Early therapy in HIV-1-infected children: Effect on HIV-1 dynamics and HIV-1-specific immune response

Marisa Zanchetta, Alessia Anselmi, Daniela Vendrame, Osvalda Rampon, Carlo Giaquinto, Antonio Mazza, Daniele Accapezzato, Vincenzo Barnaba, Anita De Rossi

Research output: Contribution to journalArticle

Abstract

Background: Perinatal HIV-1 infection is acquired in the milieu of a developing immune system, leading to high levels of uncontrolled viral replication. Few data have been reported that address the viral dynamics and immunological response in infants who initiated aggressive antiretroviral therapy (ART) shortly after birth. Methods: Six HIV-1-infected infants who started ART within 3 months of age were studied. The median follow-up was 61 months. Plasma HIV-1 RNA, cell-associated HIV-1 DNA, unspliced and multiply spliced HIV-1 mRNAs, HIV-1 antibodies, and CD4+ and CD8+ T-cell subsets were assessed in sequential peripheral blood samples. HIV-1 cellular immune response was measured by EliSpot assay. Results: All children showed a decline in plasma viraemia to undetectable levels. HIV-1 DNA persisted in four children, but only two of these had detectable HIV-1 mRNA. All viral parameters remained persistently negative in two children. Only two children produced HIV-1 antibodies, while the others, after having lost maternal antibodies, remained seronegative. No HIV-1 cellular immune response was observed in any child. Therapy interruption was performed in two children: one HIV-1-seropositive and one HIV-1-seronegative with persistently undetectable levels of all viral parameters. Rebound of HIV-1 plasma viraemia in the seronegative child was more rapid and higher than that observed in the seropositive child. Conclusions: Early ART treatment in infants modifies the natural course of infection by controlling HIV-1 replication and reducing viral load to below the threshold levels required for onset of HIV-1 immune response, but does not prevent the establishment of a reservoir of latently infected cells that precludes virus eradication.

Original languageEnglish
Pages (from-to)47-55
Number of pages9
JournalAntiviral Therapy
Volume13
Issue number1
Publication statusPublished - 2008

ASJC Scopus subject areas

  • Pharmacology

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