title: [Tenofovir DF in rescue regimens].
abstract: As with other nucleoside analogues, tenofovir (TDF) can be affected by several mutations in the reverse transcriptase gene. Most nucleoside analogue mutations (NAMs) are not induced specifically by TDF, although they can affect the activity of this drug. The impact of thymidine analogue mutations (TAMs) on tenofovir varies and, as with the remaining nucleoside analogue reverse transcriptase inhibitors, largely depends on the type and number present. Thus, the greater the number of TAMs, and the greater the number of type 1 TAMs, the more TDF activity will be affected. The 41L and 210W mutations have the greatest effect. The incidence of the 65R mutation was slight before the clinical introduction of TDF. This mutation was selected by treatments with zalcitabine monotherapy. However, after TDF came on to the market, the 65R mutation began to be more frequently reported and is currently the signature mutation of this drug. TDF has been shown to be safe and effective in patients with prior virological failure and resistance mutations in the reverse transcriptase gene. In these patients, the presence of the 41L and 210W mutations is associated with a worse response to rescue therapy containing TDF. In contrast, the presence of type 2 TAMs (67N, 70R and 219Q/E/N) has little effect on TDF activity in these patients. Importantly, in TDF therapy, the presence of the 184V mutation is associated with a more favorable virologic response than the absence of this mutation, with any of the distinct combinations of mutations present.
authors.affiliation: Unidad de Enfermedades Infecciosas/VIH, Hospital Universitario Gregorio Marañón, Madrid, España. juanclopezbq@wanadoo.es
authors.forename: Juan Carlos
authors.initials: JC
authors.lastname: López Bernaldo de Quirós
mesh_terms: D000225:Adenine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D019380:Anti-HIV Agents / Q000008:administration & dosage / Q000145:classification / Q000494:pharmacology / Q000627:therapeutic use*; D000963:Antimetabolites / Q000494:pharmacology; D017326:Clinical Trials, Phase III as Topic / Q000706:statistics & numerical data; D024921:Drug Resistance, Multiple, Viral / Q000235:genetics*; D004359:Drug Therapy, Combination; D006678:HIV / Q000201:enzymology* / Q000235:genetics; D015658:HIV Infections / Q000188:drug therapy*; D054303:HIV Reverse Transcriptase / Q000037:antagonists & inhibitors* / Q000235:genetics; D006801:Humans; D015337:Multicenter Studies as Topic; D009154:Mutation; D063065:Organophosphonates / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D016032:Randomized Controlled Trials as Topic / Q000706:statistics & numerical data; D012189:Retrospective Studies; D018894:Reverse Transcriptase Inhibitors / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D016879:Salvage Therapy; D012641:Selection, Genetic; D000068698:Tenofovir; D013936:Thymidine / Q000031:analogs & derivatives; D017211:Treatment Failure; D019562:Viral Load; D016047:Zalcitabine / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use
chemical_list: D019380:Anti-HIV Agents; D000963:Antimetabolites; D063065:Organophosphonates; D018894:Reverse Transcriptase Inhibitors; D016047:Zalcitabine; D000068698:Tenofovir; D054303:HIV Reverse Transcriptase; D000225:Adenine; D013936:Thymidine