BLQ Study: A Study of a Protease Inhibitor With Fuzeon (Enfuvirtide) in Treatment-Experienced Patients With HIV-1.

• Sponsor: Hoffmann-La Roche
• Collaborator: Trimeris
• Information provided by (Responsible Party): Hoffmann-La Roche

Study Type	Interventional
Study Design	Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
Condition	HIV Infections
Interventions	Drug: Background ARVs; Drug: PI; Drug: enfuvirtide [Fuzeon]
Enrollment	142

Participant Flow

Recruitment Details	A total of 142 participants were enrolled in this study conducted from 6 March 2006 to 20 April 2007 at 33 centers to be investigated in the United States.
Pre-assignment Details	A total of 142 participants were randomized, of which 140 received the study drug. A total of 2 randomized participants did not receive study drug.

Arm/Group Title	Enfuvirtide+PI+ARV’s
Arm/Group Description	Eligible participants received Fuzeon® (enfuvirtide) 90 milligram (mg) subcutaneously (SC) two times a day (bid) for 24 weeks plus new protease inhibitor (PI) (darunavir/ritonavir) plus other investigator-choice antiretrovirals (ARVs). Participants selected their preferred injection device among the following three options: 27 gauge (G) ½” needle/syringe, 31G 8 millimeter (mm) needle/syringe or Biojector 2000 (B2000) needle-free injection device (NFID).
Period Title: Overall Study
Started	140
Completed	107
Not Completed	33
Reason Not Completed
Adverse Event	2
Injection site reaction	1
Death	1
Failure to return	10
Withdrawal by Subject	10
Refused treatment / did not cooperate	5
Violation of selection criteria at entry	2
Other protocol violation	1
Administrative / other	1

Baseline Characteristics

Arm/Group Title		Enfuvirtide+PI+ARV’s
Arm/Group Description		Eligible participants received enfuvirtide 90 mg bid, SC injection for 24 weeks plus new PI (darunavir/ritonavir) plus other investigator-choice ARVs. Participants selected their preferred injection device among the following 3 options: 27G ½” needle/syringe, 31G 8 mm needle/syringe or B2000 NFID.
Overall Number of Baseline Participants		142
Baseline Analysis Population Description		Baseline analysis was performed on all randomized participants including two participants who does not received study drug.
Age, Continuous; Mean (Standard Deviation); Unit of measure: Years
	Number Analyzed	142 participants
		46.2 (7.68)
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	142 participants
	Female	20 14.1%
	Male	122 85.9%

Outcome Measures

1. Primary Outcome

Title	Number of Participants With Human Immunodeficiency Virus Type 1 (HIV-1) Ribonucleic Acid (RNA) Viral Load <50 Copies/mL
Description	Blood samples for HIV-1 RNA viral load measurement were collected at the Week 24 clinic visit. The number of participants with HIV-1 RNA viral load results <50 copies/mL is reported.
Time Frame	Week 24

Outcome Measure Data

Analysis Population Description

Analysis was performed on the Intent-to-treat (ITT) Population. The ITT Population included enrolled participants who received at least one dose of study medication and had at least one post baseline efficacy assessment.

Arm/Group Title	Enfuvirtide+PI+ARV’s
Arm/Group Description:	Eligible participants received enfuvirtide 90 mg bid, SC injection for 24 weeks plus new PI (darunavir/ritonavir) plus other investigator-choice ARVs. Participants selected their preferred injection device among the following 3 options: 27G ½” needle/syringe, 31G 8 mm needle/syringe or B2000 NFID.
Overall Number of Participants Analyzed	131
Measure Type: Number; Unit of Measure: participants
Imputation by neighboring visit values; At Week 24	79
Without imputation by neighboring visit;At Week 24	78

2. Primary Outcome

Title	Percentage of Participants With HIV-1 RNA Viral Load <50 Copies/mL
Description	Blood samples for HIV-1 RNA viral load measurement were collected at the Week 24 clinic visit. The percentage of participants with HIV-1 RNA results <50 copies/mL is reported.
Time Frame	Week 24

Outcome Measure Data

Analysis Population Description

Analysis was performed on the Intent-to-treat (ITT) Population. The ITT Population included enrolled participants who received at least one dose of study medication and had at least one post baseline efficacy assessment.

Arm/Group Title	Enfuvirtide+PI+ARV’s
Arm/Group Description:	Eligible participants received enfuvirtide 90 mg bid, SC injection for 24 weeks plus new PI (darunavir/ritonavir) plus other investigator-choice ARVs. Participants selected their preferred injection device among the following 3 options: 27G ½” needle/syringe, 31G 8 mm needle/syringe or B2000 NFID.
Overall Number of Participants Analyzed	131
Measure Type: Number; Number (97.5% Confidence Interval); Unit of Measure: Percentage of Participants
Imputation by neighboring visit values; At Week 24	60.3 [1]; (51.5 to NA)
Without imputation by neighboring visit;At Week 24	59.5 [1]; (50.8 to NA)

[1]

We reported lower confidence limit from 1-sided 97.5% confidence interval which was constructed using the normal approximation to the binomial distribution therefore, upper limit is not required. Hence, presented as NA.

3. Secondary Outcome

Title	Number of Participants With HIV-1 RNA Viral Load <50 Copies/mL
Description	Blood samples for HIV-1 RNA viral load measurement were collected at the Week 4 and Week 12 clinic visit. The number of participants with HIV-1 RNA results <50 copies/mL is reported.
Time Frame	Week 4 and 12

Outcome Measure Data

Analysis Population Description

Analysis was performed on the Intent-to-treat (ITT) Population. The ITT Population included enrolled participants who received at least one dose of study medication and had at least one post baseline efficacy assessment.

Arm/Group Title	Enfuvirtide+PI+ARV’s
Arm/Group Description:	Eligible participants received enfuvirtide 90 mg bid, SC injection for 24 weeks plus new PI (darunavir/ritonavir) plus other investigator-choice ARVs. Participants selected their preferred injection device among the following 3 options: 27G ½” needle/syringe, 31G 8 mm needle/syringe or B2000 NFID.
Overall Number of Participants Analyzed	131
Measure Type: Number; Unit of Measure: participants
Imputation by neighboring visit values; At Week 4	28
Without imputation by neighboring visit; At Week 4	28
Imputation by neighboring visit values; At Week 12	64
Without imputation by neighboring visit;At Week 12	63

4. Secondary Outcome

Title	Percentage of Participants With HIV-1 RNA Viral Load <50 Copies/mL
Description	Blood samples for HIV-1 RNA viral load measurement were collected at the Week 4 and Week 12 clinic visit. The percentage of participants with HIV-1 RNA Viral Load results <50 copies/mL is reported.
Time Frame	Week 4 and 12

Outcome Measure Data

Analysis Population Description

Analysis was performed on the Intent-to-treat (ITT) Population. The ITT Population included enrolled participants who received at least one dose of study medication and had at least one post baseline efficacy assessment.

Arm/Group Title	Enfuvirtide+PI+ARV’s
Arm/Group Description:	Eligible participants received enfuvirtide 90 mg bid, SC injection for 24 weeks plus new PI (darunavir/ritonavir) plus other investigator-choice ARVs. Participants selected their preferred injection device among the following 3 options: 27G ½” needle/syringe, 31G 8 mm needle/syringe or B2000 NFID.
Overall Number of Participants Analyzed	131
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: Percentage of Participants
Imputation by neighboring visit values; At Week 4	21.4; (14.0 to 28.8)
Without imputation by neighboring visit; At Week 4	21.4; (14.0 to 28.8)
Imputation by neighboring visit values; At Week 12	48.9; (39.9 to 57.8)
Without imputation by neighboring visit;At Week 12	48.1; (39.2 to 57.0)

5. Secondary Outcome

Title	Number of Participants With HIV-1 RNA Viral Load <400 Copies/mL
Description	Blood samples for HIV-1 RNA viral load measurement were collected at the Week 4, Week 12, and Week 24 clinic visit. The number of participants with HIV-1 RNA Viral Load results <400 copies/mL is reported.
Time Frame	Weeks 4, 12, and 24

Outcome Measure Data

Analysis Population Description

Analysis was performed on the Intent-to-treat (ITT) Population. The ITT Population included enrolled participants who received at least one dose of study medication and had at least one post baseline efficacy assessment.

Arm/Group Title	Enfuvirtide+PI+ARV’s
Arm/Group Description:	Eligible participants received enfuvirtide 90 mg bid, SC injection for 24 weeks plus new PI (darunavir/ritonavir) plus other investigator-choice ARVs. Participants selected their preferred injection device among the following 3 options: 27G ½” needle/syringe, 31G 8 mm needle/syringe or B2000 NFID.
Overall Number of Participants Analyzed	131
Measure Type: Number; Unit of Measure: participants
Imputation by neighboring visit values; At Week 4	74
Imputation by neighboring visit values; At Week 12	89
Imputation by neighboring visit values; At Week 24	95
Without imputation by neighboring visit;At Week 4	74
Without imputation by neighboring visit;At Week 12	88
Without imputation by neighboring visit;At Week 24	94

6. Secondary Outcome

Title	Percentage of Participants With HIV-1 RNA Viral Load <400 Copies/mL
Description	Blood samples for HIV-1 RNA viral load measurement were collected at the Week 4, Week 12, and Week 24 clinic visit. The number of participants with HIV-1 RNA Viral Load results <400 copies/mL is reported.
Time Frame	Weeks 4, 12, and 24

Outcome Measure Data

Analysis Population Description

Analysis was performed on the Intent-to-treat (ITT) Population. The ITT Population included enrolled participants who received at least one dose of study medication and had at least one post baseline efficacy assessment.

Arm/Group Title	Enfuvirtide+PI+ARV’s
Arm/Group Description:	Eligible participants received enfuvirtide 90 mg bid, SC injection for 24 weeks plus new PI (darunavir/ritonavir) plus other investigator-choice ARVs. Participants selected their preferred injection device among the following 3 options: 27G ½” needle/syringe, 31G 8 mm needle/syringe or B2000 NFID.
Overall Number of Participants Analyzed	131
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: Percentage of participants
Imputation by neighboring visit values; At Week 4	56.5; (47.6 to 65.4)
Imputation by neighboring visit values; At Week 12	67.9; (59.6 to 76.3)
Imputation by neighboring visit values; At Week 24	72.5; (64.5 to 80.5)
Without imputation by neighboring visit;At Week 4	56.5; (47.6 to 65.4)
Without imputation by neighboring visit;At Week 12	67.2; (58.8 to 75.6)
Without imputation by neighboring visit;At Week 24	71.8; (63.7 to 79.8)

7. Secondary Outcome

Title	Change From Baseline in Log 10 Plasma HIV-1 RNA Viral Load
Description	Summary statistics for change from baseline in plasma HIV-1 RNA count were presented. Change from baseline in plasma HIV-1 RNA count was derived as follows: Change from baseline = (plasma HIV-1 RNA count at Week X) – (plasma HIV-1 RNA count at baseline).
Time Frame	Baseline (Day 1), Weeks 4, 12, and 24

Outcome Measure Data

Analysis Population Description

Analysis was performed on the Intent-to-treat (ITT) Population. The ITT Population included enrolled participants who received at least one dose of study medication and had at least one post baseline efficacy assessment. Maximum number of participants available at the particular time point were analysed and reported.

Arm/Group Title	Enfuvirtide+PI+ARV’s
Arm/Group Description:	Eligible participants received enfuvirtide 90 mg bid, SC injection for 24 weeks plus new PI (darunavir/ritonavir) plus other investigator-choice ARVs. Participants selected their preferred injection device among the following 3 options: 27G ½” needle/syringe, 31G 8 mm needle/syringe or B2000 NFID.
Overall Number of Participants Analyzed	116
Mean (Standard Deviation); Unit of Measure: copies/mL
At Week 4; n = 116	-2.22 (0.783)
At Week 12; n = 109	-2.51 (0.961)
At Week 24; n = 107	-2.61 (1.099)

8. Secondary Outcome

Title	Number of Participants With Any Adverse Event (AE) and Serious Adverse Event (SAE)
Description	An AE is defined as any untoward medical occurrence in a participant or clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. SAEs are defined as those events that were fatal or immediately life-threatening, and those events that resulted in hospitalization; prolonged an existing hospitalization; resulted in disability; or was a congenital anomaly.
Time Frame	Up to Week 28

Outcome Measure Data

Analysis Population Description

Analysis was performed on the Safety Population. The Safety Population included all the participants who received at least one dose of trial medication and had a safety follow-up.

Arm/Group Title	Enfuvirtide+PI+ARV’s
Arm/Group Description:	Eligible participants received enfuvirtide 90 mg bid, SC injection for 24 weeks plus new PI (darunavir/ritonavir) plus other investigator-choice ARVs. Participants selected their preferred injection device among the following 3 options: 27G ½” needle/syringe, 31G 8 mm needle/syringe or B2000 NFID.
Overall Number of Participants Analyzed	137
Measure Type: Number; Unit of Measure: participants
Number of participants with at least one AE	15
Number of participants with at least one SAE	13

9. Secondary Outcome

Title	Change From Baseline in CD4+ Lymphocyte Count
Description	Summary statistics for change from baseline in CD4+ lymphocyte count were presented . Change from baseline in CD4+ lymphocyte count was derived as follows: Change from baseline = (CD4+ count at Week X) – (CD4+ count at baseline).
Time Frame	Baseline (Day 1), Weeks 4, 12, and 24

Outcome Measure Data

Analysis Population Description

Analysis was performed on the Intent-to-treat (ITT) Population. The ITT Population included enrolled participants who received at least one dose of study medication and had at least one post baseline efficacy assessment. Maximum number of participants available at the particular time point were analysed and reported.

Arm/Group Title	Enfuvirtide+PI+ARV’s
Arm/Group Description:	Eligible participants received enfuvirtide 90 mg bid, SC injection for 24 weeks plus new PI (darunavir/ritonavir) plus other investigator-choice ARVs. Participants selected their preferred injection device among the following 3 options: 27G ½” needle/syringe, 31G 8 mm needle/syringe or B2000 NFID.
Overall Number of Participants Analyzed	114
Mean (Standard Deviation); Unit of Measure: cells/mm^3
At Week 4; n = 114	56 (93.6)
At Week 12; n = 109	83 (112.9)
At Week 24; n = 105	89 (103.4)

10. Secondary Outcome

Title	Number of Participants Meeting Virologic Failure Criteria
Description	The participant was considered as virologic failure at Week 12 clinic visit if patient achieved HIV-RNA <50 copies/mL at Week 4, and HIV-RNA > 50 copies/mL at Week 12, and HIV-RNA >50 copies/mL confirmed at 2 to 4 weeks after Week 12 or if participants failed to achieve a viral load decrease from baseline greater or equal to 0.5 log10 at Week 12 and failed to achieve a viral load decrease from baseline greater or equal to 0.5 log10 confirmed at 2 to 4 weeks after Week 12. The participant was considered as virologic failure at Week 24 clinic visit if participant achieved HIV-RNA <50 copies/mL at week 12, and HIV-RNA >50 copies/mL at week 24/early discontinuation, and HIV-RNA >50 copies/mL confirmed at 2 to 4 weeks after week 24/early discontinuation or HIV-RNA >50 copies/mL at any time up to week 24 and HIV-RNA >50 copies/mL confirmed at 2 to 4 weeks after week 24/early discontinuation.
Time Frame	Weeks 12 and 24

Outcome Measure Data

Analysis Population Description

Analysis was performed on the Intent-to-treat (ITT) Population. The ITT Population included enrolled participants who received at least one dose of study medication and had at least one post baseline efficacy assessment.

Arm/Group Title	Enfuvirtide+PI+ARV’s
Arm/Group Description:	Eligible participants received enfuvirtide 90 mg bid, SC injection for 24 weeks plus new PI (darunavir/ritonavir) plus other investigator-choice ARVs. Participants selected their preferred injection device among the following 3 options: 27G ½” needle/syringe, 31G 8 mm needle/syringe or B2000 NFID.
Overall Number of Participants Analyzed	131
Measure Type: Number; Unit of Measure: participants
Confirmed Failure; At Week 12	2
Confirmed Failure; At Week 24	10
Suspected Failure; At Week 12	19
Suspected Failure; At Week 24	45

11. Secondary Outcome

Title	Percentage of Participants Meeting Virologic Failure Criteria
Description	The participant was considered as virologic failure at Week 12 clinic visit if patient achieved HIV-RNA <50 copies/mL at Week 4, and HIV-RNA > 50 copies/mL at Week 12, and HIV-RNA >50 copies/mL confirmed at 2 to 4 weeks after Week 12 or if participants failed to achieve a viral load decrease from baseline greater or equal to 0.5 log10 at Week 12 and failed to achieve a viral load decrease from baseline greater or equal to 0.5 log10 confirmed at 2 to 4 weeks after Week 12. The participant was considered as virologic failure at Week 24 clinic visit if participant achieved HIV-RNA <50 copies/mL at week 12, and HIV-RNA >50 copies/mL at week 24/early discontinuation, and HIV-RNA >50 copies/mL confirmed at 2 to 4 weeks after week 24/early discontinuation or HIV-RNA >50 copies/mL at any time up to week 24 and HIV-RNA >50 copies/mL confirmed at 2 to 4 weeks after week 24/early discontinuation.
Time Frame	Weeks 12 and 24

Outcome Measure Data

Analysis Population Description

Analysis was performed on the Intent-to-treat (ITT) Population. The ITT Population included enrolled participants who received at least one dose of study medication and had at least one post baseline efficacy assessment.

Arm/Group Title	Enfuvirtide+PI+ARV’s
Arm/Group Description:	Eligible participants received enfuvirtide 90 mg bid, SC injection for 24 weeks plus new PI (darunavir/ritonavir) plus other investigator-choice ARVs. Participants selected their preferred injection device among the following 3 options: 27G ½” needle/syringe, 31G 8 mm needle/syringe or B2000 NFID.
Overall Number of Participants Analyzed	131
Measure Type: Number; Unit of Measure: Percentage of participants
Confirmed Failure; At Week 12	1.5
Confirmed Failure; At Week 24	7.6
Suspected Failure; At Week 12	14.5
Suspected Failure; At Week 24	34.4

12. Secondary Outcome

Title	Number of Participants Adhering to Enfuvirtide (ENF)
Description	Adherence to ENF treatment regimen was calculated using the participant’s response to the query on the “Participant Adherence Questionnaire case report form (CRF)” about injections incomplete or missed in the last 4 days preceding the study visit. The percentage adherence to the ENF regimen at each study visit is given by: % Adherence = ([8 - the number of doses missed] / 8) x 100. The number and percentage of participants adhering to the ENF regimen were presented by adherence category (100%, ≥95%, ≥90% and ≥85%) at Weeks 4, 12, and 24.
Time Frame	Weeks 4, 12, and 24

Outcome Measure Data

Analysis Population Description

Analysis was performed on the Intent-to-treat (ITT) Population.The ITT Population included enrolled participants who received at least one dose of study medication and had at least one post baseline efficacy assessment. Maximum number of participants available at the particular time point were analysed and reported.

Arm/Group Title	Enfuvirtide+PI+ARV’s
Arm/Group Description:	Eligible participants received enfuvirtide 90 mg bid, SC injection for 24 weeks plus new PI (darunavir/ritonavir) plus other investigator-choice ARVs. Participants selected their preferred injection device among the following 3 options: 27G ½” needle/syringe, 31G 8 mm needle/syringe or B2000 NFID.
Overall Number of Participants Analyzed	125
Measure Type: Number; Unit of Measure: participants
100%; At Week 4; n = 125	108
≥95%; At Week 4; n = 125	108
≥90%; At Week 4; n = 125	108
≥85%; At Week 4; n = 125	119
100%; At Week 12; n = 113	98
≥95%; At Week 12; n = 113	98
≥90%; At Week 12; n = 113	98
≥85%; At Week 12; n = 113	106
100%; At Week 24; n = 93	79
≥95%; At Week 24; n = 93	79
≥90%; At Week 24; n = 93	79
≥85%; At Week 24; n = 93	87

13. Secondary Outcome

Title	Percentage of Participants Adhering to ENF
Description	Adherence to ENF treatment regimen was calculated using the participant’s response to the query on the “Participant Adherence Questionnaire case report form (CRF)” about injections incomplete or missed in the last 4 days preceding the study visit. The percentage adherence to the ENF regimen at each study visit is given by: % Adherence = ([8 - the number of doses missed] / 8) x 100. The number and percentage of participants adhering to the ENF regimen were presented by adherence category (100%, ≥95%, ≥90% and ≥85%) at Weeks 4, 12, and 24.
Time Frame	Weeks 4, 12, and 24

Outcome Measure Data

Analysis Population Description

Analysis was performed on the Intent-to-treat (ITT) Population. The ITT Population included enrolled participants who received at least one dose of study medication and had at least one post baseline efficacy assessment. Maximum number of participants available at the particular time point were analysed and reported.

Arm/Group Title	Enfuvirtide+PI+ARV’s
Arm/Group Description:	Eligible participants received enfuvirtide 90 mg bid, SC injection for 24 weeks plus new PI (darunavir/ritonavir) plus other investigator-choice ARVs. Participants selected their preferred injection device among the following 3 options: 27G ½” needle/syringe, 31G 8 mm needle/syringe or B2000 NFID.
Overall Number of Participants Analyzed	125
Measure Type: Number; Unit of Measure: Percentage of Participants
100%; At Week 4; n = 125	86.4
≥95%; At Week 4; n = 125	86.4
≥90%; At Week 4; n = 125	86.4
≥85%; At Week 4; n = 125	95.2
100%; At Week 12; n = 113	86.7
≥95%; At Week 12; n = 113	86.7
≥90%; At Week 12; n = 113	86.7
≥85%; At Week 12; n = 113	93.8
100%; At Week 24; n = 93	84.9
≥95%; At Week 24; n = 93	84.9
≥90%; At Week 24; n = 93	84.9
≥85%; At Week 24; n = 93	93.5

14. Secondary Outcome

Title	Number of Participants With 1 or More Injection Site Reactions Meeting the Criteria of an Serious Adverse Event
Description	Injection site reactions (ISRs) referred to any localized sign or symptom, including erythema, induration, pruritus, nodules, ecchymosis (degree of bruising/ discoloration), and pain/discomfort. Injection site reactions were monitored by trained study personnel at weeks 1, 4, 12, 16, and 24. Interruption of ENF for toxicity management of recurrent local grade 3 or 4 ISRs until the sign or symptom resolved to grade 2 was at the discretion of the investigator. Any individual injection site signs or symptoms meeting the criteria for a serious adverse event (SAE) had to be reported as an SAE. In the event of a serious ISR, the participant was to immediately discontinue ENF and withdraw from the study. If the participant was not already hospitalized, serious ISRs required a clinic visit within 72 hours of the event.
Time Frame	Week 1 to Week 24

Outcome Measure Data

Analysis Population Description

Analysis was performed on the Safety Population. The Safety Population included all the participants who received at least one dose of trial medication and had a safety follow-up.

Arm/Group Title	Enfuvirtide+PI+ARV’s
Arm/Group Description:	Eligible participants received enfuvirtide 90 mg bid, SC injection for 24 weeks plus new PI (darunavir/ritonavir) plus other investigator-choice ARVs. Participants selected their preferred injection device among the following 3 options: 27G ½” needle/syringe, 31G 8 mm needle/syringe or B2000 NFID.
Overall Number of Participants Analyzed	137
Measure Type: Number; Unit of Measure: participants
	0

15. Secondary Outcome

Title	Percentage of Participants With 1 or More Injection Site Reactions Meeting the Criteria of an Serious Adverse Event
Description	Injection site reactions (ISRs) referred to any localized sign or symptom, including erythema, induration, pruritus, nodules, ecchymosis (degree of bruising/ discoloration), and pain/discomfort. Injection site reactions were monitored by trained study personnel at weeks 1, 4, 12, 16, and 24. Interruption of ENF for toxicity management of recurrent local grade 3 or 4 ISRs until the sign or symptom resolved to grade 2 was at the discretion of the investigator. Any individual injection site signs or symptoms meeting the criteria for a serious adverse event (SAE) had to be reported as an SAE. In the event of a serious ISR, the participant was to immediately discontinue ENF and withdraw from the study. If the participant was not already hospitalized, serious ISRs required a clinic visit within 72 hours of the event.
Time Frame	Week 1 to Week 24

Outcome Measure Data

Analysis Population Description

Analysis was performed on the Safety Population. The Safety Population included all the participants who received at least one dose of trial medication and had a safety follow-up.

Arm/Group Title	Enfuvirtide+PI+ARV’s
Arm/Group Description:	Eligible participants received enfuvirtide 90 mg bid, SC injection for 24 weeks plus new PI (darunavir/ritonavir) plus other investigator-choice ARVs. Participants selected their preferred injection device among the following 3 options: 27G ½” needle/syringe, 31G 8 mm needle/syringe or B2000 NFID.
Overall Number of Participants Analyzed	137
Measure Type: Number; Unit of Measure: Percentage of participants
	0

16. Secondary Outcome

Title	Descriptive Summary of ISR Parameters (ie, Severity and Frequency of Pain and Symptoms) by Injection Device Based on an ISR Grading Tool.
Description	Injection site reactions (ISRs) referred to any localized sign or symptom, including erythema, induration, pruritus, nodules, ecchymosis (degree of bruising/ discoloration), and pain/discomfort. Injection site reactions were monitored by trained study personnel at weeks 1, 4, 12, 16, and 24. Grades 0 through 4 are a measure of intensity, not seriousness. Thus, a grade 3 or grade 4 sign or symptom could be severe, but not necessarily serious. Only active, ongoing ISR were counted. The maximum severity grade for pain/discomfort since the last visit at any injection site was recorded whether or not the maximum severity of pain/discomfort was ongoing at the time of clinical evaluation.
Time Frame	Week 24

Outcome Measure Data

Analysis Population Description

Analysis was performed on the Safety Population. The Safety Population included all the participants who received at least one dose of trial medication and had a safety follow-up. Maximum number of participants available at the particular time point were analysed and reported.

Arm/Group Title	Enfuride+PI+ARV’s
Arm/Group Description:	Eligible participants received enfuvirtide 90 mg bid, SC injection for 24 weeks plus new PI (darunavir/ritonavir) plus other investigator-choice ARVs. Participants selected their preferred injection device among the following 3 options: 27G ½” needle/syringe, 31G 8 mm needle/syringe or B2000 NFID.
Overall Number of Participants Analyzed	110
Measure Type: Number; Unit of Measure: participants
Ongoing Pain/Discomfort, Grade 0; n= 110	73
Ongoing Pain/Discomfort, Grade 1; n= 110	24
Ongoing Pain/Discomfort, Grade 2; n= 110	11
Ongoing Pain/Discomfort, Grade 3; n= 110	1
Erythema, Grade 0; n= 110	68
Erythema, Grade 1; n= 110	23
Erythema, Grade 2; n= 110	12
Erythema, Grade 3; n= 110	5
Erythema, Grade 4; n= 110	1
Erythema, Grade 3 & 4; n= 110	6
Induration, Grade 0; n= 110	57
Induration, Grade 1; n= 110	12
Induration, Grade 2; n= 110	19
Induration, Grade 3; n= 110	13
Induration, Grade 4; n= 110	8
Induration, Grade 3 & 4; n= 110	21
Pruritus, Grade 0; n= 110	96
Pruritus, Grade 1; n= 110	13
Pruritus, Grade 2; n= 110	0
Pruritus, Grade 3; n= 110	0
Nodules and Cysts, Grade 0; n= 110	90
Nodules and Cysts, Grade 1; n= 110	8
Nodules and Cysts, Grade 2; n= 110	3
Nodules and Cysts, Grade 3; n= 110	8
Nodules and Cysts, Grade 4; n= 110	0
Nodules and Cysts, Grade 3 & 4; n= 110	8
Ecchymosis, Grade 0; n= 110	82
Ecchymosis, Grade 1; n= 110	13
Ecchymosis, Grade 2; n= 110	6
Ecchymosis, Grade 3; n= 110	6
Ecchymosis, Grade 4; n= 110	2
Ecchymosis, Grade 3 & 4; n= 110	8

17. Secondary Outcome

Title	Number of Participants Discontinuing Study Medication Due to Clinical Adverse Events
Description	The total number and percentage of participants who discontinued the study medication (ENF) due to clinical adverse events (including clinically significant laboratory abnormalities and AIDS Clinical Trials Group (ACTG) grade≥3 laboratory toxicities) were noted and presented.
Time Frame	Up to Week 24

Outcome Measure Data

Analysis Population Description

Analysis was performed on the Safety Population. The Safety Population included all the participants who received at least one dose of trial medication and had a safety follow-up.

Arm/Group Title	Enfuvirtide+PI+ARV’s
Arm/Group Description:	Eligible participants received enfuvirtide 90 mg bid, SC injection for 24 weeks plus new PI (darunavir/ritonavir) plus other investigator-choice ARVs. Participants selected their preferred injection device among the following 3 options: 27G ½” needle/syringe, 31G 8 mm needle/syringe or B2000 NFID.
Overall Number of Participants Analyzed	137
Measure Type: Number; Unit of Measure: participants
Total participants with at least one AE	3
Upper Gastrointestinal haemorrhage	1
Sepsis	1
Rash	1

Adverse Events

Time Frame	Up to Week 28.
Adverse Event Reporting Description	[Not Specified]
Arm/Group Title	Enfuvirtide+PI+ARV’s
Arm/Group Description	Eligible participants received enfuvirtide 90 mg bid, SC injection for 24 weeks plus new PI (darunavir/ritonavir) plus other investigator-choice ARVs. Participants selected their preferred injection device among the following 3 options: 27G ½” needle/syringe, 31G 8 mm needle/syringe or B2000 NFID.
All-Cause Mortality
	Enfuvirtide+PI+ARV’s
	Affected / at Risk (%)
Total	--/--
Serious Adverse Events
	Enfuvirtide+PI+ARV’s
	Affected / at Risk (%)
Total	13/137 (9.49%)
Blood and lymphatic system disorders
Anaemia † 1	1/137 (0.73%)
Gastrointestinal disorders
Upper Gastrointestinal haemorrhage † 1	1/137 (0.73%)
Infections and infestations
Cellulitis † 1	2/137 (1.46%)
Pneumonia † 1	2/137 (1.46%)
Sepsis † 1	2/137 (1.46%)
Pneumocystis jiroveci Pneumonia † 1	1/137 (0.73%)
Pneumonia primary atypical † 1	1/137 (0.73%)
Sinusitis † 1	1/137 (0.73%)
Investigations
Neutrophil count decreased † 1	1/137 (0.73%)
Metabolism and nutrition disorders
Metabolic acidosis † 1	1/137 (0.73%)
Musculoskeletal and connective tissue disorders
Myopathy steroid † 1	1/137 (0.73%)
Renal and urinary disorders
Renal failure † 1	2/137 (1.46%)
Respiratory, thoracic and mediastinal disorders
Asthma † 1	1/137 (0.73%)
Dyspnoea † 1	1/137 (0.73%)
Skin and subcutaneous tissue disorders
Erythema nodosum † 1	1/137 (0.73%)
† Indicates events were collected by systematic assessment; 1 Term from vocabulary, MedDRA 10.0
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	5%
	Enfuvirtide+PI+ARV’s
	Affected / at Risk (%)
Total	0/137 (0.00%)

Limitations and Caveats

[Not Specified]

More Information

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 Study being conducted under this Agreement is part of the Overall Study. Investigator is free to publish in reputable journals or to present at professional conferences the results of the Study, but only after the first publication or presentation that involves the Overall Study. The Sponsor may request that Confidential Information be deleted and/or the publication be postponed in order to protect the Sponsor's intellectual property rights.

Results Point of Contact

Name/Title: Roche Trial Information Hotline

Organization: F. Hoffmann-La Roche AG

Phone: +41 616878333

EMail: global.trial_information@roche.com

Responsible Party:	Hoffmann-La Roche
ClinicalTrials.gov Identifier:	NCT00326963 History of Changes
Other Study ID Numbers:	ML19712
First Submitted:	May 16, 2006
First Posted:	May 17, 2006
Results First Submitted:	March 23, 2016
Results First Posted:	August 16, 2016
Last Update Posted:	August 16, 2016