There would be many advantages to initiating treatment in treatment-naive patients with regimens containing no nucleosides. Several studies in the past have looked at such treatment strategies with varied results. The question, however, still remains whether this approach will result in treatment that is not just equivalent, or more effective, but also safe.

Marianne Harris from the Canadian HIV Trials Network and an international group from Argentina, Spain, Germany and France looked at this very issue; they compared a nucleoside-sparing regimen with 2 other, more conventional, treatments.

Preliminary 48-week data was presented from this multicenter, international study. Seventy-eight patients were randomized to 3 different groups (2 with NRTIs and 1 without NRTIs), which were compared in terms of efficacy and metabolic parameters. The following are the 3 groups:

• nevirapine (NVP, Viramune) + zidovudine/lamivudine (AZT/3TC, Combivir) (27 patients),

• lopinavir/ritonavir (LPV/r, Kaletra) + zidovudine/lamivudine (24 patients), or

• a nucleoside-sparing regimen of nevirapine + lopinavir/ritonavir (26 patients).

This study is scheduled to continue for a total of 96 weeks.

Seventy-eight percent of the trial participants are male, with a median age of 36 years. Baseline demographic characteristics for these patients were well matched. The mean baseline CD4+ cell count was ~200 cells/mm³ and the viral load was ~4.9 logs in all 3 groups. In terms of efficacy, similar HIV viral load reductions were observed in all 3 groups, with CD4+ cell count increases of 133 cells for the nevirapine + zidovudine/lamivudine arm, 190 cells for the lopinavir/ritonavir arm, and 222 cells for the nevirapine + lopinavir/ritonavir arm.

Nine out of the 26 patients in the nevirapine + lopinavir/ritonavir arm developed adverse events resulting in study discontinuation, with a majority of these dropouts seen in women. There were only 4 additional discontinuations in the other 2 groups (2 in each group).

In terms of the metabolic results seen in this study, there was a statistically significant increase in triglyceride levels in both arms that contained lopinavir/ritonavir; there were no triglyceride elevations seen in the nevirapine + zidovudine/lamivudine arm.

In the nevirapine + lopinavir/ritonavir arm, the nevirapine may have helped counteract the adverse impact of lopinavir/ritonavir on lipids. A favorable change was seen in both HDL cholesterol and the total cholesterol/HDL ratio in both nevirapine arms. Lactate increase was seen in the arm using zidovudine/lamivudine, but not on the NRTI-sparing arm.

This study adds more information to an already accumulating body of data suggesting that these nucleoside-sparing regimens are probably as effective as other conventional treatment with nucleoside backbones. The differences are seen mainly in the side effects profile, specifically in some of the metabolic parameters.

As expected, thymidine-containing nucleoside analogs have been associated with some metabolic complications, including mitochondrial toxicity and hyperlactatemia. On the other hand, many protease inhibitors, including lopinavir/ritonavir, are associated with significant dyslipidemia. Nevirapine on the other hand, has not been associated with either of those complications. So it is not surprising to see that the combination of nevirapine + lopinavir/ritonavir results in a mixed combination of normal and abnormal lipid parameters.

Although the results of this nucleoside-sparing regimen are good and encouraging, this treatment approach is still experimental and should not be considered as a first choice for treatment-naive patients.