Early therapy of vertical human immunodeficiency virus type 1 (HIV-1) infection: control of viral replication and absence of persistent HIV-1-specific immune responses

Abstract

Studies of potent antiretroviral combination regimens were undertaken in young infants to evaluate the potential for long-term suppression of viral replication and to evaluate the immune consequences of such therapies. Early combination antiretroviral therapy led to a loss of plasma viremia, cultivable virus, and labile extrachromosomal replication intermediates. Despite preservation of immune function, persistent human immunodeficiency type 1 (HIV-1)-specific immune responses were not detected in most infants. The absence of detectable, persisting immune responses in most HIV-1-infected infants treated early contrasts with what is typically seen in adults who are treated early. These results are consistent with the notion that early combination antiretroviral therapy of HIV-1-infected infants allows the long-term suppression of viral replication.

Figures

FIG. 1

Peripheral blood HIV-1 load and CD4 T-lymphocyte percentages (A and C) and HIV-1-specific immune responses (B and D) in two children (P-3743 [A and B] and P-3742, [C and D]) with prolonged suppression of HIV-1 replication following early antiretroviral therapy.

FIG. 2

HIV-1-specific antibodies measured by ELISA in plasma from infants with durable (>48 weeks; n = 15; A) or incomplete/transient (n = 4; B) suppression of HIV-1 replication following early antiretroviral therapy. HIV-1-specific antibodies measured by ELISA in plasma from HIV-1-uninfected infants born to HIV-1-infected women are depicted in panel C (n = 5); HIV-1 antibodies measured in the plasma of HIV-1-infected infants who did not receive therapy over the first 12 months of life are depicted in panel D (n = 4).

FIG. 3

HLA A∗0201/Gag p17 tetramer staining of PBMC obtained prior to therapy (day 0) and at weeks 24 and 68 of therapy from an infant (P-1228) with durable control of HIV-1 replication (>96 weeks) after initiating ZDV/3TC/NVP therapy at 1 month of age. An HLA A∗0201-restricted, epitope-specific CTL line derived from an adult long-term nonprogressor was used as a positive control (53% of cells stained with tetramer; upper left).

FIG. 4

HLA A∗0201/HIV Gag p17, (A2-gag), HLA A∗0201/HIV RT (A2-pol), or HLA A∗0201/EBV BMLF1 (A2-EBV) tetramer staining of PBMC obtained at 56 weeks of therapy from HIV-1 infected, EBV-seropositive infant P-1252.