Timing of HAART defines the integrity of memory B cells and the longevity of humoral responses in HIV-1 vertically-infected children.
HIV-1 infection induces a progressive disruption of the B cell compartment impairing long-term immune responses to routine immunizations. Depletion of specific memory B cell pools occurs during the 1st stages of the infection and cannot be reestablished by antiretroviral treatment. We reasoned that an early control of viral replication through treatment could preserve the normal development of the memory B cell compartment and responses to routine childhood vaccines. Accordingly, we evaluated the effects of different highly-active antiretroviral therapy (HAART) schedules in 70 HIV-1 vertically-infected pediatric subjects by B cell phenotypic analyses, antigen-specific B cell enzyme-linked immunosorbent spot (ELISpot) and ELISA for common vaccination and HIV-1 antigens. Initiation of HAART within the 1st year of life permits the normal development and maintenance of the memory B cell compartment. On the contrary, memory B cells from patients treated later in time are remarkably reduced and their function is compromised regardless of viral control. A cause for concern is that both late-treated HIV-1 controllers and noncontrollers loose protective antibody titers against common vaccination antigens. Timing of HAART initiation is the major factor predicting the longevity of B cell responses in vaccinated HIV-1-infected children.
Pensieroso
Simone
S
Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Stockholm 171 77, Sweden.
Cagigi
Alberto
A
Palma
Paolo
P
Nilsson
Anna
A
Capponi
Claudia
C
Freda
Elio
E
Bernardi
Stefania
S
Thorstensson
Rigmor
R
Chiodi
Francesca
F
Rossi
Paolo
P
D000293:Adolescent; D000917:Antibody Formation; D023241:Antiretroviral Therapy, Highly Active; D001402:B-Lymphocytes / Q000276:immunology* / Q000821:virology*; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D004334:Drug Administration Schedule; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000276:immunology*; D015497:HIV-1 / Q000276:immunology; D006801:Humans; D007156:Immunologic Memory; D018445:Infectious Disease Transmission, Vertical; D008297:Male