ALTAIR - Alternative Antiretroviral Strategies : a Comparison of Three Initial Regimens

• Sponsor: Kirby Institute (Other)
• Overall Status: Completed
• CT.gov ID: NCT00335322
• Collaborator: The University of New South Wales (Other)
• Enrollment: 329
• Arms: 3
• Duration (Months): 57

Study Details

Study Description

Brief Summary

In treatment naïve HIV infected subjects, combination antiretroviral therapy including efavirenz combined with tenofovir and emtricitabine will offer non-inferior antiretroviral efficacy over 48 weeks, compared to either atazanavir boosted with ritonavir combined with tenofovir and emtricitabine or tenofovir and emtricitabine combined with zidovudine and abacavir, as assessed by change from baseline plasma HIV-1 RNA viral load.

Condition or Disease	Intervention/Treatment	Phase
Human Immunodeficiency Virus (HIV)	Drug: Truvada (fixed dose combination of tenofovir + emtricitabine) + Stocrin (efavirenz); Drug: Truvada (fixed dose combination of tenofovir + emtricitabine)+ ritonavir/atazanavir (r/ATV); Drug: Truvada (fixed dose combination of tenofovir + emtricitabine) + zidovudine (ZDV) + abacavir (ABC)	Phase 4

Detailed Description

The primary objective of this study is to compare the virological efficacy, as measured by the time-weighted mean change from baseline plasma HIV-RNA, and safety, of three strategic regimens of initial antiretroviral therapy (ART) containing a fixed dose formulation of tenofovir and emtricitabine, with either efavirenz or ritonavir boosted atazanavir or zidovudine plus abacavir. (Primary comparisons are regimen I versus II and I versus III as described below).

1. tenofovir (TDF) + emtricitabine (FTC) + efavirenz (EFV) II. tenofovir (TDF) + emtricitabine (FTC) + ritonavir/atazanavir (r/ATV) III. tenofovir (TDF) + emtricitabine (FTC)

• zidovudine (ZDV) + abacavir (ABC)

Secondary objectives of this study will be to undertake a range of analyses including but not limited to the following,

1. Percentage of patients < 50 copies HIV RNA/mL (and < 400 copies/mL) at week 48 and week 96 between treatment arms.

2. Time to confirmed (first of two consecutive) plasma HIV-1 RNA < 50 copies/mL (and < 400 copies/mL) between treatment arms.

3. Time to virologic failure defined as confirmed plasma HIV-1 RNA > 50 copies/mL (and 400 copies/mL) after confirmed < 50 copies/mL (where time = 0 if patient never achieves plasma virus load < 50 or <400 copies/mL).

4. Mean change from baseline of absolute CD4+ T cell count at weeks 48 and 96 between treatment arms.

5. Time to change in randomly assigned therapy (all reasons individually and on aggregate) between treatment arms.

6. Time to first virologic failure (defined as #3 above) or cessation of randomly assigned antiretroviral therapy.

7. Mean change from baseline Lipodystrophy Case Definition score at weeks 48 and 96 between treatment arms.

8. Mean change from baseline in peripheral and central adipose tissue, as measured by CT and DEXA at weeks 48 and 96 between treatment arms.

9. Mean change from baseline in fasting lipid and glycemic parameters at weeks 48 and 96 between treatment arms.

10. Comparison of total number of patients with any serious adverse events (SAEs), and the cumulative incidence of SAEs, between treatment arms.

11. Comparison of total number of patients with any adverse events (AEs), and the cumulative incidence of AEs, associated with cessation of randomly assigned therapy between treatment arms.

12. Patterns of genotypic HIV resistance associated with virological treatment failure across treatment arms.

13. Describe aspects of immune reconstitution disease.

14. Adherence to therapy and associations with virologic outcomes between treatment arms.

15. Comparison of quality of life between treatment arms.

Following the result of the scheduled week 48 data analysis, the protocol steering committee amended the study protocol as follows:

• Patients on Arms I and II will remain on the current study drugs

• Patients on Arm III may be switched at the physician's discretion to either Arm I or II

• There will be a protocol amendment to include one extra follow up visit at week 144 for all patients, regardless of treatment arm or current treatment

• All patients are to be encouraged to stay on the study up to week 144, to maximize follow up on study.

Study Design

• Study Type: Interventional
• Actual Enrollment: 329 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Randomised, Open-label, 96-week Study Comparing the Safety and Efficacy of Three Different Combination Antiretroviral Regimens as Initial Therapy for HIV Infection.
• Study Start Date: Feb 1, 2007
• Actual Primary Completion Date: Mar 1, 2011
• Actual Study Completion Date: Nov 1, 2011

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: 1 Truvada (fixed dose combination of tenofovir + emtricitabine) + Stocrin efavirenz)	Drug: Truvada (fixed dose combination of tenofovir + emtricitabine) + Stocrin (efavirenz); Truvada (tenofovir 300mg qd + 200mg qd) once daily Efavirenz 600mg qd once daily
Active Comparator: 2 Truvada (fixed dose combination of tenofovir + emtricitabine)+ ritonavir/atazanavir (r/ATV)	Drug: Truvada (fixed dose combination of tenofovir + emtricitabine)+ ritonavir/atazanavir (r/ATV); Tuvada (tenofovir 300mg qd + 200mg qd) once daily ritoanvir/atazanavir 100mg/300mg qd once daily (taken with food)
Experimental: 3 Truvada (fixed dose combination of tenofovir + emtricitabine) + zidovudine (ZDV) + abacavir (ABC)	Drug: Truvada (fixed dose combination of tenofovir + emtricitabine) + zidovudine (ZDV) + abacavir (ABC); Tuvada (tenofovir 300mg qd + 200mg qd) once daily zidovudine 250mg/300mg qd (taken in two equal doses approximately 12 hours apart) Abacavir 600mg qd

Outcome Measures

Primary Outcome Measures

1. Time-weighted Mean Change From Baseline Plasma HIV-RNA. [48 weeks]

Secondary Outcome Measures

1. Time Weighted Mean Change From Baseline Plasma HIV-RNA [144 weeks]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 16 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• HIV-1 positive by licensed diagnostic test with presumed duration of infection > 6 months from date of randomisation.

• Aged > 16 years of age (or minimum age as determined by local regulations or as legal requirements dictate).

• Antiretroviral treatment naïve.

• Qualifying plasma HIV RNA > 2,000 copies/mL and a CD4+ T cell count of ≥ 50 cells/µL.

• No evidence of harbouring a drug resistant HIV (based upon genotypic drug testing).

• Calculated creatinine clearance (CLCr) greater than or equal to 70 mL/min (Cockcroft-Gault formula).

• Able to provide written informed consent.

Exclusion Criteria:

• The following laboratory variables,

• absolute neutrophil count (ANC) < 750 cells/µL

• haemoglobin < 8.0 g/dL

• platelet count < 50,000 cells/µL

• serum AST, ALT > 5 x upper limit of normal (ULN)

• serum bilirubin > 1.5 x ULN

• Pregnant or nursing mothers.

• Current use of human growth hormone, testosterone or other anabolic steroid.

• Current use of any prohibited medications as described in product specific information.

• Acute therapy for serious infection or other serious medical illness (in the judgement of the site Principal Investigator) requiring systemic treatment and/or hospitalisation.

• Patients with current alcohol or illicit substance use that in the opinion of the site Principal Investigator would conflict with any aspect of the conduct of the trial.

• Patients unlikely to be able to remain in follow-up for the protocol-defined period.

• Patients with known renal insufficiency.

• Patients with obstructive liver disease.

• Patients with intractable diarrhoea (six loose stools/day for at least seven consecutive days).

• History of acute or chronic pancreatitis.

• Presence of cardiomyopathy (due to any cause) or any significant cardiovascular disease, such as unstable ischemic heart disease.

• Prisoners or subjects who are compulsorily detained (involuntarily incarcerated).

Contacts and Locations

Locations

No locations specified.

Sponsors and Collaborators

• Kirby Institute
• The University of New South Wales

Investigators

• Principal Investigator: David A Cooper, AO DSc MD FRACP FRCPA FRCP, Kirby Institute

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• The Kirby Institute homepage (formerly known as the National Centre in HIV Epidemiology and Clinical Research)

Publications

None provided.

• Responsible Party: Kirby Institute
• ClinicalTrials.gov Identifier: NCT00335322
• Other Study ID Numbers: NCHECR-ALTAIR
• First Posted: Jun 9, 2006
• Last Update Posted: Sep 26, 2019
• Last Verified: Sep 1, 2019

• Keywords provided by Kirby Institute: Human Immunodeficiency Virus (HIV)
• Additional relevant MeSH terms: Acquired Immunodeficiency Syndrome; HIV Infections; Immunologic Deficiency Syndromes; Ritonavir; Atazanavir Sulfate; Tenofovir; Zidovudine; Emtricitabine; Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination; Abacavir; Efavirenz

Study Results

Participant Flow

Arm/Group Title	TDF/FTC+EFV	TDF/FTC+r/ATV	TDF/FTC+AZT+ABC
Arm/Group Description	Truvada (fixed dose combination of tenofovir+emtricitabine) + Stocrin efavirenz	Truvada (fixed dose combination of tenofovir + emtricitabine)+ ritonavir/atazanavir (r/ATV)	Truvada (fixed dose combination of tenofovir + emtricitabine) + zidovudine (ZDV) + abacavir (ABC)
Period Title: Overall Study
STARTED	115	107	105
COMPLETED	114	105	103
NOT COMPLETED	1	2	2

Baseline Characteristics

Arm/Group Title	TDF/FTC+EFV	TDF/FTC+r/ATV	TDF/FTC+AZT+ABC	Total
Arm/Group Description	Truvada (fixed dose combination of tenofovir + emtricitabine)+ Stocrin efavirenz	Truvada (fixed dose combination of tenofovir + emtricitabine)+ ritonavir/atazanavir (r/ATV)	Truvada (fixed dose combination of tenofovir + emtricitabine) + zidovudine (ZDV) + abacavir (ABC)	Total of all reporting groups
Overall Participants	115	107	105	327
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%	0 0%
Between 18 and 65 years	115 100%	107 100%	105 100%	327 100%
>=65 years	0 0%	0 0%	0 0%	0 0%
Sex: Female, Male (Count of Participants)
Female	24 20.9%	30 28%	22 21%	76 23.2%
Male	91 79.1%	77 72%	83 79%	251 76.8%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%	0 0%
Asian	35 30.4%	37 34.6%	35 33.3%	107 32.7%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%	0 0%
Black or African American	10 8.7%	7 6.5%	10 9.5%	27 8.3%
White	46 40%	43 40.2%	35 33.3%	124 37.9%
More than one race	24 20.9%	20 18.7%	25 23.8%	69 21.1%
Unknown or Not Reported	0 0%	0 0%	0 0%	0 0%

Outcome Measures

1. Primary Outcome

Title	Time-weighted Mean Change From Baseline Plasma HIV-RNA.
Time Frame	48 weeks

Outcome Measure Data

Analysis Population Description

Modified ITT; all randomised pts who started drug

Arm/Group Title	TDF/FTC+EFV	TDF/FTC+r/ATV	TDF/FTC+AZT+ABC
Arm/Group Description	Truvada (fixed dose combination of tenofovir + emtricitabine) + Stocrin (efavirenz) Truvada (tenofovir 300mg qd + 200mg qd) once daily Efavirenz 600mg qd once daily	Truvada (fixed dose combination of tenofovir + emtricitabine) + ritonavir/atazanavir (r/ATV) Truvada (tenofovir 300mg qd + 200mg qd) once daily Ritonavir/atazanavi 100mg/300mg qd once daily	Truvada (fixed dose combination of tenofovir + emtricitabine) + zidovudine + abacavir Truvada (tenofovir 300mg qd + 200mg qd) once daily Zidovudine 250mg/300mg qd taken in two equal doses approx. 12 hours apart Abacavir 600mg qd
Measure Participants	114	105	103
Mean (95% Confidence Interval) [log copies/mL]	-2.59	-2.69	-2.39

2. Secondary Outcome

Title	Time Weighted Mean Change From Baseline Plasma HIV-RNA
Time Frame	144 weeks

Outcome Measure Data

Analysis Population Description

Intent to Treat

Arm/Group Title	TDF/FTC+EFV	TDF/FTC+ r/ATV	TDF/FTC + AZT+ABC
Arm/Group Description	Truvada (fixed dose combination of tenofovir + emtricitabine) + Stocrin (efavirenz): Truvada (tenofovir 300mg qd + 200mg qd) once daily Efavirenz 600mg qd once daily	Truvada (fixed dose combination of tenofovir + emtricitabine)+ ritonavir/atazanavir (r/ATV): Tuvada (tenofovir 300mg qd + 200mg qd) once daily ritoanvir/atazanavir 100mg/300mg qd once daily (taken with food)	Truvada (fixed dose combination of tenofovir + emtricitabine) + zidovudine (ZDV) + abacavir (ABC): Tuvada (tenofovir 300mg qd + 200mg qd) once daily zidovudine 250mg/300mg qd (taken in two equal doses approximately 12 hours apart) Abacavir 600mg qd
Measure Participants	114	105	103
Mean (95% Confidence Interval) [log copies/mL]	-2.77	-2.88	-2.54

Adverse Events

Time Frame	1 year
Arm/Group Title	TDF/FTC+EFV		TDF/FTC+r/ATV		TDF/FTC+AZT+ABC
Arm/Group Description	Truvada (fixed dose combination of tenofovir + emtricitabine)+ ritonavir/atazanavir (r/ATV)		Truvada (fixed dose combination of tenofovir + emtricitabine) + zidovudine (ZDV) + abacavir (ABC)
All Cause Mortality
	TDF/FTC+EFV		TDF/FTC+r/ATV		TDF/FTC+AZT+ABC
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	TDF/FTC+EFV		TDF/FTC+r/ATV		TDF/FTC+AZT+ABC
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	14/115 (12.2%)		8/105 (7.6%)		12/103 (11.7%)
Blood and lymphatic system disorders
decreased blood pressure	1/115 (0.9%)	1	0/105 (0%)	0	1/103 (1%)	3
Anemias and marrow depression	0/115 (0%)	0	0/105 (0%)	0	1/103 (1%)	2
Hematological and lymphoid tissue therapeutic procedures	0/115 (0%)	0	0/105 (0%)	0	1/103 (1%)	1
Cardiac disorders
cardiac arrhythmias	0/115 (0%)	0	1/105 (1%)	3	0/103 (0%)	0
Gastrointestinal disorders
Gastrointestinal signs and symptoms	0/115 (0%)	0	1/105 (1%)	2	1/103 (1%)	5
Gastrointestinal motility and defaecation	0/115 (0%)	0	1/105 (1%)	1	0/103 (0%)	0
General disorders
General systems disorder	0/115 (0%)	0	1/105 (1%)	2	2/103 (1.9%)	2
Hepatobiliary disorders
Hepatic and heaptobiliary disroders	0/115 (0%)	0	1/105 (1%)	1	0/103 (0%)	0
Immune system disorders
Autoimmune disorder	3/115 (2.6%)	3	0/105 (0%)	0	0/103 (0%)	0
Allergic conditions	2/115 (1.7%)	2	0/105 (0%)	0	0/103 (0%)	0
Infections and infestations
Bacterial infection	0/115 (0%)	0	0/105 (0%)	0	1/103 (1%)	1
Fungal infection	0/115 (0%)	0	0/105 (0%)	0	1/103 (1%)	1
infection class unspecified	3/115 (2.6%)	4	1/105 (1%)	1	2/103 (1.9%)	4
Viral infectious disorder	0/115 (0%)	0	0/105 (0%)	0	1/103 (1%)	1
Mycobacterial infection	0/115 (0%)	0	1/105 (1%)	1	0/103 (0%)	0
Injury, poisoning and procedural complications
Therapeutic procedure	1/115 (0.9%)	1	0/105 (0%)	0	0/103 (0%)	0
Investigations
Investigations, imaging and histopathology	1/115 (0.9%)	1	0/105 (0%)	0	0/103 (0%)	0
Musculoskeletal and connective tissue disorders
injury	1/115 (0.9%)	1	0/105 (0%)	0	1/103 (1%)	1
Pleural disorder	0/115 (0%)	0	0/105 (0%)	0	1/103 (1%)	1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Lymphoma	0/115 (0%)	0	1/105 (1%)	1	0/103 (0%)	0
Pregnancy, puerperium and perinatal conditions
maternal complications of pregnancy	0/115 (0%)	0	0/105 (0%)	0	1/103 (1%)	1
Psychiatric disorders
Seizure	0/115 (0%)	0	1/105 (1%)	2	0/103 (0%)	0
Depressed mood and disturbance	0/115 (0%)	0	0/105 (0%)	0	1/103 (1%)	1
Renal and urinary disorders
Urolithiasis	0/115 (0%)	0	0/105 (0%)	0	1/103 (1%)	1
Reproductive system and breast disorders
Cervix disorder	1/115 (0.9%)	1	0/105 (0%)	0	0/103 (0%)	0
Ovarian and fallopian tube disorders	0/115 (0%)	0	0/105 (0%)	0	1/103 (1%)	2
Respiratory, thoracic and mediastinal disorders
Respiratory disorder NEC	1/115 (0.9%)	1	0/105 (0%)	0	1/103 (1%)	1
Vascular disorders
Fatal outcome	1/115 (0.9%)	1	0/105 (0%)	0	0/103 (0%)	0
Vascular hemorrhagic disorders	1/115 (0.9%)	1	0/105 (0%)	0	1/103 (1%)	1
Venous varices	0/115 (0%)	0	1/105 (1%)	1	0/103 (0%)	0
Other (Not Including Serious) Adverse Events
	TDF/FTC+EFV		TDF/FTC+r/ATV		TDF/FTC+AZT+ABC
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	99/115 (86.1%)		95/105 (90.5%)		91/103 (88.3%)
Blood and lymphatic system disorders
Anemia	0/115 (0%)	0	3/105 (2.9%)	3	11/103 (10.7%)	11
Reduced blood pressure disorders	36/115 (31.3%)	36	4/105 (3.8%)	4	10/103 (9.7%)	10
Gastrointestinal disorders
Gastrointestinal motility and defaecation disorders	21/115 (18.3%)	21	18/105 (17.1%)	18	16/103 (15.5%)	16
Gastrointestinal signs and symptoms	24/115 (20.9%)	24	33/105 (31.4%)	33	68/103 (66%)	68
General disorders
Body temperature disorders	13/115 (11.3%)	13	8/105 (7.6%)	8	6/103 (5.8%)	6
General systems disorder	17/115 (14.8%)	17	15/105 (14.3%)	15	15/103 (14.6%)	15
Hepatobiliary disorders
heaptic and hepatobiliary disorders	4/115 (3.5%)	4	46/105 (43.8%)	46	1/103 (1%)	1
Immune system disorders
Allergic condition	11/115 (9.6%)	11	10/105 (9.5%)	10	5/103 (4.9%)	5
Infections and infestations
Bacterial infections	4/115 (3.5%)	4	9/105 (8.6%)	9	11/103 (10.7%)	11
Fungal infections	11/115 (9.6%)	11	6/105 (5.7%)	6	8/103 (7.8%)	8
Infections - pathogennot specified	45/115 (39.1%)	45	36/105 (34.3%)	36	32/103 (31.1%)	32
Viral infections	17/115 (14.8%)	17	11/105 (10.5%)	11	19/103 (18.4%)	19
Musculoskeletal and connective tissue disorders
Musculoskeletal and connective tissue disorder	11/115 (9.6%)	11	8/105 (7.6%)	8	9/103 (8.7%)	9
Nervous system disorders
headaches	11/115 (9.6%)	11	11/105 (10.5%)	11	12/103 (11.7%)	12
Psychiatric disorders
Depressed mood	7/115 (6.1%)	7	1/105 (1%)	1	4/103 (3.9%)	4
Sleep disorders	33/115 (28.7%)	33	8/105 (7.6%)	8	10/103 (9.7%)	10
Respiratory, thoracic and mediastinal disorders
Respiratory disroder NEC	15/115 (13%)	15	8/105 (7.6%)	8	15/103 (14.6%)	15
Skin and subcutaneous tissue disorders
Epidermal and dermal disorders	29/115 (25.2%)	29	14/105 (13.3%)	14	14/103 (13.6%)	14

Limitations/Caveats

Inadequate sample size for true comparison of non-inferiority

More Information

Certain Agreements

All Principal Investigators ARE 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.