October 29, 2001
The MAINTAVIR trial is a multicenter, prospective, observational study of sixty-two HIV-1 infected patients who were NNRTI naive, but had been receiving a protease inhibitor-containing HAART regimen for >12 months prior to study entry and for one or more reasons desired to change therapy.
All of the patients had a plasma viral load <400 copies/mL for >6 previous months and had a viral load <200 copies/mL at the time of enrollment. The patients were switched from their protease inhibitor (indinavir, ritonavir, nelfinavir, saquinavir or ritonavir/saquinavir) to a NNRTI, either nevirapine (NVP), with the standard two-week lead-in dosing of 200mg daily for two weeks then 400mg per day (54 patients), or efavirenz (EFV) 600mg daily (8 patients).
There is no explanation as to the determination of which NNRTI the patient received. The other components of their HAART were not altered, specifically two NRTIs: ZDV and 3TC (35 patients); d4T and ddI (7 patients); d4T and 3TC (18 patients); ZDV and ddI (2 patients) were continued following the protease inhibitor to NNRTI switch. Monthly follow-up consisted of questions regarding tolerance and evaluation of CD4+ T cell counts and HIV-1 RNA plasma loads. The triglyceride and total cholesterol levels were assessed in most patients at time of enrollment and at six months (no mention as to which patients were not evaluated or why). The endpoint of the study was virologic failure defined as viral rebound of >200 copies/mL on two consecutive occasions, one month apart. Those who experienced a viral rebound reverted to a protease inhibitor-containing regimen, either their previous regimen or an alternative one, with the maintenance of the same NRTIs.
The patients were subdivided into two groups: group A were antiretroviral-naive prior to receiving HAART (27 patients) and group B were non-naive patients who had received treatment with antiretroviral therapy before their current protease inhibitor-containing HAART (35 patients). In groups A and B, 11.1% and 25.7%, respectively, of the patients experienced virologic breakthrough within 24 months of the protease inhibitor to NNRTI switch (p<0.05). An intercurrent infection was present in five and nonadherence in three of the twelve patients who experienced virologic failure.
In addition to overall virologic maintenance, there was a statistically significant increase in mean CD4 cell count at 24 months of 177 cells/mm3. The mean triglyceride and cholesterol levels significantly decreased within six months in 35 patients and 19 patients, respectively, and were maintained at this lower level for 24 months. This data was not subdivided into groups or by whether the patients were receiving EFV or NVP as their NNRTI. The authors admit there was no objective determination of lipodystrophy, although of the 16 patients determined to have severe lipodystrophy at the time of enrollment, there was a subjective improvement in seven of these patients and a new emergence of lipodystrophy in three patients. A total of five patients discontinued treatment due to NNRTI intolerance: four in the NVP arm (two persistent myalgias, one severe rash and one hepatotoxicity) and one in the EFV arm (insomnia and vertigo on day three of EFV treatment). Of the 12 patients who had virologic failure, six were switched to their original protease inhibitor regimen and six received a new protease inhibitor regimen, with all maintaining the same NRTIs. All 12 patients achieved undetectable plasma viral loads within four weeks and at a mean of 27 months follow-up, 10 of these patients had viral loads <200 copies/mL.
The authors conclude: "this strategy has several theoretical advantages, including sparing protease inhibitors for future use . . . NNRTI regimens are simpler, generally well tolerated, more convenient for the patient thus facilitating improved adherence to the drug regimen." Furthermore, "the MAINTAVIR study demonstrates that NNRTIs are suitable candidates for use in patients who have achieved virological suppression with a PI-regimen but who wish to change therapies for reasons of toxicity or adherence." While the overall results of this study are certainly encouraging regarding the effectiveness of switching from a suppressive protease inhibitor-based HAART to a better tolerated, less toxic NNRTI-based HAART, the higher failure rate in the treatment-experienced patients is of some concern; however, it has not been shown to occur in other switch trials and all patients were subsequently re-suppressed when they returned to a protease inhibitor-based regimen. Thus, this finding may be related to other factors (as mentioned above) and not be terribly significant, but probably should be given some consideration when making a decision regarding switching therapy.
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