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

A Phase IIIB, Randomized Trial of Open-Label Efavirenz or Atazanavir With Ritonavir in Combination With Double-Blind Comparison of Emtricitabine/Tenofovir or Abacavir/Lamivudine in Antiretroviral-Naive Subjects

Currently, the preferred anti-HIV regimens used in the United States consist of two nucleoside reverse transcriptase inhibitors (NRTIs) and the nonnucleoside reverse transcriptase inhibitor (NNRTI) efavirenz (EFV). However, with new anti-HIV drugs being approved, alternative regimens need to be tested to determine if new drug combinations have increased effectiveness in treating HIV. The purpose of this study is to test the safety, tolerability, and effectiveness of four different regimens in HIV-infected adults who have never taken anti-HIV drugs.

Study Overview

• Status: Completed
• Conditions: HIV Infections
• Intervention / Treatment: Drug: Efavirenz; Drug: Emtricitabine/Tenofovir disoproxil fumarate; Drug: Abacavir/Lamivudine placebo; Drug: Abacavir/Lamivudine; Drug: Emtricitabine/Tenofovir disoproxil fumarate placebo; Drug: Atazanavir; Drug: Ritonavir

Detailed Description

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).

• Study Type: Interventional
• Enrollment (Actual): 1864
• Phase: Phase 3

Contacts and Locations

Study Locations

• Puerto Rico
  • San Juan, Puerto Rico, 00935
    • Puerto Rico-AIDS CRS (5401)
• United States
  • California
    • Los Angeles, California, United States, 90035
      • UCLA CARE Center CRS (601)
    • Los Angeles, California, United States, 90033
      • Usc Crs (1201)
    • Palo Alto, California, United States, 94304
      • Stanford CRS (501)
    • San Diego, California, United States, 92103
      • Ucsd, Avrc Crs (701)
    • San Francisco, California, United States, 94110
      • Ucsf Aids Crs (801)
    • Stanford, California, United States, 94305-5107
      • San Mateo County AIDS Program (505)
    • Stanford, California, United States, 94305-5107
      • Willow Clinic (507)
    • Torrance, California, United States, 90502
      • Harbor-UCLA Med. Ctr. CRS (603)
  • Colorado
    • Aurora, Colorado, United States, 80045
      • University of Colorado Hospital CRS (6101)
  • District of Columbia
    • Washington, District of Columbia, United States, 20007
      • Georgetown University CRS (GU CRS) (1008)
  • Florida
    • Miami, Florida, United States, 33139
      • University of Miami AIDS CRS (901)
  • Georgia
    • Atlanta, Georgia, United States, 30308
      • Emory University
    • Atlanta, Georgia, United States, 30308
      • The Ponce de Leon Center CRS (5802)
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Northwestern University CRS (2701)
    • Chicago, Illinois, United States, 60612
      • Rush Univ. Med. Ctr. ACTG CRS (2702)
    • Chicago, Illinois, United States, 60612
      • Cook County Hospital Core Center (2705)
  • Indiana
    • Indianapolis, Indiana, United States, 46202-5250
      • Indiana University Hospital (2601)
    • Indianapolis, Indiana, United States, 46202
      • Wishard Hospital (2603)
  • Iowa
    • Iowa City, Iowa, United States, 52242
      • Univ of Iowa Hosp and Clinic (1504)
  • Maryland
    • Baltimore, Maryland, United States, 21201
      • IHV Baltimore Treatment CRS (4651)
    • Baltimore, Maryland, United States, 21287
      • Johns Hopkins Adult AIDS CRS (201)
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Massachusetts General Hospital ACTG CRS (101)
    • Boston, Massachusetts, United States, 02115
      • Brigham and Women's Hosp. ACTG CRS (107)
    • Boston, Massachusetts, United States, 02215
      • Beth Israel Deaconess Med. Ctr., ACTG CRS (103)
    • Boston, Massachusetts, United States, 02118
      • Bmc Actg Crs (104)
  • Missouri
    • Saint Louis, Missouri, United States, 63110
      • Washington U CRS (2101)
  • New York
    • Buffalo, New York, United States, 14215
      • SUNY - Buffalo (Rochester) (1102)
    • New York, New York, United States, 10011
      • Cornell CRS (7804)
    • New York, New York, United States, 10032
      • HIV Prevention & Treatment CRS (30329)
    • New York, New York, United States, 10011
      • Weill Med. College of Cornell Univ., The Cornell CTU -Chelsea (7803)
    • New York, New York, United States, 10016
      • NY Univ. HIV/AIDS CRS (401)
    • New York, New York, United States, 10037
      • Harlem ACTG CRS (31483)
    • Rochester, New York, United States, 14642
      • University of Rochester ACTG CRS (1101)
    • Rochester, New York, United States, 14604
      • AIDS Community Health Ctr. ACTG CRS (1108)
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27514
      • Unc Aids Crs (3201)
    • Chapel Hill, North Carolina, United States, 27514
      • Wake County Department of Health (30076)
    • Durham, North Carolina, United States, 27710
      • Duke University Medical Center Adult CRS (1601)
    • Greensboro, North Carolina, United States, 27401
      • Moses H. Cone Memorial Hospital CRS (3203)
  • Ohio
    • Cincinnati, Ohio, United States, 45267
      • University of Cincinnati CRS (2401)
    • Cleveland, Ohio, United States, 44106
      • Case CRS (2501)
    • Cleveland, Ohio, United States, 44109
      • Metro Health CRS (2503)
    • Columbus, Ohio, United States, 43210
      • The Ohio State Univ. AIDS CRS (2301)
  • Pennsylvania
    • Norristown, Pennsylvania, United States, 19401
      • Presbyterian Medical Center - Univ. of PA (6206)
    • Philadelphia, Pennsylvania, United States, 19104
      • Hosp. of the Univ. of Pennsylvania CRS (6201)
    • Pittsburgh, Pennsylvania, United States, 15213
      • Pitt CRS (1001)
  • Rhode Island
    • Providence, Rhode Island, United States, 02906
      • The Miriam Hosp. ACTG CRS (2951)
  • Tennessee
    • Nashville, Tennessee, United States, 37232
      • Vanderbilt Therapeutics CRS (3652)
  • Texas
    • Dallas, Texas, United States, 75215
      • Peabody Health Center CRS (31443)
    • Galveston, Texas, United States, 77555-0435
      • University of Texas, Galveston (6301)
  • Washington
    • Seattle, Washington, United States, 98104
      • University of Washington AIDS CRS (1401)
    • Seattle, Washington, United States, 98104
      • University of Washington General Clinical Research (1403)

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: EFV, FTC/TDF, and placebo ABC/3TC; Participants will receive EFV, FTC/TDF, and placebo for ABC/3TC for at least 96 weeks	Drug: Efavirenz; 600 mg tablet taken orally daily; Other Names: EFV; Drug: Emtricitabine/Tenofovir disoproxil fumarate; 200 mg emtricitabine/300 mg tenofovir disoproxil fumarate tablet taken orally daily; Other Names: FTC/TDF; Drug: Abacavir/Lamivudine placebo; Placebo tablet taken orally daily; Other Names: ABC/3TC placebo
Experimental: EFV, ABC/3TC and placebo FTC/TDF; Participants will receive EFV, ABC/3TC, and placebo for FTC/TDF for at least 96 weeks	Drug: Efavirenz; 600 mg tablet taken orally daily; Other Names: EFV; Drug: Abacavir/Lamivudine; 600 mg abacavir/300 mg lamivudine tablet taken orally daily; Other Names: ABC/3TC; Drug: Emtricitabine/Tenofovir disoproxil fumarate placebo; Placebo tablet taken orally daily; Other Names: FTC/TDF placebo
Experimental: RTV-boosted ATV, FTC/TDF, and placebo ABC/3TC; Participants will receive RTV-boosted ATV, FTC/TDF, and placebo for ABC/3TC for at least 96 weeks	Drug: Emtricitabine/Tenofovir disoproxil fumarate; 200 mg emtricitabine/300 mg tenofovir disoproxil fumarate tablet taken orally daily; Other Names: FTC/TDF; Drug: Abacavir/Lamivudine placebo; Placebo tablet taken orally daily; Other Names: ABC/3TC placebo; Drug: Atazanavir; 300 mg tablet taken orally daily; Other Names: ATV; Drug: Ritonavir; 100 mg tablet taken orally daily; Other Names: RTV
Experimental: RTV-boosted ATV, ABC/3TC, and placebo FTC/TDF; Participants will receive RTV-boosted ATV, ABC/3TC, and placebo for FTC/TDF for at least 96 weeks	Drug: Abacavir/Lamivudine; 600 mg abacavir/300 mg lamivudine tablet taken orally daily; Other Names: ABC/3TC; Drug: Emtricitabine/Tenofovir disoproxil fumarate placebo; Placebo tablet taken orally daily; Other Names: FTC/TDF placebo; Drug: Atazanavir; 300 mg tablet taken orally daily; Other Names: ATV; Drug: Ritonavir; 100 mg tablet taken orally daily; Other Names: RTV

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time From Randomization to Virologic Failure	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.	Follow-up time was variable,median follow-up was 138 weeks; see 'Amount of study follow-up' outcome for details
Time From Treatment Dispensation to a Grade 3/4 Safety Event	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.	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.
Time From Treatment Dispensation to Treatment Modification	Treatment modification is defined as the 1st modification of the regimen, including a permanent discontinuation, switch, or substitution.	Follow-up time was variable,median follow-up was 138 weeks; see 'Amount of study follow-up' outcome for details

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time From Treatment Dispensation to Regimen Failure (First Occurrence of Virologic Failure or Treatment Modification)	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.	Follow-up time was variable,median follow-up was 138 weeks; see 'Amount of study follow-up' outcome for details
The Number of Participants With HIV-1 RNA Levels Less Than 50 Copies/mL		At Weeks 48 and 96
Number of Participants With HIV-1 RNA Levels Less Than 200 Copies/mL		At Weeks 48 and 96
Change in CD4 Count (Cells/mm3) From Baseline	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).	At Weeks 48 and 96
Number of Participants With Virologic Failure and Emergence of Major Resistance	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.	Follow-up time was variable,median follow-up was 138 weeks; see 'Amount of study follow-up' outcome for details
Number of Participants Experiencing Certain Targeted Clinical Events, Including Death, AIDS-defining Illness, and HIV-1 Related Events.	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	Follow-up time was variable, median follow-up was 138 weeks; see 'Amount of study follow-up' outcome for details
Change in Fasting Total Cholesterol Level From Baseline	Only fasting results are included. The protocol did not require that samples be collected fasting.	At Weeks 48 and 96
Change in Fasting High-density Lipoprotein (HDL) Cholesterol Level From Baseline	Only fasting results are included. The protocol did not require that samples be collected fasting.	At Weeks 48 and 96
Change in Fasting Non-high Density Lipoprotein (Non-HDL) Cholesterol Level From Baseline	Only fasting results are included. The protocol did not require that samples be collected fasting.	At Weeks 48 and 96
Change in Fasting Triglyceride Level From Baseline	Only fasting results are included. The protocol did not require that samples be collected fasting.	At Weeks 48 and 96

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Amount of Study Follow-up	Participants were to be followed for 96 weeks after the last enrollment. Accrual was expected to take 96 weeks, thus the planned follow-up time was 96 to 192 weeks, dependent on when in the study the participant enrolled. This outcome summarizes that total amount of actual follow-up in weeks from randomization to last contact.	Follow-up time was variable, median follow-up was 138 weeks
Number of Participants With Virologic Failure	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.	Follow-up time was variable, median follow-up was 138 weeks; see 'Amount of study follow-up' outcome for details
Cumulative Probability of Not Experiencing Virologic Failure	Kaplan-Meier estimate of the cumulative survival probability at week 48 and 96. 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.	At week 48 and 96
Number of Participants With a Grade 3/4 Safety Event	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. As-treated analysis censored at 1st modification of initially assigned regimen, participants who never started treatment were excluded.	Over all study follow-up while on initially assigned treatment, median follow-up was 120 weeks
Cumulative Probability of Not Experiencing a Grade 3/4 Safety Event	Kaplan-Meier estimate of the cumulative survival probability at week 48 and 96. 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. As-treated analysis censored at 1st modification of initially assigned regimen, participants who never started treatment were excluded.	At week 48 and 96
Number of Participants With Treatment Modification	Treatment modification is defined as the 1st modification of the regimen, including a permanent discontinuation, switch, or substitution.	Follow-up time was variable, median follow-up was 138 weeks; see 'Amount of study follow-up' outcome for details
Cumulative Probability of Not Experiencing Treatment Modification	Kaplan-Meier estimate of the cumulative survival probability at week 48 and 96. Treatment modification is defined as the 1st modification of the regimen, including a permanent discontinuation, switch, or substitution.	At week 48 and 96
Number of Participants With Regimen Failure	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.	Follow-up time was variable, median follow-up was 138 weeks; see 'Amount of study follow-up' outcome for details
Cumulative Probability of Not Experiencing Regimen Failure	Kaplan-Meier estimate of the cumulative survival probability at week 48 and 96. 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.	At week 48 and 96

Collaborators and Investigators

• Sponsor: AIDS Clinical Trials Group
• Collaborators: National Institute of Allergy and Infectious Diseases (NIAID)
• Investigators: Study Chair: Eric Daar, MD, Harbor-UCLA Medical Center, Los Angeles Biomedical Research Institute; Study Chair: Paul Sax, MD, Division of Infectious Diseases, Brigham and Women's Hospital

Publications and helpful links

General Publications

• Li B, Veturi Y, Verma A, Bradford Y, Daar ES, Gulick RM, Riddler SA, Robbins GK, Lennox JL, Haas DW, Ritchie MD. Tissue specificity-aware TWAS (TSA-TWAS) framework identifies novel associations with metabolic, immunologic, and virologic traits in HIV-positive adults. PLoS Genet. 2021 Apr 26;17(4):e1009464. doi: 10.1371/journal.pgen.1009464. eCollection 2021 Apr.
• Leonard MA, Cindi Z, Bradford Y, Bourgi K, Koethe J, Turner M, Norwood J, Woodward B, Erdem H, Basham R, Baker P, Rebeiro PF, Sterling TR, Hulgan T, Daar ES, Gulick R, Riddler SA, Sinxadi P, Ritchie MD, Haas DW. Efavirenz Pharmacogenetics and Weight Gain Following Switch to Integrase Inhibitor-Containing Regimens. Clin Infect Dis. 2021 Oct 5;73(7):e2153-e2163. doi: 10.1093/cid/ciaa1219.
• Mollan KR, Smurzynski M, Eron JJ, Daar ES, Campbell TB, Sax PE, Gulick RM, Na L, O'Keefe L, Robertson KR, Tierney C. Association between efavirenz as initial therapy for HIV-1 infection and increased risk for suicidal ideation or attempted or completed suicide: an analysis of trial data. Ann Intern Med. 2014 Jul 1;161(1):1-10. doi: 10.7326/M14-0293. Erratum In: Ann Intern Med. 2014 Aug 19;161(4):308.
• Anderson PL. Pharmacologic perspectives for once-daily antiretroviral therapy. Ann Pharmacother. 2004 Nov;38(11):1924-34. doi: 10.1345/aph.1E036. Epub 2004 Oct 12.
• Kress KD. HIV update: emerging clinical evidence and a review of recommendations for the use of highly active antiretroviral therapy. Am J Health Syst Pharm. 2004 Oct 1;61 Suppl 3:S3-14; quiz S15-6. doi: 10.1093/ajhp/61.suppl_3.S3. Erratum In: Am J Health Syst Pharm. 2004 Nov 15;61(22):2350.
• Robbins GK, De Gruttola V, Shafer RW, Smeaton LM, Snyder SW, Pettinelli C, Dube MP, Fischl MA, Pollard RB, Delapenha R, Gedeon L, van der Horst C, Murphy RL, Becker MI, D'Aquila RT, Vella S, Merigan TC, Hirsch MS; AIDS Clinical Trials Group 384 Team. Comparison of sequential three-drug regimens as initial therapy for HIV-1 infection. N Engl J Med. 2003 Dec 11;349(24):2293-303. doi: 10.1056/NEJMoa030264.
• Shafer RW, Smeaton LM, Robbins GK, De Gruttola V, Snyder SW, D'Aquila RT, Johnson VA, Morse GD, Nokta MA, Martinez AI, Gripshover BM, Kaul P, Haubrich R, Swingle M, McCarty SD, Vella S, Hirsch MS, Merigan TC; AIDS Clinical Trials Group 384 Team. Comparison of four-drug regimens and pairs of sequential three-drug regimens as initial therapy for HIV-1 infection. N Engl J Med. 2003 Dec 11;349(24):2304-15. doi: 10.1056/NEJMoa030265.
• Bednasz CJ, Venuto CS, Ma Q, Daar ES, Sax PE, Fischl MA, Collier AC, Smith KY, Tierney C, Acosta EP, Mager DE, Morse GD; AIDS Clinical Trials Group Study A5202 Team. Race/Ethnicity and Protease Inhibitor Use Influence Plasma Tenofovir Exposure in Adults Living with HIV-1 in AIDS Clinical Trials Group Study A5202. Antimicrob Agents Chemother. 2019 Mar 27;63(4):e01638-18. doi: 10.1128/AAC.01638-18. Print 2019 Apr.
• Longenecker CT, Kitch D, Sax PE, Daar ES, Tierney C, Gupta SK, McComsey GA; AIDS Clinical Trials Group Study A5224s Team. Reductions in Plasma Cystatin C After Initiation of Antiretroviral Therapy Are Associated With Reductions in Inflammation: ACTG A5224s. J Acquir Immune Defic Syndr. 2015 Jun 1;69(2):168-77. doi: 10.1097/QAI.0000000000000557.
• Sax PE, Zolopa A, Brar I, Elion R, Ortiz R, Post F, Wang H, Callebaut C, Martin H, Fordyce MW, McCallister S. Tenofovir alafenamide vs. tenofovir disoproxil fumarate in single tablet regimens for initial HIV-1 therapy: a randomized phase 2 study. J Acquir Immune Defic Syndr. 2014 Sep 1;67(1):52-8. doi: 10.1097/QAI.0000000000000225.
• Erlandson KM, Kitch D, Tierney C, Sax PE, Daar ES, Melbourne KM, Ha B, McComsey GA. Impact of randomized antiretroviral therapy initiation on glucose metabolism. AIDS. 2014 Jun 19;28(10):1451-61. doi: 10.1097/QAD.0000000000000266.
• Erlandson KM, Kitch D, Tierney C, Sax PE, Daar ES, Tebas P, Melbourne K, Ha B, Jahed NC, McComsey GA. Weight and lean body mass change with antiretroviral initiation and impact on bone mineral density. AIDS. 2013 Aug 24;27(13):2069-79. doi: 10.1097/QAD.0b013e328361d25d.
• Smith KY, Tierney C, Mollan K, Venuto CS, Budhathoki C, Ma Q, Morse GD, Sax P, Katzenstein D, Godfrey C, Fischl M, Daar ES, Collier AC; AIDS Clinical Trials Group 5202 Study Team. Outcomes by sex following treatment initiation with atazanavir plus ritonavir or efavirenz with abacavir/lamivudine or tenofovir/emtricitabine. Clin Infect Dis. 2014 Feb;58(4):555-63. doi: 10.1093/cid/cit747. Epub 2013 Nov 18.
• McComsey GA, Daar ES, O'Riordan M, Collier AC, Kosmiski L, Santana JL, Fichtenbaum CJ, Fink H, Sax PE, Libutti DE, Gerschenson M. Changes in fat mitochondrial DNA and function in subjects randomized to abacavir-lamivudine or tenofovir DF-emtricitabine with atazanavir-ritonavir or efavirenz: AIDS Clinical Trials Group study A5224s, substudy of A5202. J Infect Dis. 2013 Feb 15;207(4):604-11. doi: 10.1093/infdis/jis720. Epub 2012 Nov 29.
• Mollan K, Daar ES, Sax PE, Balamane M, Collier AC, Fischl MA, Lalama CM, Bosch RJ, Tierney C, Katzenstein D; AIDS Clinical Trials Group Study A5202 Team. HIV-1 amino acid changes among participants with virologic failure: associations with first-line efavirenz or atazanavir plus ritonavir and disease status. J Infect Dis. 2012 Dec 15;206(12):1920-30. doi: 10.1093/infdis/jis613. Epub 2012 Nov 12.
• McComsey GA, Kitch D, Sax PE, Tebas P, Tierney C, Jahed NC, Myers L, Melbourne K, Ha B, Daar ES. Peripheral and central fat changes in subjects randomized to abacavir-lamivudine or tenofovir-emtricitabine with atazanavir-ritonavir or efavirenz: ACTG Study A5224s. Clin Infect Dis. 2011 Jul 15;53(2):185-96. doi: 10.1093/cid/cir324.
• McComsey GA, Kitch D, Daar ES, Tierney C, Jahed NC, Tebas P, Myers L, Melbourne K, Ha B, Sax PE. Bone mineral density and fractures in antiretroviral-naive persons randomized to receive abacavir-lamivudine or tenofovir disoproxil fumarate-emtricitabine along with efavirenz or atazanavir-ritonavir: Aids Clinical Trials Group A5224s, a substudy of ACTG A5202. J Infect Dis. 2011 Jun 15;203(12):1791-801. doi: 10.1093/infdis/jir188.
• Daar ES, Tierney C, Fischl MA, Sax PE, Mollan K, Budhathoki C, Godfrey C, Jahed NC, Myers L, Katzenstein D, Farajallah A, Rooney JF, Pappa KA, Woodward WC, Patterson K, Bolivar H, Benson CA, Collier AC; AIDS Clinical Trials Group Study A5202 Team. Atazanavir plus ritonavir or efavirenz as part of a 3-drug regimen for initial treatment of HIV-1. Ann Intern Med. 2011 Apr 5;154(7):445-56. doi: 10.7326/0003-4819-154-7-201104050-00316. Epub 2011 Feb 14.
• Sax PE, Tierney C, Collier AC, Fischl MA, Mollan K, Peeples L, Godfrey C, Jahed NC, Myers L, Katzenstein D, Farajallah A, Rooney JF, Ha B, Woodward WC, Koletar SL, Johnson VA, Geiseler PJ, Daar ES; AIDS Clinical Trials Group Study A5202 Team. Abacavir-lamivudine versus tenofovir-emtricitabine for initial HIV-1 therapy. N Engl J Med. 2009 Dec 3;361(23):2230-40. doi: 10.1056/NEJMoa0906768. Epub 2009 Dec 1.

Study record dates

Study Major Dates

• Study Start: September 1, 2005
• Primary Completion (Actual): November 1, 2009
• Study Completion (Actual): November 1, 2009

Study Registration Dates

• First Submitted: July 7, 2005
• First Submitted That Met QC Criteria: July 7, 2005
• First Posted (Estimate): July 12, 2005

Study Record Updates

• Last Update Posted (Actual): October 12, 2018
• Last Update Submitted That Met QC Criteria: September 11, 2018
• Last Verified: September 1, 2018

More Information

Terms related to this study

• Keywords: Treatment Naive
• Additional Relevant MeSH Terms: RNA Virus Infections; Virus Diseases; Infections; Blood-Borne Infections; Communicable Diseases; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; Immunologic Deficiency Syndromes; Immune System Diseases; HIV Infections; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Reverse Transcriptase Inhibitors; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Anti-HIV Agents; Anti-Retroviral Agents; Antimetabolites; Protease Inhibitors; Cytochrome P-450 CYP3A Inhibitors; Cytochrome P-450 Enzyme Inhibitors; Cytochrome P-450 Enzyme Inducers; Cytochrome P-450 CYP3A Inducers; HIV Protease Inhibitors; Viral Protease Inhibitors; Cytochrome P-450 CYP2B6 Inducers; Cytochrome P-450 CYP2C9 Inhibitors; Cytochrome P-450 CYP2C19 Inhibitors; Tenofovir; Emtricitabine; Ritonavir; Lamivudine; Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination; Atazanavir Sulfate; Efavirenz; Abacavir; Dideoxynucleosides
• Other Study ID Numbers: ACTG A5202; 1U01AI068636 (U.S. NIH Grant/Contract); ACTG 5224s (Other Identifier: Substudy)