CCO Independent Conference Coverage of the 2005 Interscience Conference on Antimicrobial Agents and Chemotherapy*

*CCO is an independent medical education company that provides state-of-the-art medical information to healthcare professionals through conference coverage and other educational programs.

Addition of Enfuvirtide (Fuzeon) to 4-Drug Regimen Hastens Initial Viral Decay in Antiretroviral-Naive Patients

• Prospective, open-label, randomized pilot study

Summary of Key Conclusions

• Use of a 5-drug, 4-class regimen comprising tenofovir, lamivudine, efavirenz, lopinavir/ritonavir, and enfuvirtide resulted in significantly faster viral decay and greater decrease in HIV-1 RNA by Day 6 vs the same regimen without enfuvirtide
  • Antiretroviral potency of regimen increased by 22% with addition of enfuvirtide
• Results suggest faster achievement of viral suppression, but additional studies needed to assess clinical utility of this approach

Background

• Initial decreases in HIV-1 RNA with HAART referred to as first-phase viral decay
  • Represents clearance of both free plasma HIV-1 virions and productively HIV-infected CD4+ T lymphocytes
• Prior studies report sharper decline in first-phase viral decay when NNRTIs included in HAART regimens containing NRTIs and PIs
  • HAART efficacy may be enhanced by adding new drugs with different targets and mechanisms (eg, entry inhibitors)
• Current study assessed whether addition of enfuvirtide to 4-drug HAART regimen comprising tenofovir, lamivudine, efavirenz, and lopinavir/ritonavir enhances antiviral potency during first-phase viral decay in treatment-naive patients

Schematic of Study Design

Eligibility

• Inclusion criteria
  • HIV positive
  • Treatment naive
  • HIV-1 RNA > 10,000 copies/mL
  • No evidence of resistance to study drugs

Baseline Characteristics

• Baseline values well balanced between treatment groups

Characteristic	Enfuvirtide + HAART (n = 8)	HAART Alone (n = 7)
Mean HIV-1 RNA, log10 copies/mL (± SD)	4.98 (± 0.38)	5.10 (± 0.49)
Mean CD4+ cell count, cells/mm3 (± SD)	463 (± 306)	362 (± 225)

SD, standard deviation.

Description of Current Analysis

• Plasma HIV-1 RNA assessed at baseline, every 6 hours during first 3 days of treatment, and once daily thereafter until Day 6
• HIV-1 decay rates from Days 1-6 calculated for each individual using nonlinear least squares regression model
• Primary endpoint
  • Rate of first-phase HIV-1 RNA decay

Main Findings

• Use of enfuvirtide, lopinavir/ritonavir, efavirenz, tenofovir, and lamivudine resulted in better virologic outcomes vs use of lopinavir/ritonavir, efavirenz, tenofovir, and lamivudine without enfuvirtide
  • Sharper decline in rate of first-phase viral decay
  • Greater decrease in HIV-1 RNA by Day 6

Outcome	Enfuvirtide + HAART (n = 8)	HAART Alone (n = 7)	P Value
Mean rate of viral decay during Days 1-6, days-1 (± SD)	0.802 (0.127)	0.624 (0.182)	.045
Mean change in HIV-1 RNA from baseline to Day 6, log10 cells/mL (± SD)	-1.72 (0.23)	-1.27 (0.47)	.048
Mean HIV-1 RNA at Day 6, log10 cells/mL (± SD)	3.55 (0.40)	3.92 (0.36)	.079
Relative antiretroviral potency	1	0.778

Reference

Moltó J, Ruiz L, Valle M, et al. Increase antiretroviral (ARV) potency by the addition of enfuvirtide (ENF) to a four drug regimen in ARV naive HIV-infected patients. Program and abstracts of the 45th Annual Meeting of the Interscience Conference on Antimicrobial Agents and Chemotherapy; December 16-19, 2005; Washington, DC. Abstract H-528.

©2005 Clinical Care Options, LLC.