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

• Published in: Journal of the International AIDS Society Vol. 17; no. 4 Suppl 3; pp. 19776 - n/a
• Main Authors: Maggiolo, Franco, Masini, Giulia, Astuti, Noemi, Di Filippo, Elisa, Benatti, Simone, Valenti, Daniela, Callegaro, Anna Paola, Rizzi, Marco
• Format: Journal Article
• Language: English
• Published: Switzerland International AIDS Society 01-11-2014; John Wiley & Sons, Inc
• Subjects: Acquired immune deficiency syndrome; AIDS; Antiretroviral drugs; Antiviral agents; Dosage and administration; Drug therapy; Drug therapy, Combination; HIV; HIV infection; Human immunodeficiency virus; Measurement; Medical research; Medicine, Experimental; Patient outcomes; Viremia; Italy
• ISSN: 1758-2652; 1758-2652
• DOI: 10.7448/IAS.17.4.19776

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.