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Immunoreconstitution in children receiving highly active antiretroviral therapy depends on the CD4 cell percentage at baseline

Nikolic-Djokic, Divna; Essajee, Shaffiq; Rigaud, Mona; Kaul, Aditya; Chandwani, Sulachni; Hoover, William; Lawrence, Robert; Pollack, Henry; Sitnitskaya, Yekaterina; Hagmann, Stefan; Jean-Philippe, Patrick; Chen, Song He; Radding, Jayme; Krasinski, Keith; Borkowsky, William
The effect of highly active antiretroviral therapy (HAART) in 85 children infected with human immunodeficiency virus type 1 (HIV-1) was compared retrospectively among Centers for Disease Control and Prevention (CDC) immunologic groups 1-3. The duration of HAART did not vary significantly among the immunologic groups (median, 39.07 months). The CD4 cell percentage increased in 39.1%, 58.3%, and 90% of patients in CDC groups 1-3, respectively (P <.001). HAART resulted in the suppression of HIV-1 below detectable levels in 34.8%, 25%, and 32% of patients in the 3 CDC groups, respectively, and in a frequent switch from syncytium-inducing to nonsyncytium-inducing virus. Thymic excision circles increased in a subset of patients with increases in CD4 cell percentage independently of HIV RNA level. The results support the option of delaying HAART in early asymptomatic HIV-1 disease in children and the use of other markers of disease progression, in addition to virus load
PMID: 11807710
ISSN: 0022-1899
CID: 42231

Immunologic and virologic responses to HAART in severely immunocompromised HIV-1-infected children

Essajee SM; Kim M; Gonzalez C; Rigaud M; Kaul A; Chandwani S; Hoover W; Lawrence R; Spiegel H; Pollack H; Krasinski K; Borkowsky W
OBJECTIVE: To determine the long-term immunologic and virologic effects of highly active antiretroviral therapy (HAART) in children with AIDS. DESIGN: A prospective observational study. SETTING: Two pediatric HIV clinics. PARTICIPANTS: Twenty-five protease-inhibitor naive HIV-infected children (aged 2-18 years) with advanced disease (CD4 < or =6%). INTERVENTION: HAART (one protease inhibitor and one or more nucleoside analogs). Diphtheria and tetanus immunization in six patients after 18 months of therapy. MAIN OUTCOME MEASURES: Changes in percentage of CD4 cells and plasma HIV-1 RNA levels; post-treatment assays of lymphoproliferative responses to recall antigens; CD4 cell memory phenotype. RESULTS: Median duration of follow-up was 18.8 months (range, 7.5-28 months). At baseline the CD4 cell percentage was 2% (range, 0-6%), this increased significantly to 16% (range, 3-48%) above baseline at 12 months (P = 0.002). The mean maximum CD4 cell increase was 20.7% (range 4-48%) which corresponds to 657x10(6) cells/l (range, 30-2240x10(6) cells/l) above baseline. By contrast, the median viral load was not significantly lower at 12 months than at baseline (P = 0.34), and only 25% of the patients had sustained undetectable viral load. Of the reconstituted CD4 cells 70% were naive, and none of the subjects had lymphoproliferative responses to tetanus and diphtheria although 40% did develop responses to Candida, an environmental antigen. A single immunization with diphtheria and tetanus toxoid produced lymphoproliferative responses to tetanus in three out of six patients. CONCLUSIONS: HAART was associated with sustained increases in CD4 cell counts, despite a high incidence of 'virologic failure'. CD4 counts and the proportion of naive cells were higher than have been reported in adults, which may be a reflection of greater thymic activity in children. Memory cell clones for antigens encountered in the past which are not prevalent before therapy could not be expanded without additional antigenic exposure
PMID: 10630521
ISSN: 0269-9370
CID: 8585

Early diagnosis of human immunodeficiency virus infection in children less than 6 months of age: comparison of polymerase chain reaction, culture, and plasma antigen capture techniques

Borkowsky W; Krasinski K; Pollack H; Hoover W; Kaul A; Ilmet-Moore T
Three techniques were evaluated for their ability to detect human immunodeficiency virus (HIV) in infants from birth to 6 months of age. Polymerase chain reaction (PCR) and HIV cocultivation were of comparable sensitivity, detecting 90% of all positive specimens. Both techniques found positive results in approximately 5% of samples from seroreverting children. Both assays detected HIV in only half of infected newborns, suggesting that this fraction of children was infected during gestation. Plasma p24 antigen was detected in three-fourths of all samples tested but in only half of infected children during the first 2 months of life and 88% of samples from children during the next 4 months. The specificity of p24 antigen detection was 100%
PMID: 1500744
ISSN: 0022-1899
CID: 13452


Courtlandt, CD; Dreyer, BP; Fierman, AH; Berkowitz, W; Hoover, WS; Arbel, M; Taylor, SD
ISSN: 0002-922x
CID: 32090