• Time From Randomization to Virologic Failure [ Time Frame: Follow-up time was variable,median follow-up was 138 weeks; see 'Amount of study follow-up' outcome for details ] [ Designated as safety issue: No ]
  Blood samples for determining virologic failure were obtained at visit weeks 16 and 24 , and every 12 weeks thereafter. Virologic failure was defined as a confirmed plasma HIV-1 RNA level >= 1000 copies/mL at or after 16 weeks after randomization and before 24 weeks, or >=200 copies/mL at or after 24 weeks. The 5th percentile for time to virologic failure is the time (in weeks) at which 5% of the participants have experienced virologic failure.
  
  
• Time From Treatment Dispensation to a Grade 3/4 Safety Event [ Time Frame: All follow-up while on initially assigned regimen; the median (25th, 75th percentile) follow-up while on initial regimen was 120 (54, 156) weeks and the range was 0 to 205 weeks. ] [ Designated as safety issue: Yes ]
  Grade 3/4 safety event is defined as a grade 3 or 4 sign, symptom, or laboratory abnormality that is at least one grade higher than at baseline, total bilirubin and creatine kinase (CPK) were excluded. Grading used the Division of AIDS (DAIDS) 2004 Severity of Adverse Events Tables.
  
  
• Time From Treatment Dispensation to Treatment Modification [ Time Frame: Follow-up time was variable,median follow-up was 138 weeks; see 'Amount of study follow-up' outcome for details ] [ Designated as safety issue: No ]
  Treatment modification is defined as the 1st modification of the regimen, including a permanent discontinuation, switch, or substitution.
  
  

• Time From Treatment Dispensation to Regimen Failure (First Occurrence of Virologic Failure or Treatment Modification) [ Time Frame: Follow-up time was variable,median follow-up was 138 weeks; see 'Amount of study follow-up' outcome for details ] [ Designated as safety issue: No ]
  Blood samples for determining virologic failure were obtained at 16 and 24 weeks, and every 12 weeks thereafter. Virologic failure was defined as a confirmed plasma HIV-1 RNA level >= 1000 copies/mL at or after 16 weeks and before 24 weeks or >=200 copies/mL at or after 24 weeks. Treatment modification was defined as the 1st modification of the regimen, including a permanent discontinuation, switch, or substitution.
  
  
• The Number of Participants With HIV-1 RNA Levels Less Than 50 Copies/mL [ Time Frame: At Weeks 48 and 96 ] [ Designated as safety issue: No ]
  
• Number of Participants With HIV-1 RNA Levels Less Than 200 Copies/mL [ Time Frame: At Weeks 48 and 96 ] [ Designated as safety issue: No ]
  
• Change in CD4 Count (Cells/mm3) From Baseline [ Time Frame: At Weeks 48 and 96 ] [ Designated as safety issue: No ]
  Change was calculated as the CD4 count at Week 48 (or at Week 96) minus the baseline CD4 count (mean of pre-entry and entry values).
  
  
• Number of Participants With Virologic Failure and Emergence of Major Resistance [ Time Frame: Follow-up time was variable,median follow-up was 138 weeks; see 'Amount of study follow-up' outcome for details ] [ Designated as safety issue: No ]
  Emergence of resistant virus was assessed by genotypic testing performed at Stanford University for all participants who met criteria for virologic failure and retrospectively on baseline samples from these participants. Major mutations were defined by International AIDS Society-United States of America (2008), as well as T69D, L74I, G190C/E/Q/T/V for reverse transcriptase and L24I, F53L, I54V/A/T/S, G73C/S/T/A, N88D for protease.
  
  
• Number of Participants Experiencing Certain Targeted Clinical Events, Including Death, AIDS-defining Illness, and HIV-1 Related Events. [ Time Frame: Follow-up time was variable, median follow-up was 138 weeks; see 'Amount of study follow-up' outcome for details ] [ Designated as safety issue: Yes ]

  AIDS-defining illnesses were defined per CDC category C definition. HIV-1 related events were defined per CDC category B definition. Events underwent study chair review for classification. See link below for more details.

  http://www.cdc.gov/mmwr/preview/mmwrhtml/00018871.htm

  
  
• Change in Fasting Total Cholesterol Level From Baseline [ Time Frame: At Weeks 48 and 96 ] [ Designated as safety issue: Yes ]
  Only fasting results are included. The protocol did not require that samples be collected fasting.
  
  
• Change in Fasting High-density Lipoprotein (HDL) Cholesterol Level From Baseline [ Time Frame: At Weeks 48 and 96 ] [ Designated as safety issue: Yes ]
  Only fasting results are included. The protocol did not require that samples be collected fasting.
  
  
• Change in Fasting Non-high Density Lipoprotein (Non-HDL) Cholesterol Level From Baseline [ Time Frame: At Weeks 48 and 96 ] [ Designated as safety issue: Yes ]
  Only fasting results are included. The protocol did not require that samples be collected fasting.
  
  
• Change in Fasting Triglyceride Level From Baseline [ Time Frame: At Weeks 48 and 96 ] [ Designated as safety issue: Yes ]
  Only fasting results are included. The protocol did not require that samples be collected fasting.
  
  

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).