HIV Infections
Conditions
Keywords
Treatment Naive
Brief summary
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.
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).
Interventions
600 mg abacavir/300 mg lamivudine tablet taken orally daily
DRUGAtazanavir
300 mg tablet taken orally daily
DRUGEfavirenz
600 mg tablet taken orally daily
DRUGEmtricitabine/Tenofovir disoproxil fumarate
200 mg emtricitabine/300 mg tenofovir disoproxil fumarate tablet taken orally daily
DRUGRitonavir
100 mg tablet taken orally daily
Placebo tablet taken orally daily
Placebo tablet taken orally daily
Sponsors
National Institute of Allergy and Infectious Diseases (NIAID)
Advancing Clinical Therapeutics Globally for HIV/AIDS and Other Infections
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
16 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Time From Randomization to Virologic Failure | Follow-up time was variable,median follow-up was 138 weeks; see 'Amount of study follow-up' outcome for details | 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 Treatment Modification | Follow-up time was variable,median follow-up was 138 weeks; see 'Amount of study follow-up' outcome for details | Treatment modification is defined as the 1st modification of the regimen, including a permanent discontinuation, switch, or substitution. |
| Time From Treatment Dispensation to a Grade 3/4 Safety Event | 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. | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With HIV-1 RNA Levels Less Than 200 Copies/mL | At Weeks 48 and 96 | — |
| Time From Treatment Dispensation to Regimen Failure (First Occurrence of Virologic Failure or Treatment Modification) | Follow-up time was variable,median follow-up was 138 weeks; see 'Amount of study follow-up' outcome for details | 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 | At Weeks 48 and 96 | — |
| Change in CD4 Count (Cells/mm3) From Baseline | At Weeks 48 and 96 | 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 | Follow-up time was variable,median follow-up was 138 weeks; see 'Amount of study follow-up' outcome for details | 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. | Follow-up time was variable, median follow-up was 138 weeks; see 'Amount of study follow-up' outcome for details | 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 | At Weeks 48 and 96 | 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 | At Weeks 48 and 96 | 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 | At Weeks 48 and 96 | Only fasting results are included. The protocol did not require that samples be collected fasting. |
| Change in Fasting Triglyceride Level From Baseline | At Weeks 48 and 96 | Only fasting results are included. The protocol did not require that samples be collected fasting. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Cumulative Probability of Not Experiencing a Grade 3/4 Safety Event | At week 48 and 96 | 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. |
| Number of Participants With Treatment Modification | Follow-up time was variable, median follow-up was 138 weeks; see 'Amount of study follow-up' outcome for details | Treatment modification is defined as the 1st modification of the regimen, including a permanent discontinuation, switch, or substitution. |
| Cumulative Probability of Not Experiencing Treatment Modification | At week 48 and 96 | 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. |
| Number of Participants With Regimen Failure | Follow-up time was variable, median follow-up was 138 weeks; see 'Amount of study follow-up' outcome for details | 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. |
| Cumulative Probability of Not Experiencing Regimen Failure | At week 48 and 96 | 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. |
| Number of Participants With a Grade 3/4 Safety Event | Over all study follow-up while on initially assigned treatment, median follow-up was 120 weeks | 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. |
| Cumulative Probability of Not Experiencing Virologic Failure | At week 48 and 96 | 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. |
| Amount of Study Follow-up | Follow-up time was variable, median follow-up was 138 weeks | 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. |
| Number of Participants With Virologic Failure | Follow-up time was variable, median follow-up was 138 weeks; see 'Amount of study follow-up' outcome for details | 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. |
Countries
Puerto Rico, United States
Participant flow
Recruitment details
Recruited at AIDS Clinical Trials Units in the United States and Puerto Rico. Recruitment occurred between September 21, 2005 (date first subject was randomized) and November 20, 2007 (date last subject was randomized).
Pre-assignment details
1864 were randomized. Results reported for 1857 eligible participants; 7 were subsequently found ineligible and excluded from all analyses.
Participants by arm
| Arm | Count |
|---|---|
| EFV, FTC/TDF, and Placebo ABC/3TC Participants will receive EFV, FTC/TDF, and placebo for ABC/3TC for at least 96 weeks | 464 |
| EFV, Placebo FTC/TDF, and ABC/3TC Participants will receive EFV, placebo for FTC/TDF, and ABC/3TC for at least 96 weeks | 465 |
| 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 | 465 |
| RTV-boosted ATV, Placebo FTC/TDF, and ABC/3TC Participants will receive RTV-boosted ATV, placebo for FTC/TDF, and ABC/3TC for at least 96 weeks | 463 |
| Total | 1,857 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Death | 6 | 11 | 6 | 8 |
| Overall Study | Lost to Follow-up | 26 | 34 | 33 | 33 |
| Overall Study | Not able to get to clinic | 34 | 43 | 31 | 40 |
| Overall Study | Not compliant with requirements | 11 | 13 | 11 | 11 |
| Overall Study | Severe debilitation | 1 | 4 | 6 | 4 |
| Overall Study | Site Closure | 33 | 31 | 28 | 37 |
| Overall Study | Withdrawal by Subject | 10 | 5 | 8 | 8 |
Baseline characteristics
| Characteristic | EFV, FTC/TDF, and Placebo ABC/3TC | RTV-boosted ATV, FTC/TDF, and Placebo ABC/3TC | EFV, Placebo FTC/TDF, and ABC/3TC | RTV-boosted ATV, Placebo FTC/TDF, and ABC/3TC | Total |
|---|---|---|---|---|---|
| Age, Categorical <=18 years | 2 Participants | 2 Participants | 3 Participants | 3 Participants | 10 Participants |
| Age, Categorical >=65 years | 1 Participants | 2 Participants | 8 Participants | 2 Participants | 13 Participants |
| Age, Categorical Between 18 and 65 years | 461 Participants | 461 Participants | 454 Participants | 458 Participants | 1834 Participants |
| Age, Continuous | 38.2 years STANDARD_DEVIATION 9.6 | 38.9 years STANDARD_DEVIATION 10.4 | 38.4 years STANDARD_DEVIATION 10.5 | 38.0 years STANDARD_DEVIATION 9.8 | 38.4 years STANDARD_DEVIATION 10.1 |
| Baseline CD4+ count | 233.5 cells/mm3 | 224 cells/mm3 | 225 cells/mm3 | 236 cells/mm3 | 229.5 cells/mm3 |
| Baseline HIV-1 RNA | 4.7 log10 copies/mL STANDARD_DEVIATION 0.7 | 4.7 log10 copies/mL STANDARD_DEVIATION 0.7 | 4.7 log10 copies/mL STANDARD_DEVIATION 0.7 | 4.7 log10 copies/mL STANDARD_DEVIATION 0.7 | 4.7 log10 copies/mL STANDARD_DEVIATION 0.7 |
| Race/Ethnicity, Customized Asian, Pacific Islander | 5 participants | 12 participants | 8 participants | 7 participants | 32 participants |
| Race/Ethnicity, Customized Black Non-Hispanic | 151 participants | 147 participants | 164 participants | 153 participants | 615 participants |
| Race/Ethnicity, Customized Hispanic (Regardless of Race) | 104 participants | 111 participants | 106 participants | 108 participants | 429 participants |
| Race/Ethnicity, Customized More than One Race | 2 participants | 5 participants | 5 participants | 4 participants | 16 participants |
| Race/Ethnicity, Customized Native American, Alaskan Native | 4 participants | 3 participants | 5 participants | 2 participants | 14 participants |
| Race/Ethnicity, Customized Unknown | 1 participants | 1 participants | 3 participants | 0 participants | 5 participants |
| Race/Ethnicity, Customized White Non-Hispanic | 197 participants | 186 participants | 174 participants | 189 participants | 746 participants |
| Region of Enrollment Puerto Rico | 13 participants | 13 participants | 13 participants | 13 participants | 52 participants |
| Region of Enrollment United States | 451 participants | 452 participants | 452 participants | 450 participants | 1805 participants |
| Screening HIV-1 RNA <100,000 copies/mL | 265 participants | 265 participants | 266 participants | 264 participants | 1060 participants |
| Screening HIV-1 RNA >=100,000 copies/mL | 199 participants | 200 participants | 199 participants | 199 participants | 797 participants |
| Sex: Female, Male Female | 71 Participants | 78 Participants | 98 Participants | 75 Participants | 322 Participants |
| Sex: Female, Male Male | 393 Participants | 387 Participants | 367 Participants | 388 Participants | 1535 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 434 / 461 | 433 / 461 | 453 / 464 | 461 / 462 |
| serious Total, serious adverse events | 48 / 461 | 62 / 461 | 58 / 464 | 71 / 462 |
Outcome results
Primary
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.
Time frame: Follow-up time was variable,median follow-up was 138 weeks; see 'Amount of study follow-up' outcome for details
Population: Intention to treat: All eligible participants were included in the analysis, participants were analyzed per originally assigned regimen.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| EFV, FTC/TDF, and Placebo ABC/3TC | Time From Randomization to Virologic Failure | 5th percentile time to virologic failure | 36 Weeks |
| EFV, FTC/TDF, and Placebo ABC/3TC | Time From Randomization to Virologic Failure | 10th percentile time to virologic failure | 96 Weeks |
| EFV, Placebo FTC/TDF, and ABC/3TC | Time From Randomization to Virologic Failure | 10th percentile time to virologic failure | 36 Weeks |
| EFV, Placebo FTC/TDF, and ABC/3TC | Time From Randomization to Virologic Failure | 5th percentile time to virologic failure | 24 Weeks |
| RTV-boosted ATV, FTC/TDF, and Placebo ABC/3TC | Time From Randomization to Virologic Failure | 5th percentile time to virologic failure | 24 Weeks |
| RTV-boosted ATV, FTC/TDF, and Placebo ABC/3TC | Time From Randomization to Virologic Failure | 10th percentile time to virologic failure | 84 Weeks |
| RTV-boosted ATV, Placebo FTC/TDF, and ABC/3TC | Time From Randomization to Virologic Failure | 5th percentile time to virologic failure | 24 Weeks |
| RTV-boosted ATV, Placebo FTC/TDF, and ABC/3TC | Time From Randomization to Virologic Failure | 10th percentile time to virologic failure | 36 Weeks |
Primary
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.
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.
Population: As-treated: Participants who initiated treatment are included in this analysis. Follow-up while on initially assigned treatment is included in the at-risk period.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| EFV, FTC/TDF, and Placebo ABC/3TC | Time From Treatment Dispensation to a Grade 3/4 Safety Event | 5th percentile time to a grade 3/4 safety event | 2.6 Weeks |
| EFV, FTC/TDF, and Placebo ABC/3TC | Time From Treatment Dispensation to a Grade 3/4 Safety Event | 25th percentile time to a grade 3/4 safety event | 59.3 Weeks |
| EFV, FTC/TDF, and Placebo ABC/3TC | Time From Treatment Dispensation to a Grade 3/4 Safety Event | 10th percentile time to a grade 3/4 safety event | 7.9 Weeks |
| EFV, Placebo FTC/TDF, and ABC/3TC | Time From Treatment Dispensation to a Grade 3/4 Safety Event | 5th percentile time to a grade 3/4 safety event | 1.3 Weeks |
| EFV, Placebo FTC/TDF, and ABC/3TC | Time From Treatment Dispensation to a Grade 3/4 Safety Event | 25th percentile time to a grade 3/4 safety event | 16.0 Weeks |
| EFV, Placebo FTC/TDF, and ABC/3TC | Time From Treatment Dispensation to a Grade 3/4 Safety Event | 10th percentile time to a grade 3/4 safety event | 2.0 Weeks |
| RTV-boosted ATV, FTC/TDF, and Placebo ABC/3TC | Time From Treatment Dispensation to a Grade 3/4 Safety Event | 10th percentile time to a grade 3/4 safety event | 8.1 Weeks |
| RTV-boosted ATV, FTC/TDF, and Placebo ABC/3TC | Time From Treatment Dispensation to a Grade 3/4 Safety Event | 5th percentile time to a grade 3/4 safety event | 3.0 Weeks |
| RTV-boosted ATV, FTC/TDF, and Placebo ABC/3TC | Time From Treatment Dispensation to a Grade 3/4 Safety Event | 25th percentile time to a grade 3/4 safety event | 81.4 Weeks |
| RTV-boosted ATV, Placebo FTC/TDF, and ABC/3TC | Time From Treatment Dispensation to a Grade 3/4 Safety Event | 5th percentile time to a grade 3/4 safety event | 1.3 Weeks |
| RTV-boosted ATV, Placebo FTC/TDF, and ABC/3TC | Time From Treatment Dispensation to a Grade 3/4 Safety Event | 25th percentile time to a grade 3/4 safety event | 44.4 Weeks |
| RTV-boosted ATV, Placebo FTC/TDF, and ABC/3TC | Time From Treatment Dispensation to a Grade 3/4 Safety Event | 10th percentile time to a grade 3/4 safety event | 3.9 Weeks |
Primary
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.
Time frame: Follow-up time was variable,median follow-up was 138 weeks; see 'Amount of study follow-up' outcome for details
Population: Participants who initiated treatment are included in this analysis. Participants were analyzed per originally assigned regimen.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| EFV, FTC/TDF, and Placebo ABC/3TC | Time From Treatment Dispensation to Treatment Modification | 5th percentile time to treatment modification | 3.4 Weeks |
| EFV, FTC/TDF, and Placebo ABC/3TC | Time From Treatment Dispensation to Treatment Modification | 25th percentile time to treatment modification | 83.7 Weeks |
| EFV, FTC/TDF, and Placebo ABC/3TC | Time From Treatment Dispensation to Treatment Modification | 10th percentile time to treatment modification | 15.0 Weeks |
| EFV, Placebo FTC/TDF, and ABC/3TC | Time From Treatment Dispensation to Treatment Modification | 5th percentile time to treatment modification | 1.4 Weeks |
| EFV, Placebo FTC/TDF, and ABC/3TC | Time From Treatment Dispensation to Treatment Modification | 25th percentile time to treatment modification | 27.4 Weeks |
| EFV, Placebo FTC/TDF, and ABC/3TC | Time From Treatment Dispensation to Treatment Modification | 10th percentile time to treatment modification | 2.1 Weeks |
| RTV-boosted ATV, FTC/TDF, and Placebo ABC/3TC | Time From Treatment Dispensation to Treatment Modification | 10th percentile time to treatment modification | 24.9 Weeks |
| RTV-boosted ATV, FTC/TDF, and Placebo ABC/3TC | Time From Treatment Dispensation to Treatment Modification | 5th percentile time to treatment modification | 7.9 Weeks |
| RTV-boosted ATV, FTC/TDF, and Placebo ABC/3TC | Time From Treatment Dispensation to Treatment Modification | 25th percentile time to treatment modification | 108.9 Weeks |
| RTV-boosted ATV, Placebo FTC/TDF, and ABC/3TC | Time From Treatment Dispensation to Treatment Modification | 5th percentile time to treatment modification | 1.6 Weeks |
| RTV-boosted ATV, Placebo FTC/TDF, and ABC/3TC | Time From Treatment Dispensation to Treatment Modification | 25th percentile time to treatment modification | 43.6 Weeks |
| RTV-boosted ATV, Placebo FTC/TDF, and ABC/3TC | Time From Treatment Dispensation to Treatment Modification | 10th percentile time to treatment modification | 5.0 Weeks |
Secondary
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).
Time frame: At Weeks 48 and 96
Population: Intention to treat: All participants with CD4 data were included, complete-case approach.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| EFV, FTC/TDF, and Placebo ABC/3TC | Change in CD4 Count (Cells/mm3) From Baseline | Week 48 | 163 Cells/mm3 |
| EFV, FTC/TDF, and Placebo ABC/3TC | Change in CD4 Count (Cells/mm3) From Baseline | Week 96 | 220.5 Cells/mm3 |
| EFV, Placebo FTC/TDF, and ABC/3TC | Change in CD4 Count (Cells/mm3) From Baseline | Week 96 | 250.5 Cells/mm3 |
| EFV, Placebo FTC/TDF, and ABC/3TC | Change in CD4 Count (Cells/mm3) From Baseline | Week 48 | 188 Cells/mm3 |
| RTV-boosted ATV, FTC/TDF, and Placebo ABC/3TC | Change in CD4 Count (Cells/mm3) From Baseline | Week 48 | 175 Cells/mm3 |
| RTV-boosted ATV, FTC/TDF, and Placebo ABC/3TC | Change in CD4 Count (Cells/mm3) From Baseline | Week 96 | 251.5 Cells/mm3 |
| RTV-boosted ATV, Placebo FTC/TDF, and ABC/3TC | Change in CD4 Count (Cells/mm3) From Baseline | Week 48 | 177.5 Cells/mm3 |
| RTV-boosted ATV, Placebo FTC/TDF, and ABC/3TC | Change in CD4 Count (Cells/mm3) From Baseline | Week 96 | 250.3 Cells/mm3 |
Secondary
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.
Time frame: At Weeks 48 and 96
Population: Intention to treat: All participants with fasting lipids data were included, complete-case approach.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| EFV, FTC/TDF, and Placebo ABC/3TC | Change in Fasting High-density Lipoprotein (HDL) Cholesterol Level From Baseline | Week 48 | 8 mg/dL |
| EFV, FTC/TDF, and Placebo ABC/3TC | Change in Fasting High-density Lipoprotein (HDL) Cholesterol Level From Baseline | Week 96 | 9 mg/dL |
| EFV, Placebo FTC/TDF, and ABC/3TC | Change in Fasting High-density Lipoprotein (HDL) Cholesterol Level From Baseline | Week 96 | 11 mg/dL |
| EFV, Placebo FTC/TDF, and ABC/3TC | Change in Fasting High-density Lipoprotein (HDL) Cholesterol Level From Baseline | Week 48 | 10 mg/dL |
| RTV-boosted ATV, FTC/TDF, and Placebo ABC/3TC | Change in Fasting High-density Lipoprotein (HDL) Cholesterol Level From Baseline | Week 48 | 5 mg/dL |
| RTV-boosted ATV, FTC/TDF, and Placebo ABC/3TC | Change in Fasting High-density Lipoprotein (HDL) Cholesterol Level From Baseline | Week 96 | 4 mg/dL |
| RTV-boosted ATV, Placebo FTC/TDF, and ABC/3TC | Change in Fasting High-density Lipoprotein (HDL) Cholesterol Level From Baseline | Week 48 | 8 mg/dL |
| RTV-boosted ATV, Placebo FTC/TDF, and ABC/3TC | Change in Fasting High-density Lipoprotein (HDL) Cholesterol Level From Baseline | Week 96 | 7 mg/dL |
Secondary
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.
Time frame: At Weeks 48 and 96
Population: Intention to treat: All participants with fasting lipids data were included, complete-case approach.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| EFV, FTC/TDF, and Placebo ABC/3TC | Change in Fasting Non-high Density Lipoprotein (Non-HDL) Cholesterol Level From Baseline | Week 48 | 14 mg/dL |
| EFV, FTC/TDF, and Placebo ABC/3TC | Change in Fasting Non-high Density Lipoprotein (Non-HDL) Cholesterol Level From Baseline | Week 96 | 13.5 mg/dL |
| EFV, Placebo FTC/TDF, and ABC/3TC | Change in Fasting Non-high Density Lipoprotein (Non-HDL) Cholesterol Level From Baseline | Week 96 | 18 mg/dL |
| EFV, Placebo FTC/TDF, and ABC/3TC | Change in Fasting Non-high Density Lipoprotein (Non-HDL) Cholesterol Level From Baseline | Week 48 | 23 mg/dL |
| RTV-boosted ATV, FTC/TDF, and Placebo ABC/3TC | Change in Fasting Non-high Density Lipoprotein (Non-HDL) Cholesterol Level From Baseline | Week 96 | 10 mg/dL |
| RTV-boosted ATV, FTC/TDF, and Placebo ABC/3TC | Change in Fasting Non-high Density Lipoprotein (Non-HDL) Cholesterol Level From Baseline | Week 48 | 8 mg/dL |
| RTV-boosted ATV, Placebo FTC/TDF, and ABC/3TC | Change in Fasting Non-high Density Lipoprotein (Non-HDL) Cholesterol Level From Baseline | Week 96 | 18 mg/dL |
| RTV-boosted ATV, Placebo FTC/TDF, and ABC/3TC | Change in Fasting Non-high Density Lipoprotein (Non-HDL) Cholesterol Level From Baseline | Week 48 | 20 mg/dL |
Secondary
Change in Fasting Total Cholesterol Level From Baseline
Only fasting results are included. The protocol did not require that samples be collected fasting.
Time frame: At Weeks 48 and 96
Population: Intention to treat: All participants with fasting lipids data were included, complete-case approach.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| EFV, FTC/TDF, and Placebo ABC/3TC | Change in Fasting Total Cholesterol Level From Baseline | Week 48 | 22 mg/dL |
| EFV, FTC/TDF, and Placebo ABC/3TC | Change in Fasting Total Cholesterol Level From Baseline | Week 96 | 23 mg/dL |
| EFV, Placebo FTC/TDF, and ABC/3TC | Change in Fasting Total Cholesterol Level From Baseline | Week 96 | 33 mg/dL |
| EFV, Placebo FTC/TDF, and ABC/3TC | Change in Fasting Total Cholesterol Level From Baseline | Week 48 | 35 mg/dL |
| RTV-boosted ATV, FTC/TDF, and Placebo ABC/3TC | Change in Fasting Total Cholesterol Level From Baseline | Week 48 | 11 mg/dL |
| RTV-boosted ATV, FTC/TDF, and Placebo ABC/3TC | Change in Fasting Total Cholesterol Level From Baseline | Week 96 | 14 mg/dL |
| RTV-boosted ATV, Placebo FTC/TDF, and ABC/3TC | Change in Fasting Total Cholesterol Level From Baseline | Week 48 | 30 mg/dL |
| RTV-boosted ATV, Placebo FTC/TDF, and ABC/3TC | Change in Fasting Total Cholesterol Level From Baseline | Week 96 | 25 mg/dL |
Secondary
Change in Fasting Triglyceride Level From Baseline
Only fasting results are included. The protocol did not require that samples be collected fasting.
Time frame: At Weeks 48 and 96
Population: Intention to treat: All participants with fasting lipids data were included, complete-case approach.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| EFV, FTC/TDF, and Placebo ABC/3TC | Change in Fasting Triglyceride Level From Baseline | Week 48 | 10 mg/dL |
| EFV, FTC/TDF, and Placebo ABC/3TC | Change in Fasting Triglyceride Level From Baseline | Week 96 | 9 mg/dL |
| EFV, Placebo FTC/TDF, and ABC/3TC | Change in Fasting Triglyceride Level From Baseline | Week 96 | 14 mg/dL |
| EFV, Placebo FTC/TDF, and ABC/3TC | Change in Fasting Triglyceride Level From Baseline | Week 48 | 15 mg/dL |
| RTV-boosted ATV, FTC/TDF, and Placebo ABC/3TC | Change in Fasting Triglyceride Level From Baseline | Week 48 | 14 mg/dL |
| RTV-boosted ATV, FTC/TDF, and Placebo ABC/3TC | Change in Fasting Triglyceride Level From Baseline | Week 96 | 11 mg/dL |
| RTV-boosted ATV, Placebo FTC/TDF, and ABC/3TC | Change in Fasting Triglyceride Level From Baseline | Week 48 | 24 mg/dL |
| RTV-boosted ATV, Placebo FTC/TDF, and ABC/3TC | Change in Fasting Triglyceride Level From Baseline | Week 96 | 33 mg/dL |
Secondary
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
Time frame: Follow-up time was variable, median follow-up was 138 weeks; see 'Amount of study follow-up' outcome for details
Population: Intention to treat: All eligible participants were included in the analysis, participants were analyzed per originally assigned regimen.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| EFV, FTC/TDF, and Placebo ABC/3TC | Number of Participants Experiencing Certain Targeted Clinical Events, Including Death, AIDS-defining Illness, and HIV-1 Related Events. | Death | 6 Participants |
| EFV, FTC/TDF, and Placebo ABC/3TC | Number of Participants Experiencing Certain Targeted Clinical Events, Including Death, AIDS-defining Illness, and HIV-1 Related Events. | HIV-1 relatated event | 56 Participants |
| EFV, FTC/TDF, and Placebo ABC/3TC | Number of Participants Experiencing Certain Targeted Clinical Events, Including Death, AIDS-defining Illness, and HIV-1 Related Events. | AIDS-defining illness | 14 Participants |
| EFV, Placebo FTC/TDF, and ABC/3TC | Number of Participants Experiencing Certain Targeted Clinical Events, Including Death, AIDS-defining Illness, and HIV-1 Related Events. | Death | 11 Participants |
| EFV, Placebo FTC/TDF, and ABC/3TC | Number of Participants Experiencing Certain Targeted Clinical Events, Including Death, AIDS-defining Illness, and HIV-1 Related Events. | HIV-1 relatated event | 61 Participants |
| EFV, Placebo FTC/TDF, and ABC/3TC | Number of Participants Experiencing Certain Targeted Clinical Events, Including Death, AIDS-defining Illness, and HIV-1 Related Events. | AIDS-defining illness | 25 Participants |
| RTV-boosted ATV, FTC/TDF, and Placebo ABC/3TC | Number of Participants Experiencing Certain Targeted Clinical Events, Including Death, AIDS-defining Illness, and HIV-1 Related Events. | AIDS-defining illness | 20 Participants |
| RTV-boosted ATV, FTC/TDF, and Placebo ABC/3TC | Number of Participants Experiencing Certain Targeted Clinical Events, Including Death, AIDS-defining Illness, and HIV-1 Related Events. | Death | 6 Participants |
| RTV-boosted ATV, FTC/TDF, and Placebo ABC/3TC | Number of Participants Experiencing Certain Targeted Clinical Events, Including Death, AIDS-defining Illness, and HIV-1 Related Events. | HIV-1 relatated event | 57 Participants |
| RTV-boosted ATV, Placebo FTC/TDF, and ABC/3TC | Number of Participants Experiencing Certain Targeted Clinical Events, Including Death, AIDS-defining Illness, and HIV-1 Related Events. | Death | 8 Participants |
| RTV-boosted ATV, Placebo FTC/TDF, and ABC/3TC | Number of Participants Experiencing Certain Targeted Clinical Events, Including Death, AIDS-defining Illness, and HIV-1 Related Events. | HIV-1 relatated event | 63 Participants |
| RTV-boosted ATV, Placebo FTC/TDF, and ABC/3TC | Number of Participants Experiencing Certain Targeted Clinical Events, Including Death, AIDS-defining Illness, and HIV-1 Related Events. | AIDS-defining illness | 23 Participants |
Secondary
Number of Participants With HIV-1 RNA Levels Less Than 200 Copies/mL
Time frame: At Weeks 48 and 96
Population: Intention to treat: All participants with RNA data were included, complete-case approach.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| EFV, FTC/TDF, and Placebo ABC/3TC | Number of Participants With HIV-1 RNA Levels Less Than 200 Copies/mL | Number of Participants with RNA data at Week 48 | 415 Participants |
| EFV, FTC/TDF, and Placebo ABC/3TC | Number of Participants With HIV-1 RNA Levels Less Than 200 Copies/mL | Number with HIV-1 RNA <200 copies/ml at Week 48 | 398 Participants |
| EFV, FTC/TDF, and Placebo ABC/3TC | Number of Participants With HIV-1 RNA Levels Less Than 200 Copies/mL | Number of Participants with RNA data at Week 96 | 379 Participants |
| EFV, FTC/TDF, and Placebo ABC/3TC | Number of Participants With HIV-1 RNA Levels Less Than 200 Copies/mL | Number with HIV-1 RNA <200 copies/ml at Week 96 | 362 Participants |
| EFV, Placebo FTC/TDF, and ABC/3TC | Number of Participants With HIV-1 RNA Levels Less Than 200 Copies/mL | Number with HIV-1 RNA <200 copies/ml at Week 96 | 342 Participants |
| EFV, Placebo FTC/TDF, and ABC/3TC | Number of Participants With HIV-1 RNA Levels Less Than 200 Copies/mL | Number of Participants with RNA data at Week 96 | 361 Participants |
| EFV, Placebo FTC/TDF, and ABC/3TC | Number of Participants With HIV-1 RNA Levels Less Than 200 Copies/mL | Number with HIV-1 RNA <200 copies/ml at Week 48 | 377 Participants |
| EFV, Placebo FTC/TDF, and ABC/3TC | Number of Participants With HIV-1 RNA Levels Less Than 200 Copies/mL | Number of Participants with RNA data at Week 48 | 400 Participants |
| RTV-boosted ATV, FTC/TDF, and Placebo ABC/3TC | Number of Participants With HIV-1 RNA Levels Less Than 200 Copies/mL | Number of Participants with RNA data at Week 96 | 384 Participants |
| RTV-boosted ATV, FTC/TDF, and Placebo ABC/3TC | Number of Participants With HIV-1 RNA Levels Less Than 200 Copies/mL | Number with HIV-1 RNA <200 copies/ml at Week 96 | 368 Participants |
| RTV-boosted ATV, FTC/TDF, and Placebo ABC/3TC | Number of Participants With HIV-1 RNA Levels Less Than 200 Copies/mL | Number with HIV-1 RNA <200 copies/ml at Week 48 | 391 Participants |
| RTV-boosted ATV, FTC/TDF, and Placebo ABC/3TC | Number of Participants With HIV-1 RNA Levels Less Than 200 Copies/mL | Number of Participants with RNA data at Week 48 | 416 Participants |
| RTV-boosted ATV, Placebo FTC/TDF, and ABC/3TC | Number of Participants With HIV-1 RNA Levels Less Than 200 Copies/mL | Number with HIV-1 RNA <200 copies/ml at Week 96 | 346 Participants |
| RTV-boosted ATV, Placebo FTC/TDF, and ABC/3TC | Number of Participants With HIV-1 RNA Levels Less Than 200 Copies/mL | Number of Participants with RNA data at Week 48 | 411 Participants |
| RTV-boosted ATV, Placebo FTC/TDF, and ABC/3TC | Number of Participants With HIV-1 RNA Levels Less Than 200 Copies/mL | Number with HIV-1 RNA <200 copies/ml at Week 48 | 372 Participants |
| RTV-boosted ATV, Placebo FTC/TDF, and ABC/3TC | Number of Participants With HIV-1 RNA Levels Less Than 200 Copies/mL | Number of Participants with RNA data at Week 96 | 374 Participants |
Secondary
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.
Time frame: Follow-up time was variable,median follow-up was 138 weeks; see 'Amount of study follow-up' outcome for details
Population: Intention to treat: All eligible participants are included. Participants were analyzed per originally assigned regimen.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| EFV, FTC/TDF, and Placebo ABC/3TC | Number of Participants With Virologic Failure and Emergence of Major Resistance | 27 participants |
| EFV, Placebo FTC/TDF, and ABC/3TC | Number of Participants With Virologic Failure and Emergence of Major Resistance | 41 participants |
| RTV-boosted ATV, FTC/TDF, and Placebo ABC/3TC | Number of Participants With Virologic Failure and Emergence of Major Resistance | 5 participants |
| RTV-boosted ATV, Placebo FTC/TDF, and ABC/3TC | Number of Participants With Virologic Failure and Emergence of Major Resistance | 12 participants |
Secondary
The Number of Participants With HIV-1 RNA Levels Less Than 50 Copies/mL
Time frame: At Weeks 48 and 96
Population: Intention to treat: All participants with RNA data were included, complete-case approach.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| EFV, FTC/TDF, and Placebo ABC/3TC | The Number of Participants With HIV-1 RNA Levels Less Than 50 Copies/mL | Number of Participants with RNA data at Week 48 | 415 Participants |
| EFV, FTC/TDF, and Placebo ABC/3TC | The Number of Participants With HIV-1 RNA Levels Less Than 50 Copies/mL | Number with HIV-1 RNA <50 copies/ml at Week 48 | 372 Participants |
| EFV, FTC/TDF, and Placebo ABC/3TC | The Number of Participants With HIV-1 RNA Levels Less Than 50 Copies/mL | Number of Participants with RNA data at Week 96 | 379 Participants |
| EFV, FTC/TDF, and Placebo ABC/3TC | The Number of Participants With HIV-1 RNA Levels Less Than 50 Copies/mL | Number with HIV-1 RNA <50 copies/ml at Week 96 | 345 Participants |
| EFV, Placebo FTC/TDF, and ABC/3TC | The Number of Participants With HIV-1 RNA Levels Less Than 50 Copies/mL | Number with HIV-1 RNA <50 copies/ml at Week 48 | 346 Participants |
| EFV, Placebo FTC/TDF, and ABC/3TC | The Number of Participants With HIV-1 RNA Levels Less Than 50 Copies/mL | Number of Participants with RNA data at Week 96 | 361 Participants |
| EFV, Placebo FTC/TDF, and ABC/3TC | The Number of Participants With HIV-1 RNA Levels Less Than 50 Copies/mL | Number with HIV-1 RNA <50 copies/ml at Week 96 | 328 Participants |
| EFV, Placebo FTC/TDF, and ABC/3TC | The Number of Participants With HIV-1 RNA Levels Less Than 50 Copies/mL | Number of Participants with RNA data at Week 48 | 400 Participants |
| RTV-boosted ATV, FTC/TDF, and Placebo ABC/3TC | The Number of Participants With HIV-1 RNA Levels Less Than 50 Copies/mL | Number of Participants with RNA data at Week 96 | 384 Participants |
| RTV-boosted ATV, FTC/TDF, and Placebo ABC/3TC | The Number of Participants With HIV-1 RNA Levels Less Than 50 Copies/mL | Number with HIV-1 RNA <50 copies/ml at Week 48 | 348 Participants |
| RTV-boosted ATV, FTC/TDF, and Placebo ABC/3TC | The Number of Participants With HIV-1 RNA Levels Less Than 50 Copies/mL | Number with HIV-1 RNA <50 copies/ml at Week 96 | 345 Participants |
| RTV-boosted ATV, FTC/TDF, and Placebo ABC/3TC | The Number of Participants With HIV-1 RNA Levels Less Than 50 Copies/mL | Number of Participants with RNA data at Week 48 | 416 Participants |
| RTV-boosted ATV, Placebo FTC/TDF, and ABC/3TC | The Number of Participants With HIV-1 RNA Levels Less Than 50 Copies/mL | Number with HIV-1 RNA <50 copies/ml at Week 96 | 317 Participants |
| RTV-boosted ATV, Placebo FTC/TDF, and ABC/3TC | The Number of Participants With HIV-1 RNA Levels Less Than 50 Copies/mL | Number with HIV-1 RNA <50 copies/ml at Week 48 | 322 Participants |
| RTV-boosted ATV, Placebo FTC/TDF, and ABC/3TC | The Number of Participants With HIV-1 RNA Levels Less Than 50 Copies/mL | Number of Participants with RNA data at Week 48 | 411 Participants |
| RTV-boosted ATV, Placebo FTC/TDF, and ABC/3TC | The Number of Participants With HIV-1 RNA Levels Less Than 50 Copies/mL | Number of Participants with RNA data at Week 96 | 374 Participants |
Secondary
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.
Time frame: Follow-up time was variable,median follow-up was 138 weeks; see 'Amount of study follow-up' outcome for details
Population: Participants who initiated treatment are included in this analysis. Participants were analyzed per originally assigned regimen.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| EFV, FTC/TDF, and Placebo ABC/3TC | Time From Treatment Dispensation to Regimen Failure (First Occurrence of Virologic Failure or Treatment Modification) | 5th percentile time to regimen failure | 4 Weeks |
| EFV, FTC/TDF, and Placebo ABC/3TC | Time From Treatment Dispensation to Regimen Failure (First Occurrence of Virologic Failure or Treatment Modification) | 25th percentile time to regimen failure | 72 Weeks |
| EFV, FTC/TDF, and Placebo ABC/3TC | Time From Treatment Dispensation to Regimen Failure (First Occurrence of Virologic Failure or Treatment Modification) | 10th percentile time to regimen failure | 16 Weeks |
| EFV, Placebo FTC/TDF, and ABC/3TC | Time From Treatment Dispensation to Regimen Failure (First Occurrence of Virologic Failure or Treatment Modification) | 5th percentile time to regimen failure | 4 Weeks |
| EFV, Placebo FTC/TDF, and ABC/3TC | Time From Treatment Dispensation to Regimen Failure (First Occurrence of Virologic Failure or Treatment Modification) | 25th percentile time to regimen failure | 24 Weeks |
| EFV, Placebo FTC/TDF, and ABC/3TC | Time From Treatment Dispensation to Regimen Failure (First Occurrence of Virologic Failure or Treatment Modification) | 10th percentile time to regimen failure | 4 Weeks |
| RTV-boosted ATV, FTC/TDF, and Placebo ABC/3TC | Time From Treatment Dispensation to Regimen Failure (First Occurrence of Virologic Failure or Treatment Modification) | 10th percentile time to regimen failure | 16 Weeks |
| RTV-boosted ATV, FTC/TDF, and Placebo ABC/3TC | Time From Treatment Dispensation to Regimen Failure (First Occurrence of Virologic Failure or Treatment Modification) | 5th percentile time to regimen failure | 4 Weeks |
| RTV-boosted ATV, FTC/TDF, and Placebo ABC/3TC | Time From Treatment Dispensation to Regimen Failure (First Occurrence of Virologic Failure or Treatment Modification) | 25th percentile time to regimen failure | 84 Weeks |
| RTV-boosted ATV, Placebo FTC/TDF, and ABC/3TC | Time From Treatment Dispensation to Regimen Failure (First Occurrence of Virologic Failure or Treatment Modification) | 5th percentile time to regimen failure | 4 Weeks |
| RTV-boosted ATV, Placebo FTC/TDF, and ABC/3TC | Time From Treatment Dispensation to Regimen Failure (First Occurrence of Virologic Failure or Treatment Modification) | 25th percentile time to regimen failure | 36 Weeks |
| RTV-boosted ATV, Placebo FTC/TDF, and ABC/3TC | Time From Treatment Dispensation to Regimen Failure (First Occurrence of Virologic Failure or Treatment Modification) | 10th percentile time to regimen failure | 4 Weeks |
Other Pre-specified
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.
Time frame: Follow-up time was variable, median follow-up was 138 weeks
Population: Intention to treat: All eligible participants are included. Participants were analyzed per originally assigned regimen.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| EFV, FTC/TDF, and Placebo ABC/3TC | Amount of Study Follow-up | 141.4 Weeks |
| EFV, Placebo FTC/TDF, and ABC/3TC | Amount of Study Follow-up | 133.3 Weeks |
| RTV-boosted ATV, FTC/TDF, and Placebo ABC/3TC | Amount of Study Follow-up | 141.6 Weeks |
| RTV-boosted ATV, Placebo FTC/TDF, and ABC/3TC | Amount of Study Follow-up | 137.3 Weeks |
Other Pre-specified
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.
Time frame: At week 48 and 96
Population: As-treated: Participants who initiated treatment are included in this analysis. Follow-up while on initially assigned treatment is included in the at-risk period.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| EFV, FTC/TDF, and Placebo ABC/3TC | Cumulative Probability of Not Experiencing a Grade 3/4 Safety Event | Week 48 | 78 percentage of participants |
| EFV, FTC/TDF, and Placebo ABC/3TC | Cumulative Probability of Not Experiencing a Grade 3/4 Safety Event | Week 96 | 70 percentage of participants |
| EFV, Placebo FTC/TDF, and ABC/3TC | Cumulative Probability of Not Experiencing a Grade 3/4 Safety Event | Week 96 | 58 percentage of participants |
| EFV, Placebo FTC/TDF, and ABC/3TC | Cumulative Probability of Not Experiencing a Grade 3/4 Safety Event | Week 48 | 64 percentage of participants |
| RTV-boosted ATV, FTC/TDF, and Placebo ABC/3TC | Cumulative Probability of Not Experiencing a Grade 3/4 Safety Event | Week 48 | 79 percentage of participants |
| RTV-boosted ATV, FTC/TDF, and Placebo ABC/3TC | Cumulative Probability of Not Experiencing a Grade 3/4 Safety Event | Week 96 | 73 percentage of participants |
| RTV-boosted ATV, Placebo FTC/TDF, and ABC/3TC | Cumulative Probability of Not Experiencing a Grade 3/4 Safety Event | Week 48 | 73 percentage of participants |
| RTV-boosted ATV, Placebo FTC/TDF, and ABC/3TC | Cumulative Probability of Not Experiencing a Grade 3/4 Safety Event | Week 96 | 66 percentage of participants |
Other Pre-specified
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.
Time frame: At week 48 and 96
Population: Participants who initiated treatment are included in this analysis. Participants were analyzed per originally assigned regimen.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| EFV, FTC/TDF, and Placebo ABC/3TC | Cumulative Probability of Not Experiencing Regimen Failure | Week 48 | 79 percentage of participants |
| EFV, FTC/TDF, and Placebo ABC/3TC | Cumulative Probability of Not Experiencing Regimen Failure | Week 96 | 70 percentage of participants |
| EFV, Placebo FTC/TDF, and ABC/3TC | Cumulative Probability of Not Experiencing Regimen Failure | Week 96 | 54 percentage of participants |
| EFV, Placebo FTC/TDF, and ABC/3TC | Cumulative Probability of Not Experiencing Regimen Failure | Week 48 | 64 percentage of participants |
| RTV-boosted ATV, FTC/TDF, and Placebo ABC/3TC | Cumulative Probability of Not Experiencing Regimen Failure | Week 48 | 80 percentage of participants |
| RTV-boosted ATV, FTC/TDF, and Placebo ABC/3TC | Cumulative Probability of Not Experiencing Regimen Failure | Week 96 | 73 percentage of participants |
| RTV-boosted ATV, Placebo FTC/TDF, and ABC/3TC | Cumulative Probability of Not Experiencing Regimen Failure | Week 48 | 66 percentage of participants |
| RTV-boosted ATV, Placebo FTC/TDF, and ABC/3TC | Cumulative Probability of Not Experiencing Regimen Failure | Week 96 | 57 percentage of participants |
Other Pre-specified
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.
Time frame: At week 48 and 96
Population: Participants who initiated treatment are included in this analysis. Participants were analyzed per originally assigned regimen.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| EFV, FTC/TDF, and Placebo ABC/3TC | Cumulative Probability of Not Experiencing Treatment Modification | Week 48 | 80 percentage of participants |
| EFV, FTC/TDF, and Placebo ABC/3TC | Cumulative Probability of Not Experiencing Treatment Modification | Week 96 | 73 percentage of participants |
| EFV, Placebo FTC/TDF, and ABC/3TC | Cumulative Probability of Not Experiencing Treatment Modification | Week 96 | 56 percentage of participants |
| EFV, Placebo FTC/TDF, and ABC/3TC | Cumulative Probability of Not Experiencing Treatment Modification | Week 48 | 67 percentage of participants |
| RTV-boosted ATV, FTC/TDF, and Placebo ABC/3TC | Cumulative Probability of Not Experiencing Treatment Modification | Week 96 | 77 percentage of participants |
| RTV-boosted ATV, FTC/TDF, and Placebo ABC/3TC | Cumulative Probability of Not Experiencing Treatment Modification | Week 48 | 86 percentage of participants |
| RTV-boosted ATV, Placebo FTC/TDF, and ABC/3TC | Cumulative Probability of Not Experiencing Treatment Modification | Week 96 | 62 percentage of participants |
| RTV-boosted ATV, Placebo FTC/TDF, and ABC/3TC | Cumulative Probability of Not Experiencing Treatment Modification | Week 48 | 73 percentage of participants |
Other Pre-specified
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.
Time frame: At week 48 and 96
Population: Intention to treat: All eligible participants were included in the analysis, participants were analyzed per originally assigned regimen.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| EFV, FTC/TDF, and Placebo ABC/3TC | Cumulative Probability of Not Experiencing Virologic Failure | Week 48 | 94 percentage of participants |
| EFV, FTC/TDF, and Placebo ABC/3TC | Cumulative Probability of Not Experiencing Virologic Failure | Week 96 | 90 percentage of participants |
| EFV, Placebo FTC/TDF, and ABC/3TC | Cumulative Probability of Not Experiencing Virologic Failure | Week 96 | 85 percentage of participants |
| EFV, Placebo FTC/TDF, and ABC/3TC | Cumulative Probability of Not Experiencing Virologic Failure | Week 48 | 88 percentage of participants |
| RTV-boosted ATV, FTC/TDF, and Placebo ABC/3TC | Cumulative Probability of Not Experiencing Virologic Failure | Week 48 | 92 percentage of participants |
| RTV-boosted ATV, FTC/TDF, and Placebo ABC/3TC | Cumulative Probability of Not Experiencing Virologic Failure | Week 96 | 89 percentage of participants |
| RTV-boosted ATV, Placebo FTC/TDF, and ABC/3TC | Cumulative Probability of Not Experiencing Virologic Failure | Week 48 | 88 percentage of participants |
| RTV-boosted ATV, Placebo FTC/TDF, and ABC/3TC | Cumulative Probability of Not Experiencing Virologic Failure | Week 96 | 83 percentage of participants |
Other Pre-specified
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.
Time frame: Over all study follow-up while on initially assigned treatment, median follow-up was 120 weeks
Population: As-treated: Participants who initiated treatment are included in this analysis. Follow-up while on initially assigned treatment is included in the at-risk period.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| EFV, FTC/TDF, and Placebo ABC/3TC | Number of Participants With a Grade 3/4 Safety Event | 145 participants |
| EFV, Placebo FTC/TDF, and ABC/3TC | Number of Participants With a Grade 3/4 Safety Event | 182 participants |
| RTV-boosted ATV, FTC/TDF, and Placebo ABC/3TC | Number of Participants With a Grade 3/4 Safety Event | 137 participants |
| RTV-boosted ATV, Placebo FTC/TDF, and ABC/3TC | Number of Participants With a Grade 3/4 Safety Event | 156 participants |
Other Pre-specified
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.
Time frame: Follow-up time was variable, median follow-up was 138 weeks; see 'Amount of study follow-up' outcome for details
Population: Participants who initiated treatment are included in this analysis. Participants were analyzed per originally assigned regimen.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| EFV, FTC/TDF, and Placebo ABC/3TC | Number of Participants With Regimen Failure | 162 participants |
| EFV, Placebo FTC/TDF, and ABC/3TC | Number of Participants With Regimen Failure | 246 participants |
| RTV-boosted ATV, FTC/TDF, and Placebo ABC/3TC | Number of Participants With Regimen Failure | 157 participants |
| RTV-boosted ATV, Placebo FTC/TDF, and ABC/3TC | Number of Participants With Regimen Failure | 233 participants |
Other Pre-specified
Number of Participants With Treatment Modification
Treatment modification is defined as the 1st modification of the regimen, including a permanent discontinuation, switch, or substitution.
Time frame: Follow-up time was variable, median follow-up was 138 weeks; see 'Amount of study follow-up' outcome for details
Population: Participants who initiated treatment are included in this analysis. Participants were analyzed per originally assigned regimen.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| EFV, FTC/TDF, and Placebo ABC/3TC | Number of Participants With Treatment Modification | 152 participants |
| EFV, Placebo FTC/TDF, and ABC/3TC | Number of Participants With Treatment Modification | 239 participants |
| RTV-boosted ATV, FTC/TDF, and Placebo ABC/3TC | Number of Participants With Treatment Modification | 138 participants |
| RTV-boosted ATV, Placebo FTC/TDF, and ABC/3TC | Number of Participants With Treatment Modification | 216 participants |
Other Pre-specified
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.
Time frame: Follow-up time was variable, median follow-up was 138 weeks; see 'Amount of study follow-up' outcome for details
Population: Intention to treat: All eligible participants were included in the analysis, participants were analyzed per originally assigned regimen.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| EFV, FTC/TDF, and Placebo ABC/3TC | Number of Participants With Virologic Failure | 57 participants |
| EFV, Placebo FTC/TDF, and ABC/3TC | Number of Participants With Virologic Failure | 72 participants |
| RTV-boosted ATV, FTC/TDF, and Placebo ABC/3TC | Number of Participants With Virologic Failure | 57 participants |
| RTV-boosted ATV, Placebo FTC/TDF, and ABC/3TC | Number of Participants With Virologic Failure | 83 participants |