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Long-term virological outcome and resistance mutations at virological rebound in HIV-infected adults on protease inhibitor-sparing highly active antiretroviral therapy.
J Antimicrob Chemother. 2004 Jan; 53(1):95-101.JA

Abstract

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.

Authors+Show Affiliations

Viral Hepatitis and AIDS Study Group, Department of Medicine, San Sebastian Hospital, Ecija, Seville, Spain.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Clinical Trial
Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

14657091

Citation

de la Rosa, Rafael, et al. "Long-term Virological Outcome and Resistance Mutations at Virological Rebound in HIV-infected Adults On Protease Inhibitor-sparing Highly Active Antiretroviral Therapy." The Journal of Antimicrobial Chemotherapy, vol. 53, no. 1, 2004, pp. 95-101.
de la Rosa R, Ruíz-Mateos E, Rubio A, et al. Long-term virological outcome and resistance mutations at virological rebound in HIV-infected adults on protease inhibitor-sparing highly active antiretroviral therapy. J Antimicrob Chemother. 2004;53(1):95-101.
de la Rosa, R., Ruíz-Mateos, E., Rubio, A., Abad, M. A., Vallejo, A., Rivero, L., Genebat, M., Sánchez-Quijano, A., Lissen, E., & Leal, M. (2004). Long-term virological outcome and resistance mutations at virological rebound in HIV-infected adults on protease inhibitor-sparing highly active antiretroviral therapy. The Journal of Antimicrobial Chemotherapy, 53(1), 95-101.
de la Rosa R, et al. Long-term Virological Outcome and Resistance Mutations at Virological Rebound in HIV-infected Adults On Protease Inhibitor-sparing Highly Active Antiretroviral Therapy. J Antimicrob Chemother. 2004;53(1):95-101. PubMed PMID: 14657091.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Long-term virological outcome and resistance mutations at virological rebound in HIV-infected adults on protease inhibitor-sparing highly active antiretroviral therapy. AU - de la Rosa,Rafael, AU - Ruíz-Mateos,Ezequiel, AU - Rubio,Amalia, AU - Abad,María Antonia, AU - Vallejo,Alejandro, AU - Rivero,Laura, AU - Genebat,Miguel, AU - Sánchez-Quijano,Armando, AU - Lissen,Eduardo, AU - Leal,Manuel, Y1 - 2003/12/04/ PY - 2003/12/6/pubmed PY - 2004/4/24/medline PY - 2003/12/6/entrez SP - 95 EP - 101 JF - The Journal of antimicrobial chemotherapy JO - J Antimicrob Chemother VL - 53 IS - 1 N2 - 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. SN - 0305-7453 UR - https://www.unboundmedicine.com/medline/citation/14657091/Long_term_virological_outcome_and_resistance_mutations_at_virological_rebound_in_HIV_infected_adults_on_protease_inhibitor_sparing_highly_active_antiretroviral_therapy_ L2 - https://academic.oup.com/jac/article-lookup/doi/10.1093/jac/dkh012 DB - PRIME DP - Unbound Medicine ER -