Loss of Preexisting Immunological Memory Among Human Immunodeficiency Virus–Infected Women Despite Immune Reconstitution With Antiretroviral Therapy

Abstract

It is unclear whether human immunodeficiency virus (HIV) infection results in permanent loss of T-cell memory or if it affects preexisting antibodies to childhood vaccinations or infections. We conducted a matched cohort study involving 50 pairs of HIV-infected and HIV-uninfected women. Total memory T-cell responses were measured after anti-CD3 or vaccinia virus (VV) stimulation to measure T cells elicited after childhood smallpox vaccination. VV-specific antibodies were measured by means of enzyme-linked immunosorbent assay (ELISA). There was no difference between HIV-infected and HIV-uninfected study participants in terms of CD4⁺ T-cell responses after anti-CD3 stimulation (P = .19) although HIV-infected participants had significantly higher CD8⁺ T-cell responses (P = .03). In contrast, there was a significant loss in VV-specific CD4⁺ T-cell memory among HIV-infected participants (P = .04) whereas antiviral CD8⁺ T-cell memory remained intact (P > .99). VV-specific antibodies were maintained indefinitely among HIV-uninfected participants (half-life, infinity; 95% confidence interval, 309 years to infinity) but declined rapidly among HIV-infected participants (half-life; 39 years; 24–108 years; P = .001). Despite antiretroviral therapy–associated improvement in CD4⁺ T-cell counts (nadir, 350/μL after antiretroviral therapy), antigen-specific CD4⁺ T-cell memory to vaccinations or infections that occurred before HIV infection did not recover after immune reconstitution, and a previously unrealized decline in preexisting antibody responses was observed.