Abstract
In most HIV-1-infected patients, highly active antiretroviral therapy (HAART) reduces plasma viral load to + T-cell number and function. However, it is still unclear whether alterations of T-cell receptor (TCR) β-chain variable region (BV) repertoire, tightly related to disease progression, can be fully recovered by long-term treatment with HAART. This study analyzed the evolution of both T-cell subset composition and TCRBV perturbations in chronically HIV-1-infected patients with moderate immunodeficiency during 36 months of HAART. Despite persistently suppressed HIV replication, the rate of CD4+ T-cell repopulation, after an initial burst, progressively declined throughout the study period, resulting in a mean CD4+ T-cell count at the end of follow-up that was still significantly lower in HIV patients than in HIV-seronegative controls. This was seen in association with an incomplete restitution of both CD4 and CD8 TCRBV repertoire disruptions and was also demonstrated by the appearance of new TCRBV oligoclonal expansions occurring during HAART. In conclusion, these data indicate that 3 years of fully suppressive HAART may be not adequate to normalize CD4 counts and TCRBV repertoires in patients starting HAART with moderately advanced disease.
| Original language | English |
|---|---|
| Pages (from-to) | 140-154 |
| Number of pages | 15 |
| Journal | Journal of Acquired Immune Deficiency Syndromes |
| Volume | 34 |
| Issue number | 2 |
| DOIs | |
| Publication status | Published - Oct 1 2003 |
Fingerprint
Keywords
- HAART
- HIV-1
- T lymphocytes
- T-cell receptor
ASJC Scopus subject areas
- Immunology
- Virology
Cite this
Persistently biased T-cell receptor repertoires in HIV-1-infected combination antiretroviral therapy-treated patients despite sustained suppression of viral replication. / Giovannetti, Antonello; Pierdominici, Marina; Marziali, Marco; Mazzetta, Francesca; Caprini, Elisabetta; Russo, Giandomenico; Bugarini, Roberto; Bernardi, Maria Livia; Mezzaroma, Ivano; Aiuti, Fernando.
In: Journal of Acquired Immune Deficiency Syndromes, Vol. 34, No. 2, 01.10.2003, p. 140-154.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Persistently biased T-cell receptor repertoires in HIV-1-infected combination antiretroviral therapy-treated patients despite sustained suppression of viral replication
AU - Giovannetti, Antonello
AU - Pierdominici, Marina
AU - Marziali, Marco
AU - Mazzetta, Francesca
AU - Caprini, Elisabetta
AU - Russo, Giandomenico
AU - Bugarini, Roberto
AU - Bernardi, Maria Livia
AU - Mezzaroma, Ivano
AU - Aiuti, Fernando
PY - 2003/10/1
Y1 - 2003/10/1
N2 - In most HIV-1-infected patients, highly active antiretroviral therapy (HAART) reduces plasma viral load to + T-cell number and function. However, it is still unclear whether alterations of T-cell receptor (TCR) β-chain variable region (BV) repertoire, tightly related to disease progression, can be fully recovered by long-term treatment with HAART. This study analyzed the evolution of both T-cell subset composition and TCRBV perturbations in chronically HIV-1-infected patients with moderate immunodeficiency during 36 months of HAART. Despite persistently suppressed HIV replication, the rate of CD4+ T-cell repopulation, after an initial burst, progressively declined throughout the study period, resulting in a mean CD4+ T-cell count at the end of follow-up that was still significantly lower in HIV patients than in HIV-seronegative controls. This was seen in association with an incomplete restitution of both CD4 and CD8 TCRBV repertoire disruptions and was also demonstrated by the appearance of new TCRBV oligoclonal expansions occurring during HAART. In conclusion, these data indicate that 3 years of fully suppressive HAART may be not adequate to normalize CD4 counts and TCRBV repertoires in patients starting HAART with moderately advanced disease.
AB - In most HIV-1-infected patients, highly active antiretroviral therapy (HAART) reduces plasma viral load to + T-cell number and function. However, it is still unclear whether alterations of T-cell receptor (TCR) β-chain variable region (BV) repertoire, tightly related to disease progression, can be fully recovered by long-term treatment with HAART. This study analyzed the evolution of both T-cell subset composition and TCRBV perturbations in chronically HIV-1-infected patients with moderate immunodeficiency during 36 months of HAART. Despite persistently suppressed HIV replication, the rate of CD4+ T-cell repopulation, after an initial burst, progressively declined throughout the study period, resulting in a mean CD4+ T-cell count at the end of follow-up that was still significantly lower in HIV patients than in HIV-seronegative controls. This was seen in association with an incomplete restitution of both CD4 and CD8 TCRBV repertoire disruptions and was also demonstrated by the appearance of new TCRBV oligoclonal expansions occurring during HAART. In conclusion, these data indicate that 3 years of fully suppressive HAART may be not adequate to normalize CD4 counts and TCRBV repertoires in patients starting HAART with moderately advanced disease.
KW - HAART
KW - HIV-1
KW - T lymphocytes
KW - T-cell receptor
UR - http://www.scopus.com/inward/record.url?scp=0141889180&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0141889180&partnerID=8YFLogxK
U2 - 10.1097/00126334-200310010-00004
DO - 10.1097/00126334-200310010-00004
M3 - Article
C2 - 14526203
AN - SCOPUS:0141889180
VL - 34
SP - 140
EP - 154
JO - Journal of Acquired Immune Deficiency Syndromes
JF - Journal of Acquired Immune Deficiency Syndromes
SN - 1525-4135
IS - 2
ER -