title: MIV-310 reduces HIV viral load in patients failing multiple antiretroviral therapy: results from a 4-week phase II study.
abstract: BACKGROUND
  Drug resistance is an increasing problem in the treatment of HIV infection. MIV-310 (alovudine), a nucleoside reverse transcriptase inhibitor, potently inhibits the replication of highly mutated strains of HIV in vitro. We examined the efficacy of MIV-310 in highly pretreated patients.
  
  
  METHODS
  In a phase II pilot study, 15 patients failing a current antiretroviral therapy with at least two thymidine-associated mutations (TAM) were given MIV-310 7.5 mg once daily for 4 weeks, in addition to their ongoing treatment. The primary endpoint was the plasma viral load reduction at week 4.
  
  
  RESULTS
  At baseline, the median viral load was 3.93 log10 copies/ml and the median CD4 cell count was 360 cells/mm3. After 4 weeks of MIV-310 administration, the median decrease in viral load was -1.13 log10. Interestingly, the median reduction was only -0.57 log10 in the four patients on stavudine, contrasting with a median reduction of -1.88 log10 in the 11 patients not receiving concomitant stavudine. The viral load fell by a median of -1.60 log10 in patients with two to three TAM (n = 7), and by -1.88 log10 in patients with four or five TAM (n = 8). The viral load rebounded in all patients after MIV-310 cessation. No mutations were found in the reverse transcriptase coding region during MIV-310 treatment. MIV-310 was well tolerated, with no serious adverse events and no treatment withdrawals.
  
  
  CONCLUSIONS
  MIV-310 7.5 mg/day efficiently reduced the HIV viral load in patients failing a multiple-drug regimen. Further studies with different dosages and longer administration times are urgently needed.
authors.affiliation: Département des Maladies Infectieuses et Tropicales/INSERM E0214, Hôpital Pitié-Salpêtrière, Paris, France. christine.katlama@psl.ap-hop-paris.fr
authors.forename: Christine
authors.initials: C
authors.lastname: Katlama
authors.forename: Jade
authors.initials: J
authors.lastname: Ghosn
authors.forename: Roland
authors.initials: R
authors.lastname: Tubiana
authors.forename: Marc
authors.initials: M
authors.lastname: Wirden
authors.forename: Marc-Antoine
authors.initials: MA
authors.lastname: Valantin
authors.forename: Johan
authors.initials: J
authors.lastname: Harmenberg
authors.forename: Göran
authors.initials: G
authors.lastname: Mårdh
authors.forename: Bo
authors.initials: B
authors.lastname: Oberg
authors.forename: Vincent
authors.initials: V
authors.lastname: Calvez
mesh_terms: D000328:Adult; D019380:Anti-HIV Agents / Q000627:therapeutic use; D023241:Antiretroviral Therapy, Highly Active; D018791:CD4 Lymphocyte Count; D015224:Dideoxynucleosides / Q000627:therapeutic use*; D024882:Drug Resistance, Viral; D005260:Female; D005838:Genotype; D015658:HIV Infections / Q000188:drug therapy* / Q000276:immunology / Q000821:virology; D015497:HIV-1 / Q000235:genetics; D006801:Humans; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects; D012367:RNA, Viral / Q000097:blood; D018894:Reverse Transcriptase Inhibitors / Q000627:therapeutic use*; D017211:Treatment Failure; D019562:Viral Load
chemical_list: D019380:Anti-HIV Agents; D015224:Dideoxynucleosides; D012367:RNA, Viral; D018894:Reverse Transcriptase Inhibitors; C002854:alovudine