HIV Infections
Conditions
Keywords
Acute Infection, Treatment Naive
Brief summary
Although some doctors favor starting anti-HIV treatment as soon as possible after patients learn they are infected, it is not known if treatment for recently infected patients results in long-term benefits or harm. The purpose of this study is to learn whether or not people should take anti-HIV drugs when they are first infected.
Detailed description
Combination antiretroviral therapy has resulted in significantly decreased morbidity and mortality, incidence of opportunistic infections, and hospitalizations in HIV infected people. However, because of long-term toxicities associated with long-term use of antiretrovirals and the persistence of virus in latent reservoirs, it is unclear when it is best to initiate therapy in recently infected individuals. This study compared the virologic outcomes of adults recently infected with HIV who received emtricitabine/tenofovir disoproxil fumarate (FTC/TDF), coformulated as Truvada, and lopinavir/ritonavir (LPV/RTV), coformulated as Kaletra \[immediate treatment (IT arm)\], with those who received no treatment \[deferred treatment (DT arm)\]. The original study lasted 96 weeks. Participants were randomly assigned to one of two groups (IT arm vs. DT arm). For the first 36 weeks of the study, IT arm participants received FTC/TDF once daily and LPV/RTV twice daily. Some IT arm participants received a different ART regimen as determined by the participant and study staff, if appropriate. DT arm participants received no treatment for the duration of the study. At Week 37, participants from both arms were offered treatment continuation or initiation until Week 96 if they had a high viral load, low CD4 count, or experienced HIV-related symptoms (Step 2). Study visits occurred at screening, Weeks 1, 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 37, 38, 40, and every 4 weeks thereafter. Clinical assessment and blood collection occurred at all visits. Urine tests occurred at selected visits. Participants were asked to complete an adherence questionnaire at Weeks 12, 24, and 36. Per the recommendations the DSMB review in June 2009, this protocol was terminated as originally written with the exception of those participants in the IT arm in the middle of the first 36 weeks of treatment. Those participants were to continue on treatment until the end of the 36 weeks. At that point treatment decisions were made on best practice guidelines. In addition, the study duration was extended to include a 5 year follow up of participants who did not initiate long-term antiretroviral therapy (Step 3). The study was reviewed by an SMC on December 8, 2010. The SMC recommended the study close to long term follow-up because only very few participants enrolled in this portion of the study. All the results except for the CD4 analysis and time to treatment initiation and deaths were based on the database frozen on July 2, 2009. The results for the CD4 analysis and time to treatment initiation and deaths were based on the database frozen on January 30, 2012.
Interventions
DRUGEmtricitabine/ tenofovir disoproxil fumarate
once daily
DRUGLopinavir/Ritonavir
twice daily
Sponsors
National Institute of Allergy and Infectious Diseases (NIAID)
Adult AIDS Clinical Trials Group
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
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
for Step 1: * Recently infected with HIV * No prior antiretroviral therapy (ART) * CD4 count of 350 cells/mm3 or more AND a CD4% of 14% or more within 21 days prior to study entry * HIV viral load of 500 copies/ml or more within 21 days prior to study entry * Required laboratory values obtained within 21 days prior to study entry * 18 years or older * Ability and willingness to provide written informed consent * Willing to use acceptable forms of contraception
Exclusion criteria
for Step 1: * HIV progression to CDC category B or C disease * Pregnancy or breastfeeding * History of pancreatitis or coronary artery disease * Prior ART. Participants who took antiretrovirals for postexposure prophylaxis more than one year prior to study entry are not excluded. * Certain medications within 21 days prior to study entry. Participants who agree to receive an alternative ART regimen approved by the investigator will not be excluded. * Previously received an investigational anti-HIV vaccine * Current therapy with systemic corticosteroids. Patients who are taking a short course (less than 21 days) of corticosteroids are not excluded. * Current therapy with systemic chemotherapeutic agents; nephrotoxic systemic agents; immunomodulatory treatments, including interleukin-2; or investigational agents * Known allergy or sensitivity to study drugs or their formulations * Current alcohol or drug use that, in the opinion of the investigator, would interfere with the study * Serious medical or psychiatric illness that, in the opinion of the investigator, would interfere with the study * Hepatitis B surface antigen positive within 21 days prior to study entry * Known resistance to one or more components of the study drug regimen Inclusion Criteria for Step 2: * subjects in DT arm who meet one of the following five criteria will be advised to enter step 2 and initiate ART: 1. CD4 cell counts below 350 cells/mm3 on 2 consecutive determinations at least 4 weeks apart at or after the step 1, week 12 study visit 2. HIV-1 RNA above 750,000 copies/mL confirmed on 2 consecutive determinations at least 1 week apart at or after the step 1, week 4 study visit 3. HIV-1 RNA above 200,000 copies/mL on 2 consecutive determinations at least 1 week apart at or after the step 1, week 12 study visit 4. Clinical progression to CDC category B or C disease 5. CD4 count below 200 cells/mm3 or CD4 percent less than 14% at any time on study * subjects in IT arm who meet one of the following five criteria after discontinuing study medications will be advised to enter step 2 and re-initiate ART: 1. CD4 cell counts below 350 cells/mm3 on 2 consecutive determinations at least 4 weeks apart at or after the step 1, week 12 post-treatment- discontinuation study visit 2. HIV-1 RNA above 750,000 copies/mL confirmed on 2 consecutive determinations at least 1 week apart at or after the step 1, week 4 post-treatment- discontinuation study visit 3. HIV-1 RNA above 200,000 copies/mL on 2 consecutive determinations at least 1 week apart at or after the step 1, week 12 post-treatment- discontinuation study visit 4. Clinical progression to CDC category B or C disease 5. CD4 count below 200 cells/mm3 or CD4 percent less than 14% at any time on study
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Ranked Log10 HIV-1 RNA Viral Load (log10 Copies/mL) Averaged at 72 and 76 Weeks for the IT Arm and DT Arm | At Weeks 72 and 76 | The primary endpoint is (i) the average of log10 viral loads (VL) at wks 72 and 76 for participants who continued to wk 72 off ARV for the DT arm, (ii) average wk 72 and 76 VL for those who continued to wk 36 off ARV for the IT arm and (iii) an assigned VL rank for the failures who needed ARVs or met criteria for entry into Step 2 prior to these study visits. The assigned rank for the failures was either the last observed rank carried forward or the worst rank relative to the other possible outcomes. This approach was designed to, if anything, bias against finding a treatment effect. To illustrate, consider five participants who enter the study (A, B, C, D, and E), 4 of whom (A, B, C, D) make it to 72 wks off therapy with RNA levels that increase from A to D. Participant E enters Step 2 at wk 12, at which time his RNA is in the 50th percentile. This rank would be carried forward, so the rank order of the log10 HIV-1 RNA endpoints would be A B E C D. |
| Ranked log10 HIV-1 RNA Viral Load (log10 Copies/mL) Averaged at Weeks 72 and 76 for the IT Arm and Ranked log10 HIV-1 RNA Viral Load (log10 Copies/mL) Averaged at Weeks 36 and 40 for the DT Arm | IT arm (weeks 72 and 76) and DT arm ( weeks 36 and 40) | The primary endpoint is (i) average wk 36 and 40 VL for those who continued to wk 36 off ARV for the DT arm, (ii) average wk 72 and 76 VL for those who continued to wk 36 off ARV for the IT arm and (iii) an assigned VL rank for the failures who needed ARVs or met criteria for entry into Step 2 prior to these study visits. The assigned rank for the failures was either the last observed rank carried forward or the worst rank relative to the other possible outcomes. This approach was designed to, if anything, bias against finding a treatment effect. To illustrate, consider five participants who enter the study (A, B, C, D, and E), 4 of whom (A, B, C, D) make it to 72 wks off therapy with RNA levels that increase from A to D. Participant E enters Step 2 at wk 12, at which time his RNA is in the 50th percentile. This rank would be carried forward, so the rank order of the log10 HIV-1 RNA endpoints would be A B E C D. |
| Number of Participants Experiencing Either a CDC Category B or C Diagnosis, CD4<200 Cells/mm^3 or CD4 Percent <14%. | 96 weeks since randomization | — |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Time to Meeting the Clinical, Virologic, or Immunologic Criteria for Treatment Initiation or Re-initiation | 96 weeks since randomization | 5th, 10th, 25th, 50th, 75th and 90th percentiles in weeks from randomization to meeting the criteria for treatment initiation or re-initiation which include CD4 count below 350 cells/mm\^3 on two consecutive measurements at least 4 weeks apart, at least 12 weeks into the study or 12 weeks post-treatment discontinuation, confirmed CD4 count below 200 cells/mm\^3 or CD4 percent below 14% at any time on study, confirmed HIV-1 RNA level above 750,000 copies/mL 4 weeks into the study or above 200,000 copies/mL 12 weeks or more into the study, or CDC Category B or C diagnosis. |
| Change in CD4 Counts Cells/mm^3 From Week 36 for IT Arm and From Week 0 for DT Arm | IT arm (weeks 36, 60, 72, 84 and 96) and DT arm (weeks 0, 24, 36, 48 and 60) | — |
| Time to Treatment Initiation or Death | 5 years since randomization | 5th, 10th, 25th, 50th and 75th percentiles in weeks from randomization to treatment initiation or death |
| Time From Study Entry in DT Arm Participants or From Week 36 in IT Arm Participants to Meeting the Clinical, Virologic, or Immunologic Criteria for Treatment Initiation or Re-initiation | 96 weeks since randomization | 5th, 10th, 25th, 50th, 75th and 90th percentiles in weeks from randomization for DT arm or from week 36 for IT arm to meeting the criteria for treatment initiation or re-initiation which include two consecutive CD4 count below 350 cells/mm\^3 at least 4 weeks apart, at least 12 weeks into the study or 12 weeks post-treatment discontinuation, confirmed CD4 count below 200 cells/mm\^3 or CD4 percent below 14% at any time on study, confirmed HIV-1 RNA level above 750,000 copies/mL 4 weeks into the study or above 200,000 copies/mL 12 weeks or more into the study, or CDC Category B or C diagnosis. |
| Number of Participants Meeting Clinical, Virologic, or Immunologic Criteria for Treatment Initiation or Re-initiation | 96 weeks since randomization | The clinical, virologic, or immunologic criteria for treatment initiation or re-initiation include CD4 count below 350 cells/mm\^3 on two consecutive determinations at least 4 weeks apart, at least 12 weeks into the study or 12 weeks post-treatment discontinuation, (2) confirmed CD4 count below 200 cells/mm\^3 or CD4 percent below 14% at any time on study, (3) confirmed HIV-1 RNA level above 750,000 copies/mL 4 weeks into the study or above 200,000 copies/mL 12 weeks or more into the study, or (4) CDC Category B or C diagnosis. |
| Number of Participants in IT Arm Off Treatment Before 36 Weeks | At Week 36 | The study provided fixed-dose combination emtricitabine/tenofovir DF 200/300 mg orally once daily and lopinavir/ritonavir 200/50 mg administered either as two tablets twice daily or four tablets once daily, for the first 36 weeks for individuals in the IT arm. |
Countries
Peru, United States
Participant flow
Recruitment details
Participants were recruited across 27 study sites (25 in the US and 2 in Peru) in the AIDS Clinical Trials Group system between February 2005 and June 2009.
Participants by arm
| Arm | Count |
|---|---|
| IT Arm IT arm participants received emtricitabine/tenofovir disoproxil fumarate once daily and lopinavir/ritonavir twice daily | 66 |
| DT Arm DT arm participants received no Treatment | 64 |
| Total | 130 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Step 1 | Death | 0 | 2 |
| Step 1 | Lost to Follow-up | 3 | 2 |
| Step 1 | Non-compliance to study requirements | 0 | 1 |
| Step 1 | Physician Decision | 1 | 0 |
| Step 1 | Pregnancy | 1 | 0 |
| Step 1 | Subject relocated | 2 | 8 |
| Step 1 | Withdrawal by Subject | 4 | 2 |
| Step 2 | Non-compliance to study requirements | 0 | 1 |
| Step 2 | Off study per study closure | 6 | 16 |
| Step 2 | Subject relocated | 0 | 1 |
| Step 3 | Initiation of ART and off extended study | 3 | 2 |
| Step 3 | Off extended study due to study closure | 4 | 3 |
Baseline characteristics
| Characteristic | DT Arm | IT Arm | Total |
|---|---|---|---|
| Age, Continuous | 34.6 years STANDARD_DEVIATION 9.1 | 34.1 years STANDARD_DEVIATION 11.3 | 34.4 years STANDARD_DEVIATION 10.3 |
| Age, Customized 20-29 years | 23 participants | 24 participants | 47 participants |
| Age, Customized <20 years | 0 participants | 4 participants | 4 participants |
| Age, Customized 30-39 years | 21 participants | 19 participants | 40 participants |
| Age, Customized 40-49 years | 16 participants | 12 participants | 28 participants |
| Age, Customized 50-59 years | 4 participants | 4 participants | 8 participants |
| Age, Customized 60-69 years | 0 participants | 3 participants | 3 participants |
| CD4 Count Category 201-350 cells/mm^3 | 2 participants | 4 participants | 6 participants |
| CD4 Count Category 351-500 cells/mm^3 | 24 participants | 26 participants | 50 participants |
| CD4 Count Category >500 cells/mm^3 | 38 participants | 36 participants | 74 participants |
| CD4 Counts | 611 cells/mm3 STANDARD_DEVIATION 207 | 570 cells/mm3 STANDARD_DEVIATION 197 | 590 cells/mm3 STANDARD_DEVIATION 202 |
| Ethnicity Hispanic or Latino | 9 participants | 14 participants | 23 participants |
| Ethnicity Not Hispanic or Latino | 55 participants | 52 participants | 107 participants |
| HIV-1 RNA Viral Load Category >=10000 copies/mL | 48 participants | 49 participants | 97 participants |
| HIV-1 RNA Viral Load Category 1000-9999 copies/mL | 15 participants | 16 participants | 31 participants |
| HIV-1 RNA Viral Load Category 200-399 copies/mL | 1 participants | 0 participants | 1 participants |
| HIV-1 RNA Viral Load Category 400-999 copies/mL | 0 participants | 1 participants | 1 participants |
| Log10 HIV-1 RNA Viral Load | 4.4 log10 copies/mL STANDARD_DEVIATION 0.6 | 4.4 log10 copies/mL STANDARD_DEVIATION 0.6 | 4.4 log10 copies/mL STANDARD_DEVIATION 0.6 |
| Race Black/ African American | 3 participants | 10 participants | 13 participants |
| Race Other | 4 participants | 4 participants | 8 participants |
| Race Unknown | 1 participants | 3 participants | 4 participants |
| Race White | 56 participants | 49 participants | 105 participants |
| Sex: Female, Male Female | 5 Participants | 8 Participants | 13 Participants |
| Sex: Female, Male Male | 59 Participants | 58 Participants | 117 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 58 / 66 | 48 / 64 |
| serious Total, serious adverse events | 1 / 66 | 0 / 64 |
Outcome results
Primary
Number of Participants Experiencing Either a CDC Category B or C Diagnosis, CD4<200 Cells/mm^3 or CD4 Percent <14%.
Time frame: 96 weeks since randomization
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| IT Arm | Number of Participants Experiencing Either a CDC Category B or C Diagnosis, CD4<200 Cells/mm^3 or CD4 Percent <14%. | 2 participants |
| DT Arm | Number of Participants Experiencing Either a CDC Category B or C Diagnosis, CD4<200 Cells/mm^3 or CD4 Percent <14%. | 8 participants |
Primary
Ranked Log10 HIV-1 RNA Viral Load (log10 Copies/mL) Averaged at 72 and 76 Weeks for the IT Arm and DT Arm
The primary endpoint is (i) the average of log10 viral loads (VL) at wks 72 and 76 for participants who continued to wk 72 off ARV for the DT arm, (ii) average wk 72 and 76 VL for those who continued to wk 36 off ARV for the IT arm and (iii) an assigned VL rank for the failures who needed ARVs or met criteria for entry into Step 2 prior to these study visits. The assigned rank for the failures was either the last observed rank carried forward or the worst rank relative to the other possible outcomes. This approach was designed to, if anything, bias against finding a treatment effect. To illustrate, consider five participants who enter the study (A, B, C, D, and E), 4 of whom (A, B, C, D) make it to 72 wks off therapy with RNA levels that increase from A to D. Participant E enters Step 2 at wk 12, at which time his RNA is in the 50th percentile. This rank would be carried forward, so the rank order of the log10 HIV-1 RNA endpoints would be A B E C D.
Time frame: At Weeks 72 and 76
Population: Participants in follow-up at least 72 weeks since randomization were included.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| IT Arm | Ranked Log10 HIV-1 RNA Viral Load (log10 Copies/mL) Averaged at 72 and 76 Weeks for the IT Arm and DT Arm | 26.0 rank |
| DT Arm | Ranked Log10 HIV-1 RNA Viral Load (log10 Copies/mL) Averaged at 72 and 76 Weeks for the IT Arm and DT Arm | 49.3 rank |
p-value: 0.005Wilcoxon (Mann-Whitney)
Primary
Ranked log10 HIV-1 RNA Viral Load (log10 Copies/mL) Averaged at Weeks 72 and 76 for the IT Arm and Ranked log10 HIV-1 RNA Viral Load (log10 Copies/mL) Averaged at Weeks 36 and 40 for the DT Arm
The primary endpoint is (i) average wk 36 and 40 VL for those who continued to wk 36 off ARV for the DT arm, (ii) average wk 72 and 76 VL for those who continued to wk 36 off ARV for the IT arm and (iii) an assigned VL rank for the failures who needed ARVs or met criteria for entry into Step 2 prior to these study visits. The assigned rank for the failures was either the last observed rank carried forward or the worst rank relative to the other possible outcomes. This approach was designed to, if anything, bias against finding a treatment effect. To illustrate, consider five participants who enter the study (A, B, C, D, and E), 4 of whom (A, B, C, D) make it to 72 wks off therapy with RNA levels that increase from A to D. Participant E enters Step 2 at wk 12, at which time his RNA is in the 50th percentile. This rank would be carried forward, so the rank order of the log10 HIV-1 RNA endpoints would be A B E C D.
Time frame: IT arm (weeks 72 and 76) and DT arm ( weeks 36 and 40)
Population: Participants in follow-up at least 72 weeks since randomization were included.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| IT Arm | Ranked log10 HIV-1 RNA Viral Load (log10 Copies/mL) Averaged at Weeks 72 and 76 for the IT Arm and Ranked log10 HIV-1 RNA Viral Load (log10 Copies/mL) Averaged at Weeks 36 and 40 for the DT Arm | 26.0 rank |
| DT Arm | Ranked log10 HIV-1 RNA Viral Load (log10 Copies/mL) Averaged at Weeks 72 and 76 for the IT Arm and Ranked log10 HIV-1 RNA Viral Load (log10 Copies/mL) Averaged at Weeks 36 and 40 for the DT Arm | 48.5 rank |
p-value: 0.002Wilcoxon (Mann-Whitney)
Secondary
Change in CD4 Counts Cells/mm^3 From Week 36 for IT Arm and From Week 0 for DT Arm
Time frame: IT arm (weeks 36, 60, 72, 84 and 96) and DT arm (weeks 0, 24, 36, 48 and 60)
Population: One subject in IT arm with multidrug resistance at baseline was excluded from this analysis.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| IT Arm | Change in CD4 Counts Cells/mm^3 From Week 36 for IT Arm and From Week 0 for DT Arm | IT arm (wk 60- wk 36) vs. DT arm (wk 24- wk 0) | -0.11 Change in Log10 transformed CD4 Counts | Standard Deviation 0.1 |
| IT Arm | Change in CD4 Counts Cells/mm^3 From Week 36 for IT Arm and From Week 0 for DT Arm | IT arm (wk 84- wk 36) vs. DT arm (wk 48- wk 0) | -0.10 Change in Log10 transformed CD4 Counts | Standard Deviation 0.12 |
| IT Arm | Change in CD4 Counts Cells/mm^3 From Week 36 for IT Arm and From Week 0 for DT Arm | IT arm (wk 72- wk 36) vs. DT arm (wk 36- wk 0) | -0.10 Change in Log10 transformed CD4 Counts | Standard Deviation 0.12 |
| IT Arm | Change in CD4 Counts Cells/mm^3 From Week 36 for IT Arm and From Week 0 for DT Arm | IT arm (wk 96- wk 36) vs. DT arm (wk 60- wk 0) | -0.12 Change in Log10 transformed CD4 Counts | Standard Deviation 0.13 |
| DT Arm | Change in CD4 Counts Cells/mm^3 From Week 36 for IT Arm and From Week 0 for DT Arm | IT arm (wk 72- wk 36) vs. DT arm (wk 36- wk 0) | -0.03 Change in Log10 transformed CD4 Counts | Standard Deviation 0.11 |
| DT Arm | Change in CD4 Counts Cells/mm^3 From Week 36 for IT Arm and From Week 0 for DT Arm | IT arm (wk 60- wk 36) vs. DT arm (wk 24- wk 0) | -0.02 Change in Log10 transformed CD4 Counts | Standard Deviation 0.12 |
| DT Arm | Change in CD4 Counts Cells/mm^3 From Week 36 for IT Arm and From Week 0 for DT Arm | IT arm (wk 96- wk 36) vs. DT arm (wk 60- wk 0) | -0.02 Change in Log10 transformed CD4 Counts | Standard Deviation 0.15 |
| DT Arm | Change in CD4 Counts Cells/mm^3 From Week 36 for IT Arm and From Week 0 for DT Arm | IT arm (wk 84- wk 36) vs. DT arm (wk 48- wk 0) | -0.06 Change in Log10 transformed CD4 Counts | Standard Deviation 0.17 |
Secondary
Number of Participants in IT Arm Off Treatment Before 36 Weeks
The study provided fixed-dose combination emtricitabine/tenofovir DF 200/300 mg orally once daily and lopinavir/ritonavir 200/50 mg administered either as two tablets twice daily or four tablets once daily, for the first 36 weeks for individuals in the IT arm.
Time frame: At Week 36
Population: All 66 eligible subjects in IT arm were included.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| IT Arm | Number of Participants in IT Arm Off Treatment Before 36 Weeks | 8 participants |
Secondary
Number of Participants Meeting Clinical, Virologic, or Immunologic Criteria for Treatment Initiation or Re-initiation
The clinical, virologic, or immunologic criteria for treatment initiation or re-initiation include CD4 count below 350 cells/mm\^3 on two consecutive determinations at least 4 weeks apart, at least 12 weeks into the study or 12 weeks post-treatment discontinuation, (2) confirmed CD4 count below 200 cells/mm\^3 or CD4 percent below 14% at any time on study, (3) confirmed HIV-1 RNA level above 750,000 copies/mL 4 weeks into the study or above 200,000 copies/mL 12 weeks or more into the study, or (4) CDC Category B or C diagnosis.
Time frame: 96 weeks since randomization
Population: All 130 eligible subjects were included.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| IT Arm | Number of Participants Meeting Clinical, Virologic, or Immunologic Criteria for Treatment Initiation or Re-initiation | 7 Participants |
| DT Arm | Number of Participants Meeting Clinical, Virologic, or Immunologic Criteria for Treatment Initiation or Re-initiation | 23 Participants |
Secondary
Time From Study Entry in DT Arm Participants or From Week 36 in IT Arm Participants to Meeting the Clinical, Virologic, or Immunologic Criteria for Treatment Initiation or Re-initiation
5th, 10th, 25th, 50th, 75th and 90th percentiles in weeks from randomization for DT arm or from week 36 for IT arm to meeting the criteria for treatment initiation or re-initiation which include two consecutive CD4 count below 350 cells/mm\^3 at least 4 weeks apart, at least 12 weeks into the study or 12 weeks post-treatment discontinuation, confirmed CD4 count below 200 cells/mm\^3 or CD4 percent below 14% at any time on study, confirmed HIV-1 RNA level above 750,000 copies/mL 4 weeks into the study or above 200,000 copies/mL 12 weeks or more into the study, or CDC Category B or C diagnosis.
Time frame: 96 weeks since randomization
Population: Through database cutoff for DSMB review (by July 2, 2009). The analysis includes only those in the IT arm who continued ART through week 36 (n=49), compared to all in the DT arm (n=64).
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| IT Arm | Time From Study Entry in DT Arm Participants or From Week 36 in IT Arm Participants to Meeting the Clinical, Virologic, or Immunologic Criteria for Treatment Initiation or Re-initiation | 10th percentile | 10.4 weeks |
| IT Arm | Time From Study Entry in DT Arm Participants or From Week 36 in IT Arm Participants to Meeting the Clinical, Virologic, or Immunologic Criteria for Treatment Initiation or Re-initiation | 90th percentile | NA weeks |
| IT Arm | Time From Study Entry in DT Arm Participants or From Week 36 in IT Arm Participants to Meeting the Clinical, Virologic, or Immunologic Criteria for Treatment Initiation or Re-initiation | 25th percentile | 22.7 weeks |
| IT Arm | Time From Study Entry in DT Arm Participants or From Week 36 in IT Arm Participants to Meeting the Clinical, Virologic, or Immunologic Criteria for Treatment Initiation or Re-initiation | 75th percentile | NA weeks |
| IT Arm | Time From Study Entry in DT Arm Participants or From Week 36 in IT Arm Participants to Meeting the Clinical, Virologic, or Immunologic Criteria for Treatment Initiation or Re-initiation | 50th percentile | 58.1 weeks |
| IT Arm | Time From Study Entry in DT Arm Participants or From Week 36 in IT Arm Participants to Meeting the Clinical, Virologic, or Immunologic Criteria for Treatment Initiation or Re-initiation | 5th percentile | 5.1 weeks |
| DT Arm | Time From Study Entry in DT Arm Participants or From Week 36 in IT Arm Participants to Meeting the Clinical, Virologic, or Immunologic Criteria for Treatment Initiation or Re-initiation | 50th percentile | 60.0 weeks |
| DT Arm | Time From Study Entry in DT Arm Participants or From Week 36 in IT Arm Participants to Meeting the Clinical, Virologic, or Immunologic Criteria for Treatment Initiation or Re-initiation | 5th percentile | 6.9 weeks |
| DT Arm | Time From Study Entry in DT Arm Participants or From Week 36 in IT Arm Participants to Meeting the Clinical, Virologic, or Immunologic Criteria for Treatment Initiation or Re-initiation | 10th percentile | 12.3 weeks |
| DT Arm | Time From Study Entry in DT Arm Participants or From Week 36 in IT Arm Participants to Meeting the Clinical, Virologic, or Immunologic Criteria for Treatment Initiation or Re-initiation | 75th percentile | 96.0 weeks |
| DT Arm | Time From Study Entry in DT Arm Participants or From Week 36 in IT Arm Participants to Meeting the Clinical, Virologic, or Immunologic Criteria for Treatment Initiation or Re-initiation | 90th percentile | 96.0 weeks |
| DT Arm | Time From Study Entry in DT Arm Participants or From Week 36 in IT Arm Participants to Meeting the Clinical, Virologic, or Immunologic Criteria for Treatment Initiation or Re-initiation | 25th percentile | 26.3 weeks |
Secondary
Time to Meeting the Clinical, Virologic, or Immunologic Criteria for Treatment Initiation or Re-initiation
5th, 10th, 25th, 50th, 75th and 90th percentiles in weeks from randomization to meeting the criteria for treatment initiation or re-initiation which include CD4 count below 350 cells/mm\^3 on two consecutive measurements at least 4 weeks apart, at least 12 weeks into the study or 12 weeks post-treatment discontinuation, confirmed CD4 count below 200 cells/mm\^3 or CD4 percent below 14% at any time on study, confirmed HIV-1 RNA level above 750,000 copies/mL 4 weeks into the study or above 200,000 copies/mL 12 weeks or more into the study, or CDC Category B or C diagnosis.
Time frame: 96 weeks since randomization
Population: Throughout database cutoff for DSMB review (by July 2, 2009).
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| IT Arm | Time to Meeting the Clinical, Virologic, or Immunologic Criteria for Treatment Initiation or Re-initiation | 10th percentile | 13.0 weeks |
| IT Arm | Time to Meeting the Clinical, Virologic, or Immunologic Criteria for Treatment Initiation or Re-initiation | 75th percentile | NA weeks |
| IT Arm | Time to Meeting the Clinical, Virologic, or Immunologic Criteria for Treatment Initiation or Re-initiation | 90th percentile | NA weeks |
| IT Arm | Time to Meeting the Clinical, Virologic, or Immunologic Criteria for Treatment Initiation or Re-initiation | 25th percentile | 36.4 weeks |
| IT Arm | Time to Meeting the Clinical, Virologic, or Immunologic Criteria for Treatment Initiation or Re-initiation | 50th percentile | 72.0 weeks |
| IT Arm | Time to Meeting the Clinical, Virologic, or Immunologic Criteria for Treatment Initiation or Re-initiation | 5th percentile | 6.3 weeks |
| DT Arm | Time to Meeting the Clinical, Virologic, or Immunologic Criteria for Treatment Initiation or Re-initiation | 75th percentile | 96.0 weeks |
| DT Arm | Time to Meeting the Clinical, Virologic, or Immunologic Criteria for Treatment Initiation or Re-initiation | 5th percentile | 6.9 weeks |
| DT Arm | Time to Meeting the Clinical, Virologic, or Immunologic Criteria for Treatment Initiation or Re-initiation | 10th percentile | 12.3 weeks |
| DT Arm | Time to Meeting the Clinical, Virologic, or Immunologic Criteria for Treatment Initiation or Re-initiation | 50th percentile | 60.0 weeks |
| DT Arm | Time to Meeting the Clinical, Virologic, or Immunologic Criteria for Treatment Initiation or Re-initiation | 90th percentile | 96.0 weeks |
| DT Arm | Time to Meeting the Clinical, Virologic, or Immunologic Criteria for Treatment Initiation or Re-initiation | 25th percentile | 26.3 weeks |
Secondary
Time to Treatment Initiation or Death
5th, 10th, 25th, 50th and 75th percentiles in weeks from randomization to treatment initiation or death
Time frame: 5 years since randomization
Population: All eligible subjects were included except one subject in IT arm with baseline multidrug resistance.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| IT Arm | Time to Treatment Initiation or Death | 10th percentile | 36.9 weeks |
| IT Arm | Time to Treatment Initiation or Death | 50th percentile | 96.4 weeks |
| IT Arm | Time to Treatment Initiation or Death | 25th percentile | 67.1 weeks |
| IT Arm | Time to Treatment Initiation or Death | 75th percentile | 163.3 weeks |
| IT Arm | Time to Treatment Initiation or Death | 5th percentile | 36 weeks |
| DT Arm | Time to Treatment Initiation or Death | 75th percentile | 157.7 weeks |
| DT Arm | Time to Treatment Initiation or Death | 5th percentile | 13.9 weeks |
| DT Arm | Time to Treatment Initiation or Death | 10th percentile | 20.9 weeks |
| DT Arm | Time to Treatment Initiation or Death | 25th percentile | 43.7 weeks |
| DT Arm | Time to Treatment Initiation or Death | 50th percentile | 97.3 weeks |