Identification of a Reservoir for HIV-1 in Patients on Highly Active Antiretroviral Therapy

Concepedia

Diana Finzi, Monika Hermankova, Theodore C. Pierson, Lucy M. Carruth, Christopher B. Buck, Richard E. Chaisson, Thomas C. Quinn, Karen Chadwick, Joseph B. Margolick, Ronald Brookmeyer,

Science · 1997 · 3.1K citations · 20 references

DOI

TL;DR

A reservoir of nonevolving latent HIV‑1 in resting CD4⁺ T cells has implications for deciding when to discontinue HAART. The study tested the hypothesis that quiescent CD4⁺ T lymphocytes harbor proviral DNA and constitute a reservoir for HIV‑1 in patients on HAART. Researchers examined 22 patients on HAART for up to 30 months and routinely recovered replication‑competent virus from resting CD4⁺ T lymphocytes. Latent HIV‑1 was present in 0.2–16.4 per million resting CD4⁺ T cells, a frequency that did not decline with time on therapy, and the viruses lacked mutations conferring antiretroviral resistance.

Abstract

The hypothesis that quiescent CD4 + T lymphocytes carrying proviral DNA provide a reservoir for human immunodeficiency virus–type 1 (HIV-1) in patients on highly active antiretroviral therapy (HAART) was examined. In a study of 22 patients successfully treated with HAART for up to 30 months, replication-competent virus was routinely recovered from resting CD4 + T lymphocytes. The frequency of resting CD4 + T cells harboring latent HIV-1 was low, 0.2 to 16.4 per 10 6 cells, and, in cross-sectional analysis, did not decrease with increasing time on therapy. The recovered viruses generally did not show mutations associated with resistance to the relevant antiretroviral drugs. This reservoir of nonevolving latent virus in resting CD4 + T cells should be considered in deciding whether to terminate treatment in patients who respond to HAART.