A Study in Underrepresented Patient Population or Regimen Tolerability: SUPPoRT

The hope of this study is to gather data and information about the tolerability and effectiveness of Lexiva versus Sustiva in patients who have have been generally underrepresented in clinical trials.

The objective of this study is to gain tolerability and efficacy data for Norvir-boosted Lexiva versus Sustiva, both used in combination with Epzicom, as components of a first-line, once daily regimen for the treatment of HIV-1 infection in a patient population that is underrepresented in US clinical research.

• Drug: Lexiva + Norvir + Epzicom
  Once daily (QD) regimen of Lexiva (fosamprenavir 1400 mg) + Norvir (ritonavir 100 mg) + Epzicom (abacavir 600 mg / lamivudine 300 mg)
• Drug: Sustiva + Epzicom
  QD regimen of Sustiva (efavirenz 600 mg) + Epzicom (abacavir 600 mg / lamivudine 300 mg)

• Experimental: A
  Once daily (QD) regimen of Lexiva (fosamprenavir 1400 mg) + Norvir (ritonavir 100 mg) + Epzicom (abacavir 600 mg / lamivudine 300 mg).
  Intervention: Drug: Lexiva + Norvir + Epzicom
• Experimental: B
  QD regimen of Sustiva (efavirenz 600 mg) + Epzicom (abacavir 600 mg / lamivudine 300 mg)
  Intervention: Drug: Sustiva + Epzicom

Inclusion Criteria:

• INC1 Screening plasma HIV-1 RNA viral load >5000 copies/mL
• INC2 Self-identification as having any non-White/Caucasian European geographic ancestry (i.e., an individual is eligible if she/he does not have any White/Caucasian European ancestry; OR an individual is eligible if she/he indicates a mix of White/Caucasian European ancestry AND one or more other geographic ancestries);
• INC3 Adult (≥18 years)
• INC4 Antiretroviral-naïve (no treatment with any antiretroviral drug in the 28 days prior to study entry and ≤14 days of treatment ever with any antiretroviral drug)
• INC5 Negative test for the HLA-B*5701 allele
• INC6 Ability and willingness to give written informed consent

• INC7 Either gender is eligible, but enrollment of at least two female subjects to every one male subject is strongly encouraged. A female subject is eligible to participate in the study if she is of:

  a. Non-childbearing potential (i.e., physiologically incapable of becoming pregnant, including any female who is pre-menarchial or post-menopausal); or, b. Childbearing potential with a negative pregnancy test at screen and agrees to use one of the following methods of contraception (any contraception method must be used consistently and correctly, i.e., in accordance with both the Prescribing Information and the instructions of a physician): i. Agreement for complete abstinence from intercourse from 2 weeks prior to administration of investigational products, throughout the study, and for 2 weeks after discontinuation of all study medications; ii. Double barrier contraception (male condom/spermicide, male condom/diaphragm, diaphragm/spermicide); iii. Any intrauterine device (IUD) with published data showing that the expected failure rate is less than 1% per year (not all IUDs meet this criterion); iv. Any other method with published data showing that the lowest expected failure rate for the method is less than 1% per year. Note: Hormonal contraception is not recommended for use in conjunction with Lexiva due to decreased efficacy of contraception as well as increased risk of hepatic transaminase elevation. All applicable Prescribing Information should be consulted.

  v. Sterilization (female subject or male partner of female subject)

Exclusion Criteria:

• EXC1 Screening HIV-1 genotype indicating the presence of any of the following mutations in the reverse transcriptase (RT) region: K65R, L74V, K103N, Y115F, Y181C/I, Y188C/L/H or G190S/A, or a combination of two or more thymidine analog mutations (M41L, D67N, K70R, K219Q or E) that include changes at either L210 or T215, associated with resistance to abacavir, lamivudine, or efavirenz; OR within the protease region, detection of any of the following mutations associated with resistance to fosamprenavir or ritonavir: I50V, I54L/M, I84V, or the combination of the two mutations V32I+I147V
• EXC2 Positive for Hepatitis B surface antigen (HBsAg+)

• EXC3 Requirement for active treatment for hepatitis C virus infection, as indicated by both a positive HCV serology AND either:

  1. Decompensated liver disease, or
  2. Aspartate aminotransferase (AST) >3X the upper limit of normal (ULN), or
  3. Alanine aminotransferase (ALT) >3X the ULN
• EXC4 Currently pregnant, intending to become pregnant during the study period, or breast-feeding
• EXC5 Use of immunomodulators (e.g., interleukins, interferons, cyclosporine), any vaccinations, systemic cytotoxic chemotherapy, or investigational therapy within 28 days prior to study entry. Chronic treatment with prednisone at a daily dose of 10 mg or less is permitted. Acute treatment (less than 21 days) with larger doses of corticosteroids for acute therapy is permitted.
• EXC6 Active or suspected drug or alcohol use or dependence that, in the opinion of the site investigator, would interfere with adherence to study requirements
• EXC7 Judged by the investigator to be at significant risk of failing to comply with the provisions of the protocol as to cause harm to self or seriously interfere with the validity of the study results
• EXC8 Active or acute CDC Clinical Category C event at screening. (Note: Treatment for the acute event must have been completed at least 28 days prior to screening.)
• EXC9 Clinically relevant pancreatitis or clinically relevant hepatitis at screening
• EXC10 Hgb<8g/dl, platelet count <50,000/mm3, calculated creatinine clearance <50ml/min via Cockroft-Gault equation, or AST or ALT > 5X the ULN
• EXC11 Any Grade 4 laboratory abnormality