AVX754 (a New Nucleoside Reverse Transcriptase Inhibitor [NRTI]) to Treat Drug-resistant HIV

• Change from baseline in HIV RNA levels at day 21 [ Time Frame: day 21 ] [ Designated as safety issue: No ]
• Time-weighted average change from baseline in HIV RNA levels through 21 days [ Time Frame: 21 days ] [ Designated as safety issue: No ]

• Change from baseline in HIV RNA levels at day 21
• Time-weighted average change from baseline in HIV RNA levels through 21 days

• Change from baseline in HIV RNA levels at days 7, 14, 21 [ Time Frame: days 7, 14, 21 ] [ Designated as safety issue: No ]
• Proportion of subjects with HIV RNA levels <400 or <50 at days 7, 14, 21, and weeks 24 and 48 [ Time Frame: days 7, 14, 21, and weeks 24 and 48 ] [ Designated as safety issue: No ]
• Change from baseline and change in ratio of CD4+ and CD8+ cells at day 21 and weeks 24 and 48 [ Time Frame: day 21 and weeks 24 and 48 ] [ Designated as safety issue: No ]

• Change from baseline in HIV RNA levels at day 7, 14, 21
• Proportion of subjects with HIV RNA levels <400 or <50 at day 7, 14, 21, week 24 and week 48
• Change from baseline and change in ratio of CD4+ and CD8+ cells at day 21, week 24 and week 48

The study will measure how safe and effective AVX754 (a new drug for the treatment of HIV) is in treating HIV-1 infected people who have failed treatment with lamivudine.

Lamivudine or emtricitabine are commonly used in combination with other drugs for first-line treatment of HIV infection. Although effective initially, many people later on develop resistance to some or all of the drugs (including lamivudine) leading to virological failure. Resistance is associated with characteristic mutations, which for lamivudine is the M184V mutation. A change to new, active drugs must take place when patients fail their current regime, to regain control of the virus. Although there are other types of drugs available for second line treatment, there is currently no fully active, well tolerated cytidine analogue that can replace lamivudine in a second-line regimen when patients fail first line treatment. This study will measure the efficacy and safety of AVX754 (a novel cytidine analogue with activity against HIV resistant to other nucleosides) as part of a new regimen to treat patients who have failed treatment containing lamivudine, compared to the best alternative new regimen which continues to include lamivudine.

• Drug: AVX754
  apricitabine, 600mg BID or 800mg BID
  Other Name: apricitabine
• Drug: 3TC
  3TC, 150mg BID
  Other Name: lamivudine

• Experimental: 600mg BID ATC
  600mg BID ATC
  Intervention: Drug: AVX754
• Experimental: 800mg BID ATC
  800mg BID ATC
  Intervention: Drug: AVX754
• Active Comparator: 150mg BID 3TC
  150mg BID 3TC
  Intervention: Drug: 3TC

Inclusion Criteria:

• HIV-1 infected
• M184V mutation in reverse transcriptase
• Currently taking lamivudine
• Viral load >2000 copies/ml

Exclusion Criteria:

• Hepatitis B surface antigen positive
• Pregnant or breastfeeding females
• Hepatitis C RNA positive and requiring treatment