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Date of Report: 10/14/2003
Author: Susa Coffey, MD, Associate Medical Editor
Source: AETC National Resource Center
Gilead Sciences has issued a "Dear Health Care Professional" letter to warn of high rates of early virologic failure in patients treated with a once-daily triple nucleoside reverse transcriptase inhibitor (NRTI) regimen consisting of didanosine + lamivudine + tenofovir.
The letter describes interim results of a pilot study of didanosine (enteric-coated formulation, 250 mg) + lamivudine (300 mg) + tenofovir (300 mg), all dosed once daily in 24 treatment-naive patients. At week 12, virologic failure (<2 log10 reduction in HIV RNA) was seen in 91% of study subjects. Resistance testing performed on 21 patients revealed the M184I/V mutation in 95%, and K65R + M184I/V mutations in 50%. Study enrollment was terminated upon discovery of this high rate of early regimen failure.
This announcement reinforces data on high rates of early virologic failure and early emergence of NRTI-associated resistance mutations that were previously reported in several studies of other triple-NRTI regimens. These include reports on the combinations abacavir + lamivudine + tenofovir (1, 2), abacavir + lamivudine + zidovudine (3), and abacavir + didanosine + stavudine (4).
The combination of didanosine + lamivudine + tenofovir, like the other triple-NRTI regimens with demonstrated high failure rates, are not recommended for the treatment of patients with HIV infection.
The "Dear Health Care Professional" letter is available on the U.S. Food and Drug Administration website at: http://www.fda.gov/oashi/aids/new.html.
References
| 1. | | Gallant JE, Rodriguez AE, Weinberg W, Young B, Berger D, Lim ML, Liao Q, Ross L, Johnson J, Shaefer MS. Early Non-Response to Tenofovir DF (TDF) + Abacavir (ABC) and Lamivudine (3TC) in a Randomized Trial Compared to Efavirenz (EFV) + ABC and 3TC: ESS30009. 43rd Interscience Conference on Antimicrobial Agents and Chemotherapy, Chicago, September 2003. Abstract 1722a. |
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| 2. | | Farthing C, Khanlou H, Yeh V. Early Virologic Failure in a Pilot Study Evaluating the Efficacy of Abacavir, Lamivudine and Tenofovir in the Treatment Naive HIV-Infected Patients. The 2nd International AIDS Society Conference on HIV Pathogenesis and Treatment, Paris, July 2003. Abstract 43. |
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| 3. | | Gulick RM, Ribaudo HJ, Shikuma CM, Lustgarten S, Meyer WA, Klingman K, Squires KE, Snyder S, Kuritzkes, DR. ACTG 5095: A Comparative Study of Three Protease Inhibitor-Sparing Antiretroviral Regimens for the Initial Treatment of HIV Infection. The 2nd International AIDS Society Conference on HIV Pathogenesis and Treatment, Paris, July 13-16, 2003. Abstract 41. |
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| 4. | | Gerstoft J, Kirk O, Obel N, Pedersen C, Mathiesen L, Nielsen H, Katzenstein TL, Lundgren JD. Low efficacy and high frequency of adverse events in a randomized trial of the triple nucleoside regimen abacavir, stavudine and didanosine. AIDS. 2003 Sep 26;17(14):2045-2052. |
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