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Once-Daily Nevirapine XR Noninferior to Continued Twice-Daily Nevirapine
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50th Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC), September 12-15, 2010, Boston
Mark Mascolini
Six months after a switch from twice-daily immediate-release nevirapine (NVP IR) to the once-daily extended-release formulation (NVP XR), the once-daily regimen proved noninferior to continued twice-daily dosing in an open-label trial [1]. Three people (1%) randomized to NVP XR and none randomized to NVP IR dropped out because of side effects.
Study participants were adults taking twice-daily NVP IR for at least 18 weeks with a fixed-dose combination of tenofovir/emtricitabine (about 55%), abacavir/lamivudine (about 25%), or zidovudine/lamivudine (about 20%). Everyone had a viral load below 100 copies in the preceding 1 to 4 months and a load below 50 copies at screening. Study participants could not be taking a protease inhibitor and could not have used an investigational medication within 2 months. Women of child-bearing potential had to agree to use double-barrier contraception. Study participants could not have DAIDS grade 2 coagulation, hematology, or biochemistry values, grade 3 total triglycerides, or Child-Pugh stage B or C hepatic cirrhosis. The trial's primary endpoint was the proportion of people with a viral load below 50 copies at week 24 in a time-to-loss-of-virologic-response analysis.
Of 443 randomized and treated people, 295 switched to once-daily NVP XR and 148 maintained twice-daily NVP IR. Most study participants (84%) were men, and age averaged 47.5 years (+/- 9.7). Median pretreatment CD4 count stood at 530 in the NVP XR group and 542 in the NVP IR group. While 18.5% of study participants had taken NVP for under 1 year, 32.7% took the nonnucleoside for 1 to 3 years, 24.8% for 3 to 5 years, and 23.9% for more than 5 years. About one quarter of study participants had an AIDS diagnosis.
Through 24 weeks, 7 people (2.4%) treated with NVP XR and 3 (2.0%) treated with NVP IR had discontinued study medication. No one taking NVP IR dropped out because of side effects, while 3 (1%) taking NVP XR stopped treatment because of side effects--gastrointestinal complaints, headache, and dizziness.
In the primary endpoint analysis, 276 of 295 people (93.6%) randomized to NVP XR and 137 of 148 (92.6%) randomized to NVP IR had a viral load below 50 copies at 24 weeks, a result establishing the noninferiority of NVP XR to continued NVP IR. For undetermined reasons, the response rate was substantially higher with NVP XR than NVP IR (97.3% versus 86.1%) in people taking NVP with abacavir/lamivudine. Overall time to loss of virologic response did not differ significantly between the two groups after statistical adjustment for background antiretrovirals. Treatment groups did not differ in median CD4-cell gain through 24 weeks--39.8 CD4s with NVP XR and 32.5 CD4s with NVP IR.
Investigator-defined drug-related adverse events occurred in 35 people (11.9%) taking NVP XR versus 3 (2.0%) taking NVP IR. Serious adverse events developed in 17 people (5.8%) taking NVP XR versus 4 (2.7%) taking NVP IR, but no serious adverse events were judged to be drug related. Grade 3 or 4 adverse events considered drug related affected only 1 person taking NVP XR and 2 taking NVP IR. Rash and "hepatic events" were recorded in 4 people (1.3%) taking NVP XR and in none taking NVP IR. Acute hepatitis developed in one person in the NVP XR group who had HCV infection.
Reference
1. Arasteh K, Ward D, Plettenberg A, et al. 24 Wk efficacy and safety of transitioning virologically stable HIV-1 patients from IR nevirapine 200 mg BID to nevirapine XR 400 mg QD (TRANxITION). 50th Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC). September 12-15, 2010. Boston. Abstract H-207.
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