Effect of Combination Antiretroviral Therapy on T‐Cell Immunity in Acute Human Immunodeficiency Virus Type 1 Infection

Abstract

T-cell responses were evaluated prospectively in 41 patients with acute human immunodeficiency virus type 1 (HIV-1) infection (30 untreated and 11 receiving zidovudine, lamivudine, and indinavir) and in 38 uninfected adults. By 6-12 months, treated patients had significantly greater median Candida and tetanus lymphoproliferative responses (stimulation index [SI], 76 and 55, respectively) than did untreated patients (SI, 7 and 6, P=.02 and.001, respectively), and the responses of treated patients surpassed those of uninfected adults (SI, 19 and 32, P= .002 and .101, respectively). Unlike the patients in the untreated group, the patients in the treated group mounted a 6-fold increased HIV-1 p24 response (SI increase, 1.0 to 5.7, P= .01) within 3 months. HIV-1-specific cytotoxicity remained detectable in most treated patients. Thus, combination therapy administered within 3-4 months of infection was associated with improved T-cell memory responses that were distinct from those of untreated patients. The amplified HIV-1-specific T-cell responses may help maintain cytotoxic activities.

Longitudinal Assessment of Changes in HIV-Specific Effector Activity in HIV-Infected Patients Starting Highly Active Antiretroviral Therapy in Primary Infection

“…The timing of the "point of no return" in terms of the potential to rescue HIV-specific responses is consistent with data generated by Malhotra et al (20,35) using proliferation to HIV-1 Gag p24 as a measure of HIV-specific CD4 ϩ T cell responses. These authors reported that HAART started as late as 137 days after infection could rescue HIV-1 Gag p24 proliferation responses (20,35).…”

“…Delaying HAART initiation beyond the acute phase of infection may allow the breadth and magnitude of HIV-specific CD8 ϩ T cell reactivity to develop to its full potential (19) without losing the advantage of being able to preserve or rescue HIVspecific CD4 ϩ T cell responses (9,11,16,17,20,35). Due to uncertainty as to when a particular individual will reach a stage in disease progression when HIV-specific immunity no longer persists on treatment underlines the advantage to starting therapy as soon as possible after infection in individuals who are negative in the LS-EIA.…”

Early initiation of antiretroviral therapy and universal HIV testing in sub-Saharan Africa: Has WHO offered a milestone for HIV prevention?

“…Patients treated in the first 3 weeks of infection may be able to marshal maximal HIV-specific immune responses to facilitate clearance of this reservoir. [6][7][8] Intra-patient viral diversity ART may become less effective owing to viral mutations that accumulate. Later initiation, at CD4 counts less than 350, may have allowed more mutations.…”

Preservation of T Cell Proliferation Restricted by Protective HLA Alleles Is Critical for Immune Control of HIV-1 Infection

“…Of note, the proliferative capability of CD8 ϩ T cells is impaired in individuals with HIV-1 disease progression but maintained in LTNP (9), and CTL from LTNP also show strong cytolytic activity (10,11). Although loss of proliferative capacity in HIV-specific CD4 ϩ T cells occurs early in infection (12,13), only recent evidence indicates that CD8 ϩ T cells by 1 year of infection become similarly impaired (14). At present, it is unclear whether this is a consequence of sustained high levels of viremia and/or or of the nature of the response induced by specific MHC-restricted epitopes.…”