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J Infect Dis. 2019 Dec 23. pii: jiz678. doi: 10.1093/infdis/jiz678. [Epub ahead of print]

Loss of Pre-Existing Immunological Memory among HIV Infected Women Despite Immune Reconstitution with Antiretroviral Therapy.

Author information

1
Division of Neuroscience, Oregon National Primate Research Center, Oregon Health & Science University, Beaverton, USA.
2
Biostatistics Shared Resource, Knight Cancer Institute, Biostatistics & Bioinformatics Core, Oregon National Primate Research Center, Oregon Health & Science University, Portland, USA.
3
Division of Infectious Diseases, Department of Medicine, SUNY Downstate Medical Center, Brooklyn, NY, USA.
4
Department of Medicine, Georgetown University Medical Center, N.W., Washington D.C.
5
Division of Infectious Diseases, Department of Medicine, Weill Cornell Medical College of Cornell University, New York, NY.
6
Department of Pediatrics, Keck School of Medicine of USC, Los Angeles, CA.
7
Department of Epidemiology, Johns Hopkins University Bloomberg School of Public Health, Baltimore, MD.
8
Department of Urology, University of California, San Francisco, San Francisco, CA.
9
Department of Medicine, Cook County Health and Hospitals System, Chicago, IL.

Abstract

BACKGROUND:

It is unclear if HIV infection results in permanent loss of T cell memory or if it impacts pre-existing antibodies to childhood vaccinations/infections.

METHODS:

We conducted a matched cohort study involving 50 pairs of HIV+ and HIV- women. Total memory T cell responses were measured after anti-CD3 stimulation or after vaccinia virus stimulation to measure T cells elicited after childhood smallpox vaccination. Vaccinia-specific antibodies were measured by ELISA.

RESULTS:

There was no difference between HIV+ and HIV- subjects in terms of CD4+ T cell responses after anti-CD3 stimulation (P=0.19) although HIV+ subjects had significantly higher CD8+ T cell responses (P=0.033). In contrast, there was a significant loss in vaccinia-specific CD4+ T cell memory among HIV+ subjects (P=0.039) whereas antiviral CD8+ T cell memory remained intact (P=1.0). Vaccinia-specific antibodies were maintained indefinitely among HIV- subjects (half-life; infinity, 95%CI, 309 years-infinity) but declined rapidly among HIV+ subjects (half-life; 39 years, 95%CI, 24-108 years, P=0.001).

CONCLUSIONS:

Despite ART-associated improvement in CD4+ T cell counts (nadir CD4 <200 cells/mm3 with >350 cells/mm3 after ART), antigen-specific CD4+ T cell memory to vaccinations/infections that occurred before HIV infection did not recover after immune reconstitution and a previously unrealized decline in pre-existing antibody responses was observed.

KEYWORDS:

ART; HIV; antiretroviral therapy; immunological memory; smallpox; vaccination

PMID:
31867597
DOI:
10.1093/infdis/jiz678

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