Long-term effect of a four-drugs induction regimen for patients with high baseline viral load

INTRODUCTION: The long-term effects of an intensified induction regimen are unknown. In this pilot, randomized, prospective study we evaluate the effect of a short-term four-drugs induction regimen in patients with high baseline viral load. METHODS: Naive patients with HIV-RNA>100.000 copies/ml r...

Descripción completa

Detalles Bibliográficos
Autores principales: Maggiolo, Franco, Masini, Giulia, Astuti, Noemi, Di Filippo, Elisa, Benatti, Simone, Valenti, Daniela, Callegaro, Anna Paola, Rizzi, Marco
Formato: Online Artículo Texto
Lenguaje:English
Publicado: International AIDS Society 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4225274/
https://www.ncbi.nlm.nih.gov/pubmed/25397520
http://dx.doi.org/10.7448/IAS.17.4.19776
_version_ 1782343474093228032
author Maggiolo, Franco
Masini, Giulia
Astuti, Noemi
Di Filippo, Elisa
Benatti, Simone
Valenti, Daniela
Callegaro, Anna Paola
Rizzi, Marco
author_facet Maggiolo, Franco
Masini, Giulia
Astuti, Noemi
Di Filippo, Elisa
Benatti, Simone
Valenti, Daniela
Callegaro, Anna Paola
Rizzi, Marco
author_sort Maggiolo, Franco
collection PubMed
description INTRODUCTION: The long-term effects of an intensified induction regimen are unknown. In this pilot, randomized, prospective study we evaluate the effect of a short-term four-drugs induction regimen in patients with high baseline viral load. METHODS: Naive patients with HIV-RNA>100.000 copies/ml receiving TDF+FTC+EFV+RAL (group ER) for 4 months and were then simplified to TDF+FTC+EFV. Two randomized control groups treated ab-initio with TDF+FTC+EFV (E) or TDF+FTC+RAL (R) were used. RESULTS: 19 patients with a mean age of 38 years and mean baseline CD4 count of 334 (SD 216) cells/mcL and HIV-RNA of 5.47 log (SD 0.32) copies/mL were enrolled. No baseline significant difference was observed among groups. Early HIV-RNA reduction was significantly higher in ER compared to the other groups from week 1 to week 4 (P from 0.026 to 0.003) (figure 1), thereafter HIV-RNA values were comparable among the groups. At week 96, all patients had an HIV-RNA < 50 copies/mL, however only patients in the ER group had in all cases an HIV-RNA level < 3 copies/mL with a statistically significant difference compared to E (60%; P=0.038) and R (50%; P=0.020). At 96 weeks, CD4 cell median counts were 765 cells/mcL for ER, 600 cells/mcL for E and 771 for R (P=0.16), however patients in the ER group presented a lower proportion of activated CD4+CD38+HLADR+ cells (1.9% versus 3.9 and 3.8%) and CD8+CD38+HLADR+ cells (10.3% versus 16.8 and 16.5%) and a significantly better CD4/CD8 ratio (0.98 versus 0.53 and 0.61; P=0.03). CONCLUSIONS: A four-drug regimen in naive patients with high pre-therapy viral load improves early virologic response. A quick drop of HIV-RNA seems to correlate with a sustained virologic response. Although limited in time (four months), the four-drug regimens correlates with an improved immunological response as measured by the CD4/CD8 ratio or the percentage of activated CD4+ and CD8+ cells. The reasons why this happens deserve further studies. This study highlights the importance of a personalised therapy especially in high risk patients.
format Online
Article
Text
id pubmed-4225274
institution National Center for Biotechnology Information
language English
publishDate 2014
publisher International AIDS Society
record_format MEDLINE/PubMed
spelling pubmed-42252742014-11-12 Long-term effect of a four-drugs induction regimen for patients with high baseline viral load Maggiolo, Franco Masini, Giulia Astuti, Noemi Di Filippo, Elisa Benatti, Simone Valenti, Daniela Callegaro, Anna Paola Rizzi, Marco J Int AIDS Soc Poster Sessions – Abstract P244 INTRODUCTION: The long-term effects of an intensified induction regimen are unknown. In this pilot, randomized, prospective study we evaluate the effect of a short-term four-drugs induction regimen in patients with high baseline viral load. METHODS: Naive patients with HIV-RNA>100.000 copies/ml receiving TDF+FTC+EFV+RAL (group ER) for 4 months and were then simplified to TDF+FTC+EFV. Two randomized control groups treated ab-initio with TDF+FTC+EFV (E) or TDF+FTC+RAL (R) were used. RESULTS: 19 patients with a mean age of 38 years and mean baseline CD4 count of 334 (SD 216) cells/mcL and HIV-RNA of 5.47 log (SD 0.32) copies/mL were enrolled. No baseline significant difference was observed among groups. Early HIV-RNA reduction was significantly higher in ER compared to the other groups from week 1 to week 4 (P from 0.026 to 0.003) (figure 1), thereafter HIV-RNA values were comparable among the groups. At week 96, all patients had an HIV-RNA < 50 copies/mL, however only patients in the ER group had in all cases an HIV-RNA level < 3 copies/mL with a statistically significant difference compared to E (60%; P=0.038) and R (50%; P=0.020). At 96 weeks, CD4 cell median counts were 765 cells/mcL for ER, 600 cells/mcL for E and 771 for R (P=0.16), however patients in the ER group presented a lower proportion of activated CD4+CD38+HLADR+ cells (1.9% versus 3.9 and 3.8%) and CD8+CD38+HLADR+ cells (10.3% versus 16.8 and 16.5%) and a significantly better CD4/CD8 ratio (0.98 versus 0.53 and 0.61; P=0.03). CONCLUSIONS: A four-drug regimen in naive patients with high pre-therapy viral load improves early virologic response. A quick drop of HIV-RNA seems to correlate with a sustained virologic response. Although limited in time (four months), the four-drug regimens correlates with an improved immunological response as measured by the CD4/CD8 ratio or the percentage of activated CD4+ and CD8+ cells. The reasons why this happens deserve further studies. This study highlights the importance of a personalised therapy especially in high risk patients. International AIDS Society 2014-11-02 /pmc/articles/PMC4225274/ /pubmed/25397520 http://dx.doi.org/10.7448/IAS.17.4.19776 Text en © 2014 Maggiolo F et al; licensee International AIDS Society http://creativecommons.org/licenses/by/3.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Poster Sessions – Abstract P244
Maggiolo, Franco
Masini, Giulia
Astuti, Noemi
Di Filippo, Elisa
Benatti, Simone
Valenti, Daniela
Callegaro, Anna Paola
Rizzi, Marco
Long-term effect of a four-drugs induction regimen for patients with high baseline viral load
title Long-term effect of a four-drugs induction regimen for patients with high baseline viral load
title_full Long-term effect of a four-drugs induction regimen for patients with high baseline viral load
title_fullStr Long-term effect of a four-drugs induction regimen for patients with high baseline viral load
title_full_unstemmed Long-term effect of a four-drugs induction regimen for patients with high baseline viral load
title_short Long-term effect of a four-drugs induction regimen for patients with high baseline viral load
title_sort long-term effect of a four-drugs induction regimen for patients with high baseline viral load
topic Poster Sessions – Abstract P244
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4225274/
https://www.ncbi.nlm.nih.gov/pubmed/25397520
http://dx.doi.org/10.7448/IAS.17.4.19776
work_keys_str_mv AT maggiolofranco longtermeffectofafourdrugsinductionregimenforpatientswithhighbaselineviralload
AT masinigiulia longtermeffectofafourdrugsinductionregimenforpatientswithhighbaselineviralload
AT astutinoemi longtermeffectofafourdrugsinductionregimenforpatientswithhighbaselineviralload
AT difilippoelisa longtermeffectofafourdrugsinductionregimenforpatientswithhighbaselineviralload
AT benattisimone longtermeffectofafourdrugsinductionregimenforpatientswithhighbaselineviralload
AT valentidaniela longtermeffectofafourdrugsinductionregimenforpatientswithhighbaselineviralload
AT callegaroannapaola longtermeffectofafourdrugsinductionregimenforpatientswithhighbaselineviralload
AT rizzimarco longtermeffectofafourdrugsinductionregimenforpatientswithhighbaselineviralload