| Eligibility |
Inclusion Criteria
- Signed informed consent.
- HIV-1 infected patients with viremia (VL = 500/mL) on or after their first NNRTI or
INI-based cART regimen and meeting one of the two criteria below:.
i) On 1st line Non-nucleoside reverse transcriptase inhibitor (NNRTI) or Integrase
inhibitor (INI)-based Combination antiretroviral therapy (cART) with HIV-1 RNA = 500
c/ML after being on the same therapy for at least 12 weeks.
ii) Off 1st line NNRTI or INI-based Combination antiretroviral therapy (cART) for at least
2 weeks after having been on antiviral therapy for at least 4 weeks and who are
non-compliant and off first line cART without a history of virologic failure with
resistance, with a : HIV-1 RNA = 500 c/ML.
- Fully sensitive genotype and phenotype report for Atazanavir/Ritonavir (clinical
cut-off of 5.2) and Darunavir/Ritonavir (clinical cut-off ranging from 10 to 90).
- At least one NRTI other than Lamivudine (3TC) or emtricitabine (FTC) with full
sensitivity (one "active" NRTI) by genotype and phenotype, ie, PhenoSense Genotype
(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".
- Mentally able to participate in the study.
- 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
- Screening HIV genotype showing presence at baseline of any of the following Protease
inhibitor (PI) Mutation Patterns associated with genotypic resistance to Atazanavir
sulfate/ Ritonavir or Darunavir/Ritonavir will lead to exclusion:.
i) Subjects with any darunavir associated mutations* at baseline (*V11I, V32I, L33F, I47V,
I50V, I54L, I54M, T74P, L76V, I84V and L89V).
ii) Subjects with a major mutation to Atazanavir sulfate consisting of N88S.
iii) Subjects with more than 3 of any of the following Atazanavir sulfate related
mutations:D30N, M36I/V, M46I/L/T, I54V/L/T/M/A, A71V/T/I/G, G73S/A/C/T, V77I, V82A/F/T/S/I,
I84V/A, N88D or L90M.
- Subjects with < 1 fully active NRTI on PhenoSense report, other than lamivudine and
emtricitabine.
- Diagnosed with active tuberculosis.
- Chronic hepatitis B infection.
- Hepatitis C-positive patients who are not clinically stable or need treatment during
the study period.
- Acute hepatitis in the 30 days prior to study entry.
- Any gastrointestinal disease or surgical procedure that may impact the absorption of
study drug.
- Intractable diarrhea within 30 days prior to study entry.
- Presence of a newly diagnosed Human immunodeficiency virus (HIV)-related opportunistic
infection or any medical condition requiring acute therapy at the time of enrollment.
- Subject's with Cushing's syndrome.
- Untreated hypothyroidism or hyperthyroidism.
- Recent therapy with agents with significant systemic myelosuppressive, neurotoxic,
pancreatotoxic, hepatotoxic or cytotoxic potential within 3 months of study start.
- Subject's with obstructive liver disease.
- Active alcohol or illegal substance use.
- Inability to swallow capsules.
- Active peripheral neuropathy.
- Presence of cardiomypathy or any significant cardiovascular disease.
- Known, clinically significant cardiac conduction system disease.
- Physical and Laboratory Test Findings:.
i) Moderate to severe hepatic insufficiency.
ii) Screening laboratory values as follows:.
A. T4 < 4mcg/dL or >11mcg/dL and/or Thyroid-stimulating hormone (TSH) <0.5mU/L or >5.0mU/L.
B. Calculated creatinine clearance < 60 cc/min.
C. Hemoglobin < 8.0 g/dL.
D. Total serum lipase = 1.4 times the upper limit of normal (ULN).
E. Liver enzymes [Aspartate transaminase (AST), Alanine transaminase (ALT)] = 5 times the
ULN.
F. Alkaline phosphatase > 5 times the ULN.
G. Platelets < 50,000 cells/mm3.
H. Positive blood screen for hepatitis B surface antigen (HBsAg).
I. Total serum bilirubin = 1.5 times the ULN.
- Allergies and Adverse Drug Reaction:.
i) Previously demonstrated hypersensitivity to any of the components of atazanavir or the
other experimental agents in this study.
ii) Darunavir contains a sulfonamide moiety. Darunavir should be used with caution in
patients with a known sulfonamide allergy.
iii) History of allergy to atazanavir, ritonavir, or darunavir.
iv) History of allergy to NRTIs included as NRTI backbone options in this study.
v) History of clinically relevant severe drug reaction.
- Sex and Reproductive Status:.
i) Women with a positive pregnancy test on enrollment prior to study drug administration.
ii) Women who become pregnant during the study will be taken off-protocol.
iii) Women using a prohibited contraceptive method.
iv) Women who are breastfeeding.
- Other Exclusion Criteria.
i) Prisoners or subjects who are involuntarily incarcerated.
ii) Subjects who are compulsorily detained for treatment of wither a psychiatric or
physical illness.
- Other protocol-defined Inclusion/Exclusion criteria apply.
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