Efficacy and Safety of a Quadruple Combination Combivir + Abacavir + Efavirenz Regimen in Antiretroviral Treatment-Na´ve HIV-1-Infected Adults: La Francilienne
January 16, 2003
Randomized, controlled clinical trials have demonstrated the therapeutic benefits of triple antiretroviral therapies including a protease inhibitor (PI), a nonnucleoside reverse transcriptase inhibitor (NNRTI), or a nucleoside reverse transcriptase inhibitor (NRTI). Such treatments offer effective, durable control of viral replication, immune restoration, and in some cases delay in the progression to AIDS or death. However, long-term toxicities associated with PI-containing regimens, and potential difficulties with adherence to such therapies, can lead to the development of viral resistance, treatment failure, and limited options for successful subsequent therapy.Adapted from:
The current study, CNAF3008, represents an effort to find PI-sparing, compact and potent regimens to treat ART-naïve adults, and to evaluate long-term safety, tolerance, and efficacy. The study tests a regimen combining three nucleosides, combivir (3TC+ZDV) and abacavir (ABC) with an NNRTI, efavirenz (EFV). The study is a pilot using small patient numbers because of limited prior experience combining abacavir with efavirenz. The researchers performed clinical and biological assessments at baseline and at weeks 2, 4, 8, 16, 24, 32, 40, and 48.
Five women and 26 men, median age 35, enrolled in the study. Median viral load at entry was 4.69 log10 copies/mL (3.1-6.2). Median baseline CD4 cell count was 322 cells/mm (range, 98-858). Eighty-seven percent of patients experienced at least one study-related adverse event (AE); nausea and vomiting were the most common, followed by dizziness/vertigo, malaise and fatigue, skin rashes, and sleep disorders. Subjects reported six serious AEs: five cases of depression, and one of abdominal pain. The authors did not observe definite hypersensitivity reaction to abacavir.
Median cholesterol levels increased significantly, as did fasted glucose. No significant differences were detected for fasting trigyceride measurements. The study did not report any clinical signs or symptoms of lipodystrophy. Patient self-questionnaires reflected a very good adherence level, with 83 percent and 90 percent of participants at weeks 24 and 48, respectively, reporting they had not missed a dose or had missed doses less than once a week in the four preceding weeks.
The study demonstrated that a PI-sparing quadruple regimen can lead to a profound and sustained decline in plasma HIV-1 RNA levels. Participants experienced mild to moderate, expected side effects. The combination of drugs led to profound, rapid decline in VL, with a median reduction of 2.7 log10/copies mL as early as week four.
"All patients who remained on the quadruple regimen of ABC/COM/EFV reached VL<50 copies/mL through 48 weeks, irrespective of baseline VL," the authors wrote. "The results of our pilot study allow the start of larger comparative studies of triple versus quadruple therapy."
Journal of Acquired Immune Deficiency Syndromes
10.01.02; Vol. 31: P. 178-182; Pierre de Truchis; Gilles Force; Yves Welker; Denis Mechali; Mark Pulik; Kadoudja Chemlal; Elisabeth Rouveix; Alain Devidas; Danielle Praindhui; Jean-Philippe Mamet on behalf of the CNAF3008 Group