INTENSE: A Study to Evaluate the Safety and Efficacy of Adding Enfuvirtide to Oral Highly Active Antiretroviral Therapy (HAART) in Human Immunodeficiency Virus (HIV) Patients With Prior Treatment Experience

• Sponsor: Hoffmann-La Roche (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00487188
• Collaborator: (none)
• Enrollment: 47
• Locations: 39
• Arms: 2
• Duration (Months): 29
• Patients Per Site: 1.2
• Patients Per Site Per Month: 0

Study Details

Study Description

Brief Summary

To assess the efficacy of enfuvirtide (Fuzeon) added to HAART compared to treatment with HAART alone in achieving and maintaining viral load suppression.

Condition or Disease	Intervention/Treatment	Phase
HIV Infections	Drug: Enfuvirtide; Drug: Highly active antiretroviral treatment (HAART)	Phase 4

Detailed Description

This study consisted of two phases. In the Induction phase patients were randomized at

Baseline 1 (BL1) in a 1:2 ratio to receive:

• I1: HAART or

• I2: Enfuvirtide (90 mg twice a day) + HAART.

Participants who achieved viral suppression < 50 copies/mL by week 24, confirmed by week 28 or earlier, qualified to enter the Maintenance Phase which started at Baseline 2 (BL2), four weeks after confirmation of response. The Maintenance Phase consisted of three treatment groups:

• M1: HAART continued (patients from I1)

Patients on ENF+HAART (I2) were re-randomized (at a 1:1 ratio) at BL2 to:

• M2: Enfuvirtide stopped and HAART continued

• M3: Enfuvirtide + HAART continued.

The duration of the Maintenance Phase was from BL2 up to 48 weeks after BL1. BL2 could start at the earliest at Week 12 and at the latest Week 32.

Study Design

• Study Type: Interventional
• Actual Enrollment: 47 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Phase IIIb/IV Randomized, Controlled Study Evaluating an Intensification Treatment Strategy of Adding Enfuvirtide (ENF) to an Oral Highly Active AntiRetroviral Therapy (HAART) in Treatment Experienced Patients
• Study Start Date: Nov 1, 2005
• Actual Primary Completion Date: Nov 1, 2007
• Actual Study Completion Date: Apr 1, 2008

Arms and Interventions

Arm	Intervention/Treatment
Experimental: ENF + HAART Participants received Enfuvirtide (ENF) 90 mg administered by subcutaneous injection twice a day for up to 48 weeks in addition to an oral highly active antiretroviral treatment (HAART) regimen for up to 48 weeks.	Drug: Enfuvirtide; 90 mg subcutaneous injection twice a day; Other Names: Fuzeon ; Drug: Highly active antiretroviral treatment (HAART); An oral HAART regimen of 3-5 antiretrovirals was chosen by the physician and patient, based on the patient's prior treatment history and genotypic antiretroviral resistance testing.
Active Comparator: HAART Participants received an oral highly active antiretroviral treatment (HAART) regimen, consisting of 3-5 antivirals for up to 48 weeks.	Drug: Highly active antiretroviral treatment (HAART); An oral HAART regimen of 3-5 antiretrovirals was chosen by the physician and patient, based on the patient's prior treatment history and genotypic antiretroviral resistance testing.

Outcome Measures

Primary Outcome Measures

1. Number of Participants With Viral Suppression: HIV-1 RNA < 50 Copies/mL During the Induction Phase [From Baseline 1 to Week 28]

   Participants whose viral load achieved suppression (HIV-1 RNA < 50 copies/mL) at Week 24 at the latest, confirmed at Week 28 (2 consecutive assessments ≥ 28 days apart) were defined as responders. Patients who discontinued the study or did not respond to assigned treatment by week 28 were considered as non-responders.

Secondary Outcome Measures

1. Time to Achieving HIV-1 RNA < 50 Copies/mL During the Induction Phase [Baseline 1 until Week 28.]

   The time to achieving HIV-1 RNA <50 copies/mL was counted from Baseline 1 until the first of the two consecutive <50 copies/mL measurements. Patients who discontinued from the study or patients who did not have confirmed virological response by week 28 were classed as non-responders and censored at Week 24.

2. Number of Participants With Viral Suppression HIV-1 RNA < 400 Copies/mL During the Induction Phase [From Baseline 1 to Week 28]

   Participants whose viral load achieved suppression (HIV-1 RNA < 400 copies/mL) by Week 24 at the latest, confirmed at Week 28 (2 consecutive assessments ≥ 28 days apart) were defined as responders. Patients who discontinued the study or did not respond to assigned treatment by Week 28 were considered as non-responders.

3. Change From Baseline to Week 24 in Viral Load [Baseline and Week 24]

   Change from Baseline in log10 HIV-1 RNA at Week 24. Least squares means were calculated from an analysis of covariance (ANCOVA) model with treatment, a flag variable "removed ENF at re-randomization" and Baseline viral load as independent variables.

4. Change From Baseline to Week 24 in Cluster Differentiation Antigen Four Positive (CD4+) Cell Counts [Baseline and Week 24]

   Change from Baseline in CD4+ Cell Counts at Week 24. Least squares means were calculated from an ANCOVA model with treatment as an independent variable.

5. Percentage of Induction Phase Participants With Viral Load < 50 Copies/mL at 48 Weeks [Week 48]

   The percentage of participants from the Induction Phase who maintained HIV-1 RNA < 50 Copies/mL at Week 48. Patients who discontinued from the study, rebounded to ≥ 50 copies/mL (i.e., had two consecutive readings ≥ 50 copies/mL), had missing data or had virological failure by Week 48 were classed as non-responders.

6. Percentage of Maintenance Phase Participants With Viral Load < 50 Copies/mL at 48 Weeks [Week 48]

   The percentage of participants from the Maintenance Phase who maintained HIV-1 RNA < 50 copies/mL at Week 48. Patients who discontinued from the study, rebounded to ≥ 50 copies/mL (i.e., had two consecutive readings ≥ 50 copies/mL), had missing data or had virological failure by Week 48 were classed as non-responders.

7. Change From Baseline to Week 48 in Cluster Differentiation Antigen Four Positive (CD4) Cell Counts [Baseline 1 and Week 48]

   Change from Baseline in CD4 Cell Counts at Week 48. Least squares means were calculated from an ANCOVA model with treatment and baseline CD4 count as independent variables.

8. Time to Loss of Viral Response During the Maintenance Phase [From Baseline 2 to Week 48.]

   The time to loss of viral response (defined as HIV-1 RNA <50 copies/mL) was counted from Baseline 2 until the first of two consecutive ≥50 copies/mL measurements. Only patients who were qualified for entering the Maintenance Phase were included in the analysis.

9. Time to Virological Failure During the Maintenance Phase [From Baseline 2 to Week 48.]

   Time to virological failure (defined as HIV-1 RNA ≥ 400 copies/mL) was counted from Baseline 2 until the first of the two consecutive ≥400 copies/mL measurements. Only patients who were qualified for entering the Maintenance Phase were included in the analyses.

10. Number of Participants With Virological Failure During the Maintenance Phase [From Baseline 2 to Week 48.]

    Virological failure was defined by 2 consecutive HIV-1 RNA values ≥ 400 copies/mL during the Maintenance Phase.

11. Percentage of Participants Maintaining CD4+ Count During the Maintenance Phase [Baseline 2 to Week 48.]

    Maintenance of CD4+ count defined as having greater than or equal to 200 cells/mm^3 at Baseline 2 (BL2) and greater than or equal to 200 cells/mm^3 at Week 48.

12. Percentage of Participants With Improvement in CD4+ Count During the Maintenance Phase [Baseline 2 to Week 48.]

    Improvement of CD4+ count defined as having from 100 to less than 200 CD4+ cells/mm^3 at Baseline 2 (BL2) and greater than or equal to 200 cells/mm^3 at Week 48.

13. Number of Participants With Adverse Events (AEs) During the Induction Phase [Start of the study treatment until the end of the Induction Phase (Week 12 to Week 32)]

    A serious AE (SAE) is an event which: results in death, is life-threatening, disabling or incapacitating; is a congenital anomaly in the offspring of a patient who received study drug; requires or prolongs inpatient hospitalization; jeopardizes the patient or require medical or surgical intervention to prevent one of the outcomes above; any Grade 4 laboratory value considered by the investigator clinically significant or that requires an action; any injection site reaction that meets SAE criteria above. Non-serious AEs reported include pneumonia and non-serious AEs that led to discontinuation.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• HIV-1 infected adults >=18 years of age;

• currently on antiretroviral (ARV) therapy;

• previously treated with 2 or 3 different antiretroviral classes;

• HIV-1 Ribonucleic acid (RNA) >=1,000 copies/mL;

• Cluster differentiation antigen four (CD4) lymphocyte count >=200 cells/mm^3;

• females of childbearing potential must be willing to use a reliable form of effective barrier contraception for the duration of the study and for 30 days after the last dose of study drug.

Exclusion Criteria:

• history of prior use of enfuvirtide or T-1249;

• women who are pregnant, breastfeeding or planning to become pregnant during the study;

• active, untreated opportunistic infection;

• patients on treatment interruption, or patients interrupting ARV therapy within 4 weeks of screening or during the screening period for reasons either than toxicity management.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1		Cleveland	Ohio	United States	44109
2		Austin	Texas	United States	78705
3		Dallas	Texas	United States	75246
4		Vancouver	British Columbia	Canada	V6Z 2C7
5		Le Kremlin-bicetre		France	94275
6		Nantes		France	44035
7		Paris		France	75018
8		Poitiers		France	86021
9		Villeneuve-sur-lot		France	47307
10		Berlin		Germany	12157
11		Bonn		Germany	53127
12		Erlangen		Germany	91054
13		Frankfurt Am Main		Germany	60596
14		Ramat Gan		Israel	52662
15		Bagno A Ripoli		Italy	50011
16		Bari		Italy	70100
17		Brescia		Italy	25123
18		Milano		Italy	20127
19		Milano		Italy	20157
20		Roma		Italy	00149
21		Roma		Italy	00185
22		Mexico City		Mexico	14000
23		Amsterdam		Netherlands	1105 AZ
24		Tilburg		Netherlands	5022 GC
25		Barcelona		Spain	08026
26		Barcelona		Spain	08036
27		Barcelona		Spain	08370
28		Barcelona		Spain	08901
29		Cádiz		Spain	11009
30		Córdoba		Spain	14004
31		Huelva		Spain	21005
32		Madrid		Spain	28034
33		Madrid		Spain	28041
34		Madrid		Spain	28046
35		Malaga		Spain	29010
36		San Sebastian		Spain	20014
37		Sevilla		Spain	41013
38		Valencia		Spain	46014
39		Zürich		Switzerland	8091

Sponsors and Collaborators

• Hoffmann-La Roche

Investigators

• Study Director: Clinical Trials, Hoffmann-La Roche

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Hoffmann-La Roche
• ClinicalTrials.gov Identifier: NCT00487188
• Other Study ID Numbers: MV18406
• First Posted: Jun 15, 2007
• Last Update Posted: Aug 13, 2015
• Last Verified: Jul 1, 2015

• Additional relevant MeSH terms: HIV Infections; Anti-Retroviral Agents; Enfuvirtide

Study Results

Participant Flow

Recruitment Details	A total of 47 patients were enrolled into the study at 20 investigational sites in France, Italy, Spain, Mexico, Germany and the US. Study starting 15NOV2005 and ending 5NOV2007.
Pre-assignment Detail	In the Induction Phase participants were randomized (2:1 ratio) to receive ENF + HAART or HAART. In the Maintenance Phase participants in the HAART group who responded (viral load < 50 copies/mL) continued to receive HAART; those who responded in the ENF + HAART group were re-randomized (1:1 ratio) to receive ENF + HAART or HAART (ENF removed).

Arm/Group Title	ENF + HAART	HAART	HAART (ENF Removed)
Arm/Group Description	Participants received enfuvirtide 90 mg subcutaneously twice a day in combination with highly active antiretroviral treatment during the Induction and Maintenance Phase for up to 48 weeks of treatment.	Participants received highly active antiretroviral treatment during the Induction and Maintenance Phase for up to 48 weeks of treatment.	Participants who had received ENF + HAART during the Induction Phase and responded to treatment by Week 24 continued to receive HAART alone during the Maintenance Phase, for a total of 48 weeks of treatment.
Period Title: Induction Phase
STARTED	31	16	0
Safety Population	29	18	0
COMPLETED	22	9	0
NOT COMPLETED	9	7	0
Period Title: Induction Phase
STARTED	10	8	9
COMPLETED	7	8	8
NOT COMPLETED	3	0	1

Baseline Characteristics

Arm/Group Title	ENF+HAART	HAART	Total
Arm/Group Description	Participants received enfuvirtide 90 mg subcutaneously twice a day in combination with highly active antiretroviral treatment.	Participants received highly active antiretroviral treatment.	Total of all reporting groups
Overall Participants	29	18	47
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	44.1 (7.04)	41.9 (10.57)	43.3 (8.52)
Sex: Female, Male (Count of Participants)
Female	7 24.1%	3 16.7%	10 21.3%
Male	22 75.9%	15 83.3%	37 78.7%

Outcome Measures

1. Primary Outcome

Title	Number of Participants With Viral Suppression: HIV-1 RNA < 50 Copies/mL During the Induction Phase
Description	Participants whose viral load achieved suppression (HIV-1 RNA < 50 copies/mL) at Week 24 at the latest, confirmed at Week 28 (2 consecutive assessments ≥ 28 days apart) were defined as responders. Patients who discontinued the study or did not respond to assigned treatment by week 28 were considered as non-responders.
Time Frame	From Baseline 1 to Week 28

Outcome Measure Data

Analysis Population Description

Intent-to-Treat Population 1 (ITT1) population (patients evaluable for efficacy in the induction phase)

Arm/Group Title	ENF+HAART	HAART
Arm/Group Description	Participants received enfuvirtide 90 mg subcutaneously twice a day in combination with highly active antiretroviral treatment.	Participants received highly active antiretroviral treatment.
Measure Participants	31	16
Number [Participants]	20 69%	8 44.4%

2. Secondary Outcome

Title	Time to Achieving HIV-1 RNA < 50 Copies/mL During the Induction Phase
Description	The time to achieving HIV-1 RNA <50 copies/mL was counted from Baseline 1 until the first of the two consecutive <50 copies/mL measurements. Patients who discontinued from the study or patients who did not have confirmed virological response by week 28 were classed as non-responders and censored at Week 24.
Time Frame	Baseline 1 until Week 28.

Outcome Measure Data

Analysis Population Description

Intent-to-Treat Population 1 (ITT1) population (patients evaluable for efficacy in the induction phase).

Arm/Group Title	ENF+HAART	HAART
Arm/Group Description	Participants received enfuvirtide 90 mg subcutaneously twice a day in combination with highly active antiretroviral treatment.	Participants received highly active antiretroviral treatment.
Measure Participants	31	16
Median (Inter-Quartile Range) [days]	57.0	141.0

3. Secondary Outcome

Title	Number of Participants With Viral Suppression HIV-1 RNA < 400 Copies/mL During the Induction Phase
Description	Participants whose viral load achieved suppression (HIV-1 RNA < 400 copies/mL) by Week 24 at the latest, confirmed at Week 28 (2 consecutive assessments ≥ 28 days apart) were defined as responders. Patients who discontinued the study or did not respond to assigned treatment by Week 28 were considered as non-responders.
Time Frame	From Baseline 1 to Week 28

Outcome Measure Data

Analysis Population Description

ITT1 population (patients evaluable for efficacy in the induction phase)

Arm/Group Title	ENF+HAART	HAART
Arm/Group Description	Participants received enfuvirtide 90 mg subcutaneously twice a day in combination with highly active antiretroviral treatment.	Participants received highly active antiretroviral treatment.
Measure Participants	31	16
Number [Participants]	21 72.4%	8 44.4%

4. Secondary Outcome

Title	Change From Baseline to Week 24 in Viral Load
Description	Change from Baseline in log10 HIV-1 RNA at Week 24. Least squares means were calculated from an analysis of covariance (ANCOVA) model with treatment, a flag variable "removed ENF at re-randomization" and Baseline viral load as independent variables.
Time Frame	Baseline and Week 24

Outcome Measure Data

Analysis Population Description

Intent-to-Treat Population 1 (ITT1) population (patients evaluable for efficacy in the Induction Phase). Baseline values were carried forward (i.e. the change from baseline set to zero) for patients with missing data at week 24 or who withdrew prior to the week 24 time window.

Arm/Group Title	ENF+HAART	HAART
Arm/Group Description	Participants received enfuvirtide 90 mg subcutaneously twice a day in combination with highly active antiretroviral treatment.	Participants received highly active antiretroviral treatment.
Measure Participants	31	16
Least Squares Mean (95% Confidence Interval) [log10 copies/mL]	-1.402 (0.69)	-1.156 (0.61)

5. Secondary Outcome

Title	Change From Baseline to Week 24 in Cluster Differentiation Antigen Four Positive (CD4+) Cell Counts
Description	Change from Baseline in CD4+ Cell Counts at Week 24. Least squares means were calculated from an ANCOVA model with treatment as an independent variable.
Time Frame	Baseline and Week 24

Outcome Measure Data

Analysis Population Description

Intent-to-Treat Population 1 (ITT1) population (patients evaluable for efficacy in the Induction Phase). Baseline values were carried forward (i.e. the change from baseline set to zero) for patients with missing data at week 24 or who withdrew prior to the week 24 time window.

Arm/Group Title	ENF+HAART	HAART
Arm/Group Description	Participants received enfuvirtide 90 mg subcutaneously twice a day in combination with highly active antiretroviral treatment.	Participants received highly active antiretroviral treatment.
Measure Participants	31	16
Least Squares Mean (95% Confidence Interval) [cells/mm^3]	20.81	17.88

6. Secondary Outcome

Title	Percentage of Induction Phase Participants With Viral Load < 50 Copies/mL at 48 Weeks
Description	The percentage of participants from the Induction Phase who maintained HIV-1 RNA < 50 Copies/mL at Week 48. Patients who discontinued from the study, rebounded to ≥ 50 copies/mL (i.e., had two consecutive readings ≥ 50 copies/mL), had missing data or had virological failure by Week 48 were classed as non-responders.
Time Frame	Week 48

Outcome Measure Data

Analysis Population Description

Induction Phase Intent-to-Treat Population 1 (ITT1).

Arm/Group Title	ENF+HAART	HAART
Arm/Group Description	Participants received enfuvirtide (ENF) 90 mg subcutaneously twice a day in combination with highly active antiretroviral treatment (HAART) in the Induction Phase. In the Maintenance Phase, participants either continued to receive ENF+HAART or HAART alone. This group contains all patients who were randomized to ENF+HAART at BL1 and follows the patients throughout 48 weeks, regardless of which arm they were randomized to at BL2.	Participants received highly active antiretroviral treatment during both the Induction and Maintenance Phase.
Measure Participants	31	16
Number [percentage of participants]	45.2 155.9%	25.0 138.9%

7. Secondary Outcome

Title	Percentage of Maintenance Phase Participants With Viral Load < 50 Copies/mL at 48 Weeks
Description	The percentage of participants from the Maintenance Phase who maintained HIV-1 RNA < 50 copies/mL at Week 48. Patients who discontinued from the study, rebounded to ≥ 50 copies/mL (i.e., had two consecutive readings ≥ 50 copies/mL), had missing data or had virological failure by Week 48 were classed as non-responders.
Time Frame	Week 48

Outcome Measure Data

Analysis Population Description

Maintenance Phase Intent-to-Treat Population 2 (ITT2).

Arm/Group Title	ENF+HAART	HAART
Arm/Group Description	Participants received enfuvirtide (ENF) 90 mg subcutaneously twice a day in combination with highly active antiretroviral treatment (HAART) in the Induction Phase. In the Maintenance Phase, participants either continued to receive ENF+HAART or HAART alone. This group contains all patients who entered the Maintenance phase from the ENF+HAART Induction phase, regardless of which arm they were randomized to at BL2.	Participants received highly active antiretroviral treatment during both the Induction and Maintenance Phase.
Measure Participants	19	8
Number [percentage of participants]	73.7 254.1%	50.0 277.8%

8. Secondary Outcome

Title	Change From Baseline to Week 48 in Cluster Differentiation Antigen Four Positive (CD4) Cell Counts
Description	Change from Baseline in CD4 Cell Counts at Week 48. Least squares means were calculated from an ANCOVA model with treatment and baseline CD4 count as independent variables.
Time Frame	Baseline 1 and Week 48

Outcome Measure Data

Analysis Population Description

Intent-to-Treat Population 2 (ITT2) population (patients evaluable for efficacy in the Maintenance Phase). Baseline values were carried forward (i.e. the change from baseline set to zero) for patients with missing data at week 48 or who withdrew prior to the week 48 time window.

Arm/Group Title	ENF+HAART	HAART
Arm/Group Description	Participants received enfuvirtide (ENF) 90 mg subcutaneously twice a day in combination with highly active antiretroviral treatment (HAART) in the Induction Phase. In the Maintenance Phase, participants either continued to receive ENF+HAART or HAART alone. This group contains all patients who entered the Maintenance phase from the ENF+HAART Induction phase, regardless of which arm they were randomized to at BL2.	Participants received highly active antiretroviral treatment during both the Induction and Maintenance Phase.
Measure Participants	19	8
Least Squares Mean (95% Confidence Interval) [cells/mm^3]	73.09	50.79

9. Secondary Outcome

Title	Time to Loss of Viral Response During the Maintenance Phase
Description	The time to loss of viral response (defined as HIV-1 RNA <50 copies/mL) was counted from Baseline 2 until the first of two consecutive ≥50 copies/mL measurements. Only patients who were qualified for entering the Maintenance Phase were included in the analysis.
Time Frame	From Baseline 2 to Week 48.

Outcome Measure Data

Analysis Population Description

Maintenance Phase Intent-to-Treat Population 2 (ITT2)

Arm/Group Title	ENF+HAART	HAART
Arm/Group Description	Participants received enfuvirtide (ENF) 90 mg subcutaneously twice a day in combination with highly active antiretroviral treatment (HAART) in the Induction Phase. In the Maintenance Phase, participants either continued to receive ENF+HAART or HAART alone. This group contains all patients who entered the Maintenance phase from the ENF+HAART Induction phase, regardless of which arm they were randomized to at BL2.	Participants received highly active antiretroviral treatment during both the Induction and Maintenance Phase.
Measure Participants	19	8
Median (Inter-Quartile Range) [days]	NA	NA

10. Secondary Outcome

Title	Time to Virological Failure During the Maintenance Phase
Description	Time to virological failure (defined as HIV-1 RNA ≥ 400 copies/mL) was counted from Baseline 2 until the first of the two consecutive ≥400 copies/mL measurements. Only patients who were qualified for entering the Maintenance Phase were included in the analyses.
Time Frame	From Baseline 2 to Week 48.

Outcome Measure Data

Analysis Population Description

Maintenance Phase Intent-to-Treat Population 2 (ITT2)

Arm/Group Title	ENF+HAART	HAART
Arm/Group Description	Participants received enfuvirtide (ENF) 90 mg subcutaneously twice a day in combination with highly active antiretroviral treatment (HAART) in the Induction Phase. In the Maintenance Phase, participants either continued to receive ENF+HAART or HAART alone. This group contains all patients who entered the Maintenance Phase from the ENF+HAART Induction Phase, regardless of which arm they were randomized to at BL2.	Participants received highly active antiretroviral treatment during both the Induction and Maintenance Phase.
Measure Participants	19	8
Median (Inter-Quartile Range) [days]	NA	NA

11. Secondary Outcome

Title	Number of Participants With Virological Failure During the Maintenance Phase
Description	Virological failure was defined by 2 consecutive HIV-1 RNA values ≥ 400 copies/mL during the Maintenance Phase.
Time Frame	From Baseline 2 to Week 48.

Outcome Measure Data

Analysis Population Description

Maintenance Phase Intent-to-Treat Population 2 (ITT2)

Arm/Group Title	ENF+HAART	HAART
Arm/Group Description	Participants received enfuvirtide (ENF) 90 mg subcutaneously twice a day in combination with highly active antiretroviral treatment (HAART) in the Induction Phase. In the Maintenance Phase, participants either continued to receive ENF+HAART or HAART alone. This group contains all patients who entered the Maintenance Phase from the ENF+HAART Induction Phase, regardless of which arm they were randomized to at BL2.	Participants received highly active antiretroviral treatment during both the Induction and Maintenance Phase.
Measure Participants	19	8
Number [Participants]	3 10.3%	0 0%

12. Secondary Outcome

Title	Percentage of Participants Maintaining CD4+ Count During the Maintenance Phase
Description	Maintenance of CD4+ count defined as having greater than or equal to 200 cells/mm^3 at Baseline 2 (BL2) and greater than or equal to 200 cells/mm^3 at Week 48.
Time Frame	Baseline 2 to Week 48.

Outcome Measure Data

Analysis Population Description

Maintenance Phase ITT2 population with a Baseline 2 CD4+ count of greater than or equal to 200 cells/mm^3.

Arm/Group Title	ENF + HAART	HAART	HAART (ENF Removed)
Arm/Group Description	Participants received enfuvirtide 90 mg subcutaneously twice a day in combination with highly active antiretroviral treatment during the Induction and Maintenance Phase for up to 48 weeks of treatment.	Participants received highly active antiretroviral treatment during the Induction and Maintenance Phase for up to 48 weeks of treatment.	Participants who had received ENF + HAART during the Induction Phase and responded to treatment by Week 24 continued to receive HAART alone during the Maintenance Phase, for a total of 48 weeks of treatment.
Measure Participants	9	8	8
Week 48 CD4+ Count ≥200 cells/mm^3	66.67 229.9%	75.00 416.7%	75.00 159.6%
Week 48 CD4+ Count Missing	33.33 114.9%	25.00 138.9%	12.50 26.6%

13. Secondary Outcome

Title	Percentage of Participants With Improvement in CD4+ Count During the Maintenance Phase
Description	Improvement of CD4+ count defined as having from 100 to less than 200 CD4+ cells/mm^3 at Baseline 2 (BL2) and greater than or equal to 200 cells/mm^3 at Week 48.
Time Frame	Baseline 2 to Week 48.

Outcome Measure Data

Analysis Population Description

Maintenance Phase ITT2 population with a Baseline 2 CD4+ count of ≥100 to <200 cells/mm^3.

Arm/Group Title	ENF + HAART	HAART	HAART (ENF Removed)
Arm/Group Description	Participants received enfuvirtide 90 mg subcutaneously twice a day in combination with highly active antiretroviral treatment during the Induction and Maintenance Phase for up to 48 weeks of treatment.	Participants received highly active antiretroviral treatment during the Induction and Maintenance Phase for up to 48 weeks of treatment.	Participants who had received ENF + HAART during the Induction Phase and responded to treatment by Week 24 continued to receive HAART alone during the Maintenance Phase, for a total of 48 weeks of treatment.
Measure Participants	1	0	1
Week 48 CD4+ Count ≥200 cells/mm^3	100.00 344.8%	100.00 555.6%
Week 48 CD4+ Count Missing	0 0%	0 0%

14. Secondary Outcome

Title	Number of Participants With Adverse Events (AEs) During the Induction Phase
Description	A serious AE (SAE) is an event which: results in death, is life-threatening, disabling or incapacitating; is a congenital anomaly in the offspring of a patient who received study drug; requires or prolongs inpatient hospitalization; jeopardizes the patient or require medical or surgical intervention to prevent one of the outcomes above; any Grade 4 laboratory value considered by the investigator clinically significant or that requires an action; any injection site reaction that meets SAE criteria above. Non-serious AEs reported include pneumonia and non-serious AEs that led to discontinuation.
Time Frame	Start of the study treatment until the end of the Induction Phase (Week 12 to Week 32)

Outcome Measure Data

Analysis Population Description

Safety Population

Arm/Group Title	ENF+HAART	HAART
Arm/Group Description	Participants received enfuvirtide 90 mg subcutaneously twice a day in combination with highly active antiretroviral treatment.	Participants received highly active antiretroviral treatment.
Measure Participants	29	18
Serious Adverse Event	3 10.3%	3 16.7%
Non-serious Adverse Event	3 10.3%	1 5.6%
Adverse Events Leading to Withdrawal	5 17.2%	1 5.6%

Adverse Events

Time Frame	From the start of the study treatment until 28 days after the last dose of the study medication.
Adverse Event Reporting Description	Per protocol, AEs of pneumonia (non-serious and serious), AEs that lead to discontinuation, and AEs that are serious were reported. Unless fatal, any acquired immunodeficiency syndrome (AIDS)-defining events (ADEs), as defined by the 1993 Center for Disease Control (CDC) AIDS Surveillance Case Definitions, are excluded from the definition of SAE.
Arm/Group Title	Induction: ENF+HAART		Induction Phase: HAART		Maintenance Phase: ENF + HAART		Maintenance Phase: HAART (ENF Removed)		Maintenance Phase: HAART
Arm/Group Description	During the Induction Phase participants received enfuvirtide 90 mg subcutaneously twice a day in combination with highly active antiretroviral treatment for a maximum of 32 weeks.		During the Induction Phase participants received highly active antiretroviral treatment for a maximum of 32 weeks.		During the Maintenance Phase, participants who had received ENF+HAART and who responded to treatment during the Induction Phase continued to receive enfuvirtide 90 mg subcutaneously twice a day in combination with highly active antiretroviral treatment for up to 48 weeks of total treatment.		During the Maintenance Phase, participants who had received ENF+HAART and who responded to treatment during the Induction Phase continued to receive HAART alone during the Maintenance Phase, for up to a total of 48 weeks treatment.		During the Maintenance Phase, participants who had received HAART alone and who responded to treatment during the Induction Phase continued to receive highly active antiretroviral treatment for up to 48 weeks of total treatment.
All Cause Mortality
	Induction: ENF+HAART		Induction Phase: HAART		Maintenance Phase: ENF + HAART		Maintenance Phase: HAART (ENF Removed)		Maintenance Phase: HAART
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Induction: ENF+HAART		Induction Phase: HAART		Maintenance Phase: ENF + HAART		Maintenance Phase: HAART (ENF Removed)		Maintenance Phase: HAART
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	3/29 (10.3%)		3/18 (16.7%)		2/10 (20%)		3/9 (33.3%)		0/8 (0%)
Blood and lymphatic system disorders
ANAEMIA	1/29 (3.4%)		0/18 (0%)		0/10 (0%)		0/9 (0%)		0/8 (0%)
Gastrointestinal disorders
ABDOMINAL PAIN	0/29 (0%)		1/18 (5.6%)		0/10 (0%)		0/9 (0%)		0/8 (0%)
VOMITING	0/29 (0%)		1/18 (5.6%)		0/10 (0%)		0/9 (0%)		0/8 (0%)
General disorders
INJECTION SITE REACTION	1/29 (3.4%)		0/18 (0%)		0/10 (0%)		0/9 (0%)		0/8 (0%)
Hepatobiliary disorders
HEPATIC FAILURE	0/29 (0%)		1/18 (5.6%)		0/10 (0%)		0/9 (0%)		0/8 (0%)
HEPATIC FUNCTION ABNORMAL	0/29 (0%)		0/18 (0%)		1/10 (10%)		0/9 (0%)		0/8 (0%)
Infections and infestations
PAROTITIS	0/29 (0%)		1/18 (5.6%)		0/10 (0%)		0/9 (0%)		0/8 (0%)
POSTOPERATIVE WOUND INFECTION	0/29 (0%)		1/18 (5.6%)		0/10 (0%)		0/9 (0%)		0/8 (0%)
INFECTION	0/29 (0%)		0/18 (0%)		0/10 (0%)		1/9 (11.1%)		0/8 (0%)
PNEUMONIA	0/29 (0%)		0/18 (0%)		1/10 (10%)		0/9 (0%)		0/8 (0%)
Musculoskeletal and connective tissue disorders
RHABDOMYOLYSIS	1/29 (3.4%)		0/18 (0%)		0/10 (0%)		0/9 (0%)		0/8 (0%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
ANAL CANCER	0/29 (0%)		0/18 (0%)		0/10 (0%)		1/9 (11.1%)		0/8 (0%)
Renal and urinary disorders
RENAL FAILURE	1/29 (3.4%)		0/18 (0%)		0/10 (0%)		0/9 (0%)		0/8 (0%)
CALCULUS URETERIC	0/29 (0%)		0/18 (0%)		0/10 (0%)		1/9 (11.1%)		0/8 (0%)
Respiratory, thoracic and mediastinal disorders
RESPIRATORY DISTRESS	0/29 (0%)		0/18 (0%)		1/10 (10%)		0/9 (0%)		0/8 (0%)
Other (Not Including Serious) Adverse Events
	Induction: ENF+HAART		Induction Phase: HAART		Maintenance Phase: ENF + HAART		Maintenance Phase: HAART (ENF Removed)		Maintenance Phase: HAART
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	9/29 (31%)		11/18 (61.1%)		2/10 (20%)		4/9 (44.4%)		3/8 (37.5%)
Blood and lymphatic system disorders
THROMBOCYTOPENIA	0/29 (0%)		1/18 (5.6%)		0/10 (0%)		0/9 (0%)		0/8 (0%)
Ear and labyrinth disorders
TINNITUS	0/29 (0%)		1/18 (5.6%)		0/10 (0%)		0/9 (0%)		1/8 (12.5%)
Eye disorders
CONJUNCTIVITIS	0/29 (0%)		1/18 (5.6%)		0/10 (0%)		0/9 (0%)		0/8 (0%)
Gastrointestinal disorders
DIARRHOEA	2/29 (6.9%)		5/18 (27.8%)		0/10 (0%)		0/9 (0%)		0/8 (0%)
ABDOMINAL DISTENSION	1/29 (3.4%)		2/18 (11.1%)		0/10 (0%)		0/9 (0%)		0/8 (0%)
VOMITING	2/29 (6.9%)		1/18 (5.6%)		0/10 (0%)		0/9 (0%)		0/8 (0%)
NAUSEA	1/29 (3.4%)		1/18 (5.6%)		0/10 (0%)		0/9 (0%)		0/8 (0%)
ODYNOPHAGIA	1/29 (3.4%)		1/18 (5.6%)		0/10 (0%)		0/9 (0%)		0/8 (0%)
ABDOMINAL PAIN UPPER	0/29 (0%)		1/18 (5.6%)		0/10 (0%)		0/9 (0%)		0/8 (0%)
DRY MOUTH	0/29 (0%)		1/18 (5.6%)		0/10 (0%)		0/9 (0%)		0/8 (0%)
FLATULENCE	0/29 (0%)		1/18 (5.6%)		0/10 (0%)		0/9 (0%)		0/8 (0%)
CONSTIPATION	0/29 (0%)		0/18 (0%)		0/10 (0%)		1/9 (11.1%)		1/8 (12.5%)
DYSPHAGIA	0/29 (0%)		0/18 (0%)		1/10 (10%)		0/9 (0%)		0/8 (0%)
TOOTHACHE	0/29 (0%)		1/18 (5.6%)		0/10 (0%)		0/9 (0%)		0/8 (0%)
General disorders
CHEST PAIN	0/29 (0%)		1/18 (5.6%)		0/10 (0%)		0/9 (0%)		0/8 (0%)
PAIN	0/29 (0%)		0/18 (0%)		0/10 (0%)		0/9 (0%)		1/8 (12.5%)
Hepatobiliary disorders
HEPATIC FAILURE	0/29 (0%)		1/18 (5.6%)		0/10 (0%)		0/9 (0%)		0/8 (0%)
Immune system disorders
DRUG HYPERSENSITIVITY	0/29 (0%)		1/18 (5.6%)		0/10 (0%)		0/9 (0%)		0/8 (0%)
Infections and infestations
CELLULITIS	2/29 (6.9%)		0/18 (0%)		0/10 (0%)		0/9 (0%)		0/8 (0%)
PHARYNGITIS	0/29 (0%)		1/18 (5.6%)		1/10 (10%)		1/9 (11.1%)		1/8 (12.5%)
BRONCHITIS	0/29 (0%)		1/18 (5.6%)		0/10 (0%)		0/9 (0%)		0/8 (0%)
FOLLICULITIS	0/29 (0%)		1/18 (5.6%)		0/10 (0%)		0/9 (0%)		1/8 (12.5%)
GINGIVAL ABSCESS	0/29 (0%)		0/18 (0%)		0/10 (0%)		0/9 (0%)		1/8 (12.5%)
NASOPHARYNGITIS	0/29 (0%)		1/18 (5.6%)		0/10 (0%)		0/9 (0%)		1/8 (12.5%)
ABSCESS JAW	0/29 (0%)		0/18 (0%)		0/10 (0%)		1/9 (11.1%)		0/8 (0%)
INFLUENZA	0/29 (0%)		0/18 (0%)		0/10 (0%)		0/9 (0%)		1/8 (12.5%)
ONYCHOMYCOSIS	0/29 (0%)		0/18 (0%)		1/10 (10%)		0/9 (0%)		0/8 (0%)
PNEUMONIA BACTERIAL	0/29 (0%)		0/18 (0%)		0/10 (0%)		1/9 (11.1%)		0/8 (0%)
Injury, poisoning and procedural complications
SKIN INJURY	0/29 (0%)		0/18 (0%)		1/10 (10%)		0/9 (0%)		0/8 (0%)
Investigations
TRANSAMINASES INCREASED	0/29 (0%)		2/18 (11.1%)		0/10 (0%)		0/9 (0%)		0/8 (0%)
PLATELET COUNT DECREASED	0/29 (0%)		0/18 (0%)		0/10 (0%)		0/9 (0%)		1/8 (12.5%)
Metabolism and nutrition disorders
ANOREXIA	0/29 (0%)		1/18 (5.6%)		0/10 (0%)		0/9 (0%)		0/8 (0%)
HYPERCHOLESTEROLAEMIA	0/29 (0%)		0/18 (0%)		0/10 (0%)		1/9 (11.1%)		0/8 (0%)
HYPERTRIGLYCERIDAEMIA	0/29 (0%)		0/18 (0%)		0/10 (0%)		1/9 (11.1%)		0/8 (0%)
Musculoskeletal and connective tissue disorders
MUSCULOSKELETAL CHEST PAIN	0/29 (0%)		1/18 (5.6%)		0/10 (0%)		0/9 (0%)		1/8 (12.5%)
Nervous system disorders
HEADACHE	1/29 (3.4%)		1/18 (5.6%)		0/10 (0%)		0/9 (0%)		0/8 (0%)
DIZZINESS	0/29 (0%)		1/18 (5.6%)		0/10 (0%)		0/9 (0%)		0/8 (0%)
Psychiatric disorders
INSOMNIA	0/29 (0%)		1/18 (5.6%)		0/10 (0%)		0/9 (0%)		0/8 (0%)
Respiratory, thoracic and mediastinal disorders
EPISTAXIS	0/29 (0%)		1/18 (5.6%)		0/10 (0%)		0/9 (0%)		1/8 (12.5%)
PULMONARY CONGESTION	0/29 (0%)		1/18 (5.6%)		0/10 (0%)		0/9 (0%)		0/8 (0%)
COUGH	1/29 (3.4%)		0/18 (0%)		1/10 (10%)		1/9 (11.1%)		1/8 (12.5%)
Skin and subcutaneous tissue disorders
RASH	1/29 (3.4%)		1/18 (5.6%)		0/10 (0%)		0/9 (0%)		0/8 (0%)

Limitations/Caveats

[Not Specified]

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Certain Agreements

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

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.