Early therapy in HIV-1-infected children: effect on HIV-1 dynamics and HIV-1-specific immune response.
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 followup 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.
Zanchetta
Marisa
M
AIDS Reference Center, Unit of Viral Oncology, Department of Oncology and Surgical Sciences, University of Padova, IOV-IRCCS, Italy.
Anselmi
Alessia
A
Vendrame
Daniela
D
Rampon
Osvalda
O
Giaquinto
Carlo
C
Mazza
Antonio
A
Accapezzato
Daniele
D
Barnaba
Vincenzo
V
De Rossi
Anita
A
D019380:Anti-HIV Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D015496:CD4-Positive T-Lymphocytes; D002675:Child, Preschool; D015658:HIV Infections / Q000188:drug therapy* / Q000276:immunology* / Q000821:virology; D015497:HIV-1 / Q000187:drug effects* / Q000276:immunology* / Q000502:physiology; D006801:Humans; D007223:Infant; D018445:Infectious Disease Transmission, Vertical; D012333:RNA, Messenger / Q000302:isolation & purification; D012367:RNA, Viral / Q000097:blood
D019380:Anti-HIV Agents; D012333:RNA, Messenger; D012367:RNA, Viral