Plasma HIV RNA decline and emergence of drug resistance mutations among patients with multiple virologic failures receiving resistance testing-guided HAART

Valerio Tozzi, Rita Bellagamba, Filippo Castiglione, Alessanda Amendola, Jelena Ivanovic, Emanuele Nicastri, Raffaella Libertone, Giampiero D'Offizi, Giuseppina Liuzzi, Caterina Gori, Federica Forbici, Roberta D'Arrigo, Ada Bertoli, Maria Flora Salvatori, Maria Rosaria Capobianchi, Andrea Antinori, Carlo Federico Perno, Pasquale Narciso

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Abstract

Early recognition of virologic failure in patients with extensive drug resistance receiving salvage-HAART is essential to avoid exposure to subinhibitory regimens. We studied plasma viral load (PVL) decline and rates of drug-resistance mutation (DRM) accumulation in such patients. A prospective, 48 week study of 38 heavily pretreated patients receiving genotypic resistance testing (GRT)-guided HAART was conducted. The rate of PVL decline was studied by weekly PVL determinations. To assess DRM accumulation, serial GRTs were performed in all nonresponders (never reaching PVL 50 copies/ml after suppression). Over 48 weeks, 10 patients (26%) were nonresponders. Receiving less then two fully active drugs and having an elevated number of PI and NRTI mutations at baseline were strongly associated with virologic failure. There was no evidence of a difference in the change from baseline PVL to week 1 and 2 between responders and nonresponders. By contrast, PVL reductions from week 2 to week 3 and thereafter were significantly greater for responders (p <0.01). Among nonresponders, the incidence rates per patient-month (95% CI) of emergent DRM were 0.67 (0.13-1.20), 0.40 (0.00-0.74), and 0.37 (0.00-0.75) at weeks 4, 8, and 24, respectively. Having limited baseline resistance, receiving at least two fully active drugs, and showing constant PVL reductions from week 2 to week 3 and thereafter were predictive of virologic response. In contrast, early changes in PVL levels were not. Virologic failure was associated with detection of emergent DRMs. Virologic rebound in patients on salvage-HAART should be addressed aggressively.

Original languageEnglish
Pages (from-to)787-796
Number of pages10
JournalAIDS Research and Human Retroviruses
Volume24
Issue number6
DOIs
Publication statusPublished - Jun 1 2008

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ASJC Scopus subject areas

  • Immunology
  • Virology

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