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Antimicrobial Agents and Chemotherapy, March 2003, p. 1176, Vol. 47, No. 3
0066-4804/03/$08.00+0 DOI: 10.1128/AAC.47.3.1176.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.
| LETTER TO THE EDITOR |
Stavudine Protective Function and Emergence of Lamivudine Resistance
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Joly et al. presented an interesting paper (1) comparing the efficacy and toxicity of zidovudine (AZT) versus that of stavudine (d4T), in combination with lamivudine (3TC) and indinavir, in 170 patients treated with AZT, dideoxyinosine, and/or dideoxycytosine in a randomized comparative multicenter trial (Novavir trial). No M184V mutation was detected in the reverse transcriptase gene before starting highly active antiretroviral therapy (HAART). At week 80, 15 patients in the AZT arm and 14 patients in the d4T arm reached virological failure, defined as plasma human immunodeficiency virus type 1 (HIV-1) RNA levels of >5,000 copies/ml. Time to virological failure did not differ between the two arms (P = 0.98). In the d4T and AZT arms, 67 and 73% of patients, respectively, had HIV-1 RNA levels of <500 copies/ml (P = 0.50). Moreover, the proportions of patients with HIV-1 RNA levels of <50 copies/ml at weeks 8, 16, and 24 were similar in the two arms.
In this study, no details about the genotypic resistance pattern of the 29 patients failing an AZT- or d4T-including regimen were reported. In a previous study (2) conducted on 56 HIV-seropositive patients treated with 3TC or d4T, including dual antiretroviral therapy, we observed that d4T-3TC was at least as effective as the AZT-3TC regimen in terms of viral suppression and immune recovery. Interestingly, a higher prevalence of M184V mutation was found in patients failing AZT-3TC therapy than that in patients treated with the d4T-3TC regimen: 41 and 14%, respectively. This difference had only a weak statistical significance (P = 0.05) because of the limited power of the study. However, in the discussion section, we suggested the occurrence of a hypothetical protective role of d4T on the emergence of 3TC resistance. Until now, no other studies have confirmed this observation.
It could be noteworthy to verify whether the d4T protective function on the emergence of 3TC resistance has been reported in HIV-infected patients failing HAART during the Novavir trial.
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- Joly, V., P. Flandre, V. Meiffredy, F. Brun-Vezinet, J.-A. Gastaut, C. Goujard, G. Remy, D. Descamps, A. Ruffault, A. Certain, J.-P. Aboulker, and P. Yeni for the Novavir Study Group. 2002. Efficacy of zidovudine compared to stavudine, both in combination with lamivudine and indinavir, in human immunodeficiency virus-infected nucleoside-experienced patients with no prior exposure to lamivudine, stavudine, or protease inhibitors (Novavir trial). Antimicrob. Agents Chemother. 46:1906-1913.
[Abstract/Free Full Text] - Sarmati, L., E. Nicastri, S. G. Parisi, G. D'Ettorre, P. Narciso, G. Mancino, I. Gallo, V. Abbadessa, N. E. Dalle, C. Traina, V. Vullo, and M. Andreoni. 2001. Failure of stavudine-lamivudine combination therapy in antiretroviral-naïve patients with AZT-like HIV-1 resistance mutations. J. Med. Virol. 65:631-636.[CrossRef][Medline]
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Emanuele Nicastri
National Institute of Infectious Diseases IRCCS L. Spallanzani
Loredana Sarmati
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| * Phone and fax: 39 06 725 96873, E-mail: andreoni{at}uniroma2.it |
Authors' Reply
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When considering the 12-month-extended follow-up, we observed that 35 patients—17 and 18 patients receiving d4T-3TC-IDV and AZT-3TC-IDV, respectively—reached virological failure defined as a viral load of >5,000 copies/ml in two consecutive samples. Genotypic resistance data were available at the baseline and at the time of failure in 27 out of these 35 patients. Sixteen and 11 patients were in the zidovudine and stavudine arms, respectively. The M184V mutation was never found at baseline, i.e., before initiating HAART. At the time of failure, the M184V mutation was found in 13 of 16 patients (81%) of the zidovudine arm and 9 of 11 patients (82%) of the stavudine arm. Thus, we did not observe any protective role of stavudine on the emergence of genotypic resistance to lamivudine. It has to be stressed that, in our study, lamivudine was administered in the context of HAART, in combination with indinavir, contrarily to the study of Sarmati et al. (1), in which patients were subject to dual-nucleoside therapy.
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TopLetterReferencesLetter References |
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- Sarmati, L., E. Nicastri, S. G. Parisi, G. D'Ettorre, P. Narciso, G. Mancino, I. Gallo, V. Abbadessa, N. E. Dalle, C. Traina, V. Vullo, and M. Andreoni. 2001. Failure of stavudine-lamivudine combination therapy in antiretroviral-naïve patients with AZT-like HIV-1 resistance mutations. J. Med. Virol. 65:631-636.
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Véronique Joly* Diane Descamps Philippe Flandre Patrick Yeni Agence Française de Recherche sur le SIDA Paris, France
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| * Phone and fax: 39 06 725 96873, E-mail: andreoni{at}uniroma2.it |
Antimicrobial Agents and Chemotherapy, March 2003, p. 1176, Vol. 47, No. 3
0066-4804/03/$08.00+0 DOI: 10.1128/AAC.47.3.1176.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.
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