Inclusion Criteria:
1. Signed informed consent prior to trial participation.
2. HIV-1 infected males or females at least 18 years of age.
3. Weight > 60 kg and < 100 kg
4. Acceptable laboratory screening values as defined in the exclusion criteria.
5. Three class ARV experienced, including current PI regimen for at least 12 weeks, at least one other PI based regimen for at least 12 weeks, treatment with at least one NNRTI and with at least 2 nucleoside agents.
6. Screening Virologic Phenotype demonstrating lopinavir phenotypic fold resistance between 10 and 80 (if patients have had Virologic Phenotype within 8 weeks of study screening this may be used as the qualifying lopinavir phenotypic fold resistance).
7. HIV-1 viral load 1000 copies/mL at screening.
8. Acceptable screening laboratory values that indicate adequate baseline organ function. Laboratory values are considered to be acceptable if the following apply:
- Total Cholesterol ≤ DAIDS Grade 3
- Total Triglycerides ≤ DAIDS Grade 3
- ALT and AST ≤DAIDS Grade 3).
- Any Grade GGT is acceptable.
- Any Grade CK is acceptable as long as there is no concurrent myopathy.
- All other laboratory test values ≤DAIDS Grade 2.
9. Willingness to discontinue treatment with NNRTIs throughout 48 weeks of study participation (prior or current treatment with enfuvirtide is permitted).
10. Acceptable medical history, as assessed by the investigator, with an unremarkable chest X-ray and ECG within 1 year of study participation.
11. Willingness to abstain from ingesting substances during the study which may alter plasma study drug levels by interaction with the cytochrome P450 system (these are listed in the informed consent under the risks of lopinavir/ritonavir).
12. A prior AIDS-defining event is acceptable as long as it has resolved or the patient has been on stable therapy for at least 12 weeks.
Exclusion Criteria:
1. ARV medication naïve.
2. Patients on recent drug holiday, defined as off ARV medications for at least 7 consecutive days within the last 28 days
3. Female patients of child-bearing potential who:
- have a positive serum pregnancy test at screening or during the study,
- are breast feeding,
- are planning to become pregnant,
- are not willing to a use barrier method of contraception, or
- require ethinyl estradiol administration.
4. Prior high-dose LPV/RTV therapy (higher than recommended doses in package insert).
5. Active diarrhea not controlled with antidiarrheal medications (not to exceed 3 bowel movements/day), malabsorption, or GI intolerance to lopinavir/ritonavir
6. Use of investigational medications within 30 days before study entry or during the trial.
7. Are receiving medications that are contraindicated with, or result in significant drug-drug interactions, with LPV and/or RTV (including, but not limited to triazolam, astemizole, ergot medications, cisapride, midazolam, bepridils, or rifampin).
8. Use of immunomodulatory drugs within 30 days before study entry or during the trial (e.g. interferon, cyclosporin, hydroxyurea, interleukin 2).
9. Active malignancy requiring chemotherapy or radiation.
10. Inability to adhere to the requirements of the protocol, including active substance abuse as assessed by the investigator.
11. In the opinion of the investigator, likely survival of less than 6 months because of underlying disease.