Second-line Treatment of HIV-1 With Ritonavir Boosted Atazanavir or Darunavir With an Optimized NRTI Backbone

Allocation: Randomization will be stratified

- ATV = Atazanavir

- DRV = Darunavir

- RTV = Ritonavir

Inclusion Criteria:

1. Signed informed consent

2. HIV-1 infected patients with viremia (VL > 1000c/mL) on or after their first NNRTI or
INI-based cART regimen and meeting one of the two criteria below:

- On 1st line Non-nucleoside reverse transcriptase inhibitor (NNRTI) or Integrase
inhibitor (INI)-based Combination antiretroviral therapy (cART) with HIV-1 RNA >
1000 c/ML after being on the same therapy for at least 12 weeks

- Off 1st line NNRTI or INI-based cART for at least 2 weeks after having been on
antiviral therapy for at least 4 weeks: HIV-1 RNA > 1000 c/ML

3. At least one NRTI other than 3TC or FTC with full sensitivity (one "active" NRTI) by
genotype and phenotype, ie, PhenoSense GT, report must provide a "sensitive" net
assessment of susceptibility. An NRTI or PI (reported with or without ritonavir) with
a "partially sensitive" net assessment will not be considered "fully sensitive"

4. Mentally able to participate in the study

5. Men and women ≥ 18 years old

- Women of child bearing potential who engage in vaginal intercourse and who are
not clinically sterilized must use highly effective methods of birth control
during the study

Exclusion Criteria:

1. Screening HIV genotype showing any major Protease inhibitor (PI)
resistance-associated mutations (RAMs)

2. Any past exposure to protease inhibitors

3. Subjects with < 1 fully active Nucleoside reverse transcriptase inhibitor (NRTI) on
PhenoSense report, other than Lamivudine (3TC) or Emtricitabine (FTC)

4. Diagnosed with active tuberculosis

5. Chronic hepatitis B infection

6. Hepatitis C-positive patients who are not clinically stable or need treatment during
the study period

7. Acute hepatitis in the 30 days prior to study entry

8. Any gastrointestinal disease or surgical procedure that may impact the absorption of
study drug

9. Intractable diarrhea within 30 days prior to study entry

10. Presence of a newly diagnosed Human immunodeficiency virus (HIV)-related
opportunistic infection or any medical condition requiring acute therapy at the time
of enrollment

11. Subject's with Cushing's syndrome

12. Untreated hypothyroidism or hyperthyroidism

13. Recent therapy with agents with significant systemic myelosuppressive, neurotoxic,
pancreatotoxic, hepatotoxic or cytotoxic potential within 3 months of study start

14. Subject's with obstructive liver disease

15. Active alcohol or illegal substance use

16. Inability to swallow capsules

17. Active peripheral neuropathy

18. Presence of cardiomypathy or any significant cardiovascular disease

19. Known, clinically significant cardiac conduction system disease

20. Physical and Laboratory Test Findings:

- Moderate to severe hepatic insufficiency

- Screening laboratory values as follows:

- Calculated creatinine clearance < 60 cc/min

- Hemoglobin < 8.0 g/dL

- Total serum lipase ≥ 1.4 times the upper limit of normal (ULN)

- Liver enzymes [Aspartate transaminase (AST), Alanine transaminase (ALT)] ≥
5 times the ULN

- Alkaline phosphatase > 5 times the ULN

- Platelets < 50,000 cells/mm3

- Positive blood screen for hepatitis B surface antigen (HBsAg)

- Total serum bilirubin ≥ 1.5 times the ULN

21. Allergies and Adverse Drug Reaction:

- Previously demonstrated hypersensitivity to any of the components of atazanavir
or the other experimental agents in this study

- Darunavir contains a sulfonamide moiety. Darunavir should be used with caution
in patients with a known sulfonamide allergy

- History of allergy to atazanavir, ritonavir, or darunavir

- History of allergy to NRTIs included as NRTI backbone options in this study

- History of clinically relevant severe drug reaction

22. Sex and Reproductive Status:

- Women with a positive pregnancy test on enrollment prior to study drug
administration

- Women who become pregnant during the study will be taken off-protocol

- Women using a prohibited contraceptive method

- Women who are breastfeeding

23. Other Exclusion Criteria

- Prisoners or subjects who are involuntarily incarcerated

- Subjects who are compulsorily detained for treatment of wither a psychiatric or
physical illness