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A5288/MULTI-OCTAVE: Management Using Latest Technologies to Optimize Combination Therapy After Viral Failure (MULTI-OCTAVE)

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ClinicalTrials.gov Identifier: NCT01641367
Recruitment Status : Active, not recruiting
First Posted : July 16, 2012
Results First Posted : February 20, 2018
Last Update Posted : February 20, 2018
Sponsor:
Collaborators:
National Institute of Allergy and Infectious Diseases (NIAID)
AbbVie
Gilead Sciences
Janssen Pharmaceuticals
Merck Sharp & Dohme Corp.
Dimagi Inc.
Information provided by (Responsible Party):
AIDS Clinical Trials Group

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition HIV-1 Infection
Interventions Drug: Darunavir
Drug: Etravirine
Drug: Emtricitabine/tenofovir disoproxil fumarate
Drug: Raltegravir
Drug: Second line ART regimens - based on a boosted protease inhibitor (bPI) plus two nucleoside analogues (NRTIs)
Drug: Study provided drugs according to patient resistance profile (DRV, ETR, RTV, FTC/TDF) + any in country available drug as applicable & available
Other: SOC adherence versus SOC+CPI adherence
Enrollment 545
Recruitment Details Participants were enrolled between 22FEB2013 and 21DEC2015 at non-US based clinical research sites. Participants were followed until 48 weeks after the last participant enrolled to Step 1.
Pre-assignment Details  
Arm/Group Title Experimental: Cohort A Experimental: Sub-cohort B1 Experimental: Sub-cohort B2 Experimental: Sub-cohort B3 Experimental: Cohort C Experimental: Cohort D
Hide Arm/Group Description

Under Protocol version 1.0:

No resistance to NRTIs, PIs, or NNRTI

• Continue current second-line regimen; NRTIs could be modified

Changed under LOA#2 to:

No LPV/RTV resistance and susceptible to at least one NRTI, regardless of NNRTI resistance or prior RAL exposure • Continue second-line regimen which may include LPV/RTV; NRTIs could be modified

Changed under LOA#3 to:

No LPV/RTV resistance and susceptible to at least one NRTI, regardless of NNRTI resistance or prior RAL exposure

• Continue PI backbone; NRTIs could be modified. If on a RAL-containing regimen, RAL must be discontinued.

Under Protocol version 1.0:

Susceptible to DRV/RTV and ETR with or without resistance to NRTIs (and may have resistance to other PIs) and without active hepatitis B infection at screening • Best available NRTIs, RAL, & DRV/RTV

Changed under LOA#2 to:

Resistance to LPV/RTV but susceptible to DRV/RTV and ETR and with no prior RAL exposure and regardless of NRTI resistance (and without active hepatitis B infection at screening) OR Resistance to all NRTIs (i.e. susceptible to none) but susceptible to DRV/RTV and ETR and with no prior RAL exposure (and without active hepatitis B infection at screening)

• Best available NRTIs, RAL, & DRV/RTV

Under Protocol version 1.0:

Susceptible to DRV/RTV and ETR with or without resistance to NRTIs (and may have resistance to other PIs) and without active hepatitis B infection at screening • ETR, RAL, and DRV/RTV

Changed under LOA#2 to:

Resistance to LPV/RTV but susceptible to DRV/RTV and ETR and with no prior RAL exposure and regardless of NRTI resistance (and without active hepatitis B infection at screening) OR Resistance to all NRTIs (i.e. susceptible to none) but susceptible to DRV/RTV and ETR and with no prior RAL exposure (and without active hepatitis B infection at screening)

• ETR, RAL, and DRV/RTV

Under Protocol version 1.0:

Susceptible to DRV/RTV and ETR with or without resistance to NRTIs (and may have resistance to other PIs) and with active hepatitis B infection at screening • RAL, DRV/RTV, and FTC/TDF or TDF+3TC

Changed under LOA#2 to:

Resistance to LPV/RTV but susceptible to DRV/RTV and ETR and with no prior RAL exposure and regardless of NRTI resistance (with active hepatitis B infection at screening) OR Resistance to all NRTIs (i.e. susceptible to none) but susceptible to DRV/RTV and ETR and with no prior RAL exposure (with active hepatitis B infection at screening)

• RAL, DRV/RTV, and FTC/TDF or TDF+3TC

Under Protocol version 1.0:

Resistance to NRTIs and ETR or resistance to ETR alone (and may have resistance to PIs other than DRV) • Best available NRTIs, RAL, and DRV/RTV

Changed under LOA#2:

Resistance to LPV/RTV and ETR but susceptible to DRV/RTV and with no prior RAL exposure and regardless of NRTI resistance OR Resistance to ETR and to all NRTIs (i.e. susceptible to none) but susceptible to DRV/RTV and with no prior RAL exposure

• Best available NRTIs, RAL, and DRV/RTV

Under Protocol version 1.0:

Multiple NRTI resistance and/or DRV/RTV resistance or prior RAL exposure:

• Best available regimen, including study-provided and any locally available drugs

Changed under LOA#2:

Not eligible for Cohort A, B, or C:

• Best available regimen, including study-provided and any locally available drugs

Updated under protocol v2.0:

• Best available ART regimen, including study-provided and any locally available non-experimental drugs

Period Title: Overall Study
Started 287 74 72 8 70 34
Completed [1] 253 73 68 8 67 33
Not Completed 34 1 4 0 3 1
Reason Not Completed
Death             18             1             2             0             1             1
Lost to Follow-up             16             0             2             0             2             0
[1]
Completed the study = participant must have had the last step 1/2 visit between 22NOV2016-13FEB2017
Arm/Group Title Experimental: Cohort A Experimental: Sub-cohort B1 Experimental: Sub-cohort B2 Experimental: Sub-cohort B3 Experimental: Cohort C Experimental: Cohort D Total
Hide Arm/Group Description

Under Protocol version 1.0:

No resistance to NRTIs, PIs, or NNRTI

• Continue current second-line regimen; NRTIs could be modified

Changed under LOA#2 to:

No LPV/RTV resistance and susceptible to at least one NRTI, regardless of NNRTI resistance or prior RAL exposure • Continue second-line regimen which may include LPV/RTV; NRTIs could be modified

Changed under LOA#3 to:

No LPV/RTV resistance and susceptible to at least one NRTI, regardless of NNRTI resistance or prior RAL exposure

• Continue PI backbone; NRTIs could be modified. If on a RAL-containing regimen, RAL must be discontinued.

Under Protocol version 1.0:

Susceptible to DRV/RTV and ETR with or without resistance to NRTIs (and may have resistance to other PIs) and without active hepatitis B infection at screening • Best available NRTIs, RAL, & DRV/RTV

Changed under LOA#2 to:

Resistance to LPV/RTV but susceptible to DRV/RTV and ETR and with no prior RAL exposure and regardless of NRTI resistance (and without active hepatitis B infection at screening) OR Resistance to all NRTIs (i.e. susceptible to none) but susceptible to DRV/RTV and ETR and with no prior RAL exposure (and without active hepatitis B infection at screening)

• Best available NRTIs, RAL, & DRV/RTV

Under Protocol version 1.0:

Susceptible to DRV/RTV and ETR with or without resistance to NRTIs (and may have resistance to other PIs) and without active hepatitis B infection at screening • ETR, RAL, and DRV/RTV

Changed under LOA#2 to:

Resistance to LPV/RTV but susceptible to DRV/RTV and ETR and with no prior RAL exposure and regardless of NRTI resistance (and without active hepatitis B infection at screening) OR Resistance to all NRTIs (i.e. susceptible to none) but susceptible to DRV/RTV and ETR and with no prior RAL exposure (and without active hepatitis B infection at screening)

• ETR, RAL, and DRV/RTV

Under Protocol version 1.0:

Susceptible to DRV/RTV and ETR with or without resistance to NRTIs (and may have resistance to other PIs) and with active hepatitis B infection at screening • RAL, DRV/RTV, and FTC/TDF or TDF+3TC

Changed under LOA#2 to:

Resistance to LPV/RTV but susceptible to DRV/RTV and ETR and with no prior RAL exposure and regardless of NRTI resistance (with active hepatitis B infection at screening) OR Resistance to all NRTIs (i.e. susceptible to none) but susceptible to DRV/RTV and ETR and with no prior RAL exposure (with active hepatitis B infection at screening)

• RAL, DRV/RTV, and FTC/TDF or TDF+3TC

Under Protocol version 1.0:

Resistance to NRTIs and ETR or resistance to ETR alone (and may have resistance to PIs other than DRV) • Best available NRTIs, RAL, and DRV/RTV

Changed under LOA#2:

Resistance to LPV/RTV and ETR but susceptible to DRV/RTV and with no prior RAL exposure and regardless of NRTI resistance OR Resistance to ETR and to all NRTIs (i.e. susceptible to none) but susceptible to DRV/RTV and with no prior RAL exposure

• Best available NRTIs, RAL, and DRV/RTV

Under Protocol version 1.0:

Multiple NRTI resistance and/or DRV/RTV resistance or prior RAL exposure:

• Best available regimen, including study-provided and any locally available drugs

Changed under LOA#2:

Not eligible for Cohort A, B, or C:

• Best available regimen, including study-provided and any locally available drugs

Updated under protocol v2.0:

• Best available ART regimen, including study-provided and any locally available non-experimental drugs

Total of all reporting groups
Overall Number of Baseline Participants 287 74 72 8 70 34 545
Hide Baseline Analysis Population Description
All enrolled participants.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 287 participants 74 participants 72 participants 8 participants 70 participants 34 participants 545 participants
40  (11) 42  (10) 42  (9) 40  (10) 42  (10) 42  (10) 41  (10)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 287 participants 74 participants 72 participants 8 participants 70 participants 34 participants 545 participants
Female
160
  55.7%
29
  39.2%
28
  38.9%
4
  50.0%
23
  32.9%
14
  41.2%
258
  47.3%
Male
127
  44.3%
45
  60.8%
44
  61.1%
4
  50.0%
47
  67.1%
20
  58.8%
287
  52.7%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 287 participants 74 participants 72 participants 8 participants 70 participants 34 participants 545 participants
Hispanic or Latino
38
  13.2%
7
   9.5%
9
  12.5%
0
   0.0%
1
   1.4%
8
  23.5%
63
  11.6%
Not Hispanic or Latino
241
  84.0%
62
  83.8%
59
  81.9%
8
 100.0%
60
  85.7%
24
  70.6%
454
  83.3%
Unknown or Not Reported
8
   2.8%
5
   6.8%
4
   5.6%
0
   0.0%
9
  12.9%
2
   5.9%
28
   5.1%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 287 participants 74 participants 72 participants 8 participants 70 participants 34 participants 545 participants
American Indian or Alaska Native
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Asian
62
  21.6%
21
  28.4%
17
  23.6%
3
  37.5%
35
  50.0%
8
  23.5%
146
  26.8%
Native Hawaiian or Other Pacific Islander
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Black or African American
195
  67.9%
49
  66.2%
49
  68.1%
5
  62.5%
34
  48.6%
21
  61.8%
353
  64.8%
White
7
   2.4%
1
   1.4%
3
   4.2%
0
   0.0%
0
   0.0%
3
   8.8%
14
   2.6%
More than one race
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
1
   2.9%
1
   0.2%
Unknown or Not Reported
23
   8.0%
3
   4.1%
3
   4.2%
0
   0.0%
1
   1.4%
1
   2.9%
31
   5.7%
Region of Enrollment  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 287 participants 74 participants 72 participants 8 participants 70 participants 34 participants 545 participants
Brazil
25
   8.7%
8
  10.8%
8
  11.1%
0
   0.0%
0
   0.0%
8
  23.5%
49
   9.0%
Haiti
34
  11.8%
3
   4.1%
5
   6.9%
1
  12.5%
2
   2.9%
0
   0.0%
45
   8.3%
India
55
  19.2%
18
  24.3%
16
  22.2%
2
  25.0%
32
  45.7%
5
  14.7%
128
  23.5%
Kenya
32
  11.1%
9
  12.2%
8
  11.1%
1
  12.5%
7
  10.0%
2
   5.9%
59
  10.8%
Malawi
18
   6.3%
6
   8.1%
2
   2.8%
0
   0.0%
9
  12.9%
2
   5.9%
37
   6.8%
Peru
18
   6.3%
2
   2.7%
1
   1.4%
0
   0.0%
1
   1.4%
0
   0.0%
22
   4.0%
South Africa
58
  20.2%
7
   9.5%
11
  15.3%
0
   0.0%
7
  10.0%
1
   2.9%
84
  15.4%
Thailand
7
   2.4%
3
   4.1%
1
   1.4%
1
  12.5%
3
   4.3%
3
   8.8%
18
   3.3%
Uganda
34
  11.8%
13
  17.6%
17
  23.6%
2
  25.0%
6
   8.6%
9
  26.5%
81
  14.9%
Zimbabwe
6
   2.1%
5
   6.8%
3
   4.2%
1
  12.5%
3
   4.3%
4
  11.8%
22
   4.0%
Plasma HIV-1 RNA, categorical   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 287 participants 74 participants 72 participants 8 participants 70 participants 34 participants 545 participants
< 40 copies/mL
11
   3.8%
1
   1.4%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
12
   2.2%
40 - < 200 copies/mL
11
   3.8%
2
   2.7%
1
   1.4%
1
  12.5%
2
   2.9%
1
   2.9%
18
   3.3%
200 - < 1000 copies/mL
32
  11.1%
5
   6.8%
3
   4.2%
1
  12.5%
9
  12.9%
2
   5.9%
52
   9.5%
1000 - < 10,000 copies/mL
59
  20.6%
17
  23.0%
20
  27.8%
3
  37.5%
12
  17.1%
10
  29.4%
121
  22.2%
10,000 - < 100,000 copies/mL
106
  36.9%
21
  28.4%
18
  25.0%
1
  12.5%
20
  28.6%
9
  26.5%
175
  32.1%
100,000 - < 1,000,000 copies/mL
60
  20.9%
27
  36.5%
25
  34.7%
2
  25.0%
22
  31.4%
10
  29.4%
146
  26.8%
1,000,000 - < 10,000,000 copies/mL
8
   2.8%
1
   1.4%
4
   5.6%
0
   0.0%
5
   7.1%
2
   5.9%
20
   3.7%
>= 10,000,000 copies/mL
0
   0.0%
0
   0.0%
1
   1.4%
0
   0.0%
0
   0.0%
0
   0.0%
1
   0.2%
[1]
Measure Description: Baseline Plasma HIV-1 RNA is defined as the last available result on or before the date of study entry
CD4+ T-Cell Count, categorical   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 287 participants 74 participants 72 participants 8 participants 70 participants 34 participants 545 participants
< 50 cells/mm^3
50
  17.4%
17
  23.0%
11
  15.3%
1
  12.5%
9
  12.9%
7
  20.6%
95
  17.4%
50 - < 200 cells/mm^3
108
  37.6%
27
  36.5%
25
  34.7%
1
  12.5%
31
  44.3%
10
  29.4%
202
  37.1%
200 - < 350 cells/mm^3
79
  27.5%
15
  20.3%
23
  31.9%
5
  62.5%
19
  27.1%
7
  20.6%
148
  27.2%
350 - < 500 cells/mm^3
30
  10.5%
12
  16.2%
6
   8.3%
1
  12.5%
6
   8.6%
8
  23.5%
63
  11.6%
>= 500 cells/mm^3
20
   7.0%
3
   4.1%
7
   9.7%
0
   0.0%
5
   7.1%
2
   5.9%
37
   6.8%
[1]
Measure Description: Baseline CD4+ T-cell count is defined as the last available result on or before the date of study entry
IV drug history, categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 287 participants 74 participants 72 participants 8 participants 70 participants 34 participants 545 participants
Never
286
  99.7%
74
 100.0%
72
 100.0%
8
 100.0%
70
 100.0%
34
 100.0%
544
  99.8%
Previously
1
   0.3%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
1
   0.2%
Hepatitis B Surface Antigen Result, categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 287 participants 74 participants 72 participants 8 participants 70 participants 34 participants 545 participants
Positive
14
   4.9%
0
   0.0%
0
   0.0%
8
 100.0%
3
   4.3%
4
  11.8%
29
   5.3%
Negative
273
  95.1%
74
 100.0%
72
 100.0%
0
   0.0%
66
  94.3%
30
  88.2%
515
  94.5%
Indeterminate
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
1
   1.4%
0
   0.0%
1
   0.2%
1.Primary Outcome
Title Proportion of Participants With Plasma HIV-1 RNA ≤200 Copies/mL at 48 Weeks
Hide Description

The measurement closest to exactly 48 weeks (ie, 7x48=336 days) after the date of entry, within the window of 48 weeks ± 6 weeks (specifically 295 to 378 days after randomization, inclusive).

The analysis in the protocol and in the Stat. Analysis Plan involved estimating the proportion of participants in the overall study population with HIV-1 RNA ≤200 copies/mL at week 48 with a 95% confidence interval calculated via a Wald approach. Death or lost to follow-up before week 48 was considered as HIV-1 RNA>200 copies/mL at week 48. Missing results at week 48 were considered as HIV-1 RNA >200 copies/mL at week 48 unless the immediately preceding and succeeding HIV-1 RNA measurements were ≤200 copies/mL. Since the primary analysis was on the total study population, overall results were also submitted. All participants in B3 had HIV-1 RNA ≤200 copies/mL at week 48. Therefore, Wald confidence interval could not be computed for B3 and Clopper-Pearson Exact confidence interval is provided.

Time Frame 48 weeks after the date of entry
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
All enrolled participants
Arm/Group Title Overall Study Experimental: Cohort A Experimental: Sub-cohort B1 Experimental: Sub-cohort B2 Experimental: Sub-cohort B3 Experimental: Cohort C Experimental: Cohort D
Hide Arm/Group Description:
Entire enrolled population spanning all arms and interventions.

Under Protocol version 1.0:

No resistance to NRTIs, PIs, or NNRTI

• Continue current second-line regimen; NRTIs could be modified

Changed under LOA#2 to:

No LPV/RTV resistance and susceptible to at least one NRTI, regardless of NNRTI resistance or prior RAL exposure • Continue second-line regimen which may include LPV/RTV; NRTIs could be modified

Changed under LOA#3 to:

No LPV/RTV resistance and susceptible to at least one NRTI, regardless of NNRTI resistance or prior RAL exposure

• Continue PI backbone; NRTIs could be modified. If on a RAL-containing regimen, RAL must be discontinued.

Under Protocol version 1.0:

Susceptible to DRV/RTV and ETR with or without resistance to NRTIs (and may have resistance to other PIs) and without active hepatitis B infection at screening • Best available NRTIs, RAL, & DRV/RTV

Changed under LOA#2 to:

Resistance to LPV/RTV but susceptible to DRV/RTV and ETR and with no prior RAL exposure and regardless of NRTI resistance (and without active hepatitis B infection at screening) OR Resistance to all NRTIs (i.e. susceptible to none) but susceptible to DRV/RTV and ETR and with no prior RAL exposure (and without active hepatitis B infection at screening)

• Best available NRTIs, RAL, & DRV/RTV

Under Protocol version 1.0:

Susceptible to DRV/RTV and ETR with or without resistance to NRTIs (and may have resistance to other PIs) and without active hepatitis B infection at screening • ETR, RAL, and DRV/RTV

Changed under LOA#2 to:

Resistance to LPV/RTV but susceptible to DRV/RTV and ETR and with no prior RAL exposure and regardless of NRTI resistance (and without active hepatitis B infection at screening) OR Resistance to all NRTIs (i.e. susceptible to none) but susceptible to DRV/RTV and ETR and with no prior RAL exposure (and without active hepatitis B infection at screening)

• ETR, RAL, and DRV/RTV

Under Protocol version 1.0:

Susceptible to DRV/RTV and ETR with or without resistance to NRTIs (and may have resistance to other PIs) and with active hepatitis B infection at screening • RAL, DRV/RTV, and FTC/TDF or TDF+3TC

Changed under LOA#2 to:

Resistance to LPV/RTV but susceptible to DRV/RTV and ETR and with no prior RAL exposure and regardless of NRTI resistance (with active hepatitis B infection at screening) OR Resistance to all NRTIs (i.e. susceptible to none) but susceptible to DRV/RTV and ETR and with no prior RAL exposure (with active hepatitis B infection at screening)

• RAL, DRV/RTV, and FTC/TDF or TDF+3TC

Under Protocol version 1.0:

Resistance to NRTIs and ETR or resistance to ETR alone (and may have resistance to PIs other than DRV) • Best available NRTIs, RAL, and DRV/RTV

Changed under LOA#2:

Resistance to LPV/RTV and ETR but susceptible to DRV/RTV and with no prior RAL exposure and regardless of NRTI resistance OR Resistance to ETR and to all NRTIs (i.e. susceptible to none) but susceptible to DRV/RTV and with no prior RAL exposure

• Best available NRTIs, RAL, and DRV/RTV

Under Protocol version 1.0:

Multiple NRTI resistance and/or DRV/RTV resistance or prior RAL exposure:

• Best available regimen, including study-provided and any locally available drugs

Changed under LOA#2:

Not eligible for Cohort A, B, or C:

• Best available regimen, including study-provided and any locally available drugs

Updated under protocol v2.0:

• Best available ART regimen, including study-provided and any locally available non-experimental drugs

Overall Number of Participants Analyzed 545 287 74 72 8 70 34
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: proportion of participants
0.64
(0.60 to 0.68)
0.44
(0.38 to 0.49)
0.88
(0.80 to 0.95)
0.88
(0.88 to 0.95)
1.00
(0.63 to 1.00)
0.90
(0.83 to 0.97)
0.74
(0.59 to 0.88)
2.Secondary Outcome
Title Suppression Rate of Plasma HIV-1 RNA to ≤200 Copies/mL at Week 24 and 72
Hide Description Secondary outcome measures will be entered by December 2018.
Time Frame Baseline to week 24 and 72
Outcome Measure Data Not Reported
3.Secondary Outcome
Title Time to Confirmed VF Defined as First HIV-1 RNA >1000 Copies/mL at or After 24 Weeks.
Hide Description

The VF has to be confirmed by the next HIV-1 RNA measurement also being >1000 copies/mL (irrespective of the time between the initial and confirmatory measurements provided that they are obtained on different days, and irrespective of ART being received at the times of these measurements). For the purposes of this outcome measure, a week 24 measurement includes any HIV-1 RNA measurement obtained at ≥7*22=154 days after randomization (to allow for the protocol-defined 14 day window for scheduling the week 24 visit)

Secondary outcome measures will be entered by December 2018.

Time Frame Throughout study; participants are expected to be followed for an average of 84 weeks
Outcome Measure Data Not Reported
4.Secondary Outcome
Title Time to Confirmed VF Defined as First HIV-1 RNA >1000 Copies/mL at or After 24 Weeks With a New Resistance-associated Mutation Detected in Population-based Sequencing.
Hide Description

The new resistance-associated mutation is defined as one not present in the last population-based sequence obtained prior to randomization

Secondary outcome measures will be reported by December 2018.

Time Frame Throughout study; participants are expected to be followed for an average of 84 weeks
Outcome Measure Data Not Reported
5.Secondary Outcome
Title Change in CD4+ T-cell Count From Baseline at Week 24, 48, and 72.
Hide Description

Baseline is defined as the last measurement obtained on or before the earlier of the following two dates: the date of randomization plus three days (this is the time allowed in the protocol for starting study-defined ART) and the date of starting the study-defined ARV regimen (this second date applies only to Cohorts B, C and D as there is no change of regimen for patients in Cohort A)

Secondary outcome measures will be entered by December 2018.

Time Frame Baseline to week 24, 48, and 72
Outcome Measure Data Not Reported
6.Secondary Outcome
Title Time From Randomization to Death.
Hide Description Secondary outcome measures will be entered by December 2018.
Time Frame Throughout study; participants are expected to be followed for an average of 84 weeks
Outcome Measure Data Not Reported
7.Secondary Outcome
Title Time From Randomization to the First of Death, an AIDS-defining Event or a Non-AIDS-defining Event.
Hide Description Secondary outcome measures will be entered by December 2018.
Time Frame Throughout study; participants are expected to be followed for an average of 84 weeks
Outcome Measure Data Not Reported
8.Secondary Outcome
Title Time From Randomization to the First of Death or Hospitalization.
Hide Description Secondary outcome measures will be entered by December 2018.
Time Frame Throughout study; participants are expected to be followed for an average of 84 weeks
Outcome Measure Data Not Reported
9.Secondary Outcome
Title Time From Randomization to Treatment Modification or Discontinuation.
Hide Description

Treatment modification is defined as the first occurrence of a substitution or subtraction of one or more drugs in the study regimen or of the addition of a new drug. This would not include splitting any fixed dose combination medications if the participant continues on the active drugs of the combination.

Secondary outcome measures will be entered by December 2018.

Time Frame Throughout study; participants are expected to be followed for an average of 84 weeks
Outcome Measure Data Not Reported
10.Secondary Outcome
Title Time From Randomization to Treatment Modification or Discontinuation Due to Toxicity.
Hide Description Secondary outcome measures will be entered by December 2018.
Time Frame Throughout study; participants are expected to be followed for an average of 84 weeks
Outcome Measure Data Not Reported
11.Secondary Outcome
Title Change From Baseline in Fasting Values of Total Cholesterol at Week 24, 48 and 72.
Hide Description Baseline is defined as the last measurement obtained on or before the earlier of the following two dates: the date of randomization plus three days (this is the time allowed in the protocol for starting study-defined ART) and the date of starting the study-defined ARV regimen (this second date applies only to Cohorts B, C and D as there is no change of regimen for patients in Cohort A) Secondary outcome measures will be entered by December 2018.
Time Frame Baseline to week 24, 48 and 72
Outcome Measure Data Not Reported
12.Secondary Outcome
Title Change From Baseline in Fasting Values of HDL-C at Week 24, 48 and 72.
Hide Description Baseline is defined as the last measurement obtained on or before the earlier of the following two dates: the date of randomization plus three days (this is the time allowed in the protocol for starting study-defined ART) and the date of starting the study-defined ARV regimen (this second date applies only to Cohorts B, C and D as there is no change of regimen for patients in Cohort A)] Secondary outcome measures will be entered by December 2018.
Time Frame Baseline to week 24, 48 and 72
Outcome Measure Data Not Reported
13.Secondary Outcome
Title Change From Baseline in Fasting Values of Calculated LDL-C at Week 24, 48 and 72.
Hide Description Baseline is defined as the last measurement obtained on or before the earlier of the following two dates: the date of randomization plus three days (this is the time allowed in the protocol for starting study-defined ART) and the date of starting the study-defined ARV regimen (this second date applies only to Cohorts B, C and D as there is no change of regimen for patients in Cohort A) Secondary outcome measures will be entered by December 2018.
Time Frame Baseline to week 24, 48 and 72
Outcome Measure Data Not Reported
14.Secondary Outcome
Title Change From Baseline in Fasting Values of Triglycerides at Week 24, 48 and 72.
Hide Description Baseline is defined as the last measurement obtained on or before the earlier of the following two dates: the date of randomization plus three days (this is the time allowed in the protocol for starting study-defined ART) and the date of starting the study-defined ARV regimen (this second date applies only to Cohorts B, C and D as there is no change of regimen for patients in Cohort A) Secondary outcome measures will be entered by December 2018.
Time Frame Baseline to week 24, 48 and 72
Outcome Measure Data Not Reported
15.Secondary Outcome
Title Change From Baseline in Fasting Values of Glucose at Week 24, 48 and 72.
Hide Description Baseline is defined as the last measurement obtained on or before the earlier of the following two dates: the date of randomization plus three days (this is the time allowed in the protocol for starting study-defined ART) and the date of starting the study-defined ARV regimen (this second date applies only to Cohorts B, C and D as there is no change of regimen for patients in Cohort A) Secondary outcome measures will be entered by December 2018.
Time Frame Baseline to week 24, 48 and 72
Outcome Measure Data Not Reported
16.Secondary Outcome
Title Time From Randomization to the Development of IRIS.
Hide Description Secondary outcome measures will be entered by December 2018.
Time Frame Throughout study; participants are expected to be followed for an average of 84 weeks
Outcome Measure Data Not Reported
17.Secondary Outcome
Title Time to First Dose Modification Due to Grade 3 or 4 Toxicity.
Hide Description Secondary outcome measures will be entered by December 2018.
Time Frame Throughout study; participants are expected to be followed for an average of 84 weeks
Outcome Measure Data Not Reported
Time Frame From enrollment to the end of step 1/2 follow up. Participants were followed in Steps 1 and 2 until 48 weeks after the last participant was enrolled to Step 1. Median follow-up time was 72 weeks, maximum of 204 weeks.
Adverse Event Reporting Description Version 2.0 of the DAIDS EAE Manual was used for this study. At entry, signs, symptoms and laboratory values regardless of grade that occurred <30 days before entry were reported. Post-entry, signs/symptoms and laboratory values grade ≥3, or caused a change in treatment/ART regardless of grade, were reported. Diagnoses identified on the study-specific list, or caused a change in treatment, were recorded at all visits. Used DAIDS AE Grading Table, Version 1.0, December 2004 (clarified AUG09)
 
Arm/Group Title Experimental: Cohort A Experimental: Sub-cohort B1 Experimental: Sub-cohort B2 Experimental: Sub-cohort B3 Experimental: Cohort C Experimental: Cohort D
Hide Arm/Group Description

Under Protocol version 1.0:

No resistance to NRTIs, PIs, or NNRTI

• Continue current second-line regimen; NRTIs could be modified

Changed under LOA#2 to:

No LPV/RTV resistance and susceptible to at least one NRTI, regardless of NNRTI resistance or prior RAL exposure • Continue second-line regimen which may include LPV/RTV; NRTIs could be modified

Changed under LOA#3 to:

No LPV/RTV resistance and susceptible to at least one NRTI, regardless of NNRTI resistance or prior RAL exposure

• Continue PI backbone; NRTIs could be modified. If on a RAL-containing regimen, RAL must be discontinued.

Under Protocol version 1.0:

Susceptible to DRV/RTV and ETR with or without resistance to NRTIs (and may have resistance to other PIs) and without active hepatitis B infection at screening • Best available NRTIs, RAL, & DRV/RTV

Changed under LOA#2 to:

Resistance to LPV/RTV but susceptible to DRV/RTV and ETR and with no prior RAL exposure and regardless of NRTI resistance (and without active hepatitis B infection at screening) OR Resistance to all NRTIs (i.e. susceptible to none) but susceptible to DRV/RTV and ETR and with no prior RAL exposure (and without active hepatitis B infection at screening)

• Best available NRTIs, RAL, & DRV/RTV

Under Protocol version 1.0:

Susceptible to DRV/RTV and ETR with or without resistance to NRTIs (and may have resistance to other PIs) and without active hepatitis B infection at screening • ETR, RAL, and DRV/RTV

Changed under LOA#2 to:

Resistance to LPV/RTV but susceptible to DRV/RTV and ETR and with no prior RAL exposure and regardless of NRTI resistance (and without active hepatitis B infection at screening) OR Resistance to all NRTIs (i.e. susceptible to none) but susceptible to DRV/RTV and ETR and with no prior RAL exposure (and without active hepatitis B infection at screening)

• ETR, RAL, and DRV/RTV

Under Protocol version 1.0:

Susceptible to DRV/RTV and ETR with or without resistance to NRTIs (and may have resistance to other PIs) and with active hepatitis B infection at screening • RAL, DRV/RTV, and FTC/TDF or TDF+3TC

Changed under LOA#2 to:

Resistance to LPV/RTV but susceptible to DRV/RTV and ETR and with no prior RAL exposure and regardless of NRTI resistance (with active hepatitis B infection at screening) OR Resistance to all NRTIs (i.e. susceptible to none) but susceptible to DRV/RTV and ETR and with no prior RAL exposure (with active hepatitis B infection at screening)

• RAL, DRV/RTV, and FTC/TDF or TDF+3TC

Under Protocol version 1.0:

Resistance to NRTIs and ETR or resistance to ETR alone (and may have resistance to PIs other than DRV) • Best available NRTIs, RAL, and DRV/RTV

Changed under LOA#2:

Resistance to LPV/RTV and ETR but susceptible to DRV/RTV and with no prior RAL exposure and regardless of NRTI resistance OR Resistance to ETR and to all NRTIs (i.e. susceptible to none) but susceptible to DRV/RTV and with no prior RAL exposure

• Best available NRTIs, RAL, and DRV/RTV

Under Protocol version 1.0:

Multiple NRTI resistance and/or DRV/RTV resistance or prior RAL exposure:

• Best available regimen, including study-provided and any locally available drugs

Changed under LOA#2:

Not eligible for Cohort A, B, or C:

• Best available regimen, including study-provided and any locally available drugs

Updated under protocol v2.0:

• Best available ART regimen, including study-provided and any locally available non-experimental drugs

All-Cause Mortality
Experimental: Cohort A Experimental: Sub-cohort B1 Experimental: Sub-cohort B2 Experimental: Sub-cohort B3 Experimental: Cohort C Experimental: Cohort D
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   18/287 (6.27%)   1/74 (1.35%)   2/72 (2.78%)   0/8 (0.00%)   1/70 (1.43%)   1/34 (2.94%) 
Show Serious Adverse Events Hide Serious Adverse Events
Experimental: Cohort A Experimental: Sub-cohort B1 Experimental: Sub-cohort B2 Experimental: Sub-cohort B3 Experimental: Cohort C Experimental: Cohort D
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   61/287 (21.25%)   8/74 (10.81%)   13/72 (18.06%)   1/8 (12.50%)   9/70 (12.86%)   6/34 (17.65%) 
Blood and lymphatic system disorders             
Anaemia  1  2/287 (0.70%)  0/74 (0.00%)  1/72 (1.39%)  0/8 (0.00%)  0/70 (0.00%)  1/34 (2.94%) 
Anaemia megaloblastic  1  0/287 (0.00%)  1/74 (1.35%)  0/72 (0.00%)  0/8 (0.00%)  0/70 (0.00%)  0/34 (0.00%) 
Leukopenia  1  0/287 (0.00%)  0/74 (0.00%)  0/72 (0.00%)  0/8 (0.00%)  0/70 (0.00%)  1/34 (2.94%) 
Lymphopenia  1  1/287 (0.35%)  0/74 (0.00%)  0/72 (0.00%)  0/8 (0.00%)  0/70 (0.00%)  0/34 (0.00%) 
Cardiac disorders             
Acute myocardial infarction  1  1/287 (0.35%)  0/74 (0.00%)  0/72 (0.00%)  0/8 (0.00%)  0/70 (0.00%)  0/34 (0.00%) 
Eye disorders             
Ulcerative keratitis  1  1/287 (0.35%)  0/74 (0.00%)  0/72 (0.00%)  0/8 (0.00%)  0/70 (0.00%)  0/34 (0.00%) 
Gastrointestinal disorders             
Abdominal pain  1  0/287 (0.00%)  0/74 (0.00%)  0/72 (0.00%)  1/8 (12.50%)  0/70 (0.00%)  0/34 (0.00%) 
Diarrhoea  1  1/287 (0.35%)  0/74 (0.00%)  0/72 (0.00%)  0/8 (0.00%)  0/70 (0.00%)  0/34 (0.00%) 
Gastrointestinal disorder  1  1/287 (0.35%)  0/74 (0.00%)  0/72 (0.00%)  0/8 (0.00%)  0/70 (0.00%)  0/34 (0.00%) 
General disorders             
Death  1  3/287 (1.05%)  0/74 (0.00%)  0/72 (0.00%)  0/8 (0.00%)  1/70 (1.43%)  0/34 (0.00%) 
Systemic inflammatory response syndrome  1  1/287 (0.35%)  0/74 (0.00%)  0/72 (0.00%)  0/8 (0.00%)  0/70 (0.00%)  0/34 (0.00%) 
Hepatobiliary disorders             
Hepatitis acute  1  0/287 (0.00%)  1/74 (1.35%)  0/72 (0.00%)  0/8 (0.00%)  1/70 (1.43%)  0/34 (0.00%) 
Hepatotoxicity  1  0/287 (0.00%)  0/74 (0.00%)  1/72 (1.39%)  0/8 (0.00%)  0/70 (0.00%)  0/34 (0.00%) 
Immune system disorders             
Immunosuppression  1  1/287 (0.35%)  0/74 (0.00%)  0/72 (0.00%)  0/8 (0.00%)  0/70 (0.00%)  0/34 (0.00%) 
Infections and infestations             
Amoebiasis  1  1/287 (0.35%)  0/74 (0.00%)  0/72 (0.00%)  0/8 (0.00%)  0/70 (0.00%)  0/34 (0.00%) 
Appendicitis perforated  1  1/287 (0.35%)  0/74 (0.00%)  0/72 (0.00%)  0/8 (0.00%)  0/70 (0.00%)  0/34 (0.00%) 
Atypical pneumonia  1  1/287 (0.35%)  0/74 (0.00%)  0/72 (0.00%)  0/8 (0.00%)  0/70 (0.00%)  0/34 (0.00%) 
Bacteraemia  1  4/287 (1.39%)  0/74 (0.00%)  1/72 (1.39%)  0/8 (0.00%)  1/70 (1.43%)  0/34 (0.00%) 
Cerebral toxoplasmosis  1  2/287 (0.70%)  0/74 (0.00%)  0/72 (0.00%)  0/8 (0.00%)  0/70 (0.00%)  0/34 (0.00%) 
Dengue fever  1  0/287 (0.00%)  0/74 (0.00%)  0/72 (0.00%)  1/8 (12.50%)  0/70 (0.00%)  0/34 (0.00%) 
Disseminated tuberculosis  1  1/287 (0.35%)  0/74 (0.00%)  0/72 (0.00%)  0/8 (0.00%)  0/70 (0.00%)  0/34 (0.00%) 
Encephalitis  1  1/287 (0.35%)  0/74 (0.00%)  0/72 (0.00%)  0/8 (0.00%)  0/70 (0.00%)  0/34 (0.00%) 
Gastroenteritis  1  3/287 (1.05%)  2/74 (2.70%)  0/72 (0.00%)  0/8 (0.00%)  0/70 (0.00%)  0/34 (0.00%) 
HIV-associated neurocognitive disorder  1  1/287 (0.35%)  0/74 (0.00%)  0/72 (0.00%)  0/8 (0.00%)  0/70 (0.00%)  0/34 (0.00%) 
Herpes zoster  1  1/287 (0.35%)  0/74 (0.00%)  1/72 (1.39%)  0/8 (0.00%)  0/70 (0.00%)  0/34 (0.00%) 
Leptospirosis  1  1/287 (0.35%)  0/74 (0.00%)  0/72 (0.00%)  0/8 (0.00%)  0/70 (0.00%)  0/34 (0.00%) 
Lower respiratory tract infection  1  1/287 (0.35%)  0/74 (0.00%)  0/72 (0.00%)  0/8 (0.00%)  0/70 (0.00%)  0/34 (0.00%) 
Malaria  1  3/287 (1.05%)  0/74 (0.00%)  0/72 (0.00%)  0/8 (0.00%)  0/70 (0.00%)  0/34 (0.00%) 
Mastoiditis  1  0/287 (0.00%)  0/74 (0.00%)  1/72 (1.39%)  0/8 (0.00%)  0/70 (0.00%)  0/34 (0.00%) 
Meningitis  1  2/287 (0.70%)  0/74 (0.00%)  0/72 (0.00%)  0/8 (0.00%)  0/70 (0.00%)  0/34 (0.00%) 
Meningitis bacterial  1  0/287 (0.00%)  0/74 (0.00%)  1/72 (1.39%)  0/8 (0.00%)  0/70 (0.00%)  0/34 (0.00%) 
Meningitis cryptococcal  1  3/287 (1.05%)  0/74 (0.00%)  0/72 (0.00%)  0/8 (0.00%)  0/70 (0.00%)  1/34 (2.94%) 
Meningitis pneumococcal  1  1/287 (0.35%)  0/74 (0.00%)  0/72 (0.00%)  0/8 (0.00%)  0/70 (0.00%)  0/34 (0.00%) 
Neurocryptococcosis  1  0/287 (0.00%)  0/74 (0.00%)  1/72 (1.39%)  0/8 (0.00%)  0/70 (0.00%)  0/34 (0.00%) 
Oesophageal candidiasis  1  1/287 (0.35%)  0/74 (0.00%)  0/72 (0.00%)  0/8 (0.00%)  0/70 (0.00%)  0/34 (0.00%) 
Otitis media acute  1  1/287 (0.35%)  0/74 (0.00%)  0/72 (0.00%)  0/8 (0.00%)  0/70 (0.00%)  0/34 (0.00%) 
Peritonitis  1  1/287 (0.35%)  0/74 (0.00%)  0/72 (0.00%)  0/8 (0.00%)  0/70 (0.00%)  0/34 (0.00%) 
Pneumocystis jirovecii pneumonia  1  2/287 (0.70%)  0/74 (0.00%)  0/72 (0.00%)  0/8 (0.00%)  0/70 (0.00%)  0/34 (0.00%) 
Pneumonia  1  2/287 (0.70%)  0/74 (0.00%)  0/72 (0.00%)  0/8 (0.00%)  0/70 (0.00%)  1/34 (2.94%) 
Pneumonia bacterial  1  2/287 (0.70%)  0/74 (0.00%)  0/72 (0.00%)  0/8 (0.00%)  0/70 (0.00%)  0/34 (0.00%) 
Pneumonia haemophilus  1  1/287 (0.35%)  0/74 (0.00%)  0/72 (0.00%)  0/8 (0.00%)  0/70 (0.00%)  0/34 (0.00%) 
Pulmonary tuberculosis  1  1/287 (0.35%)  0/74 (0.00%)  1/72 (1.39%)  0/8 (0.00%)  0/70 (0.00%)  0/34 (0.00%) 
Pyelonephritis  1  1/287 (0.35%)  1/74 (1.35%)  0/72 (0.00%)  0/8 (0.00%)  0/70 (0.00%)  0/34 (0.00%) 
Scrub typhus  1  0/287 (0.00%)  0/74 (0.00%)  0/72 (0.00%)  0/8 (0.00%)  1/70 (1.43%)  0/34 (0.00%) 
Sepsis  1  3/287 (1.05%)  0/74 (0.00%)  0/72 (0.00%)  0/8 (0.00%)  1/70 (1.43%)  0/34 (0.00%) 
Septic shock  1  1/287 (0.35%)  0/74 (0.00%)  0/72 (0.00%)  0/8 (0.00%)  0/70 (0.00%)  0/34 (0.00%) 
Urinary tract infection  1  2/287 (0.70%)  0/74 (0.00%)  0/72 (0.00%)  0/8 (0.00%)  0/70 (0.00%)  0/34 (0.00%) 
Wound infection  1  1/287 (0.35%)  0/74 (0.00%)  0/72 (0.00%)  0/8 (0.00%)  0/70 (0.00%)  0/34 (0.00%) 
Injury, poisoning and procedural complications             
Ankle fracture  1  1/287 (0.35%)  0/74 (0.00%)  0/72 (0.00%)  0/8 (0.00%)  0/70 (0.00%)  0/34 (0.00%) 
Hand fracture  1  1/287 (0.35%)  0/74 (0.00%)  0/72 (0.00%)  0/8 (0.00%)  0/70 (0.00%)  0/34 (0.00%) 
Tibia fracture  1  1/287 (0.35%)  0/74 (0.00%)  0/72 (0.00%)  0/8 (0.00%)  0/70 (0.00%)  0/34 (0.00%) 
Traumatic fracture  1  1/287 (0.35%)  0/74 (0.00%)  0/72 (0.00%)  0/8 (0.00%)  0/70 (0.00%)  0/34 (0.00%) 
Upper limb fracture  1  0/287 (0.00%)  0/74 (0.00%)  1/72 (1.39%)  0/8 (0.00%)  0/70 (0.00%)  0/34 (0.00%) 
Investigations             
Blood alkaline phosphatase increased  1  1/287 (0.35%)  0/74 (0.00%)  0/72 (0.00%)  0/8 (0.00%)  0/70 (0.00%)  0/34 (0.00%) 
Weight decreased  1  1/287 (0.35%)  0/74 (0.00%)  0/72 (0.00%)  0/8 (0.00%)  0/70 (0.00%)  0/34 (0.00%) 
White blood cell count decreased  1  1/287 (0.35%)  0/74 (0.00%)  0/72 (0.00%)  0/8 (0.00%)  0/70 (0.00%)  0/34 (0.00%) 
Metabolism and nutrition disorders             
Cachexia  1  1/287 (0.35%)  0/74 (0.00%)  0/72 (0.00%)  0/8 (0.00%)  0/70 (0.00%)  0/34 (0.00%) 
Dehydration  1  3/287 (1.05%)  1/74 (1.35%)  0/72 (0.00%)  0/8 (0.00%)  0/70 (0.00%)  0/34 (0.00%) 
Electrolyte imbalance  1  1/287 (0.35%)  0/74 (0.00%)  0/72 (0.00%)  0/8 (0.00%)  0/70 (0.00%)  0/34 (0.00%) 
Hypercholesterolaemia  1  0/287 (0.00%)  0/74 (0.00%)  0/72 (0.00%)  0/8 (0.00%)  0/70 (0.00%)  1/34 (2.94%) 
Hyperglycaemia  1  1/287 (0.35%)  0/74 (0.00%)  1/72 (1.39%)  0/8 (0.00%)  0/70 (0.00%)  1/34 (2.94%) 
Hypophosphataemia  1  0/287 (0.00%)  0/74 (0.00%)  0/72 (0.00%)  0/8 (0.00%)  0/70 (0.00%)  1/34 (2.94%) 
Musculoskeletal and connective tissue disorders             
Osteonecrosis  1  1/287 (0.35%)  1/74 (1.35%)  0/72 (0.00%)  0/8 (0.00%)  0/70 (0.00%)  0/34 (0.00%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)             
Cervix carcinoma  1  0/287 (0.00%)  1/74 (1.35%)  0/72 (0.00%)  0/8 (0.00%)  0/70 (0.00%)  0/34 (0.00%) 
Myelodysplastic syndrome  1  1/287 (0.35%)  0/74 (0.00%)  0/72 (0.00%)  0/8 (0.00%)  0/70 (0.00%)  0/34 (0.00%) 
Oesophageal carcinoma  1  0/287 (0.00%)  0/74 (0.00%)  1/72 (1.39%)  0/8 (0.00%)  0/70 (0.00%)  0/34 (0.00%) 
Prostate cancer  1  0/287 (0.00%)  0/74 (0.00%)  1/72 (1.39%)  0/8 (0.00%)  0/70 (0.00%)  0/34 (0.00%) 
Nervous system disorders             
Dizziness  1  1/287 (0.35%)  0/74 (0.00%)  0/72 (0.00%)  0/8 (0.00%)  0/70 (0.00%)  0/34 (0.00%) 
Dystonia  1  1/287 (0.35%)  0/74 (0.00%)  0/72 (0.00%)  0/8 (0.00%)  0/70 (0.00%)  0/34 (0.00%) 
Facial paralysis  1  1/287 (0.35%)  0/74 (0.00%)  0/72 (0.00%)  0/8 (0.00%)  0/70 (0.00%)  0/34 (0.00%) 
Seizure  1  1/287 (0.35%)  0/74 (0.00%)  0/72 (0.00%)  0/8 (0.00%)  0/70 (0.00%)  0/34 (0.00%) 
Syncope  1  1/287 (0.35%)  0/74 (0.00%)  0/72 (0.00%)  0/8 (0.00%)  0/70 (0.00%)  0/34 (0.00%) 
Tension headache  1  1/287 (0.35%)  0/74 (0.00%)  0/72 (0.00%)  0/8 (0.00%)  0/70 (0.00%)  0/34 (0.00%) 
Pregnancy, puerperium and perinatal conditions             
Abortion  1  0/287 (0.00%)  0/74 (0.00%)  0/72 (0.00%)  0/8 (0.00%)  1/70 (1.43%)  0/34 (0.00%) 
Abortion threatened  1  0/287 (0.00%)  0/74 (0.00%)  0/72 (0.00%)  0/8 (0.00%)  1/70 (1.43%)  0/34 (0.00%) 
Foetal hypokinesia  1  1/287 (0.35%)  0/74 (0.00%)  0/72 (0.00%)  0/8 (0.00%)  0/70 (0.00%)  0/34 (0.00%) 
Pregnancy  1  5/287 (1.74%)  1/74 (1.35%)  1/72 (1.39%)  0/8 (0.00%)  2/70 (2.86%)  0/34 (0.00%) 
Stillbirth  1  1/287 (0.35%)  0/74 (0.00%)  0/72 (0.00%)  0/8 (0.00%)  0/70 (0.00%)  0/34 (0.00%) 
Renal and urinary disorders             
Glomerulonephritis  1  1/287 (0.35%)  0/74 (0.00%)  0/72 (0.00%)  0/8 (0.00%)  0/70 (0.00%)  0/34 (0.00%) 
Renal failure  1  0/287 (0.00%)  0/74 (0.00%)  0/72 (0.00%)  0/8 (0.00%)  1/70 (1.43%)  0/34 (0.00%) 
Renal impairment  1  1/287 (0.35%)  0/74 (0.00%)  0/72 (0.00%)  0/8 (0.00%)  0/70 (0.00%)  0/34 (0.00%) 
Respiratory, thoracic and mediastinal disorders             
Idiopathic interstitial pneumonia  1  0/287 (0.00%)  0/74 (0.00%)  1/72 (1.39%)  0/8 (0.00%)  0/70 (0.00%)  0/34 (0.00%) 
Respiratory failure  1  1/287 (0.35%)  0/74 (0.00%)  0/72 (0.00%)  0/8 (0.00%)  0/70 (0.00%)  0/34 (0.00%) 
Skin and subcutaneous tissue disorders             
Angioedema  1  0/287 (0.00%)  1/74 (1.35%)  0/72 (0.00%)  0/8 (0.00%)  0/70 (0.00%)  0/34 (0.00%) 
Vascular disorders             
Hypovolaemic shock  1  0/287 (0.00%)  0/74 (0.00%)  1/72 (1.39%)  0/8 (0.00%)  0/70 (0.00%)  0/34 (0.00%) 
Jugular vein thrombosis  1  1/287 (0.35%)  0/74 (0.00%)  0/72 (0.00%)  0/8 (0.00%)  0/70 (0.00%)  0/34 (0.00%) 
Pelvic venous thrombosis  1  0/287 (0.00%)  1/74 (1.35%)  0/72 (0.00%)  0/8 (0.00%)  0/70 (0.00%)  0/34 (0.00%) 
1
Term from vocabulary, MedDRA 20.1
Indicates events were collected by systematic assessment
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Experimental: Cohort A Experimental: Sub-cohort B1 Experimental: Sub-cohort B2 Experimental: Sub-cohort B3 Experimental: Cohort C Experimental: Cohort D
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   283/287 (98.61%)   72/74 (97.30%)   69/72 (95.83%)   8/8 (100.00%)   69/70 (98.57%)   33/34 (97.06%) 
Eye disorders             
Conjunctivitis allergic  1  1/287 (0.35%)  2/74 (2.70%)  0/72 (0.00%)  1/8 (12.50%)  0/70 (0.00%)  0/34 (0.00%) 
Eye pain  1  2/287 (0.70%)  0/74 (0.00%)  1/72 (1.39%)  1/8 (12.50%)  0/70 (0.00%)  0/34 (0.00%) 
Gastrointestinal disorders             
Abdominal pain  1  18/287 (6.27%)  3/74 (4.05%)  5/72 (6.94%)  0/8 (0.00%)  2/70 (2.86%)  3/34 (8.82%) 
Abdominal pain upper  1  7/287 (2.44%)  1/74 (1.35%)  3/72 (4.17%)  0/8 (0.00%)  1/70 (1.43%)  2/34 (5.88%) 
Abdominal tenderness  1  2/287 (0.70%)  2/74 (2.70%)  0/72 (0.00%)  1/8 (12.50%)  0/70 (0.00%)  0/34 (0.00%) 
Diarrhoea  1  22/287 (7.67%)  6/74 (8.11%)  7/72 (9.72%)  0/8 (0.00%)  0/70 (0.00%)  3/34 (8.82%) 
Peptic ulcer  1  3/287 (1.05%)  1/74 (1.35%)  2/72 (2.78%)  0/8 (0.00%)  0/70 (0.00%)  2/34 (5.88%) 
Vomiting  1  23/287 (8.01%)  2/74 (2.70%)  3/72 (4.17%)  0/8 (0.00%)  3/70 (4.29%)  1/34 (2.94%) 
General disorders             
Chest pain  1  10/287 (3.48%)  1/74 (1.35%)  2/72 (2.78%)  1/8 (12.50%)  0/70 (0.00%)  0/34 (0.00%) 
Chills  1  3/287 (1.05%)  1/74 (1.35%)  4/72 (5.56%)  1/8 (12.50%)  0/70 (0.00%)  2/34 (5.88%) 
Fatigue  1  5/287 (1.74%)  2/74 (2.70%)  4/72 (5.56%)  1/8 (12.50%)  1/70 (1.43%)  0/34 (0.00%) 
Oedema peripheral  1  2/287 (0.70%)  0/74 (0.00%)  1/72 (1.39%)  0/8 (0.00%)  0/70 (0.00%)  2/34 (5.88%) 
Pain  1  2/287 (0.70%)  3/74 (4.05%)  0/72 (0.00%)  1/8 (12.50%)  0/70 (0.00%)  0/34 (0.00%) 
Pyrexia  1  53/287 (18.47%)  8/74 (10.81%)  8/72 (11.11%)  2/8 (25.00%)  8/70 (11.43%)  9/34 (26.47%) 
Hepatobiliary disorders             
Hepatitis acute  1  0/287 (0.00%)  0/74 (0.00%)  0/72 (0.00%)  1/8 (12.50%)  0/70 (0.00%)  0/34 (0.00%) 
Infections and infestations             
Acarodermatitis  1  2/287 (0.70%)  1/74 (1.35%)  1/72 (1.39%)  0/8 (0.00%)  1/70 (1.43%)  2/34 (5.88%) 
Acute sinusitis  1  6/287 (2.09%)  1/74 (1.35%)  2/72 (2.78%)  1/8 (12.50%)  0/70 (0.00%)  1/34 (2.94%) 
Bacteraemia  1  4/287 (1.39%)  0/74 (0.00%)  0/72 (0.00%)  0/8 (0.00%)  0/70 (0.00%)  3/34 (8.82%) 
Bacterial vaginosis  1  1/287 (0.35%)  2/74 (2.70%)  0/72 (0.00%)  0/8 (0.00%)  0/70 (0.00%)  3/34 (8.82%) 
Body tinea  1  1/287 (0.35%)  0/74 (0.00%)  0/72 (0.00%)  0/8 (0.00%)  0/70 (0.00%)  3/34 (8.82%) 
Chronic hepatitis B  1  1/287 (0.35%)  0/74 (0.00%)  0/72 (0.00%)  1/8 (12.50%)  0/70 (0.00%)  0/34 (0.00%) 
Conjunctivitis bacterial  1  1/287 (0.35%)  1/74 (1.35%)  0/72 (0.00%)  1/8 (12.50%)  0/70 (0.00%)  1/34 (2.94%) 
Gastroenteritis  1  5/287 (1.74%)  1/74 (1.35%)  4/72 (5.56%)  0/8 (0.00%)  0/70 (0.00%)  2/34 (5.88%) 
Helminthic infection  1  0/287 (0.00%)  0/74 (0.00%)  1/72 (1.39%)  1/8 (12.50%)  0/70 (0.00%)  0/34 (0.00%) 
Herpes zoster  1  9/287 (3.14%)  3/74 (4.05%)  3/72 (4.17%)  0/8 (0.00%)  4/70 (5.71%)  0/34 (0.00%) 
Influenza  1  3/287 (1.05%)  1/74 (1.35%)  2/72 (2.78%)  0/8 (0.00%)  0/70 (0.00%)  2/34 (5.88%) 
Nasopharyngitis  1  2/287 (0.70%)  1/74 (1.35%)  2/72 (2.78%)  0/8 (0.00%)  0/70 (0.00%)  2/34 (5.88%) 
Oral candidiasis  1  19/287 (6.62%)  1/74 (1.35%)  2/72 (2.78%)  0/8 (0.00%)  2/70 (2.86%)  0/34 (0.00%) 
Pneumonia bacterial  1  11/287 (3.83%)  1/74 (1.35%)  0/72 (0.00%)  0/8 (0.00%)  2/70 (2.86%)  2/34 (5.88%) 
Purulent discharge  1  4/287 (1.39%)  2/74 (2.70%)  1/72 (1.39%)  1/8 (12.50%)  0/70 (0.00%)  0/34 (0.00%) 
Upper respiratory tract infection  1  19/287 (6.62%)  2/74 (2.70%)  7/72 (9.72%)  2/8 (25.00%)  6/70 (8.57%)  3/34 (8.82%) 
Urinary tract infection  1  15/287 (5.23%)  7/74 (9.46%)  0/72 (0.00%)  1/8 (12.50%)  2/70 (2.86%)  3/34 (8.82%) 
Vulvovaginal candidiasis  1  7/287 (2.44%)  4/74 (5.41%)  2/72 (2.78%)  1/8 (12.50%)  0/70 (0.00%)  1/34 (2.94%) 
Investigations             
Alanine aminotransferase increased  1  41/287 (14.29%)  12/74 (16.22%)  6/72 (8.33%)  1/8 (12.50%)  11/70 (15.71%)  6/34 (17.65%) 
Aspartate aminotransferase increased  1  68/287 (23.69%)  14/74 (18.92%)  13/72 (18.06%)  2/8 (25.00%)  18/70 (25.71%)  8/34 (23.53%) 
Blood alkaline phosphatase abnormal  1  1/287 (0.35%)  1/74 (1.35%)  0/72 (0.00%)  0/8 (0.00%)  1/70 (1.43%)  2/34 (5.88%) 
Blood alkaline phosphatase increased  1  68/287 (23.69%)  20/74 (27.03%)  16/72 (22.22%)  1/8 (12.50%)  26/70 (37.14%)  7/34 (20.59%) 
Blood bicarbonate decreased  1  94/287 (32.75%)  22/74 (29.73%)  23/72 (31.94%)  3/8 (37.50%)  27/70 (38.57%)  14/34 (41.18%) 
Blood bilirubin increased  1  106/287 (36.93%)  19/74 (25.68%)  12/72 (16.67%)  3/8 (37.50%)  22/70 (31.43%)  6/34 (17.65%) 
Blood cholesterol increased  1  65/287 (22.65%)  41/74 (55.41%)  40/72 (55.56%)  3/8 (37.50%)  31/70 (44.29%)  16/34 (47.06%) 
Blood creatinine increased  1  37/287 (12.89%)  10/74 (13.51%)  8/72 (11.11%)  1/8 (12.50%)  9/70 (12.86%)  4/34 (11.76%) 
Blood glucose decreased  1  32/287 (11.15%)  6/74 (8.11%)  10/72 (13.89%)  0/8 (0.00%)  7/70 (10.00%)  0/34 (0.00%) 
Blood glucose increased  1  72/287 (25.09%)  15/74 (20.27%)  22/72 (30.56%)  0/8 (0.00%)  21/70 (30.00%)  11/34 (32.35%) 
Blood phosphorus decreased  1  75/287 (26.13%)  25/74 (33.78%)  21/72 (29.17%)  1/8 (12.50%)  20/70 (28.57%)  12/34 (35.29%) 
Blood potassium decreased  1  34/287 (11.85%)  12/74 (16.22%)  4/72 (5.56%)  0/8 (0.00%)  4/70 (5.71%)  5/34 (14.71%) 
Blood potassium increased  1  14/287 (4.88%)  0/74 (0.00%)  4/72 (5.56%)  1/8 (12.50%)  5/70 (7.14%)  0/34 (0.00%) 
Blood pressure increased  1  6/287 (2.09%)  2/74 (2.70%)  1/72 (1.39%)  0/8 (0.00%)  1/70 (1.43%)  2/34 (5.88%) 
Blood sodium decreased  1  145/287 (50.52%)  44/74 (59.46%)  32/72 (44.44%)  8/8 (100.00%)  42/70 (60.00%)  16/34 (47.06%) 
Blood sodium increased  1  42/287 (14.63%)  4/74 (5.41%)  7/72 (9.72%)  1/8 (12.50%)  4/70 (5.71%)  2/34 (5.88%) 
Blood triglycerides increased  1  8/287 (2.79%)  6/74 (8.11%)  5/72 (6.94%)  0/8 (0.00%)  3/70 (4.29%)  2/34 (5.88%) 
Haemoglobin decreased  1  40/287 (13.94%)  8/74 (10.81%)  9/72 (12.50%)  2/8 (25.00%)  6/70 (8.57%)  7/34 (20.59%) 
Low density lipoprotein increased  1  65/287 (22.65%)  42/74 (56.76%)  37/72 (51.39%)  2/8 (25.00%)  32/70 (45.71%)  16/34 (47.06%) 
Neutrophil count decreased  1  64/287 (22.30%)  21/74 (28.38%)  20/72 (27.78%)  2/8 (25.00%)  15/70 (21.43%)  9/34 (26.47%) 
Platelet count decreased  1  23/287 (8.01%)  5/74 (6.76%)  1/72 (1.39%)  0/8 (0.00%)  8/70 (11.43%)  2/34 (5.88%) 
Weight decreased  1  25/287 (8.71%)  1/74 (1.35%)  3/72 (4.17%)  0/8 (0.00%)  1/70 (1.43%)  2/34 (5.88%) 
White blood cell count decreased  1  22/287 (7.67%)  11/74 (14.86%)  5/72 (6.94%)  0/8 (0.00%)  7/70 (10.00%)  5/34 (14.71%) 
Metabolism and nutrition disorders             
Decreased appetite  1  17/287 (5.92%)  3/74 (4.05%)  4/72 (5.56%)  0/8 (0.00%)  2/70 (2.86%)  2/34 (5.88%) 
Musculoskeletal and connective tissue disorders             
Arthralgia  1  8/287 (2.79%)  4/74 (5.41%)  3/72 (4.17%)  1/8 (12.50%)  1/70 (1.43%)  3/34 (8.82%) 
Back pain  1  5/287 (1.74%)  4/74 (5.41%)  5/72 (6.94%)  0/8 (0.00%)  1/70 (1.43%)  0/34 (0.00%) 
Costochondritis  1  0/287 (0.00%)  1/74 (1.35%)  0/72 (0.00%)  1/8 (12.50%)  0/70 (0.00%)  0/34 (0.00%) 
Myalgia  1  6/287 (2.09%)  1/74 (1.35%)  1/72 (1.39%)  0/8 (0.00%)  1/70 (1.43%)  2/34 (5.88%) 
Pain in extremity  1  7/287 (2.44%)  1/74 (1.35%)  4/72 (5.56%)  0/8 (0.00%)  1/70 (1.43%)  3/34 (8.82%) 
Nervous system disorders             
Headache  1  27/287 (9.41%)  6/74 (8.11%)  10/72 (13.89%)  2/8 (25.00%)  3/70 (4.29%)  3/34 (8.82%) 
Neuropathy peripheral  1  2/287 (0.70%)  3/74 (4.05%)  2/72 (2.78%)  0/8 (0.00%)  2/70 (2.86%)  2/34 (5.88%) 
Paraesthesia  1  0/287 (0.00%)  0/74 (0.00%)  1/72 (1.39%)  0/8 (0.00%)  1/70 (1.43%)  2/34 (5.88%) 
Seizure  1  5/287 (1.74%)  0/74 (0.00%)  0/72 (0.00%)  0/8 (0.00%)  0/70 (0.00%)  2/34 (5.88%) 
Renal and urinary disorders             
Dysuria  1  13/287 (4.53%)  5/74 (6.76%)  1/72 (1.39%)  0/8 (0.00%)  1/70 (1.43%)  1/34 (2.94%) 
Pollakiuria  1  5/287 (1.74%)  2/74 (2.70%)  0/72 (0.00%)  0/8 (0.00%)  0/70 (0.00%)  2/34 (5.88%) 
Urine odour abnormal  1  0/287 (0.00%)  0/74 (0.00%)  1/72 (1.39%)  1/8 (12.50%)  1/70 (1.43%)  0/34 (0.00%) 
Reproductive system and breast disorders             
Cervical dysplasia  1  1/287 (0.35%)  1/74 (1.35%)  0/72 (0.00%)  1/8 (12.50%)  0/70 (0.00%)  1/34 (2.94%) 
Vaginal discharge  1  5/287 (1.74%)  5/74 (6.76%)  1/72 (1.39%)  0/8 (0.00%)  1/70 (1.43%)  3/34 (8.82%) 
Vulvovaginal pruritus  1  5/287 (1.74%)  4/74 (5.41%)  2/72 (2.78%)  0/8 (0.00%)  0/70 (0.00%)  1/34 (2.94%) 
Respiratory, thoracic and mediastinal disorders             
Cough  1  50/287 (17.42%)  7/74 (9.46%)  14/72 (19.44%)  2/8 (25.00%)  9/70 (12.86%)  8/34 (23.53%) 
Dyspnoea  1  14/287 (4.88%)  2/74 (2.70%)  4/72 (5.56%)  1/8 (12.50%)  1/70 (1.43%)  1/34 (2.94%) 
Nasal congestion  1  8/287 (2.79%)  4/74 (5.41%)  4/72 (5.56%)  1/8 (12.50%)  1/70 (1.43%)  5/34 (14.71%) 
Oropharyngeal pain  1  2/287 (0.70%)  4/74 (5.41%)  1/72 (1.39%)  0/8 (0.00%)  2/70 (2.86%)  2/34 (5.88%) 
Oropharyngeal plaque  1  17/287 (5.92%)  1/74 (1.35%)  2/72 (2.78%)  0/8 (0.00%)  2/70 (2.86%)  0/34 (0.00%) 
Rhinorrhoea  1  18/287 (6.27%)  4/74 (5.41%)  8/72 (11.11%)  0/8 (0.00%)  5/70 (7.14%)  0/34 (0.00%) 
Sinus pain  1  2/287 (0.70%)  1/74 (1.35%)  0/72 (0.00%)  1/8 (12.50%)  0/70 (0.00%)  0/34 (0.00%) 
Skin and subcutaneous tissue disorders             
Blister  1  9/287 (3.14%)  1/74 (1.35%)  1/72 (1.39%)  0/8 (0.00%)  2/70 (2.86%)  2/34 (5.88%) 
Erythema  1  3/287 (1.05%)  1/74 (1.35%)  1/72 (1.39%)  0/8 (0.00%)  0/70 (0.00%)  2/34 (5.88%) 
Pruritus  1  9/287 (3.14%)  9/74 (12.16%)  3/72 (4.17%)  1/8 (12.50%)  3/70 (4.29%)  0/34 (0.00%) 
Rash  1  2/287 (0.70%)  4/74 (5.41%)  3/72 (4.17%)  0/8 (0.00%)  0/70 (0.00%)  0/34 (0.00%) 
Rash generalised  1  0/287 (0.00%)  0/74 (0.00%)  0/72 (0.00%)  0/8 (0.00%)  0/70 (0.00%)  2/34 (5.88%) 
Skin lesion  1  11/287 (3.83%)  1/74 (1.35%)  2/72 (2.78%)  1/8 (12.50%)  1/70 (1.43%)  4/34 (11.76%) 
Urticaria  1  0/287 (0.00%)  0/74 (0.00%)  0/72 (0.00%)  1/8 (12.50%)  0/70 (0.00%)  0/34 (0.00%) 
Vascular disorders             
Hypertension  1  8/287 (2.79%)  2/74 (2.70%)  0/72 (0.00%)  0/8 (0.00%)  1/70 (1.43%)  3/34 (8.82%) 
1
Term from vocabulary, MedDRA 20.1
Indicates events were collected by systematic assessment
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT 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.
Results Point of Contact
Name/Title: ACTG Clinicaltrials.gov Coordinator
Organization: ACTG Network Coordinating Center, Social and Scientific Systems, Inc.
Phone: (301) 628-3313
Responsible Party: AIDS Clinical Trials Group
ClinicalTrials.gov Identifier: NCT01641367     History of Changes
Other Study ID Numbers: ACTG A5288
1U01AI068636 ( U.S. NIH Grant/Contract )
First Submitted: June 28, 2012
First Posted: July 16, 2012
Results First Submitted: November 20, 2017
Results First Posted: February 20, 2018
Last Update Posted: February 20, 2018