Genotypic resistance profile and clinical progression of treatment-experienced HIV type 1-infected patients with virological failure

S. Di Giambenedetto, M. Colafigli, C. Pinnetti, A. Bacarelli, A. Cingolani, E. Tamburrini, R. Cauda, A. De Luca

Research output: Contribution to journalArticle

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Abstract

We explored the relationship between HIV-1 drug resistance in treatment-experienced patients and disease progression in a cohort of patients undergoing resistance testing to guide treatment decisions. A total of 601 treatment-failing individuals tested for genotypic HIV-1 drug resistance between 1998 and 2004 were selected. At genotypic testing, median HIV-1 RNA levels and CD4 counts were 3.8 log copies/ml and 293 cells/μl, respectively; 84% had resistance mutations to nucleoside reverse transcriptase inhibitors (NRTIs), 42% had resistance mutations to non-NRTIs, 51% had major resistance mutations to protease inhibitors (PI), 12% had no major resistance mutations to any drug class, 22% had mutations to one class, 42% had mutations to two classes, and 23% had mutations to three classes. During a follow-up of 714.7 patients/year, 80 patients showed an AIDS-defining event or died. In multivariable models adjusting for prior AIDS, baseline CD4 counts, HIV-1 RNA, and calendar year, viral resistance variables associated with increased hazards of clinical progression were the presence of reverse transcriptase substitution T215F (p = 0.002) and the presence of three or more protease substitutions among L33F/I/V, V82A/F/L/T, I84V, and L90M (p = 0.003). Resistance to three drug classes remained independently predictive of clinical progression only when calendar year was not used as an adjustment factor. Prevention and treatment of multiple drug class resistance are clinical priorities for HIV-infected patients. In recent years, improved treatment options may have helped in reducing part of the resistance-associated clinical progression.

Original languageEnglish
Pages (from-to)149-154
Number of pages6
JournalAIDS Research and Human Retroviruses
Volume24
Issue number2
DOIs
Publication statusPublished - Feb 1 2008

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HIV-1
Mutation
Reverse Transcriptase Inhibitors
CD4 Lymphocyte Count
Drug Resistance
Therapeutics
Acquired Immunodeficiency Syndrome
RNA
RNA-Directed DNA Polymerase
Multiple Drug Resistance
Protease Inhibitors
Nucleosides
Pharmaceutical Preparations
Disease Progression
Peptide Hydrolases
HIV

ASJC Scopus subject areas

  • Immunology
  • Virology

Cite this

Genotypic resistance profile and clinical progression of treatment-experienced HIV type 1-infected patients with virological failure. / Di Giambenedetto, S.; Colafigli, M.; Pinnetti, C.; Bacarelli, A.; Cingolani, A.; Tamburrini, E.; Cauda, R.; De Luca, A.

In: AIDS Research and Human Retroviruses, Vol. 24, No. 2, 01.02.2008, p. 149-154.

Research output: Contribution to journalArticle

Di Giambenedetto, S. ; Colafigli, M. ; Pinnetti, C. ; Bacarelli, A. ; Cingolani, A. ; Tamburrini, E. ; Cauda, R. ; De Luca, A. / Genotypic resistance profile and clinical progression of treatment-experienced HIV type 1-infected patients with virological failure. In: AIDS Research and Human Retroviruses. 2008 ; Vol. 24, No. 2. pp. 149-154.
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