Clinical implications of genotypic resistance to the newer antiretroviral drugs in HIV-1-infected patients with virological failure.
Virological suppression rates achieved with the new antiretroviral drugs in patients with virological failure and resistance to multiple drug classes are nearly matching the rates seen in treatment-naive patients. Knowledge of cross-resistance patterns to drugs of the same class is key for successful use of etravirine, tipranavir, and darunavir in treatment-experienced patients. Determination of human immunodeficiency virus type 1 (HIV-1) tropism is cardinal for maraviroc. The impressive potency of raltegravir must not preclude its use with other active drugs because of its limited genetic barrier. These new agents have demonstrated superiority in virtually all efficacy parameters in their pivotal salvage trials, but comparative data between them are still very scarce. This review discusses the clinical implication of resistance to these new drugs. Specific genotypic resistance scores have been developed for tipranavir and etravirine, and mutations conferring resistance to darunavir are well understood. Determining the most active drugs and successfully combining them is the key challenge in salvage regimens.
Lluita contra la SIDA Foundation, Hospital Germans Trias, Universitat Autònoma of Barcelona, Barcelona, Spain. jmllibre@flsida.org
Josep M
JM
Llibre
Jonathan M
JM
Schapiro
Bonaventura
B
Clotet
D000818:Animals; D044966:Anti-Retroviral Agents / Q000494:pharmacology* / Q000627:therapeutic use*; D024882:Drug Resistance, Viral; D005838:Genotype; D015658:HIV Infections / Q000188:drug therapy* / Q000821:virology*; D015497:HIV-1 / Q000187:drug effects* / Q000235:genetics / Q000302:isolation & purification; D006801:Humans; D020125:Mutation, Missense; D012367:RNA, Viral / Q000235:genetics; D016879:Salvage Therapy / Q000379:methods*; D017211:Treatment Failure
D044966:Anti-Retroviral Agents; D012367:RNA, Viral