Department of Infectious and Tropical Diseases, La Sapienza University, Rome, Italy.
Received 4 January, 2005
Accepted 26 January, 2005
The long-term success of the current antiretroviral regimens is closely related not only to the intrinsic properties of anti-HIV drugs but also to improvements in the safety, tolerability and convenience of such regimens. In recent years, several simplification/switching strategies have been evaluated with the aim of maintaining virological suppression and CD4 cell response, improving patient adherence and quality of life, and managing or preventing drug toxicity [1,2]. Reported studies have clearly indicated that non-nucleoside reverse transcriptase inhibitor-based regimens are an effective option for virologically suppressed patients switching from a protease inhibitor (PI)-based regimen [3,4]. Switching to a triple nucleoside reverse transcriptase inhibitor (NRTI) combination consisting of abacavir/lamivudine/zidovudine is also a simple and effective regimen associated with improved adherence and blood lipid levels; however, it has been reported to be associated with a high risk of virological failure in patients harbouring NRTI resistance mutations [3,5,6]. A single class quadruple nucleoside/nucleotide reverse transcriptase inhibitor therapy has not been evaluated in simplification/switching strategies for patients with virological suppression on current therapy. In this prospective observational study we evaluated whether a combination of abacavir/lamivudine/zidovudine plus tenofovir could be a safe and effective switching option for virologically suppressed patients switching from a PI-based regimen.
The study population included 21 HIV-infected patients (11 men and 10 women; age, mean years ± SD 43.8 ± 1.64) who had undetectable viral loads (< 50 copies/ml) over the past 12 months of a stable PI-based therapy. All patients were antiretroviral naive at the time of highly active antiretroviral therapy (HAART) initiation. The reason for switching from PI was lipodystrophy in 17 cases and voluntary treatment simplification in the remaining four cases. All patients were treated with a fixed-dose combination of abacavir/lamivudine/zidovudine (two pills twice a day) plus tenofovir (one pill once a day). The previous NRTI backbone included stavudine, zidovudine, didanosine and lamivudine. Patients had not received abacavir or non-nucleoside reverse transcriptase inhibitors. The type of PI in the initial HAART regimen was indinavir in 10 patients and lopinavir/ritonavir in 11 patients. The duration of PI-based regimens before switching was 192 ± 19.03 (mean ± SD) weeks. The nadir of CD4 cell counts was 211 ± 159 cells/μl and the nadir of viral loads was 192 000 ± 59 450 copies/μl. At the time of treatment switch, the CD4 cell count (mean ± SD) was 475 ± 185 cells/μl; the mean levels of cholesterol and triglycerides were within normal ranges (195 and 169 mg/dl, respectively), but 13 patients (61.9%) were receiving lipid-lowering drugs.
After 70.1 ± 5.95 weeks of follow-up during the simplification/switching regimen, the level of viral load remained below 50 copies/ml in all patients studied. The CD4 cell count was 629 ± 190 cells/μl, which represents a significant mean increase of 154 cells/μl (24.4%) compared with pre-switch baseline values (P = 0.002). No significant differences were found in the cholesterol and triglyceride levels. However, the percentage of patients taking lipid-lowering agents declined significantly in comparison with pre-switch therapy (38 versus 61,9%; P < 0.05). No modifications in lipodystrophy were seen. The only side-effects were nausea and dyspepsia, which were seen in five patients. PI-based regimens are highly effective in inducing a durable viral suppression, but are associated with a wide variety of toxic effects, which compromise the success of current antiretroviral drugs. A relevant complication of HAART is the emergence of dyslipidemia, which could increase the risk of cardiovascular diseases in chronically treated patients. Strategies to improve the lipid profile in patients receiving PI by switching to efavirenz, nevirapine or abacavir have been well investigated [3,7]. In addition, preliminary findings have indicated significant lipid improvements for patients who have substituted stavudine with tenofovir . In the present study we have shown that the need for lipid-lowering agents was significantly reduced after switching from PI-containing HAART to a simplified regimen including abacavir/lamivudine/zidovudine plus tenofovir. The lack of improvement in lipodystrophy is probably a result of the short period of follow-up. Current treatment guidelines do not recommend the use of tenofovir in antiretroviral regimens when only combined with NRTI because of the high rate of virological failure with such combinations. Our preliminary data indicate that treatment with a combination of abacavir/lamivudine/zidovudine plus tenofovir after the discontinuation of PI maintains an undetectable viral load and induces a sustained immunological improvement for a period of more than a year. In summary, in the setting of switching/simplified strategies for fully virologically suppressed patients, a compact single-class quadruple nucleoside/nucleotide reverse transcriptase inhibitor regimen of abacavir/lamivudine/zidovudine plus tenofovir may be a safe and attractive treatment option. Larger trials and longer treatment periods will better define the risk of virological failure for this simplified regimen.
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