Study to Determine the Antiviral Activity and Safety of Alovudine in Nucleoside-experienced HIV-infected Subjects Experiencing Virologic Failure

Inclusion criteria

• Signed informed consent before any trial procedure
• HIV-1 infected males or females ≥18 years of age
• Screening genotypic resistance report indicating two or more of the following nucleoside reverse transcriptase inhibitors (NRTI) resistance mutations: 41, 67, 70, 210 and 215
• Stable NRTI regimen without stavudine and zidovudine for at least 6 weeks before screening and stable antiretroviral (ARV) background treatment for 3 months before screening
• HIV-1 viral load ≥1000 copies/mL and <75,000 copies/mL at screening
• Change in viral load between previous test within 3 months before screening, using local laboratory for routine tests, and screening test was <1.0 log10 copies/mL
• Acceptable medical history, as assessed by the investigator
• Current stable ARV medication regimen between screening (Visit 1) and Visit 2

Exclusion criteria

• ARV medication naïve
• Patients on recent drug holiday, defined as off ARV medications for at least 7 consecutive days within the previous 3 months
• Female patients of child-bearing potential who :

• have a positive serum pregnancy test
• are breast feeding,
• are planning to become pregnant, or
• are not willing to use a barrier method of contraception
• Prior alovudine use
• Use of investigational medications within 30 days before study entry or during the trial
• Use of immunomodulatory drugs within 3 months before study entry or during the trial (e.g. interferon, cyclosporine, hydroxyurea, interleukin-2)
• Current use of rifampin, rifabutine, isoniazid, pyrazinamide, stavudine, zidovudine, ganciclovir, chronic use of hepatotoxic drugs, anti-tumour therapy or probenecid
• Laboratory values:

• Neutrophils of Grade 2 or greater abnormality
• Hemoglobin of Grade 2 or greater abnormality
• Platelets: Grade 2 or greater abnormality
• Creatinine of ≥1.25 Upper limit of the normal (ULN)
• Lipase of Grade 1 or greater abnormality
• Alanine aminotransaminase (ALT) or Aspartate aminotransaminase (AST) of Grade 2 or greater abnormality
• Direct bilirubin of Grade 1 or greater abnormality
• CD4 ≤50 cells/mm3
• Hepatitis B (+HBsAg or +HBcAB) or C +Hepatitis C virus (+HCV AB ) co-infection, chronic hepatitis, on-going hepatitis or pancreatitis
• Any new or active AIDS-defining event within 30 days before study entry
• Inability to adhere to the requirements of the protocol, including active substance abuse as assessed by the investigator
• In the opinion of the investigator, likely survival of less than 6 months because of underlying disease