Both CD31⁺and CD31⁻Naive CD4⁺T Cells Are Persistent HIV Type 1–Infected Reservoirs in Individuals Receiving Antiretroviral Therapy

Abstract

After ART, both CD31(+) and CD31⁻ naive CD4(+) T cells expand, and both subsets represent a stable, persistent reservoir of HIV-1.

The HIV-1 reservoir in eight patients on long-term suppressive antiretroviral therapy is stable with few genetic changes over time

“…Previous studies have suggested that cellular proliferation of transitional memory T cells and naïve T cells also maintain the HIV-1 reservoir in patients on suppressive cART, but the evidence was indirect (14,15). We identified a single individual treated during chronic infection whose virus population was enriched for a single clone containing a 380-bp deletion, which essentially eliminated the protease gene.…”

“…In addition to HIV-1 infection in memory T cells, we also detected HIV-1 in isolated naïve T cells from both peripheral blood and GALT, although at much lower frequencies. Despite the low infection frequency and the small percentage that this cellular subset contributes to the total viral reservoir, the long life span of naïve T cells suggest they may still be an important viral reservoir in patients on long-term suppressive cART (15,41). We found evidence that the HIV-1 infection frequencies of cells from peripheral blood were generally higher in patients who initiated therapy during chronic infection compared with patients who initiated therapy during acute/early infection, as has been observed by others (14,42), and extended these findings to confirm similar trends in GALT.…”

“…Central and transitional memory T cells have recently been identified as major contributors to the HIV-1 reservoir in the memory T-cell population (14). Naïve T cells have also been demonstrated to contain HIV-1 DNA in patients on suppressive therapy, although at a lower infection frequency than the memory T-cell population (15). In addition, many other cell types, including monocyte/macrophages, have been proposed to play a role in HIV-1 persistence (reviewed in ref.…”

Persistent Simian Immunodeficiency Virus Infection Drives Differentiation, Aberrant Accumulation, and Latent Infection of Germinal Center Follicular T Helper Cells

“…ϩ T cells in both viremic and suppressed individuals (42)(43)(44). Further, PD-1 NEG CD4 ϩ T cells also contain ϳ70% naive and ϳ30% memory cells, which may explain why RNA levels were so low in the sorted PD-1 LOW subsets in Fig.…”

Establishment and Reversal of HIV-1 Latency in Naive and Central Memory CD4+T CellsIn Vitro

“…This finding indicates that quantification of viral DNA alone is not necessarily predictive of the size of the inducible latent reservoir and suggests caution in labeling a cellular reservoir of latent HIV-1 as "major" based solely on the frequency of infection. In addition to the memory CD4 ϩ T cell subsets, HIV-1 DNA is almost always detected in T N cells in both viremic and suppressed individuals, although with a much lower frequency than in the T CM and T TM compartments (6,7,(10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20)(21). Interestingly, in 2013 Saez-Cirion et al reported that in some HIV-1-infected individuals who received ART within 10 weeks of primary infection, viremia could be controlled for at least 24 months posttreatment interruption (8).…”