Long-lasting protection of activity of nucleoside reverse transcriptase inhibitors and protease inhibitors (PIs) by boosted PI containing regimens

Publication

Long-lasting protection of activity of nucleoside reverse transcriptase inhibitors and protease inhibitors (PIs) by boosted PI containing regimens

Journal Paper/Review - Nov 26, 2012

Scherrer Alexandra U, Günthard Huldrych F, Ledergerber Bruno, Bernasconi Enos, Vernazza Pietro, Elzi Luigia, Cavassini Matthias, Calmy Alexandra, Furrer Hansjakob, Aubert Vincent, Klimkait Thomas, Yerly Sabine, Böni Jürg, Swiss HIV Cohort Study (SHCS)

Citation

Scherrer A, Günthard H, Ledergerber B, Bernasconi E, Vernazza P, Elzi L, Cavassini M, Calmy A, Furrer H, Aubert V, Klimkait T, Yerly S, Böni J, Swiss HIV Cohort Study (SHCS). Long-lasting protection of activity of nucleoside reverse transcriptase inhibitors and protease inhibitors (PIs) by boosted PI containing regimens. PloS one 2012; 7:e50307.

Type

Journal Paper/Review (English)

Journal

PloS one 2012; 7

Publication Date

Nov 26, 2012

Issn Electronic

1932-6203

Pages

e50307

Brief description/objective

BACKGROUND
The accumulation of mutations after long-lasting exposure to a failing combination antiretroviral therapy (cART) is problematic and severely reduces the options for further successful treatments.

METHODS
We studied patients from the Swiss HIV Cohort Study who failed cART with nucleoside reverse transcriptase inhibitors (NRTIs) and either a ritonavir-boosted PI (PI/r) or a non-nucleoside reverse transcriptase inhibitor (NNRTI). The loss of genotypic activity <3, 3-6, >6 months after virological failure was analyzed with Stanford algorithm. Risk factors associated with early emergence of drug resistance mutations (<6 months after failure) were identified with multivariable logistic regression.

RESULTS
Ninety-nine genotypic resistance tests from PI/r-treated and 129 from NNRTI-treated patients were analyzed. The risk of losing the activity of ≥1 NRTIs was lower among PI/r- compared to NNRTI-treated individuals <3, 3-6, and >6 months after failure: 8.8% vs. 38.2% (p = 0.009), 7.1% vs. 46.9% (p<0.001) and 18.9% vs. 60.9% (p<0.001). The percentages of patients who have lost PI/r activity were 2.9%, 3.6% and 5.4% <3, 3-6, >6 months after failure compared to 41.2%, 49.0% and 63.0% of those who have lost NNRTI activity (all p<0.001). The risk to accumulate an early NRTI mutation was strongly associated with NNRTI-containing cART (adjusted odds ratio: 13.3 (95% CI: 4.1-42.8), p<0.001).

CONCLUSIONS
The loss of activity of PIs and NRTIs was low among patients treated with PI/r, even after long-lasting exposure to a failing cART. Thus, more options remain for second-line therapy. This finding is potentially of high relevance, in particular for settings with poor or lacking virological monitoring.