Nine Month Course of Anti-HIV Medications for People Recently Infected With HIV

This study has been terminated.

(The DSMB concluded that the findings regarding the primary analysis would persist and that no additional study goals would be achieved by continuing the study.)

Sponsor:

Collaborators:

National Institute of Allergy and Infectious Diseases (NIAID)

Adult AIDS Clinical Trials Group

Information provided by (Responsible Party):

AIDS Clinical Trials Group

ClinicalTrials.gov Identifier:

NCT00090779

First received: September 3, 2004

Last updated: November 16, 2012

Last verified: November 2012

History of Changes

Results First Received: July 2, 2012

Study Type:	Interventional
Study Design:	Allocation: Randomized; Endpoint Classification: Efficacy Study; Intervention Model: Parallel Assignment; Masking: Open Label; Primary Purpose: Treatment
Condition:	HIV Infections
Interventions:	Drug: Emtricitabine/ tenofovir disoproxil fumarate Drug: Lopinavir/Ritonavir

Participant Flow

Hide Participant Flow

Recruitment Details

Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
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.

Pre-Assignment Details

Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
No text entered.

Reporting Groups

	Description
IT Arm	On step 1, IT arm participants received 36 weeks of emtricitabine/tenofovir disoproxil fumarate once daily and lopinavir/ritonavir twice daily. Participants in IT arm who met clinical, virologic or immunologic criteria for treatment re-initiation entered step 2 and re-initiated ART. At the time of the end of original randomized study, study participants in IT arm who did not enter Step 2 and did not initiate ART without meeting eligibility criteria for Step 2 had the opportunity to take part in a long-term follow-up study (step 3) for up to a total duration of five years in order to ascertain information about HIV-1 RNA, CD4+ T-cell count, occurrence of CDC Category B or C diagnoses, and initiation of ART.
DT Arm	On step 1, DT arm participants received no Treatment,unless subsequent disease progression criteria were met. Participants in DT arm who met clinical, virologic or immunologic criteria for treatment initiation entered step 2 and initiated ART. At the time of the end of original randomized study, study participants in DT arm who did not enter Step 2 and did not initiate ART without meeting eligibility criteria for Step 2 had the opportunity to take part in a long-term follow-up study (step 3) for up to a total duration of five years in order to ascertain information about HIV-1 RNA, CD4+ T-cell count, occurrence of CDC Category B or C diagnoses, and initiation of ART.

Description

IT Arm

On step 1, IT arm participants received 36 weeks of emtricitabine/tenofovir disoproxil fumarate once daily and lopinavir/ritonavir twice daily. Participants in IT arm who met clinical, virologic or immunologic criteria for treatment re-initiation entered step 2 and re-initiated ART. At the time of the end of original randomized study, study participants in IT arm who did not enter Step 2 and did not initiate ART without meeting eligibility criteria for Step 2 had the opportunity to take part in a long-term follow-up study (step 3) for up to a total duration of five years in order to ascertain information about HIV-1 RNA, CD4+ T-cell count, occurrence of CDC Category B or C diagnoses, and initiation of ART.

DT Arm

On step 1, DT arm participants received no Treatment,unless subsequent disease progression criteria were met. Participants in DT arm who met clinical, virologic or immunologic criteria for treatment initiation entered step 2 and initiated ART. At the time of the end of original randomized study, study participants in DT arm who did not enter Step 2 and did not initiate ART without meeting eligibility criteria for Step 2 had the opportunity to take part in a long-term follow-up study (step 3) for up to a total duration of five years in order to ascertain information about HIV-1 RNA, CD4+ T-cell count, occurrence of CDC Category B or C diagnoses, and initiation of ART.

Participant Flow for 3 periods

Period 1: Step 1

	IT Arm	DT Arm
STARTED	66	64
COMPLETED	55 ^[1]	49 ^[1]
NOT COMPLETED	11	15
Withdrawal by Subject	4	2
Lost to Follow-up	3	2
Death	0	2
Physician Decision	1	0
Pregnancy	1	0
Non-compliance to study requirements	0	1
Subject relocated	2	8

[1]	Results are based on the database frozen on July 2, 2009 per DSMB recommendation of study closure.

Period 2: Step 2

	IT Arm	DT Arm
STARTED	6 ^[1]	19 ^[2]
COMPLETED	0	1
NOT COMPLETED	6	18
Off study per study closure	6	16
Subject relocated	0	1
Non-compliance to study requirements	0	1

[1]	One subject who had two consecutive CD4<350cells/mm^3 did not enter step 2.
[2]	Three with two consecutive CD4<350cells/mm^3 and one with CDC category B event didn't enter step 2.

Period 3: Step 3

	IT Arm	DT Arm
STARTED	7	5
COMPLETED	0	0
NOT COMPLETED	7	5
Initiation of ART and off extended study	3	2
Off extended study due to study closure	4	3

Baseline Characteristics

Hide Baseline Characteristics

Reporting Groups

	Description
IT Arm	IT arm participants received emtricitabine/tenofovir disoproxil fumarate once daily and lopinavir/ritonavir twice daily
DT Arm	DT arm participants received no Treatment
Total	Total of all reporting groups

Baseline Measures

	IT Arm	DT Arm	Total
Number of Participants [units: participants]	66	64	130
Age [units: years] Mean ± Standard Deviation	34.1 ± 11.3	34.6 ± 9.1	34.4 ± 10.3
Age, Customized [units: participants]
<20 years	4	0	4
20-29 years	24	23	47
30-39 years	19	21	40
40-49 years	12	16	28
50-59 years	4	4	8
60-69 years	3	0	3
Gender [units: participants]
Female	8	5	13
Male	58	59	117
Race [units: participants]
White	49	56	105
Black/ African American	10	3	13
Other	4	4	8
Unknown	3	1	4
Ethnicity [units: participants]
Hispanic or Latino	14	9	23
Not Hispanic or Latino	52	55	107
CD4 Counts [units: cells/mm3] Mean ± Standard Deviation	570 ± 197	611 ± 207	590 ± 202
CD4 Count Category [units: participants]
201-350 cells/mm^3	4	2	6
351-500 cells/mm^3	26	24	50
>500 cells/mm^3	36	38	74
Log10 HIV-1 RNA Viral Load [units: log10 copies/mL] Mean ± Standard Deviation	4.4 ± 0.6	4.4 ± 0.6	4.4 ± 0.6
HIV-1 RNA Viral Load Category [units: participants]
200-399 copies/mL	0	1	1
400-999 copies/mL	1	0	1
1000-9999 copies/mL	16	15	31
>=10000 copies/mL	49	48	97

Outcome Measures

Hide All Outcome Measures

1. Primary:

Ranked Log10 HIV-1 RNA Viral Load (log10 Copies/mL) Averaged at 72 and 76 Weeks for the IT Arm and DT Arm [ Time Frame: At Weeks 72 and 76 ]

Measure Type	Primary
Measure Title	Ranked Log10 HIV-1 RNA Viral Load (log10 Copies/mL) Averaged at 72 and 76 Weeks for the IT Arm and DT Arm
Measure Description	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
Safety Issue	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Participants in follow-up at least 72 weeks since randomization were included.

Reporting Groups

	Description
IT Arm	IT arm participants received emtricitabine/tenofovir disoproxil fumarate once daily and lopinavir/ritonavir twice daily
DT Arm	DT arm participants received no Treatment

Measured Values

	IT Arm	DT Arm
Number of Participants Analyzed [units: participants]	39	40
Ranked Log10 HIV-1 RNA Viral Load (log10 Copies/mL) Averaged at 72 and 76 Weeks for the IT Arm and DT Arm [units: rank] Median ( Full Range )	26.0 ( 1.0 to 70.0 )	49.3 ( 4.0 to 70.0 )

Statistical Analysis 1 for Ranked Log10 HIV-1 RNA Viral Load (log10 Copies/mL) Averaged at 72 and 76 Weeks for the IT Arm and DT Arm

Groups ^[1]	All groups
Method ^[2]	Wilcoxon (Mann-Whitney)
P Value ^[3]	0.005

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	No text entered.
[2]	Other relevant information, such as adjustments or degrees of freedom:
	No text entered.
[3]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	No text entered.

2. 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 [ Time Frame: IT arm (weeks 72 and 76) and DT arm ( weeks 36 and 40) ]

Measure Type	Primary
Measure Title	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
Measure Description	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)
Safety Issue	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Participants in follow-up at least 72 weeks since randomization were included.

Reporting Groups

	Description
IT Arm	IT arm participants received emtricitabine/tenofovir disoproxil fumarate once daily and lopinavir/ritonavir twice daily
DT Arm	DT arm participants received no Treatment

Measured Values

	IT Arm	DT Arm
Number of Participants Analyzed [units: participants]	39	40
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 [units: rank] Median ( Full Range )	26.0 ( 1.0 to 70.0 )	48.5 ( 28.0 to 67.5 )

Statistical Analysis 1 for 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

Groups ^[1]	All groups
Method ^[2]	Wilcoxon (Mann-Whitney)
P Value ^[3]	0.002

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	No text entered.
[2]	Other relevant information, such as adjustments or degrees of freedom:
	No text entered.
[3]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	No text entered.

3. 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 ]

Measure Type	Primary
Measure Title	Number of Participants Experiencing Either a CDC Category B or C Diagnosis, CD4<200 Cells/mm^3 or CD4 Percent <14%.
Measure Description	No text entered.
Time Frame	96 weeks since randomization
Safety Issue	Yes

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
No text entered.

Reporting Groups

	Description
IT Arm	IT arm participants received emtricitabine/tenofovir disoproxil fumarate once daily and lopinavir/ritonavir twice daily
DT Arm	DT arm participants received no Treatment

Measured Values

	IT Arm	DT Arm
Number of Participants Analyzed [units: participants]	66	64
Number of Participants Experiencing Either a CDC Category B or C Diagnosis, CD4<200 Cells/mm^3 or CD4 Percent <14%. [units: participants]	2	8

No statistical analysis provided for Number of Participants Experiencing Either a CDC Category B or C Diagnosis, CD4<200 Cells/mm^3 or CD4 Percent <14%.

4. 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) ]

Measure Type	Secondary
Measure Title	Change in CD4 Counts Cells/mm^3 From Week 36 for IT Arm and From Week 0 for DT Arm
Measure Description	No text entered.
Time Frame	IT arm (weeks 36, 60, 72, 84 and 96) and DT arm (weeks 0, 24, 36, 48 and 60)
Safety Issue	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
One subject in IT arm with multidrug resistance at baseline was excluded from this analysis.

Reporting Groups

	Description
IT Arm	IT arm participants received emtricitabine/tenofovir disoproxil fumarate once daily and lopinavir/ritonavir twice daily
DT Arm	DT arm participants received no Treatment

Measured Values

	IT Arm	DT Arm
Number of Participants Analyzed [units: participants]	65	64
Change in CD4 Counts Cells/mm^3 From Week 36 for IT Arm and From Week 0 for DT Arm [units: Change in Log10 transformed CD4 Counts] Mean ± Standard Deviation
IT arm (wk 60- wk 36) vs. DT arm (wk 24- wk 0)	-0.11 ± 0.10	-0.02 ± 0.12
IT arm (wk 72- wk 36) vs. DT arm (wk 36- wk 0)	-0.10 ± 0.12	-0.03 ± 0.11
IT arm (wk 84- wk 36) vs. DT arm (wk 48- wk 0)	-0.10 ± 0.12	-0.06 ± 0.17
IT arm (wk 96- wk 36) vs. DT arm (wk 60- wk 0)	-0.12 ± 0.13	-0.02 ± 0.15

No statistical analysis provided for Change in CD4 Counts Cells/mm^3 From Week 36 for IT Arm and From Week 0 for DT Arm

5. Secondary:

Number of Participants Meeting Clinical, Virologic, or Immunologic Criteria for Treatment Initiation or Re-initiation [ Time Frame: 96 weeks since randomization ]

Measure Type	Secondary
Measure Title	Number of Participants Meeting Clinical, Virologic, or Immunologic Criteria for Treatment Initiation or Re-initiation
Measure Description	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
Safety Issue	Yes

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
All 130 eligible subjects were included.

Reporting Groups

	Description
IT Arm	IT arm participants received emtricitabine/tenofovir disoproxil fumarate once daily and lopinavir/ritonavir twice daily
DT Arm	DT arm participants received no Treatment

Measured Values

	IT Arm	DT Arm
Number of Participants Analyzed [units: participants]	66	64
Number of Participants Meeting Clinical, Virologic, or Immunologic Criteria for Treatment Initiation or Re-initiation [units: Participants]	7	23

No statistical analysis provided for Number of Participants Meeting Clinical, Virologic, or Immunologic Criteria for Treatment Initiation or Re-initiation

6. Secondary:

Number of Participants in IT Arm Off Treatment Before 36 Weeks [ Time Frame: At Week 36 ]

Measure Type	Secondary
Measure Title	Number of Participants in IT Arm Off Treatment Before 36 Weeks
Measure Description	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
Safety Issue	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
All 66 eligible subjects in IT arm were included.

Reporting Groups

	Description
IT Arm	IT arm participants received emtricitabine/tenofovir disoproxil fumarate once daily and lopinavir/ritonavir twice daily

Measured Values

	IT Arm
Number of Participants Analyzed [units: participants]	66
Number of Participants in IT Arm Off Treatment Before 36 Weeks [units: participants]	8

No statistical analysis provided for Number of Participants in IT Arm Off Treatment Before 36 Weeks

7. Secondary:

Time to Meeting the Clinical, Virologic, or Immunologic Criteria for Treatment Initiation or Re-initiation [ Time Frame: 96 weeks since randomization ]

Measure Type	Secondary
Measure Title	Time to Meeting the Clinical, Virologic, or Immunologic Criteria for Treatment Initiation or Re-initiation
Measure Description	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
Safety Issue	Yes

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Throughout database cutoff for DSMB review (by July 2, 2009).

Reporting Groups

	Description
IT Arm	IT arm participants received emtricitabine/tenofovir disoproxil fumarate once daily and lopinavir/ritonavir twice daily
DT Arm	DT arm participants received no Treatment

Measured Values

	IT Arm	DT Arm
Number of Participants Analyzed [units: participants]	65	64
Time to Meeting the Clinical, Virologic, or Immunologic Criteria for Treatment Initiation or Re-initiation [units: weeks] Number ( 95% Confidence Interval )
5th percentile	6.3 ( 0 to 13.0 )	6.9 ( 2.3 to 12.3 )
10th percentile	13.0 ( 0 to 26.1 )	12.3 ( 2.3 to 18.3 )
25th percentile	36.4 ( 19.9 to 50.4 )	26.3 ( 16.9 to 36.4 )
50th percentile	72.0 ( 52.4 to 94.1 )	60.0 ( 36.4 to 93.9 )
75th percentile	NA ( NA to NA ) ^[1]	96.0 ( 72.0 to 96.0 )
90th percentile	NA ( NA to NA ) ^[2]	96.0 ( 96.0 to NA ) ^[3]

[1]	Not estimable as the estimates for survival function at all weeks is above 25%
[2]	Not estimable as the estimates for survival function at all weeks is above 10%
[3]	Not estimable as the upper limit for survival function at all weeks is above 10%

No statistical analysis provided for Time to Meeting the Clinical, Virologic, or Immunologic Criteria for Treatment Initiation or Re-initiation

8. 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 [ Time Frame: 96 weeks since randomization ]

Measure Type	Secondary
Measure Title	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
Measure Description	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
Safety Issue	Yes

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
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).

Reporting Groups

	Description
IT Arm	IT arm participants received emtricitabine/tenofovir disoproxil fumarate once daily and lopinavir/ritonavir twice daily
DT Arm	DT arm participants received no Treatment

Measured Values

	IT Arm	DT Arm
Number of Participants Analyzed [units: participants]	65	64
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 [units: weeks] Number ( 95% Confidence Interval )
5th percentile	5.1 ( 0.4 to 13.0 )	6.9 ( 2.3 to 12.3 )
10th percentile	10.4 ( 0.4 to 16.4 )	12.3 ( 2.3 to 18.3 )
25th percentile	22.7 ( 13.0 to 39.3 )	26.3 ( 16.9 to 36.4 )
50th percentile	58.1 ( 36.0 to NA ) ^[1]	60.0 ( 36.4 to 93.9 )
75th percentile	NA ( NA to NA ) ^[2]	96.0 ( 72.0 to 96.0 )
90th percentile	NA ( NA to NA ) ^[3]	96.0 ( 96.0 to NA ) ^[4]

[1]	Not estimable as the upper limit for survival function at all weeks is above 50%
[2]	Not estimable as the estimates for survival function at all weeks is above 25%
[3]	Not estimable as the estimates for survival function at all weeks is above 10%
[4]	Not estimable as the upper limit for survival function at all weeks is above 10%

No statistical analysis provided for 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

9. Secondary:

Time to Treatment Initiation or Death [ Time Frame: 5 years since randomization ]

Measure Type	Secondary
Measure Title	Time to Treatment Initiation or Death
Measure Description	5th, 10th, 25th, 50th and 75th percentiles in weeks from randomization to treatment initiation or death
Time Frame	5 years since randomization
Safety Issue	Yes

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
All eligible subjects were included except one subject in IT arm with baseline multidrug resistance.

Reporting Groups

	Description
IT Arm	IT arm participants received emtricitabine/tenofovir disoproxil fumarate once daily and lopinavir/ritonavir twice daily
DT Arm	DT arm participants received no Treatment

Measured Values

	IT Arm	DT Arm
Number of Participants Analyzed [units: participants]	65	64
Time to Treatment Initiation or Death [units: weeks] Number ( 95% Confidence Interval )
5th percentile	36 ( 0 to 36.9 )	13.9 ( 6.4 to 20.9 )
10th percentile	36.9 ( 0 to 51.9 )	20.9 ( 6.4 to 37.0 )
25th percentile	67.1 ( 44.0 to 94.6 )	43.7 ( 31.6 to 96.0 )
50th percentile	96.4 ( 94.0 to 157.9 )	97.3 ( 94.0 to 146.4 )
75th percentile	163.3 ( 97.7 to NA ) ^[1]	157.7 ( 99.9 to NA ) ^[1]

[1]	Not estimable as the upper limit for survival function at all weeks is above 25%

No statistical analysis provided for Time to Treatment Initiation or Death

Serious Adverse Events

Show Serious Adverse Events

Other Adverse Events

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More Information

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Certain Agreements:

Principal Investigators are NOT employed by the organization sponsoring the study.

There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

The agreement is:

	The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
	The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
	Other disclosure agreement that restricts the right of the PI to discuss or publish trial results after the trial is completed. Restriction Description: In accordance with the Clinical Trials Agreement between NIAID (DAIDS) and company collaborators, NIAID (DAIDS) provides companies with a copy of any abstract, press release, or manuscript prior to submission for publication with sufficient time for company review and comment. The publication/other disclosure can be delayed for up to 30 additional business days for manuscripts and five (5) business days for abstracts, to preserve U.S. or foreign patent or other intellectual property rights”.

Limitations and Caveats

Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
No text entered.

Results Point of Contact:

Name/Title: Clinicaltrials.gov Coordinator
Organization: Center for Biostatistics in AIDS Research, Harvard School of Public Health
phone: (617) 432-2829
e-mail: CBAR.ClinicalTrials.Gov@sdac.harvard.edu

Publications of Results:

Messer K, Vaida F, Hogan C. Robust analysis of biomarker data with informative missingness using a two-stage hypothesis test in an HIV treatment interruption trial: AIEDRP AIN503/ACTG A5217. Contemp Clin Trials. 2006 Jul 25; [Epub ahead of print]

Hogan CM, Degruttola V, Sun X, Fiscus SA, Del Rio C, Hare CB, Markowitz M, Connick E, Macatangay B, Tashima KT, Kallungal B, Camp R, Morton T, Daar ES, Little S; A5217 Study Team. The setpoint study (ACTG A5217): effect of immediate versus deferred antiretroviral therapy on virologic set point in recently HIV-1-infected individuals. J Infect Dis. 2012 Jan;205(1):87-96. Epub 2011 Dec 15.

Other Publications:

Fidler S, Oxenius A, Brady M, Clarke J, Cropley I, Babiker A, Zhang HT, Price D, Phillips R, Weber J. Virological and immunological effects of short-course antiretroviral therapy in primary HIV infection. AIDS. 2002 Oct 18;16(15):2049-54.

Kassutto S, Rosenberg ES. Primary HIV type 1 infection. Clin Infect Dis. 2004 May 15;38(10):1447-53. Epub 2004 Apr 30.

Little SJ, Holte S, Routy JP, Daar ES, Markowitz M, Collier AC, Koup RA, Mellors JW, Connick E, Conway B, Kilby M, Wang L, Whitcomb JM, Hellmann NS, Richman DD. Antiretroviral-drug resistance among patients recently infected with HIV. N Engl J Med. 2002 Aug 8;347(6):385-94.

Pilcher CD, Eron JJ Jr, Galvin S, Gay C, Cohen MS. Acute HIV revisited: new opportunities for treatment and prevention. J Clin Invest. 2004 Apr;113(7):937-45. Review.

Responsible Party:	AIDS Clinical Trials Group
ClinicalTrials.gov Identifier:	NCT00090779 History of Changes
Other Study ID Numbers:	ACTG A5217, 1U01AI068636, AIEDRP AIN503, ACTG A5217
Study First Received:	September 3, 2004
Results First Received:	July 2, 2012
Last Updated:	November 16, 2012
Health Authority:	United States: Federal Government

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