody levels upon HBV vaccination compared with HAART-treated children and age-matched healthy controls. 70,71 Interesting data on the response to HBV vaccines in HIV-1 infected children can be found in relation to re-vaccination and HAART.…”