JAC Advance Access published online on December 4, 2003
Journal of Antimicrobial Chemotherapy, doi:10.1093/jac/dkh012
© 2003 by The British Society for Antimicrobial Chemotherapy
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Original article
1 Department of Medicine, San Sebastian Hospital,
Ecija, Seville;
* Corresponding author. E-mail: mleal{at}cica.es.
Received 1 July 2003
; revised 6 September 2003
; accepted 3 October 2003
Objective: To assess the durability
of the undetectability of HIV plasma viraemia (pV) and to determine
the factors associated with virological rebound (VR) in HIV-infected
adults on protease inhibitor (PI)-sparing highly active antiretroviral
therapy (HAART). The development of resistance mutations during
virologically successful therapy and VR was also analysed. Materials and methods: One hundred and twenty-six
HIV-infected adults on PI-sparing HAART were prospectively followed
from April 1998 to December 2002: Group 1, naive
for antiretroviral drugs (n = 26); Group
2, previously PI-HAART-exposed patients (n = 19); Group 3, previously exposed to suboptimal therapy
(n = 81). Genotypic resistance tests on
peripheral blood mononuclear cells or on plasma RNA (when feasible)
were carried out when undetectable HIV pV was demonstrated for at
least 48 weeks. Additionally, patients showing a therapy adherence >95% developing
VR were also tested at rebound, at simplification and during previous
suboptimal therapy exposure. Results: The median follow-up time was 630 [329-903] days.
VR was considered as two consecutive pV levels >50 copies/mL.
Twenty-two (17.5%) patients developed VR. Only therapy
adherence <95% was independently associated with
VR (adjusted hazard ratio: 8.42; 95% CI: 3.33-21.27).
Twenty (40%) of the 50 patients with pV < 50
copies/mL for at least 48 weeks showed at least one thymidine-associated
mutation (TAM) but none had NNRTI-resistance mutations. Ten (83.3%)
of 12 available adherent patients showing VR harboured NNRTI-resistance-associated
mutations; 50% of them were considered as wild-type strains
at simplification time. However, the TAM number and resistance mutations
profile found on suboptimal exposure were very similar to those
found at VR on simplification therapy. Conclusions: PI-sparing HAART allows maintenance
of successful long-term control of HIV replication, adherence to
therapy being the main factor associated with VR. However, a small
proportion of patients on simplification regimen may develop VR
regardless of therapy compliance. VR on PI-sparing HAART is characterized
by the emergence of NNRTI cross-resistance mutations. Finally, TAMs ‘archived’ during previous
suboptimal exposures are partially involved in subsequent VR on
simplification HAART.
Keywords: PI-sparing HAART, simplification therapy, virological
rebound, resistance mutations
Long-term virological outcome and resistance mutations
at virological rebound in HIV-infected adults on protease inhibitor-sparing
highly active antiretroviral therapy
2 Department
of Biochemistry, Virgen del Rocío University Hospital,
Seville;
3 Department of Medical
Biochemistry and Molecular Biology, University of Seville, Seville;
4 Department of Internal Medicine,
Virgen del Rocío University Hospital, Avda. Manuel Siurot
s/n, 41013 Seville, Spain
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