Efavirenz or Atazanavir/Ritonavir Given With Emtricitabine/Tenofovir Disoproxil Fumarate or Abacavir/Lamivudine in HIV Infected Treatment-Naive Adults

Antiretroviral (ARV) treatment regimens consisting of EFV and two NRTIs are the most commonly
prescribed regimens for the initial therapy of HIV-infected people in the United States. Such
regimens are popular because the drugs are easy to administer, have overall excellent
efficacy, and are well tolerated. However, because of concerns about long-term drug toxicity,
the development of drug resistance, and potential complications in pregnant women, it is
imperative that other drug combinations be investigated as possible alternative initial
regimens. Drugs recently approved by the Food and Drug Administration (FDA) for HIV treatment
include the protease inhibitor (PI) atazanavir (ATV) and the two NRTI coformulations
emtricitabine/tenofovir disoproxil fumarate (FTC/TDF) and abacavir/lamivudine (ABC/3TC). Data
are limited on the efficacy of these new drugs when part of anti-HIV drug regimens. This
study will evaluate and compare the safety, tolerability, and efficacy of four different
treatment regimens in HIV-infected treatment-naive adults.

The treatment portion of this study will last 96 weeks after the last participant is
enrolled. Participants will be randomly assigned to one of four arms:

- Arm 1 participants will receive EFV, FTC/TDF, and placebo for ABC/3TC.

- Arm 2 participants will receive EFV, ABC/3TC, and placebo for FTC/TDF.

- Arm 3 participants will receive ritonavir (RTV)-boosted ATV, FTC/TDF, and placebo for
ABC/3TC.

- Arm 4 participants will receive RTV-boosted ATV, ABC/3TC and placebo for FTC/TDF.

NOTE: Lopinavir/ritonavir may be used in substitution of other drugs for certain
participants.

Study visits will occur at study entry; Weeks 1, 2, 4, 8, 16, and 24; and every 12 weeks
thereafter. A physical exam, blood collection, and urine collection will occur at most
visits. Two pharmacokinetic blood samples will be collected from participants between Weeks 4
and 24. Participants will undergo adherence training at study entry and will be asked to
complete adherence questionnaires at selected study visits. Some participants will be asked
to participate in ACTG A5224s, a metabolic substudy of ACTG A5202.

The Data Safety Monitoring Board (DSMB) for A5202 met in January 2008 to review the study.
After reviewing the study information, the DSMB noted that certain study regimens were
significantly less effective than others. Specifically, ABC/3TC-containing regimens were not
as effective in controlling the virus as TDF/FTC-containing regimens for participants
entering the study with high viral loads. The DSMB also commented that participants assigned
to ABC/3TC had a shorter time until they experienced side effects than participants assigned
to TDF/FTC. The DSMB had no safety concerns for the other drug comparisons.

Based on DSMB review, in Feb 2008 participants who started the study with high viral loads
were told whether they were taking ABC/3TC or TDF/FTC and offered the option to continue or
change their NRTI study drug component, after discussion with their doctor. For participants
who started the study with lower screening viral loads, study treatment continued without
change.

For 74 participant the reason for first treatment modification was "unblinded and switched"
as a consequence of the DSMB results (33 on EFV, ABC/3TC, and placebo FTC/TDF arm; 1 on
RTV-boosted ATV, FTC/TDF, and placebo ABC/3TC arm; and 40 on RTV-boosted ATV, ABC/3TC, and
placebo FTC/TDF arm).

Inclusion Criteria:

- HIV-infected. A resistance assay must be obtained if the participant has evidence of
recent infection. More information on this criterion can be found in the protocol.

- Antiretroviral naive, defined as 7 days or less of ARV treatment at any time prior to
study entry. Participants who have received ARVs as part of postexposure prophylaxis
or who have received an investigational drug that was not an NRTI, NNRTI, or PI are
eligible for this study.

- HIV viral load greater than 1,000 copies/ml within 90 days prior to study entry

- Certain laboratory values obtained within 30 days prior to study entry. More
information on this criterion can be found in the protocol

- Willing to use acceptable forms of contraception

- Parent or guardian able and willing to provide written informed consent, if applicable

- Hepatitis B surface antigen (HBsAg) negative at study entry

Exclusion Criteria:

- Immunomodulators (e.g., interleukins, interferons, cyclosporine), HIV vaccine,
systemic cytotoxic chemotherapy, or investigational therapy within 30 days prior to
study entry. Individuals receiving either stable physiologic glucocorticoid doses,
corticosteroids for acute therapy for pneumocystis pneumonia, or a short course (2
weeks or less) of pharmacologic glucocorticoid therapy will not be excluded.

- Known allergy/sensitivity to study drugs or their formulations

- Active alcohol or drug use that, in the opinion of the investigator, would interfere
with adherence to study requirements

- Serious illness requiring systemic treatment or hospitalization. Patients who have
completed therapy or are clinically stable on therapy for at least 7 days prior to
study entry are not excluded.

- Known clinically relevant cardiac conduction system disease

- Requirement for any current medications that are prohibited with any study treatment.

- Evidence of any major drug resistance-associated mutation on any genotype or evidence
of significant resistance on any phenotype performed at any time prior to study entry.

- Current imprisonment or involuntary incarceration for psychiatric or physical (e.g.,
infectious disease) illness

- Breastfeeding. Women who become pregnant during the study will be unblinded and
required to permanently discontinue their study regimens.