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Previous Volume 349:1036-1046 September 11, 2003 Number 11 Next

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ABSTRACT

Background We assessed the strategy of substituting nevirapine, efavirenz, or abacavir for a protease inhibitor in patients infected with human immunodeficiency virus type 1 (HIV-1) in whom virologic suppression had been achieved.

Methods We randomly assigned 460 adults who were taking two nucleoside reverse-transcriptase inhibitors and at least one protease inhibitor and whose plasma HIV-1 RNA levels had been less than 200 copies per milliliter for at least the previous six months to switch from the protease inhibitor to nevirapine (155 patients), efavirenz (156), or abacavir (149). The primary end point was death, progression to the acquired immunodeficiency syndrome, or an increase in HIV-1 RNA levels to 200 copies or more per milliliter.

Results At 12 months, the Kaplan–Meier estimates of the likelihood of reaching the end point were 10 percent in the nevirapine group, 6 percent in the efavirenz group, and 13 percent in the abacavir group (P=0.10 according to an intention-to-treat analysis). HIV-1 RNA could be amplified in 21 of the 29 patients in whom virologic failure developed during treatment with study medication (72 percent), and resistance mutations to the study medication and to at least one of the nucleoside reverse-transcriptase inhibitors in the regimen that failed were detected in all but 1 of the 21 patients. Twenty-three of the 29 patients with virologic failure during treatment with study medication had received prior suboptimal therapy with nucleoside reverse-transcriptase inhibitors. Fewer patients in the abacavir group (6 percent) than in the nevirapine group (17 percent) or the efavirenz group (17 percent) discontinued the study medication because of adverse events (P=0.01). The proportion of patients with fasting lipid levels warranting therapeutic intervention decreased significantly in the abacavir group, but the prevalence of clinical lipodystrophy did not change significantly in the three groups.

Conclusions When therapy was switched from a protease inhibitor to nevirapine, efavirenz, or abacavir in patients with virologic suppression, there was a trend toward a higher rate of virologic failure among those given abacavir.

Source Information

From the Hospital Clínic, Barcelona (E.M., J.A.A., A.C., E.L., J.M.G.); Hospital de Bellvitge, L'Hospitalet (D.P.); Hospital de Mútua de Terrassa, Terrassa (D.D.); Hospital de Vall d'Hebrón, Barcelona (E.R.); Hospital de la Santa Creu i Sant Pau, Barcelona (P.D.); Hospital del Mar, Barcelona (H.K.); Hospital Son Dureta, Palma de Mallorca (M.R.); Hospital General de Granollers, Granollers (E.P.); Hospital de Mataró, Mataró (L.F.); Hospital Sant Jaume, Calella (J.M.L.); Hospital Parc Taulí, Sabadell (F.S.); Hospital Joan XXIII–Universitat Rovira i Virgili, Tarragona (C.R.); Hospital Creu Roja, L'Hospitalet (C.C.); Hospital de Viladecans, Viladecans (M.J.); and Hospital de Terrassa, Terrassa (M.A.) — all in Spain.

Address reprint requests to Dr. Martinez at the Infectious Diseases Unit, Hospital Clinic–Institut d'Investigacions Biomediques August Pi i Sunyer, University of Barcelona, Villarroel 170, 08036 Barcelona, Spain, or at esteban{at}fundsoriano.es.

Full Text of this Article

Related Letters:

Substitution for Protease Inhibitors in HIV Therapy
Hirschel B., Mikhail E., Martínez E., de Lazzari E., Gatell J. M.
Extract | Full Text | PDF  
N Engl J Med 2003; 349:2460-2461, Dec 18, 2003. Correspondence

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