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• W2065229737 abstract "T S Li and colleagues (June 6, p 1628)1Li TS Tubiana R Katlama C Calvez V Ait Mohand Autran B Long-lasting recovery in CD4 T cell function and viral load reduction after highly active antiretroviral therapy in advanced HIV-1 disease.Lancet. 1998; 351: 1682-1686Summary Full Text Full Text PDF PubMed Scopus (511) Google Scholar report potential immune reconstitution in HIV-1 infected adults treated with Highly Active Anti-Retroviral Therapy (HAART) after sustained suppression of virus replication. There is less information available on immune reconstitution in HAART-treated children. We followed two 7 year-old HIV-1 infected children with AIDS for changes in immune markers during 36 weeks of HAART. Both patients received open-label nelfinavir (25 mg/kg three times daily), lamivudine (4 mg/kg twice daily), and stavudine (1 mg/kg twice daily), and both had 1-year pretreatment on dual antiretroviral therapy. One child (child 1) had previously been ventilated for Pneumocystis carinii pneumonia; she had a viral load of 5·4 log10 (HIV RNA copies/mL); a CD4 count of 233 cells/μL, and was naive for all three drugs at the start of HAART. Child 2 had cerebral toxoplasmosis, with a viral load of greater than 5·9 log10, a CD4 count of 92 cells/μL, and had been on lamivudine and stavudine for 3 months before addition of nelfinavir. Both patients had greater than a 2 log10 reduction in viral load within the first 12 weeks, indicating a good virological response to HAART; CD4 counts rose to 388 cells/μL and 349 cells/μL in the two children during the same period. Increases in the proportion of circulating memory cells within the first month were responsible for the initial improvement in CD4 counts; a significant proportion of these cells were activated as defined by co-expression of HLA-DR. Between weeks 4 and 12, the proportion of circulating naive CD4 cells increased in both patients, which might reflect thymus-dependent regeneration.1Li TS Tubiana R Katlama C Calvez V Ait Mohand Autran B Long-lasting recovery in CD4 T cell function and viral load reduction after highly active antiretroviral therapy in advanced HIV-1 disease.Lancet. 1998; 351: 1682-1686Summary Full Text Full Text PDF PubMed Scopus (511) Google Scholar In child 2, naive cells constituted 75% of the circulating CD4 T cell pool by week 36; at this time her CD4 count had risen to 1000 cells/μL and she was still responding to treatment with a viral load of 3·0 log10. By contrast, child 1 showed no change in total CD4 T cell number or the percentage of circulating naive CD4 T cells between weeks 12 and 36. This situation correlated with a virological relapse, as defined by two consecutive increases of greater than 0·5 log in viral load. The percentage of CD8 T cells in child 2 that expressed CD28 rose from 35% at week 0 to 65% by week 28; low expression of this marker is associated with progressive HIV-1 infection.2Borthwock NJ Bofill M Gombert WM et al.Lymphocyte activation in HIV-1 infection. II. Functional defects of CD28-T cells.AIDS. 1994; 8: 431-441Crossref PubMed Scopus (196) Google Scholar Child 1 had no significant sustained changes in CD28 expression during the 36 week period. N Pakker and colleagues3Pakker NG Notermans DW de Boer RJ et al.Biphasic kinetics of peripheral blood T cells after triple combination therapy in HIV-1 infection: a composite of redistribution and proliferation.Nat Med. 1998; 4: 208-214Crossref PubMed Scopus (642) Google Scholar argued that changes in T cell subgroups in HAART-treated adults exhibit biphasic kinetics: early redistribution of activated memory cells is followed by generation of naive T cells.3Pakker NG Notermans DW de Boer RJ et al.Biphasic kinetics of peripheral blood T cells after triple combination therapy in HIV-1 infection: a composite of redistribution and proliferation.Nat Med. 1998; 4: 208-214Crossref PubMed Scopus (642) Google Scholar In child 2, we observed improvements in the CD4 and CD8 T cell compartments over 6 months consistent with this hypothesis. Our results are also consistent with Li and colleagues who show that adult immune reconstitution requires sustained suppression of HIV-1 replication: child 1 did not show long-lasting improvements in immune markers which coincided with a rebound in viral load. Results from an audit of UK paediatric HIV-1 treatment with HAART indicate that sustained suppression of viral load replication in children is currently difficult to obtain.4Mitchla Z, Sharland M, Delmas N, Gibb D, et al. UK experience of nelfinavir in paediatric HIV-1 infection. 12th World Conference AIDS. Geneva, July, 1998: 12258 (abstr).Google Scholar However, the observation that the ten-fold increase in CD4 counts in child 2 was mainly due to increases in circulating naive T cells raises the possibility that immune reconstitution may occur more rapidly in HIV-infected children than in adults. We thank Sheila Donaghey and Wendy Faulknall. This work was funded by the Roche HIV Focus Group, Welwyn Garden City, Herts, UK." @default.
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• W2065229737 title "Immune reconstitution in HAART-treated children with AIDS" @default.
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• W2065229737 doi "https://doi.org/10.1016/s0140-6736(05)79289-8" @default.
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