JAC Advance Access published online on November 25, 2003
Journal of Antimicrobial Chemotherapy, doi:10.1093/jac/dkh006
© 2003 by The British Society for Antimicrobial Chemotherapy
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Original article
1 Service Universitaire
de Virologie, Centre Hospitalier Régional de Lille, Lille;
* Corresponding author. E-mail: l-bocket{at}chru-lille.fr.
Received 11 July 2003
; revised 8 September 2003
; accepted 3 October 2003
Aims: The aims of this study were
to: (i) determine the incidence of thymidine-associated mutations
(TAMs) in an observational clinical cohort of naive HIV-1 patients
who stopped first-line therapy including either zidovudine or stavudine;
and (ii) assess the immunological and virological responses to subsequent second-line
therapy in patients who switched from zidovudine to stavudine or
conversely. Patients and methods: Plasma samples from 165
patients who stopped first-line antiretroviral therapy containing
either zidovudine or stavudine were examined for the presence of
drug-resistant genotypes. Subsequent second-line immunological and
virological follow-up was performed in 136 patients who switched from
zidovudine to stavudine and conversely. Results: Among the 93 patients who stopped first-line
therapy including zidovudine and the 72 who stopped first-line therapy
including stavudine, genotypic resistance testing was available
for 67 (72%) and 54 (75%), respectively. The presence
of TAMs was significantly more frequent in the zidovudine than the
stavudine group (23.8% versus 5.5; P = 0.006).
The short- and long-term immunological and virological responses
to second-line therapy were comparable in the zidovudine and stavudine
groups, despite different baseline profiles of viral resistance
(median increase in CD4 cells/mm3 at 1 year of therapy,
118 versus 119; viral load <400 copies/mL, 47% versus
47%). Conclusions: These results suggest that TAMs
occur in more patients on antiretroviral regimens including zidovudine
than on regimens including stavudine. Although the results from
observational studies should be interpreted cautiously, these findings
may be useful in determining the optimal sequencing of zidovudine and
stavudine for the treatment of naive HIV-1-infected patients.
Keywords: HIV-1 drug resistance, antiretroviral therapy,
zidovudine, stavudine
Thymidine analogue mutations in antiretroviral-naive
HIV-1 patients on triple therapy including either zidovudine or
stavudine
2 Service Universitaire des Maladies Infectieuses
et du Voyageur, Centre Hospitalier de Tourcoing, Tourcoing; Centre de Recherches Economiques, Sociologiques
et de Gestion, Labores, CNRS U362, Lille, France
3 Service Universitaire des Maladies Infectieuses
et du Voyageur, Centre Hospitalier de Tourcoing, Tourcoing;
CiteULike 
Connotea 
Del.icio.us What's this?