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Long-term safety and efficacy of nevirapine, stavudine and lamivudine in a real-world setting

Shalit, Peterab; Farrell, Patab; Lindgren, Pamelaa

Research Letters

aSwedish Medical Center/Seattle, Washington, USA: and bUniversity of Washington/Seattle, Washington, USA.

Received: 19 September 2000;

revised: 5 January 2001; accepted: 10 January 2001.

Recent studies have demonstrated the efficacy of protease inhibitor-sparing regimens including non-nucleoside reverse transcriptase inhibitors (NNRTI) in treatment-naive patients [1–3]. Long-term side-effects of protease inhibitors, including lipodystrophy and hyperlipidemia, as well as their often complicated dosing regimens, have led to considerable interest in the use of the NNRTI as first-line therapy. To date, however, only limited clinical trial data have been presented that demonstrate long-term virological suppression with this class of agent [4].

The purpose of this community-based study, therefore, was to investigate the long-term safety and efficacy of a regimen of nevirapine, stavudine and lamivudine in a real world setting. Twenty-six treatment-naive patients were prospectively enrolled in a study of a highly active antiretroviral therapy regimen of nevirapine, stavudine and lamivudine at a community-based clinic. The median age of the group was 43 years (range 25–66), 25 of the patients were men. The median baseline viral load was 38 138 copies/ml (range 4846–212 852 copies/ml), and the median baseline CD4 cell count was 360 cells/mm3 (range 98–920 cells/mm3). The mecian length of time to follow-up was 31 months (range 8–40 months). Ninety-two per cent (24/26) had viral loads of less than 50 copies/ml at their last visit, with one patient having a viral load of 657 copies/ml, and one being off medication. This group of patients maintained a viral load of less than 50 copies/ml for a mean of 19 months (range 7–38 months). Thirteen of these patients had been virologically suppressed for over 2 years at latest follow-up. The median CD4 cell count at the last follow-up was 575 cells/mm3. The regimen of nevirapine, stavudine and lamivudine, therefore, provided a potent and durable response in this population.

This regimen also proved to be remarkably well tolerated, with reports of two cases of peripheral neuropathy secondary to stavudine, but no nevirapine-associated clinical side-effects. Some slight elevations in transaminase levels were observed after initiating therapy; serum glutamic-oxaloacetic transaminase increased from 26.6 to 28.7 U/l, and serum glutamate-pyruvate transaminase increased from 25.8 to 38.6 U/l. However, transaminase levels did not increase in any individual to greater than two times the upper limit of normal at any point, and were not clinically relevant.

This simple nevirapine-based combination regimen of three tablets twice a day, with no food restrictions, provided durable virological suppression for up to 38 months in a community-based cohort of treatment-naive patients. Highly active antiretroviral therapy containing nevirapine can, therefore, be effectively used as a long-term protease inhibitor-sparing regimen. No loss of virological control was seen in this cohort, reducing concerns for the emergence of NNRTI-associated resistance over time. This study was not designed to look at lipodystrophy. However, lipid abnormalities and fat redistribution have not been associated with nevirapine; indeed, nevirapine has been associated with improvements in hyperlipidemia and lipodystrophy after a switch from protease inhibitors [5], adding additional appeal for regimens such as the one described here. The lack of both short- and long-term side-effects with this potent regimen also makes it a very attractive alternative for treatment-naive subjects. The improved quality of life associated with a simple regimen and absence of side-effects is likely to impact positively on drug adherence, and could explain the durability of this nevirapine-based antiretroviral regimen in such a high proportion of patients.

Peter Shalitab

Pat Farrellab

Pamela Lindgrena

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© 2001 Lippincott Williams & Wilkins, Inc.