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Switch From NNRTI Regimen to Trizivir: viral load & choleserol changes
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"Comparison of metabolic abnormalities 48 weeks after switching from highly active antiretroviral therapy containing a non-nucleoside reverse transcriptase inhibitor to Trizivir versus continued highly active antiretroviral therapy"
AIDS 2003; 17(12):1855-1856
RESEARCH LETTERS
C. Katlamaa; B. Gazzardb; J. Mallolasc; D. Schürmannd; M. Moronie; N. Demontyf; Z. Antoung; D. Gordong. Pitie-Salpetriere Hospital, Paris, France; bChelsea and Westminster Hospital, London, UK; cHospital Clinic i Provincial, Barcelona, Spain; dUniversitatsklinikum Charité, Berlin, Germany; eOspedale Sacco, Milan, Italy; fCHU, Liege; and gGlaxoSmithKline.
Forty patients participating in the TRIZAL study were treated with a non-nucleoside reverse transcriptase inhibitor (NNRTI)-containing regimen before being randomly assigned either to continue their baseline therapy or to switch to a triple nucleoside regimen. No difference was observed in treatment efficacy between the two groups, and total cholesterol was observed to
improve significantly in the switch group. Switch maintenance may be an appropriate strategy in patients treated with an NNRTI.
Highly active antiretroviral therapy (HAART) regimens are effective in reducing viral replication but can be difficult to take, cause significant toxicity and result in metabolic abnormalities. The success of HAART will result in large numbers of patients exposed to these complications over many years, and these adverse events may result in significant morbidity and mortality per se. HAART-related lipid abnormalities are a particular concern because it is clear that these abnormalities result in significant morbidity and mortality in non-HIV populations. Their significance in HIV populations is not established at this time, but it would seem sensible to consider their potential role when selecting
treatment strategies.
Switch maintenance (switching HAART in virologically controlled patients) from protease inhibitor (PI)-containing regimens to triple nucleoside regimens or non-nucleoside reverse transcriptase inhibitor (NNRTI)-containing regimens is
a strategy that has been investigated in several trials. Switching from a PI-containing regimen to triple nucleoside therapy or a nevirapine-containing regimen has been shown to maintain virological control and improve the lipid profile. In contrast, switching the PI to efavirenz maintains virological control but does not improve the lipid profile.
Many patients now initiate treatment with an NNRTI, and these regimens, like PI-containing regimens, can result in lipid abnormalities. Data are required to demonstrate whether switch maintenance from an NNRTI-containing regimen to
a triple nucleoside regimen can similarly improve the lipid profile while maintaining virological control.
TRIZAL is a randomized, open label, multicentre study, which investigated a switch maintenance strategy in patients treated with HAART for at least 6 months with a plasma HIV-1-RNA level of less than 50 copies/ml within 14 days of enrollment. Patients were randomly assigned to remain on their initial HAART regimen or switch to Trizivir (zidovudine, lamivudine, abacavir). Follow-up was for 48 weeks and 209 patients were recruited. Results demonstrated
that Trizivir maintained virological control, reduced total cholesterol and triglycerides, and improved the clinical assessment of lipodystrophy relative to the continued HAART group.
Of the 209 patients participating in the TRIZAL study, 40 were treated with an NNRTI before randomization. Twenty of these patients were randomly assigned to remain on their original NNRTI-containing HAART and 20 switched to
Trizivir.
Of the 20 patients continuing their original HAART, 11 (55%) were taking efavirenz, eight (40%) nevirapine and one (5%) delavirdine. Of the 20 patients who switched to Trizivir, four (20%) were taking efavirenz and 16 (80%)
were taking nevirapine. At 48 weeks, 15 patients (75%) and 13 patients (65%) remained undetectable (< 50 copies/ml) in the Trizivir and NNRTI groups, respectively (P = 0.49). Reduction in fasting total cholesterol was significantly
better in the Trizivir arm than the NNRTI arm at 4 weeks, and this difference was maintained throughout the study. At week 48, total cholesterol reduced by 1.35 mmol/l (-3.18, -0.32), 52 mg/dL, and 0.41 mmol/l (-2.01, 1.33), 15.8 mg/dL, in the Trizivir and NNRTI arms, respectively (P < 0.001). Triglycerides did not change significantly in either group.
These data provide the first evidence that switching to Trizivir from NNRTI results in the maintenance of viraemia control and an improvement in total cholesterol. The induction of therapy with an NNRTI followed by a switch to
Trizivir may provide a good long-term balance of efficacy and tolerability.
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