HIV/AIDS Express Report

9th Conference on Retroviruses and Opportunistic Infections Seattle, Washington

Publication date: 2002-04-01

Retrovirus Conference Highlights on Dosing Simplification, Virologic Response, and Investigational ART Agents

This report was reviewed for medical and scientific accuracy by Susan E. Boruchoff, MD, Associate Professor of Medicine, Division of Allergy, Immunology and Infectious Diseases, UMDNJ-Robert Wood Johnson Medical School, New Brunswick, New Jersey

Introduction

The introduction of highly active antiretroviral therapy (HAART) was a major advance for patients with HIV-1 infection, often changing the prognosis of AIDS from a death sentence to that of a chronically managed disease. Continuing gains in pharmacologic treatment come in small increments, and the current focus of researchers is to develop more simplified treatment regimens and novel agents that will enhance adherence and provide potent viral suppression and immune reconstitution. One of the encouraging studies reported at this meeting demonstrates the potential for a regimen containing once-daily lopinavir/ritonavir (LPV/r; Kaletra®, Abbott Laboratories) in treatment-naïve patients for whom a simplified treatment regimen is preferred.¹ Though preliminary, these are encouraging results for naïve patients in whom a once-daily protease inhibitor is preferred. A second study demonstrated that patients achieve durable viral suppression from LPV/r regardless of baseline CD4 cell count and baseline viral load, while response to nelfinavir is dependent on these two parameters.² Further, LPV/r demonstrated a significantly longer time to loss of virologic response as compared to nelfinavir. Other positive news for patients with HIV-1 infection is that several novel agents in various stages of development hold promise as additional or alternative options in both treatment-naïve and treatment-experienced patients.

Regimen Simplification

LPV/r QD vs. BID

A once-daily LPV/r based regimen achieved similar viral suppression at 48 weeks compared to the standard twice-daily LPV/r-based regimen in antiretroviral (ART)-naïve patients, according to results of a study presented at the meeting.¹ Although this was a small study that included 38 patients, the results suggest that once-daily LPV/r is an option for treatment-naïve patients for whom a once-daily regimen is preferable. Potential benefits of a once-daily regimen include not only dosing simplification but also improved adherence, which is associated with a lower risk of disease progression.^3,4

"Although this study is exploratory and further study is needed, the results are nevertheless encouraging. The study suggests similar efficacy and safety results in treatment-naïve patients taking once-daily Kaletra and twice-daily Kaletra with two NRTIs," said Joseph Eron, MD, Associate Professor of Medicine, University of North Carolina, Chapel Hill, North Carolina, and Director of Clinical Care at the UNC Center for AIDS Research. "The tolerability profile and once-daily dosing of Kaletra may promote patient adherence, a critical factor in achieving long-term viral suppression," he added.

The primary objective of the pilot study (M99-056) was to compare the pharmacokinetics of LPV/r 400/100 mg administered twice daily (n = 19) to LPV/r 800/200 mg administered once daily (n = 19). The once-daily dose involved six capsules of LPV/r taken with food, whereas the twice-daily regimen utilized three capsules per dose taken with food. Patients in each treatment arm also took 2 nucleoside reverse transcriptase inhibitors (NRTIs), d4T (30 mg or 40 mg twice daily) and 3TC (150 mg twice daily). In addition to being ART-naïve, patients' entry criteria included plasma HIV RNA levels > 50 copies/mL with no minimum CD4 cell count.

Pharmacokinetic data showed that the once-daily and twice-daily regimens achieved similar steady state lopinavir C_max (µg/mL) (mean ± standard deviation (SD), 10.94 ± 2.81 vs. 9.81 ± 3.66 , respectively) and 24-hour area-under-the-curve (AUC₂₄) (µg-h/mL) (mean ± SD, 164.9 ± 67.5 vs. 185.2 ± 73.4, respectively). Overall median lopinavir Inhibitory Quotient (IQ) [C