Evaluation of the Pathogenesis of Decreasing CD4⁺T Cell Counts in Human Immunodeficiency Virus Type 1–Infected Patients Receiving Successfully Suppressive Antiretroviral Therapy

Abstract

Most human immunodeficiency virus (HIV)–infected individuals experience increases in peripheral CD4+ T cell counts with suppressive antiretroviral therapy (ART) that achieves plasma HIV RNA levels that are less than the limit of detection. However, some individuals experience decreasing CD4+ T cell counts despite suppression of plasma viremia. We evaluated 4 patients with a history of CD4+ T cell decline despite successfully suppressive ART, from a median of 719 cells/mm3 (range, 360–1141 cells/mm3) to 227 cells/mm3 (range, 174–311 cells/mm3) over a period of 18–24 months; 3 of the patients were receiving tenofovir and didanosine, which may have contributed to this decrease. There was no evidence of HIV replication, nor of antiretroviral drug resistance in the blood or lymphoid tissue, or increased proliferation or decreased thymic production of naive CD4+ T cells. All 4 patients had significant fibrosis of the T cell zone of lymphoid tissue, which appeared to be an important factor in the failure to reconstitute T cells.

HIV-Associated Bacterial Pneumonia

“…In the cell cytoplasm, viral RNA is recognized by intracellular pathogen recognition receptors known as Toll-like receptors (TLRs)-7 and -9 [20][21][22][23], and possibly by the more recently described cytoplasmic pathogen nucleic acid sensors [24]. This leads, in turn, to excessive and sustained production of: i) type I interferon (IFN); ii) the tryptophan catabolizing enzyme, indoleamine 2,3-dioxygenase; and iii) the cytokine, transforming growth factor β (TGF-β), all of which contribute to immune dysfunction [20,[25][26][27][28][29][30][31][32][33]. These immunosuppressive mechanisms are summarized in Table 1.…”

“…These immunosuppressive mechanisms are summarized in Table 1. With respect to TGF-β-mediated pro-fibrotic activity, it is noteworthy, that extensive fibrosis of the T cell zone of lymphoid tissue has been proposed to be a significant factor in the failure of T cell reconstitution following initiation of antiretroviral therapy (ART), despite viral suppression [33].…”

Effect of Highly Active Antiretroviral Therapy on T-Cell Sub-population Profile in Human Immunodeficiency Virus-1 Infected Patients

“…In many cases, HAART has lowered viral load to levels that are not detectable by current methods and has improved the health of AIDS patients to the point that they can again function at a normal level [84]. The success of HAART in treating AIDS has opened discussion of whether it might be possible to eradicate all viruses from an infected individual and thus actually cure AIDS.…”

“…The success of HAART in treating AIDS has opened discussion of whether it might be possible to eradicate all viruses from an infected individual and thus actually cure AIDS. Most AIDS experts are not convinced that this is possible, mainly because of the persistence of latently infected CD4 + T cells and macrophages, which can serve as a reservoir of infectious virus if the provirus should be activated [84,85]. Even with a viral load beneath the level of detection by PCR assays, the immune system may not recover sufficiently to clear virus.…”

Du VIH/sida aux tumeurs malignes associées

“…Les souches virales -VIH-1 et VIH-2 -ont une forte affinité pour ces catégories cellulaires qui jouent des fonctions déterminantes dans l'immunorégulation, qu'elle soit humorale (TH2) ou à médiation cellulaire (TH1). La réplication du VIH dans les cellules de l'immunité génère les effets cytopathogènes, les déplétions cellulaires et les phénomènes apoptotiques observés au cours de l'infection [3,17].…”