We found a match
Your institution may have access to this item. Find your institution then sign in to continue.
- Title
Highly multidrug-resistant HIV: clonal analysis and therapeutic strategies.
- Authors
Todesco, Eve; Sayon, Sophie; Fourati, Slim; Tubiana, Roland; Simon, Anne; Ktorza, Nadine; Schneider, Luminita; Peytavin, Gilles; Malet, Isabelle; Van den Eede, Peter; Katlama, Christine; Calvez, Vincent; Marcelin, Anne-Genevieve; Wirden, Marc
- Abstract
Objectives There are today HIV-infected patients in therapeutic impasses because of highly multidrug-resistant (HMDR) viruses. We studied the distribution of resistance mutations at clonal level, and we analysed the therapeutic strategies used in such cases to achieve undetectable viraemia. Methods The HMDR profile was defined as a genotypic sensitivity score (GSS) ≤1.5 for etravirine and raltegravir with full resistance to darunavir. About 30 clones per gene and per patient were sequenced. Virtual phenotypes were determined. Efficacy of therapeutic strategies was evaluated by follow-up of viral loads, CD4 cell counts and trough concentrations of drugs. Results Among 1310 patients on treatment and with genotypic resistance testing, 25 (2%) were resistant to darunavir and 11 (0.8%) had an HMDR profile. Five-hundred clones could be analysed for four of them. HMDR profiles were harboured by the great majority of clones and all resistance mutations were located on the same strains for all genes. Despite this and a regimen with a GSS <2.0 in three patients, they achieved a viraemia <20 copies/mL. These results were obtained using different strategies: high doses of drugs; combination of antiretrovirals with full or intermediate susceptibility, such as tipranavir, etravirine or maraviroc; and use of alternative compounds, such as foscarnet or interferon. Conclusion Patients with HMDR HIV were uncommon, but, in such cases, all resistance mutations were borne on the same majority strains. In this study, tipranavir was the only protease inhibitor with full or intermediate susceptibility. Despite very limited therapeutic options, an undetectable viraemia can be achieved by combining different strategies.
- Subjects
MULTIDRUG resistance; HIV; ANTI-HIV agents; VIREMIA; DARUNAVIR; TIPRANAVIR (Drug); ETRAVIRINE (Drug); MARAVIROC (Drug)
- Publication
Journal of Antimicrobial Chemotherapy (JAC), 2013, Vol 68, Issue 12, p2882
- ISSN
0305-7453
- Publication type
Article
- DOI
10.1093/jac/dkt272