This is a double-blind Phase 2a study to test the safety and efficacy of an investigational HIV drug, amdoxovir (300 mg or 500 mg twice daily) compared with tenofovir DF 300 mg once daily in HIV-1 infected antiretroviral therapy-experienced subjects who are currently failing antiretroviral therapy. There are three treatment groups (N=45). Subjects will be randomized to receive either amdoxovir 300 mg twice daily (n=15) or amdoxovir 500 mg twice daily (n=15) or tenofovir DF 300 mg once daily (n=15); each in combination with zidovudine 300 mg twice daily.

The study will assess initially amdoxovir (300 mg or 500 mg twice daily) or tenofovir DF 300 mg once daily, both in combination zidovudine 300 mg twice daily plus failing third drug, but then with lopinavir/ritonavir (400 mg/100 mg twice daily) after Week 2. Subjects who received amdoxovir (300 mg or 500 mg twice daily) and benefited from the drug may choose to enroll in the 36-week open-label study.

Inclusion Criteria:

• Male or female ≥ 18 years old with HIV-1 RNA ≥ 2,000 copies/mL and currently failing therapy.
• Has M184I/V mutation in addition to 0-2 thymidine analog mutations (TAMs) at screening.
• Agree to be abstinent or use two reliable forms of contraception (for females) and one form for men when participating in sexual activity that could result in pregnancy.

Exclusion Criteria:

• Current or recent (last 30 days of study entry) AIDS defining diseases.
• Genotypic resistance testing at screening indicating K65R, L74V, Q151M mutation.
• Prior exposure to lopinavir/ritonavir or amdoxovir.
• Impaired hepatic function (ALT > 5 x ULN).
• Women who are pregnant or breast feeding.