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Atazanavir Compared To Nelfinavir: 48 weeks
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Giuseppe Panataleo reported 48-week data from an international study comparing atazanavir to nelfinavir at the opening day oral sessions October 29 in Athens at the 8th European Conference on Clinical Aspects and treatment of HIV-Infection (ECCATHI). Pantaleo is with the Division of Immunology and Allergy at the Center Hospitalier Universitaire Vaudois in Lausanne, Switzerland.
Atazanavir is a new protease inhibitor in phase III development that will be taken once daily (2 capsules) along with other drugs in a HAART regimen. In this study, 467 treatment-naive patients received d4T (40 mg twice daily) plus 3TC (150 mg twice daily) and were blindly randomized to one of two doses of atazanavir (400 mg or 600 mg once per day) or to receive open-label nelfinavir 1,250 mg twice per day. 178 patients received 400 mg of atazanavir, 195 600 mg, and 91 received nelfinavir.
Pantaleo reported that after 48 weeks patients receiving atazanavir in this study had less increases in cholesterol, fasting LDL (bad cholesterol) and fasting triglycerides than the patients receiving nelfinavir. The patients receiving atazanavir had increases in cholesterol, triglycerides and LDL cholesterol of 5-8% compared to increases for patients receiving nelfinavir of 25% for cholesterol, 23% for LDL cholesterol, and 50% for triglycerides. The most common side effect reported for the patients taking nelfinavir was diarrhea (56%). The rate of diarrhea was 15-20% in the atazanavir arm. Hyperbilirubinemia has been reported to occur with use of atazanavir. In this study it was reported as a serious adverse event in <1% of patients treated with the drug, but Pantaleo did not elaborate further on the experience in this study regarding managing hyperbilirubinemia. Pantaleo did report a discontinuation rate due to treatment adverse event of 7% in the 600 mg atazanavir group and 3% in the 400 mg atazanavir group compared to a discontinuation rate for treatment-related adverse event of 4% in the nelfinavir group. The overall discontinuation rates were similar between the regimens: 16% in each of the atazanavir arms vs 19% in the nelfinavir group. Viral load reduction data is reported below.
All the drugs taken in the nelfinavir arm were taken twice per day. In the atazanavir arm d4T and 3TC were taken twice per day and the atazanavir was taken once per day. It would be interesting to see adherence data reflecting how patients are able to adapt to taking one of their meds once per day while the others are twice per day.
BASELINE CHARACTERISTICS
Interestingly, there is a high rate of about women (38%) and non-caucasians (45%) enrolled in this study. The viral loads and CD4s counts were about equal in the nelfinavir and atazanavir arms: 58,000 in the 400 mg atazanavir arm, 50,000 in the 600 mg arm, and 51,000 in the nelfinavir arm; 260-283 CD4 in the atazanavir arms vs 273 in the nelfinavir arms. 10-12% of enrolled patients had AIDS.
RESULTS
By 4 weeks viral load dropped almost 2 logs in all the treatment arms and by 16 weeks and at 48 weeks the mean viral load reduction was about 2.5 log for all 3 treatment groups. CD4 counts increased about 240 in each arm.
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| Viral Load |
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Atazanavir |
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Nelfinavir |
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400 600 |
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| HIV-RNA Log |
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-2.51 -2.58 |
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-2.31 |
| <400 ITT |
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64% 67% |
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53% |
| On treatment |
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74% 75% |
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60% |
| <50 ITT |
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35% 36% |
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34% |
| On treatment |
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40% 41% |
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36% |
| CD4s |
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234 243 |
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211 |
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Patients in the 400 mg atazanavir arm experienced increases in total cholesterol of 5%, LDL cholesterol of 5.2%, triglycerides of 7.1%; patients in the atazanavir 600 mg arm had increases in lipids of 6% for total cholesterol, 7% for LDL cholesterol, and 8% for triglycerides. Study patients receiving nelfinavir had increases of 25% in total cholesterol, 23.2% in LDL cholesterol, and 50% in triglycerides. Pantaleo reported p<0.05 for nelfinavir vs atazanavir. And p=0.0001 for nelfinavir at 48 weeks vs nelfinavir at baseline.
Adverse Events
(grade 1-4, reported with a frequency of 20% in any group)
Diarrhea was the most common side effect for nelfinavir (56%). Diarrhea was 15% in the 600 mg atazanavir arm and 20% in the 400 mg arm (p<0.0001). Infection was 48% in the nelfinavir arm vs 55% in the 600 mg atazanavir arm and 42% in the 400 mg arm. Headache was about 25% in all 3 arms. Abdominal pain was 13% in the nelfinavir arm, and 19% in the 400 mg atazanavir arm and 22% in the 600 mg arm. Peripheral neuropathy was 18-22% across all 3 arms. Rash was 19-22% across all 3 arms. And nausea was 18-21% across all 3 arms. |
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