Nevirapine or Atazanavir/Ritonavir Given With Emtricitabine/Tenofovir in Human Immunodeficiency Virus (HIV)-1-infected Treatment Naive Adults

• Sponsor: Boehringer Ingelheim (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00389207
• Collaborator: (none)
• Enrollment: 576
• Locations: 68
• Arms: 3
• Patients Per Site: 8.5

Study Details

Study Description

Brief Summary

Primary purpose of this study is to compare the efficacy and safety of two different nevirapine (Viramune) dosing regimens (once daily (QD) and twice daily (BID) application) and of atazanavir/ritonavir (Reyataz/Norvir), all on an emtricitabine/tenofovir disoproxil fumarate (DF) (Truvada) background. Patients will receive either nevirapine (NVP) 200 mg twice daily, or NVP 400 mg once daily , or ritonavir-boosted atazanavir (ATZ/r), all in combination with emtricitabine (FTC) and tenofovir DF (TDF).

All patients receiving NVP will start at 200 mg once daily for 2 weeks, because it has been demonstrated that this lead-in dosing regimen reduces the frequency of NVP-induced rash. At Visit 3 (Week 2), patients increase the NVP dose to either 200 mg twice daily or to 400 mg once daily. Patients receiving ATZ/r will be treated with ATZ 300 mg once daily, boosted by 100 mg ritonavir (RTV) once daily. Background antiretroviral therapy for all patients consists of one tablet of Truvada. Treatment duration is 48 weeks (primary endpoint) with an extension to 144 weeks. Patients may also participate in the metabolic sub-study, comparing NVP and ATZ/r for signs and symptoms of lipodystrophy and serum lipid/glycaemic abnormalities.

Condition or Disease	Intervention/Treatment	Phase
HIV Infections	Drug: nevirapine bid; Drug: nevirapine qd; Drug: atazanavir	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 576 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Randomized, Open Label Study Evaluating the Lipid Profile Difference and Efficacy of a Combined Therapy Including Tenofovir, Emtricitabine + Atazanavir / r or NVP in Naive HIV - 1 Infected Patients.
• Study Start Date: Oct 1, 2006
• Actual Primary Completion Date: Feb 1, 2011

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: NVP bid nevirapine (NVP) 200 mg BID in combination with emtricitabine (FTC) and tenofovir DF (TDF)	Drug: nevirapine bid; nevirapine twice daily
Experimental: NVP qd nevirapine (NVP) 400 mg QD in combination with emtricitabine (FTC) and tenofovir DF (TDF)	Drug: nevirapine qd; nevirapine once daily
Active Comparator: ATZ/r ritonavir-boosted atazanavir in combination with emtricitabine (FTC) and tenofovir DF (TDF)	Drug: atazanavir; atazanavir once daily

Outcome Measures

Primary Outcome Measures

1. Treatment Response at Week 48 [From baseline to Week 48]

   Treatment response is defined as a viral load (VL) <50 copies/mL measured at two consecutive visits prior to Week 48 and without subsequent rebound or change of antiretroviral (ARV) therapy prior to Week 48.

Secondary Outcome Measures

1. Treatment Response at Week 48 (TLOVR Algorithm) [From baseline to Week 48]

   Treatment response is defined as a VL <50 copies/mL measured at two consecutive visits up to Week 48 and without subsequent rebound or change of ARV therapy up to Week 48, based on time to loss of virologic response (TLOVR) algorithm, as a sensitivity analysis for the primary analysis.

2. Proportion of Patients With VL < 50 Copies/ml [From baseline to Weeks 4, 8, 12, 24, 36, 48, 60, 72, 84, 96, 108, 120, 132 and 144/EOT]

   VL <50 copies/mL among observed patients on treatment at each visit, with the final visit at Week 144 or end of trial (EOT) for the patient

3. Proportion of Patients With VL < 400 Copies/ml [From baseline to Weeks 4, 8, 12, 24, 36, 48, 60, 72, 84, 96, 108, 120, 132 and 144/EOT]

   VL <400 copies/mL among observed patients on treatment at each visit, with the final visit at Week 144 or end of trial (EOT)

4. Change in CD4+ Count From Baseline [From baseline to Weeks 4, 8, 12, 24, 36, 48, 60, 72, 84, 96, 108, 120, 132 and 144/EOT]

   Change in CD4+ cell count from baseline among patients on treatment at each visit, with the final visit at Week 144 or EOT

5. Change in Framingham Score From Baseline [From baseline to Weeks 48, 96 and 144/EOT]

   Change in the estimated risk of cardiovascular disease using the Framingham algorithm from baseline to after 48, 96 and 144 weeks, last observation carried forward (LOCF). The score is based on age, gender, systolic blood pressure, total cholesterol, high density lipoprotein cholesterol and smoking status. Scores range from 0 to 21 with higher scores indicating a greater risk.

6. Change in Mental Health Summary (MHS) Score From Baseline [From baseline to Weeks 48, 96 and 144/EOT]

   Quality of life (QoL) assessment by change in MHS score from baseline to after 48, 96 and 144 weeks (observed cases), from the Medical Outcomes Study HIV Health Survey (MOS-HIV), a 35-item self-administered questionnaire including 10 scales covering: health perceptions, pain, physical functioning, role functioning, social and cognitive functioning, mental health, energy/fatigue, health distress, and QoL. The MHS is a weighted average of the 10 scales and ranges from 0 to 100 with higher scores indicating better QoL.

7. Change in Physical Health Summary (PHS) Score From Baseline [From baseline to Weeks 48, 96 and 144/EOT]

   QoL assessment by change in PHS score from baseline to after 48, 96 and 144 weeks (observed cases), from the MOS-HIV, a 35-item self-administered questionnaire including 10 scales covering: health perceptions, pain, physical functioning, role functioning, social and cognitive functioning, mental health, energy/fatigue, health distress, and QoL. The PHS is a weighted average of the 10 scales and ranges from 0 to 100 with higher scores indicating better QoL.

8. Number of Patients Hospitalized [From baseline to Week 24, Week 24 to 48, Week 48 to 96, and Week 96 to 144/EOT]

   Cost effectiveness assessment by number of patients hospitalized

9. Non-scheduled Physician Visits [From baseline to Week 24, Week 24 to 48, Week 48 to 96, and Week 96 to 144/EOT]

   Cost effectiveness assessment by number of patients with non-scheduled physician visits

10. Genotypic Resistance Associated With Virologic Failure [From baseline to Week 48]

    Number of treatment-emergent drug-associated substitutions in patients with virological failure up to Week 48. The total number of genotypic mutations in those patients who were virologic failures is given, not the number of patients with mutations.

11. Treatment-emergent AIDS-defining Illness [From baseline to Week 144]

    Treatment-emergent AIDS-defining illness (tr.-emerg. AIDS-def.illness) including worsening during treatment

12. Treatment-emergent AIDS-defining Illness Leading to Death [From baseline to Week 144]

    Patients with an AIDS-defining illness leading to death broken out by treatment. Statistical analysis shows time to death from AIDS-defining illness.

13. Lipodystrophy [From baseline to Week 144]

    Number of patients with AE lipodystrophy

14. Serum Lipid Abnormalities [From baseline to Week 144]

    Number of patients with AE elevated serum lipids (i.e. hypercholesterolaemia)

15. Glycaemic Abnormalities [From baseline to Week 144]

    Number of patients with AE elevated serum glucose

16. Treatment Response at Week 96 [From baseline to Week 96]

    Treatment response is defined as a viral load (VL) <50 copies/mL measured at two consecutive visits prior to Week 96 and without subsequent rebound or change of antiretroviral (ARV) therapy prior to Week 96.

17. Treatment Response at Week 144 [From baseline to Week 144]

    Treatment response is defined as a viral load (VL) <50 copies/mL measured at two consecutive visits prior to Week 144 and without subsequent rebound or change of antiretroviral (ARV) therapy prior to Week 144.

18. Proportion of Patients With Virological Rebound With VL >=50 Copies/mL After CVR (Confirmed Virological Response) at Week 24, 48, 96, 144 [at Week 24, 48, 96, 144]

    The analyses of virologic rebound were performed on the original values at each visit(ORGV) rather than calculated results within time windows (CAL)

19. Proportion of Patients With Virological Rebound With VL >=400 Copies/mL After CVR at Week 24, 48, 96, 144 [at Week 24, 48, 96, 144]

    The analyses of virologic rebound were performed on the original values at each visit(ORGV) rather than calculated results within time windows (CAL)

20. Proportion of Patients With Virologic Failure at Week 48, 96, 144 [at Week 48, 96, 144]

21. Time to Treatment Response (First Confirmed VL<50 Copies/mL) [baseline to week 144]

    Time to treatment response was defined as the time from start of treatment until the first measurement of the first confirmed virological response

22. Time to Loss of Virologic Response (Rebound) [Baseline to week 144]

    Time to loss of virologic response (TLOVR) was defined as the time from start of treatment to the first measurement showing VL ≥ 50 copies/mL in the first virologic rebound, after having a confirmed virological response.

23. Time to Treatment Failure [baseline to week 144]

    Treatment failure is defined as the occurrence of the first of at least one of the following events: early discontinuation of trial drug, change in ARV therapy, failure to achieve an HIV RNA count < 50 copies/mL up to Visit 10 (week 48) or loss of virologic response

24. Change in the Calculated Glomerular Filtration Rate (GFR) at Week 48, 96 and 144 [From baseline to Week 48, 96, 144]

    Calculations based on the MDRD algorithm.

25. Proportion of Patients With >= DAIDS Grade 2 Laboratory Abnormalities [week 148]

26. Proportion of Patients Reporting Rash of Any Severity [week 148]

    Proportion of Patients reporting rash of any severity

27. Proportion of Patients Reporting Hepatic Events of Any Severity [week 148]

    Proportion of Patients reporting hepatic events of any severity

28. Proportion of Patients Reporting CNS (Central Nervous System) Side Effects of Any Severity [week 148]

    Proportion of Patients reporting CNS (central nervous system) side effects of any severity

29. Change of Cholesterol Values From Baseline to Week 48, 96, 144 [baseline to week 48, 96, 144]

    Changes frombaseline in total cholesterol, LDL-cholesterol(LDL-c) and HDL

30. Changes of Apolipoprotein Values From Baseline to Week 48, 96, 144 [baseline to week 48, 96, 144]

    Changes frombaseline apolipoprotein A1 & B

31. Change of hsCRP From Baseline to Week 48, 96, 144 [baseline to week 48, 96, 144]

    Change of hsCRP from baseline to week 48, 96, 144

32. Change of Total Triglycerides From Baseline to Week 48, 96, 144 [baseline to week 48, 96, 144]

    Change of total triglycerides from baseline to week 48, 96, 144

33. Change of Total Cholesterol to HDL-cholesterol Ratio From Baseline to Week 48, 96, 144 [baseline to week 48, 96, 144]

    Change of Total cholesterol to HDL-cholesterol ratio from baseline to week 48, 96, 144

Eligibility Criteria

Criteria

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

Inclusion criteria:

Inclusion Criteria:

1. Signed informed consent in accordance with Good Clinical Practice (GCP) and local regulatory requirements prior to trial participation

2. HIV-1-infected males or females >= 18 years of age with positive serology confirmed by Western blot

3. No previous antiretroviral treatment (of more than 7 days)

4. Males with CD4+ counts of < 400 cells/mm3 and females with CD4+ counts of < 250 cells/mm3

5. NVP- and ATZ/r susceptibility based on HIV-1 genotypic resistance report

6. Adequate renal function defined as a calculated creatinine clearance (CLCr) >= 50 ml/min according to the Cockcroft-Gault formula

7. Karnofsky score >= 70

8. Acceptable medical history, as assessed by the investigator

Exclusion criteria:

Exclusion Criteria:

1. Active drug abuse or chronic alcoholism at the investigator's discretion

2. Hepatic cirrhosis stage Child-Pugh B or C

3. Female patients of child-bearing potential who:

• have a positive serum pregnancy test at screening or during the study,

• are breast feeding,

• are planning to become pregnant,

• are not willing to use a barrier method of contraception, or are not willing to use methods of contraception other than ethinyl estradiol containing oral contraceptives

1. Laboratory parameters Division of Acquired Immunodeficiency Syndrome (DAIDS) > grade 2 (triglycerides > DAIDS grade 3; total cholesterol no restrictions)

2. Active hepatitis B or C disease, defined as HBsAg-positive or Hepatitis C-Virus-Ribo Nucleic Acid (HCV-RNA)- positive with Aspartate Transaminase/Alanine Transaminase (AST/ALT) > 2.5x Upper Limit of Normal (ULN) (DAIDS grade 1)

3. Hypersensitivity to any ingredients of the test products

4. Have therapy with nephrotoxic drugs (e.g., aminoglycosides, amphotericin B, vancomycin, cidofovir, foscarnet, cisplatin, pentamidine, tacrolimus, cyclosporine) or potential competitors of renal excretion (e.g., cidofovir, acyclovir, valacyclovir, ganciclovir, valganciclovir, probenecid, high-dose non-steroidal anti-inflammatory drugs (i.e., ibuprofen)) within 3 months prior to study screening or are expected to receive these during the study

5. Patients who are receiving other concomitant treatments which are not permitted

6. Use of other investigational medications within 30 days before study entry or during the trial

7. Use of immunomodulatory drugs within 30 days before study entry or during the trial (e.g., interferon, cyclosporin, hydroxyurea, interleukin 2, chronic treatment with prednisone)

8. Patients with Progressive Multifocal Leukoencephalopathy (PML), Visceral Kaposi's Sarcoma (KS), and/or any lymphoma

9. Any AIDS defining illness that is unresolved, symptomatic or not stable on treatment for at least 12 weeks at screening visit

10. Patients who are receiving systemic treatment for malignant disease

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	1100.1470.54004 Boehringer Ingelheim Investigational Site	Capital Federal		Argentina
2	1100.1470.54002 Boehringer Ingelheim Investigational Site	Córdoba		Argentina
3	1100.1470.54003 Boehringer Ingelheim Investigational Site	Mar del Plata		Argentina
4	1100.1470.54001 Boehringer Ingelheim Investigational Site	Rosario		Argentina
5	1100.1470.49001 Boehringer Ingelheim Investigational Site	Berlin		Germany
6	1100.1470.49002 Boehringer Ingelheim Investigational Site	Berlin		Germany
7	1100.1470.49003 Boehringer Ingelheim Investigational Site	Bochum		Germany
8	1100.1470.49018 Boehringer Ingelheim Investigational Site	Bonn		Germany
9	1100.1470.49014 Boehringer Ingelheim Investigational Site	Düsseldorf		Germany
10	1100.1470.49008 Boehringer Ingelheim Investigational Site	Erlangen		Germany
11	1100.1470.49036 Boehringer Ingelheim Investigational Site	Frankfurt am Main		Germany
12	1100.1470.49035 Boehringer Ingelheim Investigational Site	Frankfurt		Germany
13	1100.1470.49033 Boehringer Ingelheim Investigational Site	Freiburg/Breisgau		Germany
14	1100.1470.49016 Boehringer Ingelheim Investigational Site	Hamburg		Germany
15	1100.1470.49031 Boehringer Ingelheim Investigational Site	Hamburg		Germany
16	1100.1470.49037 Boehringer Ingelheim Investigational Site	Hamburg		Germany
17	1100.1470.49020 Boehringer Ingelheim Investigational Site	Hannover		Germany
18	1100.1470.49038 Boehringer Ingelheim Investigational Site	Magdeburg		Germany
19	1100.1470.49034 Boehringer Ingelheim Investigational Site	München		Germany
20	1100.1470.49000 Boehringer Ingelheim Investigational Site	Ulm		Germany
21	1100.1470.49032 Boehringer Ingelheim Investigational Site	Würzburg		Germany
22	1100.1470.39001 Boehringer Ingelheim Investigational Site	Bergamo		Italy
23	1100.1470.39003 Boehringer Ingelheim Investigational Site	Bologna		Italy
24	1100.1470.39012 Ospedale Sant'Anna	Como		Italy
25	1100.1470.39006 Boehringer Ingelheim Investigational Site	Ferrara		Italy
26	1100.1470.39010 Boehringer Ingelheim Investigational Site	Lecco		Italy
27	1100.1470.39004 Boehringer Ingelheim Investigational Site	Torino		Italy
28	1100.1470.39009 Boehringer Ingelheim Investigational Site	Torrette Di Ancona		Italy
29	1100.1470.39007 Boehringer Ingelheim Investigational Site	Varese		Italy
30	1100.1470.55006 Boehringer Ingelheim Investigational Site	Aguascalientes		Mexico
31	1100.1470.55004 Boehringer Ingelheim Investigational Site	Col Obregón		Mexico
32	1100.1470.55008 Boehringer Ingelheim Investigational Site	Col. Los Filtros, San Luis Potosí		Mexico
33	1100.1470.55001 Boehringer Ingelheim Investigational Site	Col. Toriello Guerra		Mexico
34	1100.1470.55007 Boehringer Ingelheim Investigational Site	Guadalajara Jal.		Mexico
35	1100.1470.55003 Boehringer Ingelheim Investigational Site	Tlalpan-México D,F		Mexico
36	1100.1470.48003 Boehringer Ingelheim Investigational Site	Bydgoszcz		Poland
37	1100.1470.48001 Boehringer Ingelheim Investigational Site	Chorzow		Poland
38	1100.1470.48002 Boehringer Ingelheim Investigational Site	Szczecin		Poland
39	1100.1470.48004 Boehringer Ingelheim Investigational Site	Warsaw		Poland
40	1100.1470.35102 Boehringer Ingelheim Investigational Site	Cascais		Portugal
41	1100.1470.35101 Boehringer Ingelheim Investigational Site	Lisboa		Portugal
42	1100.1470.35103 Boehringer Ingelheim Investigational Site	Porto		Portugal
43	1100.1470.40001 Boehringer Ingelheim Investigational Site	Bucharest		Romania
44	1100.1470.40002 Boehringer Ingelheim Investigational Site	Bucharest		Romania
45	1100.1470.34013 Boehringer Ingelheim Investigational Site	Alcalá de Henares (Madrid)		Spain
46	1100.1470.34008 Boehringer Ingelheim Investigational Site	Badalona		Spain
47	1100.1470.34002 Boehringer Ingelheim Investigational Site	Barcelona		Spain
48	1100.1470.34003 Boehringer Ingelheim Investigational Site	Barcelona		Spain
49	1100.1470.34009 Boehringer Ingelheim Investigational Site	L'Hospitalet de Llobregat		Spain
50	1100.1470.34010 Boehringer Ingelheim Investigational Site	Madrid		Spain
51	1100.1470.34012 Boehringer Ingelheim Investigational Site	Madrid		Spain
52	1100.1470.34014 Boehringer Ingelheim Investigational Site	Madrid		Spain
53	1100.1470.34015 Boehringer Ingelheim Investigational Site	Madrid		Spain
54	1100.1470.34019 Boehringer Ingelheim Investigational Site	Malaga		Spain
55	1100.1470.34007 Boehringer Ingelheim Investigational Site	Sabadell (Barcelona)		Spain
56	1100.1470.34004 Boehringer Ingelheim Investigational Site	San Sebastian		Spain
57	1100.1470.34006 Boehringer Ingelheim Investigational Site	Santa Cruz de Tenerife		Spain
58	1100.1470.34011 Boehringer Ingelheim Investigational Site	Vigo		Spain
59	1100.1470.41004 Boehringer Ingelheim Investigational Site	Bern		Switzerland
60	1100.1470.41001 Boehringer Ingelheim Investigational Site	Lugano		Switzerland
61	1100.1470.41003 Boehringer Ingelheim Investigational Site	St. Gallen		Switzerland
62	1100.1470.41002 Boehringer Ingelheim Investigational Site	Zürich		Switzerland
63	1100.1470.44004 Boehringer Ingelheim Investigational Site	Birmingham		United Kingdom
64	1100.1470.44001 Boehringer Ingelheim Investigational Site	London		United Kingdom
65	1100.1470.44002 Boehringer Ingelheim Investigational Site	London		United Kingdom
66	1100.1470.44005 Boehringer Ingelheim Investigational Site	London		United Kingdom
67	1100.1470.44006 Boehringer Ingelheim Investigational Site	London		United Kingdom
68	1100.1470.44003 Boehringer Ingelheim Investigational Site	Manchester		United Kingdom

Sponsors and Collaborators

• Boehringer Ingelheim

Investigators

• Study Chair: Boehringer Ingelheim, Boehringer Ingelheim

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• Related Info

Publications

None provided.

• Responsible Party: Boehringer Ingelheim
• ClinicalTrials.gov Identifier: NCT00389207
• Other Study ID Numbers: 1100.1470; 2005-004330-40
• First Posted: Oct 18, 2006
• Last Update Posted: Jan 27, 2014
• Last Verified: Dec 1, 2013

• Additional relevant MeSH terms: HIV Infections; Atazanavir Sulfate; Nevirapine

Study Results

Participant Flow

Arm/Group Title	Nevirapine QD	Nevirapine BID	Atazanvir/Ritonavir
Arm/Group Description	Nevirapine (NVP) 400mg QD on a background of the fixed combination Truvada® (emitricitabine 200mg QD and tenofovir 300mg QD)	NVP 200mg BID on a background of the fixed combination Truvada®	Atazanvir 300mg QD boosted by ritonavir 100mg QD (ATZ/r) on a background of the fixed combination Truvada®
Period Title: Overall Study
STARTED	188	188	193
COMPLETED	125	116	152
NOT COMPLETED	63	72	41

Baseline Characteristics

Arm/Group Title	Nevirapine QD	Nevirapine BID	Atazanvir/Ritonavir	Total
Arm/Group Description	Nevirapine (NVP) 400mg QD on a background of the fixed combination Truvada® (emitricitabine 200mg QD and tenofovir 300mg QD)	NVP 200mg BID on a background of the fixed combination Truvada®	ATZ/r on a background of the fixed combination Truvada®	Total of all reporting groups
Overall Participants	188	188	193	569
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	38.4 (9.7)	40.0 (10.5)	37.6 (9.5)	38.6 (9.9)
Sex: Female, Male (Count of Participants)
Female	36 19.1%	25 13.3%	31 16.1%	92 16.2%
Male	152 80.9%	163 86.7%	162 83.9%	477 83.8%
Baseline HIV viral load category (participants) [Number]
Baseline HIV viral load ≤ 100,000 copies/mL	71 37.8%	71 37.8%	65 33.7%	207 36.4%
Baseline HIV viral load > 100,000 copies/mL	117 62.2%	117 62.2%	128 66.3%	362 63.6%
Baseline log10 HIV viral load (log 10 Copies/mL) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [log 10 Copies/mL]	5.1 (0.7)	5.1 (0.6)	5.1 (0.7)	5.1 (0.7)
Baseline CD4+ cell count (Cells/mm^3) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Cells/mm^3]	183.3 (95.5)	202.9 (93.6)	193.2 (95.8)	193.2 (95.1)

Outcome Measures

1. Primary Outcome

Title	Treatment Response at Week 48
Description	Treatment response is defined as a viral load (VL) <50 copies/mL measured at two consecutive visits prior to Week 48 and without subsequent rebound or change of antiretroviral (ARV) therapy prior to Week 48.
Time Frame	From baseline to Week 48

Outcome Measure Data

Analysis Population Description

Full Analysis Set (FAS) defined as all randomized and treated patients but numbers are reduced as indicated due to empty cells in analyses adjusting for baseline categories

Arm/Group Title	Nevirapine QD	Nevirapine BID	Nevirapine QD+BID	Atazanvir/Ritonavir
Arm/Group Description	Nevirapine (NVP) 400mg QD on a background of the fixed combination Truvada® (emitricitabine 200mg QD and tenofovir 300mg QD)	NVP 200mg BID on a background of the fixed combination Truvada®	NVP 400mg QD or 200mg BID on a background of the fixed combination Truvada®	ATZ/r on a background of the fixed combination Truvada®
Measure Participants	188	188	376	193
Number of responders	126	124	250	126
Number of non-responders	62	64	126	67

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Nevirapine QD+BID, Atazanvir/Ritonavir
	Comments
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	Non-inferiority margin 12% (or 0.12 as proportion)
Statistical Test of Hypothesis	p-Value	0.684
	Comments	Test for superiority following confirmation of non-inferiority
	Method	Cochran-Mantel-Haenszel
	Comments	Controlling for screening VL and CD4+ categories (only 373 NVP patients due to empty cells)
Method of Estimation	Estimation Parameter	Risk Difference (RD)
	Estimated Value	0.016
	Confidence Interval	() 95%; -0.062 to 0.095
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Nevirapine QD, Atazanvir/Ritonavir
	Comments
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	Non-inferiority margin 12% (or 0.12 as proportion)
Statistical Test of Hypothesis	p-Value	0.584
	Comments	Test for superiority following confirmation of non-inferiority
	Method	Cochran-Mantel-Haenszel
	Comments	Analysis controlling for screening viral load and CD4+ count categories. N=186 NVP QD patients and N=193 ATZ/r patients.
Method of Estimation	Estimation Parameter	Risk Difference (RD)
	Estimated Value	0.025
	Confidence Interval	() 95%; -0.065 to 0.115
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Nevirapine BID, Atazanvir/Ritonavir
	Comments
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	Non-inferiority margin 12% (or 0.12 as proportion)
Statistical Test of Hypothesis	p-Value	0.855
	Comments	Test for superiority following confirmation of non-inferiority
	Method	Cochran-Mantel-Haenszel
	Comments	Analysis controlling for screening viral load and CD4+ count categories. N=187 NVP QD patients and N=193 ATZ/r patients.
Method of Estimation	Estimation Parameter	Risk Difference (RD)
	Estimated Value	0.009
	Confidence Interval	() 95%; -0.084 to 0.101
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Secondary Outcome

Title	Treatment Response at Week 48 (TLOVR Algorithm)
Description	Treatment response is defined as a VL <50 copies/mL measured at two consecutive visits up to Week 48 and without subsequent rebound or change of ARV therapy up to Week 48, based on time to loss of virologic response (TLOVR) algorithm, as a sensitivity analysis for the primary analysis.
Time Frame	From baseline to Week 48

Outcome Measure Data

Analysis Population Description

FAS but numbers are reduced as indicated due to empty cells in analysis adjusting for baseline categories

Arm/Group Title	Nevirapine QD+BID	Atazanvir/Ritonavir
Arm/Group Description	NVP 400mg QD or 200mg BID on a background of the fixed combination Truvada®	ATZ/r on a background of the fixed combination Truvada®
Measure Participants	376	193
Number of responders	261	142
Number of non-responders	115	51

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Nevirapine QD, Nevirapine BID
	Comments
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	Non-inferiority margin 12% (or 0.12 as proportion)
Statistical Test of Hypothesis	p-Value	0.321
	Comments	Test for superiority following confirmation of non-inferiority
	Method	Cochran-Mantel-Haenszel
	Comments	Analysis controlling for screening viral load and CD4+ count categories. N=373 NVP QD patients and N=193 ATZ/r patients.
Method of Estimation	Estimation Parameter	Risk Difference (RD)
	Estimated Value	-0.038
	Confidence Interval	() 95%; -0.112 to 0.037
	Parameter Dispersion	Type: Value:
	Estimation Comments

3. Secondary Outcome

Title	Proportion of Patients With VL < 50 Copies/ml
Description	VL <50 copies/mL among observed patients on treatment at each visit, with the final visit at Week 144 or end of trial (EOT) for the patient
Time Frame	From baseline to Weeks 4, 8, 12, 24, 36, 48, 60, 72, 84, 96, 108, 120, 132 and 144/EOT

Outcome Measure Data

Analysis Population Description

FAS with varying numbers missing or not on treatment per visit

Arm/Group Title	Nevirapine QD+BID	Atazanvir/Ritonavir
Arm/Group Description	NVP 400mg QD or 200mg BID on a background of the fixed combination Truvada®	ATZ/r on a background of the fixed combination Truvada®
Measure Participants	376	193
Proportion with VL<50 copies /mL at Week 4	0.107	0.09
Proportion with VL<50 copies /mL at Week 8	0.304	0.25
Proportion with VL<50 copies /mL at Week 12	0.515	0.412
Proportion with VL<50 copies /mL at Week 24	0.842	0.779
Proportion with VL<50 copies /mL at Week 36	0.907	0.83
Proportion with VL<50 copies /mL at Week 48	0.931	0.886
Proportion with VL<50 copies /mL at Week 60	0.959	0.901
Proportion with VL<50 copies /mL at Week 72	0.965	0.915
Proportion with VL<50 copies /mL at Week 84	0.972	0.896
Proportion with VL<50 copies /mL at Week 96	0.98	0.924
Proportion with VL<50 copies /mL at Week 108	0.964	0.968
Proportion with VL<50 copies /mL at Week 120	0.976	0.955
Proportion with VL<50 copies /mL at Week 132	0.971	0.947
Proportion with VL<50 copies /mL at Week 144/EOT	0.952	0.929

4. Secondary Outcome

Title	Proportion of Patients With VL < 400 Copies/ml
Description	VL <400 copies/mL among observed patients on treatment at each visit, with the final visit at Week 144 or end of trial (EOT)
Time Frame	From baseline to Weeks 4, 8, 12, 24, 36, 48, 60, 72, 84, 96, 108, 120, 132 and 144/EOT

Outcome Measure Data

Analysis Population Description

FAS with varying numbers missing or not on treatment per visit

Arm/Group Title	Nevirapine QD+BID	Atazanvir/Ritonavir
Arm/Group Description	NVP 400mg QD or 200mg BID on a background of the fixed combination Truvada®	ATZ/r on a background of the fixed combination Truvada®
Measure Participants	376	193
Proportion with VL<400 copies /mL at Week 4	0.365	0.287
Proportion with VL<400 copies /mL at Week 8	0.714	0.679
Proportion with VL<400 copies /mL at Week 12	0.856	0.834
Proportion with VL<400 copies /mL at Week 24	0.924	0.956
Proportion with VL<400 copies /mL at Week 36	0.968	0.966
Proportion with VL<400 copies /mL at Week 48	0.985	0.977
Proportion with VL<400 copies /mL at Week 60	0.993	0.988
Proportion with VL<400 copies /mL at Week 72	0.996	0.988
Proportion with VL<400 copies /mL at Week 84	0.988	0.994
Proportion with VL<400 copies /mL at Week 96	1.000	0.987
Proportion with VL<400 copies /mL at Week 108	0.996	1.000
Proportion with VL<400 copies /mL at Week 120	1.000	0.994
Proportion with VL<400 copies /mL at Week 132	0.996	0.993
Proportion with VL<400 copies /mL at Week 144/EOT	0.991	0.986

5. Secondary Outcome

Title	Change in CD4+ Count From Baseline
Description	Change in CD4+ cell count from baseline among patients on treatment at each visit, with the final visit at Week 144 or EOT
Time Frame	From baseline to Weeks 4, 8, 12, 24, 36, 48, 60, 72, 84, 96, 108, 120, 132 and 144/EOT

Outcome Measure Data

Analysis Population Description

FAS with varying numbers missing or not on treatment per visit

Arm/Group Title	Nevirapine QD+BID	Atazanvir/Ritonavir
Arm/Group Description	NVP 400mg QD or 200mg BID on a background of the fixed combination Truvada®	ATZ/r on a background of the fixed combination Truvada®
Measure Participants	376	193
Change in CD4+ count to Week 4	77.2 (93.5)	86.1 (94.4)
Change in CD4+ count to Week 8	105.6 (108.0)	98.0 (91.1)
Change in CD4+ count to Week 12	120.3 (113.9)	110.9 (111.6)
Change in CD4+ count to Week 24	134.4 (114.9)	133.8 (110.7)
Change in CD4+ count to Week 36	160.1 (123.0)	163.4 (119.8)
Change in CD4+ count to Week 48	168.2 (127.0)	183.6 (121.6)
Change in CD4+ count to Week 60	184.8 (129.6)	208.2 (144.2)
Change in CD4+ count to Week 72	213.7 (165.7)	231.9 (165.4)
Change in CD4+ count to Week 84	223.0 (147.1)	246.4 (149.4)
Change in CD4+ count to Week 96	217.7 (133.5)	251.6 (149.8)
Change in CD4+ count to Week 108	231.2 (148.9)	267.2 (161.2)
Change in CD4+ count to Week 120	231.3 (147.6)	269.2 (169.9)
Change in CD4+ count to Week 132	243.4 (164.8)	281.3 (147.3)
Change in CD4+ count to Week 144/EOT	251.0 (151.6)	285.8 (164.8)

6. Secondary Outcome

Title	Change in Framingham Score From Baseline
Description	Change in the estimated risk of cardiovascular disease using the Framingham algorithm from baseline to after 48, 96 and 144 weeks, last observation carried forward (LOCF). The score is based on age, gender, systolic blood pressure, total cholesterol, high density lipoprotein cholesterol and smoking status. Scores range from 0 to 21 with higher scores indicating a greater risk.
Time Frame	From baseline to Weeks 48, 96 and 144/EOT

Outcome Measure Data

Analysis Population Description

FAS with varying numbers missing

Arm/Group Title	Nevirapine QD+BID	Atazanvir/Ritonavir
Arm/Group Description	NVP 400mg QD or 200mg BID on a background of the fixed combination Truvada®	ATZ/r on a background of the fixed combination Truvada®
Measure Participants	376	193
Change in Framingham score to Week 48	0.50 (2.79)	0.66 (2.92)
Change in Framingham score to Week 96	0.93 (3.15)	1.19 (3.25)
Change in Framingham score to Week 144/EOT	1.14 (3.40)	0.82 (3.03)

7. Secondary Outcome

Title	Change in Mental Health Summary (MHS) Score From Baseline
Description	Quality of life (QoL) assessment by change in MHS score from baseline to after 48, 96 and 144 weeks (observed cases), from the Medical Outcomes Study HIV Health Survey (MOS-HIV), a 35-item self-administered questionnaire including 10 scales covering: health perceptions, pain, physical functioning, role functioning, social and cognitive functioning, mental health, energy/fatigue, health distress, and QoL. The MHS is a weighted average of the 10 scales and ranges from 0 to 100 with higher scores indicating better QoL.
Time Frame	From baseline to Weeks 48, 96 and 144/EOT

Outcome Measure Data

Analysis Population Description

FAS with varying numbers missing

Arm/Group Title	Nevirapine QD+BID	Atazanvir/Ritonavir
Arm/Group Description	NVP 400mg QD or 200mg BID on a background of the fixed combination Truvada®	ATZ/r on a background of the fixed combination Truvada®
Measure Participants	376	193
Change in MHS score to Week 48	6.09 (9.31)	4.52 (7.84)
Change in MHS score to Week 96	6.10 (9.75)	4.89 (9.58)
Change in MHS score to Week 144/EOT	4.76 (10.33)	4.70 (10.14)

8. Secondary Outcome

Title	Change in Physical Health Summary (PHS) Score From Baseline
Description	QoL assessment by change in PHS score from baseline to after 48, 96 and 144 weeks (observed cases), from the MOS-HIV, a 35-item self-administered questionnaire including 10 scales covering: health perceptions, pain, physical functioning, role functioning, social and cognitive functioning, mental health, energy/fatigue, health distress, and QoL. The PHS is a weighted average of the 10 scales and ranges from 0 to 100 with higher scores indicating better QoL.
Time Frame	From baseline to Weeks 48, 96 and 144/EOT

Outcome Measure Data

Analysis Population Description

FAS with varying numbers missing

Arm/Group Title	Nevirapine QD+BID	Atazanvir/Ritonavir
Arm/Group Description	NVP 400mg QD or 200mg BID on a background of the fixed combination Truvada®	ATZ/r on a background of the fixed combination Truvada®
Measure Participants	376	193
Change in PHS score to Week 48	3.34 (7.77)	3.35 (8.52)
Change in PHS score to Week 96	3.19 (7.83)	3.00 (7.34)
Change in PHS score to Week 144/EOT	2.22 (8.77)	3.35 (8.42)

9. Secondary Outcome

Title	Number of Patients Hospitalized
Description	Cost effectiveness assessment by number of patients hospitalized
Time Frame	From baseline to Week 24, Week 24 to 48, Week 48 to 96, and Week 96 to 144/EOT

Outcome Measure Data

Analysis Population Description

FAS with varying numbers missing

Arm/Group Title	Nevirapine QD+BID	Atazanvir/Ritonavir
Arm/Group Description	NVP 400mg QD or 200mg BID on a background of the fixed combination Truvada®	ATZ/r on a background of the fixed combination Truvada®
Measure Participants	376	193
Number hospitalized between baseline and Week 24	8	2
Number hospitalized between Week 24 and Week 48	6	5
Number hospitalized between Week 48 and Week 96	5	5
Number hospitalized between Week 96 and Wk 144/EOT	9	1

10. Secondary Outcome

Title	Non-scheduled Physician Visits
Description	Cost effectiveness assessment by number of patients with non-scheduled physician visits
Time Frame	From baseline to Week 24, Week 24 to 48, Week 48 to 96, and Week 96 to 144/EOT

Outcome Measure Data

Analysis Population Description

FAS with varying numbers missing

Arm/Group Title	Nevirapine QD+BID	Atazanvir/Ritonavir
Arm/Group Description	NVP 400mg QD or 200mg BID on a background of the fixed combination Truvada®	ATZ/r on a background of the fixed combination Truvada®
Measure Participants	376	193
Number between baseline and Week 24	74	35
Number between Week 24 and Week 48	45	35
Number between Week 48 and Week 96	58	28
Number between Week 96 and Wk 144/EOT	58	35

11. Secondary Outcome

Title	Genotypic Resistance Associated With Virologic Failure
Description	Number of treatment-emergent drug-associated substitutions in patients with virological failure up to Week 48. The total number of genotypic mutations in those patients who were virologic failures is given, not the number of patients with mutations.
Time Frame	From baseline to Week 48

Outcome Measure Data

Analysis Population Description

All patients with virologic failure assessed for genotypic resistance

Arm/Group Title	Nevirapine QD+BID	Atazanvir/Ritonavir
Arm/Group Description	NVP 400mg QD or 200mg BID on a background of the fixed combination Truvada®	ATZ/r on a background of the fixed combination Truvada®
Measure Participants	30	2
Emtricitabine-associated substitutions at Week 48	21	0
Tenofovir-associated substitutions at Week 48	11	0
Nevirapine-associated substitutions at Week 48	34	0

12. Secondary Outcome

Title	Treatment-emergent AIDS-defining Illness
Description	Treatment-emergent AIDS-defining illness (tr.-emerg. AIDS-def.illness) including worsening during treatment
Time Frame	From baseline to Week 144

Outcome Measure Data

Analysis Population Description

FAS

Arm/Group Title	Nevirapine QD+BID	Atazanvir/Ritonavir
Arm/Group Description	NVP 400mg QD or 200mg BID on a background of the fixed combination Truvada®	ATZ/r on a background of the fixed combination Truvada®
Measure Participants	376	193
Number with tr.-emerg. AIDS-def.illness	26	7
Number without tr.-emerg. AIDS-def.illness	350	186

13. Secondary Outcome

Title	Treatment-emergent AIDS-defining Illness Leading to Death
Description	Patients with an AIDS-defining illness leading to death broken out by treatment. Statistical analysis shows time to death from AIDS-defining illness.
Time Frame	From baseline to Week 144

Outcome Measure Data

Analysis Population Description

FAS

Arm/Group Title	Nevirapine QD+BID	Atazanvir/Ritonavir
Arm/Group Description	NVP 400mg QD or 200mg BID on a background of the fixed combination Truvada®	ATZ/r on a background of the fixed combination Truvada®
Measure Participants	376	193
Number with AIDS-def. illness leading to death	3	0
Number without AIDS-def. illness leading to death	373	193

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Nevirapine QD, Nevirapine BID
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0403
	Comments
	Method	Regression, Cox
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.461
	Confidence Interval	() 95%; 0.220 to 0.966
	Parameter Dispersion	Type: Value:
	Estimation Comments

14. Secondary Outcome

Title	Lipodystrophy
Description	Number of patients with AE lipodystrophy
Time Frame	From baseline to Week 144

Outcome Measure Data

Analysis Population Description

FAS

Arm/Group Title	Nevirapine QD+BID	Atazanvir/Ritonavir
Arm/Group Description	NVP 400mg QD or 200mg BID on a background of the fixed combination Truvada®	ATZ/r on a background of the fixed combination Truvada®
Measure Participants	376	193
Number with lipodystrophy	1	1
Number without lipodystrophy	375	192

15. Secondary Outcome

Title	Serum Lipid Abnormalities
Description	Number of patients with AE elevated serum lipids (i.e. hypercholesterolaemia)
Time Frame	From baseline to Week 144

Outcome Measure Data

Analysis Population Description

FAS

Arm/Group Title	Nevirapine QD+BID	Atazanvir/Ritonavir
Arm/Group Description	NVP 400mg QD or 200mg BID on a background of the fixed combination Truvada®	ATZ/r on a background of the fixed combination Truvada®
Measure Participants	376	193
Number with serum lipid abnormalities	9	4
Number without serum lipid abnormalities	367	189

16. Secondary Outcome

Title	Glycaemic Abnormalities
Description	Number of patients with AE elevated serum glucose
Time Frame	From baseline to Week 144

Outcome Measure Data

Analysis Population Description

FAS

Arm/Group Title	Nevirapine QD+BID	Atazanvir/Ritonavir
Arm/Group Description	NVP 400mg QD or 200mg BID on a background of the fixed combination Truvada®	ATZ/r on a background of the fixed combination Truvada®
Measure Participants	376	193
Number with glycaemic abnormalities	0	3
Number without glycaemic abnormalities	376	190

17. Secondary Outcome

Title	Treatment Response at Week 96
Description	Treatment response is defined as a viral load (VL) <50 copies/mL measured at two consecutive visits prior to Week 96 and without subsequent rebound or change of antiretroviral (ARV) therapy prior to Week 96.
Time Frame	From baseline to Week 96

Outcome Measure Data

Analysis Population Description

Full Analysis Set (FAS) defined as all randomized and treated patients but numbers are reduced as indicated due to empty cells in analyses adjusting for baseline categories

Arm/Group Title	Nevirapine QD	Nevirapine BID	Nevirapine QD+BID	Atazanvir/Ritonavir
Arm/Group Description	Nevirapine (NVP) 400mg QD on a background of the fixed combination Truvada® (emitricitabine 200mg QD and tenofovir 300mg QD)	NVP 200mg BID on a background of the fixed combination Truvada®	NVP 400mg QD or 200mg BID on a background of the fixed combination Truvada®	ATZ/r on a background of the fixed combination Truvada®
Measure Participants	188	188	376	193
Number of responders	131 69.7%	122 64.9%	253 131.1%	149 26.2%
Number of non-responders	57 30.3%	66 35.1%	123 63.7%	44 7.7%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Nevirapine QD+BID, Atazanvir/Ritonavir
	Comments
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	Non-inferiority margin 12% (or 0.12 as proportion)
Statistical Test of Hypothesis	p-Value	0.0109
	Comments	Test for superiority following confirmation of non-inferiority
	Method	Cochran-Mantel-Haenszel
	Comments	Analysis controlling for screening viral load and CD4+ count categories. N=373 NVP QD+BID patients and N=193 ATZ/r patients
Method of Estimation	Estimation Parameter	Risk Difference (RD)
	Estimated Value	-0.097
	Confidence Interval	() 95%; -0.171 to -0.022
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Nevirapine QD, Atazanvir/Ritonavir
	Comments
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	Non-inferiority margin 12% (or 0.12 as proportion)
Statistical Test of Hypothesis	p-Value	0.1033
	Comments	Test for superiority following confirmation of non-inferiority
	Method	Cochran-Mantel-Haenszel
	Comments	Analysis controlling for screening viral load and CD4+ count categories. N=186 NVP QD patients and N=193 ATZ/r patients.
Method of Estimation	Estimation Parameter	Risk Difference (RD)
	Estimated Value	-0.072
	Confidence Interval	() 95%; -0.158 to 0.015
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Nevirapine BID, Atazanvir/Ritonavir
	Comments
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	Non-inferiority margin 12% (or 0.12 as proportion)
Statistical Test of Hypothesis	p-Value	0.0073
	Comments	Test for superiority following confirmation of non-inferiority
	Method	Cochran-Mantel-Haenszel
	Comments	Analysis controlling for screening viral load and CD4+ count categories. N=187 NVP QD patients and N=193 ATZ/r patients.
Method of Estimation	Estimation Parameter	Risk Difference (RD)
	Estimated Value	-0.122
	Confidence Interval	() 95%; -0.212 to -0.033
	Parameter Dispersion	Type: Value:
	Estimation Comments

18. Secondary Outcome

Title	Treatment Response at Week 144
Description	Treatment response is defined as a viral load (VL) <50 copies/mL measured at two consecutive visits prior to Week 144 and without subsequent rebound or change of antiretroviral (ARV) therapy prior to Week 144.
Time Frame	From baseline to Week 144

Outcome Measure Data

Analysis Population Description

Full Analysis Set (FAS) defined as all randomized and treated patients but numbers are reduced as indicated due to empty cells in analyses adjusting for baseline categories.

Arm/Group Title	Nevirapine QD	Nevirapine BID	Nevirapine QD+BID	Atazanvir/Ritonavir
Arm/Group Description	Nevirapine (NVP) 400mg QD on a background of the fixed combination Truvada® (emitricitabine 200mg QD and tenofovir 300mg QD)	NVP 200mg BID on a background of the fixed combination Truvada®	NVP 400mg QD or 200mg BID on a background of the fixed combination Truvada®	ATZ/r on a background of the fixed combination Truvada®
Measure Participants	188	188	376	193
Number of responders	121 64.4%	113 60.1%	234 121.2%	143 25.1%
Number of non-responders	67 35.6%	75 39.9%	142 73.6%	50 8.8%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Nevirapine QD+BID, Atazanvir/Ritonavir
	Comments
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	Non-inferiority margin 12% (or 0.12 as proportion)
Statistical Test of Hypothesis	p-Value	0.0031
	Comments	Test for superiority following confirmation of non-inferiority
	Method	Cochran-Mantel-Haenszel
	Comments	Analysis controlling for screening viral load and CD4+ count categories. N=373 NVP QD+BID patients and N=193 ATZ/r patients.
Method of Estimation	Estimation Parameter	Risk Difference (RD)
	Estimated Value	-0.117
	Confidence Interval	() 95%; -0.194 to -0.040
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Nevirapine QD, Atazanvir/Ritonavir
	Comments
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	Non-inferiority margin 12% (or 0.12 as proportion)
Statistical Test of Hypothesis	p-Value	0.0365
	Comments	Test for superiority following confirmation of non-inferiority
	Method	Cochran-Mantel-Haenszel
	Comments	Analysis controlling for screening viral load and CD4+ count categories. N=186 NVP QD patients and N=193 ATZ/r patients.
Method of Estimation	Estimation Parameter	Risk Difference (RD)
	Estimated Value	-0.096
	Confidence Interval	() 95%; -0.186 to -0.006
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Nevirapine BID, Atazanvir/Ritonavir
	Comments
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	Non-inferiority margin 12% (or 0.12 as proportion)
Statistical Test of Hypothesis	p-Value	0.0033
	Comments	Test for superiority following confirmation of non-inferiority
	Method	Cochran-Mantel-Haenszel
	Comments	Analysis controlling for screening viral load and CD4+ count categories. N=187 NVP QD patients and N=193 ATZ/r patients.
Method of Estimation	Estimation Parameter	Risk Difference (RD)
	Estimated Value	-0.139
	Confidence Interval	() 95%; -0.231 to -0.046
	Parameter Dispersion	Type: Value:
	Estimation Comments

19. Secondary Outcome

Title	Proportion of Patients With Virological Rebound With VL >=50 Copies/mL After CVR (Confirmed Virological Response) at Week 24, 48, 96, 144
Description	The analyses of virologic rebound were performed on the original values at each visit(ORGV) rather than calculated results within time windows (CAL)
Time Frame	at Week 24, 48, 96, 144

Outcome Measure Data

Analysis Population Description

Full Analysis Set (FAS) defined as all randomized and treated patients.

Arm/Group Title	Nevirapine QD	Nevirapine BID	Nevirapine QD+BID	Atazanvir/Ritonavir
Arm/Group Description	Nevirapine (NVP) 400mg QD on a background of the fixed combination Truvada® (emitricitabine 200mg QD and tenofovir 300mg QD)	NVP 200mg BID on a background of the fixed combination Truvada®	NVP 400mg QD or 200mg BID on a background of the fixed combination Truvada®	ATZ/r on a background of the fixed combination Truvada®
Measure Participants	188	188	376	193
virologic rebound after CVR at Week 24	3 1.6%	2 1.1%	5 2.6%	5 0.9%
virologic rebound after CVR at Week 48	4 2.1%	5 2.7%	9 4.7%	12 2.1%
virologic rebound after CVR at Week 96	4 2.1%	6 3.2%	10 5.2%	10 1.8%
virologic rebound after CVR at Week 144	8 4.3%	9 4.8%	17 8.8%	15 2.6%

20. Secondary Outcome

Title	Proportion of Patients With Virological Rebound With VL >=400 Copies/mL After CVR at Week 24, 48, 96, 144
Description	The analyses of virologic rebound were performed on the original values at each visit(ORGV) rather than calculated results within time windows (CAL)
Time Frame	at Week 24, 48, 96, 144

Outcome Measure Data

Analysis Population Description

Full Analysis Set (FAS) defined as all randomized and treated patients.

Arm/Group Title	Nevirapine QD	Nevirapine BID	Nevirapine QD+BID	Atazanvir/Ritonavir
Arm/Group Description	Nevirapine (NVP) 400mg QD on a background of the fixed combination Truvada® (emitricitabine 200mg QD and tenofovir 300mg QD)	NVP 200mg BID on a background of the fixed combination Truvada®	NVP 400mg QD or 200mg BID on a background of the fixed combination Truvada®	ATZ/r on a background of the fixed combination Truvada®
Measure Participants	188	188	376	193
virologic rebound after CVR at Week 24	2 1.1%	2 1.1%	4 2.1%	2 0.4%
virologic rebound after CVR at Week 48	3 1.6%	3 1.6%	6 3.1%	2 0.4%
virologic rebound after CVR at Week 96	3 1.6%	6 3.2%	9 4.7%	2 0.4%
virologic rebound after CVR at Week 144	4 2.1%	6 3.2%	10 5.2%	5 0.9%

21. Secondary Outcome

Title	Proportion of Patients With Virologic Failure at Week 48, 96, 144
Time Frame	at Week 48, 96, 144

Outcome Measure Data

Analysis Population Description

Full Analysis Set (FAS) defined as all randomized and treated patients but numbers are reduced as indicated due to empty cells in analyses adjusting for baseline categories

Arm/Group Title	Nevirapine QD	Nevirapine BID	Nevirapine QD+BID	Atazanvir/Ritonavir
Arm/Group Description	Nevirapine (NVP) 400mg QD on a background of the fixed combination Truvada® (emitricitabine 200mg QD and tenofovir 300mg QD)	NVP 200mg BID on a background of the fixed combination Truvada®	NVP 400mg QD or 200mg BID on a background of the fixed combination Truvada®	ATZ/r on a background of the fixed combination Truvada®
Measure Participants	188	188	376	193
virologic failure at Week 48	20 10.6%	25 13.3%	45 23.3%	25 4.4%
virologic failure at Week 96	15 8%	25 13.3%	40 20.7%	13 2.3%
virologic failure at Week 144	19 10.1%	28 14.9%	47 24.4%	17 3%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Nevirapine BID, Atazanvir/Ritonavir
	Comments	week 48
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	H0: Difference in proportions = 0
Statistical Test of Hypothesis	p-Value	0.9784
	Comments
	Method	Cochran Chi-Squared
	Comments
Method of Estimation	Estimation Parameter	Difference in proportions
	Estimated Value	0.001
	Confidence Interval	(2-Sided) 95%; -0.065 to 0.066
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Nevirapine BID, Atazanvir/Ritonavir
	Comments	week 96
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	H0: Difference in proportions = 0
Statistical Test of Hypothesis	p-Value	0.0331
	Comments
	Method	Cochran Chi-Squared
	Comments
Method of Estimation	Estimation Parameter	Difference in proportions
	Estimated Value	0.064
	Confidence Interval	(2-Sided) 95%; 0.005 to 0.123
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Nevirapine BID, Atazanvir/Ritonavir
	Comments	week 144
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	H0: Difference in proportions = 0
Statistical Test of Hypothesis	p-Value	0.0691
	Comments
	Method	Cochran Chi-Squared
	Comments
Method of Estimation	Estimation Parameter	Difference in proportions
	Estimated Value	0.058
	Confidence Interval	(2-Sided) 95%; -0.005 to 0.121
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Nevirapine QD, Atazanvir/Ritonavir
	Comments	week 48
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	H0: Difference in proportions = 0
Statistical Test of Hypothesis	p-Value	0.4585
	Comments
	Method	Cochran Chi-Squared
	Comments
Method of Estimation	Estimation Parameter	Difference in proportions
	Estimated Value	-0.023
	Confidence Interval	(2-Sided) 95%; -0.084 to 0.038
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Nevirapine QD, Atazanvir/Ritonavir
	Comments	week 96
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	H0: Difference in proportions = 0
Statistical Test of Hypothesis	p-Value	0.5438
	Comments
	Method	Cochran Chi-Squared
	Comments
Method of Estimation	Estimation Parameter	Difference in proportions
	Estimated Value	0.015
	Confidence Interval	(2-Sided) 95%; -0.034 to 0.064
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Nevirapine QD, Atazanvir/Ritonavir
	Comments	week 144
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	H0: Difference in proportions = 0
Statistical Test of Hypothesis	p-Value	0.5659
	Comments
	Method	Cochran Chi-Squared
	Comments
Method of Estimation	Estimation Parameter	Difference in proportions
	Estimated Value	0.016
	Confidence Interval	(2-Sided) 95%; -0.039 to 0.071
	Parameter Dispersion	Type: Value:
	Estimation Comments

22. Secondary Outcome

Title	Time to Treatment Response (First Confirmed VL<50 Copies/mL)
Description	Time to treatment response was defined as the time from start of treatment until the first measurement of the first confirmed virological response
Time Frame	baseline to week 144

Outcome Measure Data

Analysis Population Description

Full Analysis Set (FAS) defined as all randomized and treated patients but numbers are reduced as indicated due to empty cells in analyses adjusting for baseline categories

Arm/Group Title	Nevirapine QD	Nevirapine BID	Nevirapine QD+BID	Atazanvir/Ritonavir
Arm/Group Description	Nevirapine (NVP) 400mg QD on a background of the fixed combination Truvada® (emitricitabine 200mg QD and tenofovir 300mg QD)	NVP 200mg BID on a background of the fixed combination Truvada®	NVP 400mg QD or 200mg BID on a background of the fixed combination Truvada®	ATZ/r on a background of the fixed combination Truvada®
Measure Participants	188	188	376	193
Median (Inter-Quartile Range) [weeks]	12.00	12.14	12.00	23.71

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Nevirapine QD+BID, Atazanvir/Ritonavir
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0002
	Comments
	Method	Regression, Cox
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.692
	Confidence Interval	() 95%; 0.570 to 0.839
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Nevirapine QD+BID, Atazanvir/Ritonavir
	Comments	Cox regression on responders only (N=289 in Nevirapine QD+BID and N=175 in Atazanvir/ritonavir)
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Regression, Cox
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.630
	Confidence Interval	() 95%; 0.519 to 0.764
	Parameter Dispersion	Type: Value:
	Estimation Comments

23. Secondary Outcome

Title	Time to Loss of Virologic Response (Rebound)
Description	Time to loss of virologic response (TLOVR) was defined as the time from start of treatment to the first measurement showing VL ≥ 50 copies/mL in the first virologic rebound, after having a confirmed virological response.
Time Frame	Baseline to week 144

Outcome Measure Data

Analysis Population Description

Full Analysis Set (FAS) defined as all randomized and treated patients but numbers are reduced as indicated due to empty cells in analyses adjusting for baseline categories

Arm/Group Title	Nevirapine QD	Nevirapine BID	Nevirapine QD+BID	Atazanvir/Ritonavir
Arm/Group Description	Nevirapine (NVP) 400mg QD on a background of the fixed combination Truvada® (emitricitabine 200mg QD and tenofovir 300mg QD)	NVP 200mg BID on a background of the fixed combination Truvada®	NVP 400mg QD or 200mg BID on a background of the fixed combination Truvada®	ATZ/r on a background of the fixed combination Truvada®
Measure Participants	188	188	376	193
Median (Inter-Quartile Range) [weeks]	143.86	143.21	143.71	143.00

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Nevirapine QD+BID, Atazanvir/Ritonavir
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.1329
	Comments
	Method	Regression, Cox
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.762
	Confidence Interval	() 95%; 0.535 to 1.086
	Parameter Dispersion	Type: Value:
	Estimation Comments

24. Secondary Outcome

Title	Time to Treatment Failure
Description	Treatment failure is defined as the occurrence of the first of at least one of the following events: early discontinuation of trial drug, change in ARV therapy, failure to achieve an HIV RNA count < 50 copies/mL up to Visit 10 (week 48) or loss of virologic response
Time Frame	baseline to week 144

Outcome Measure Data

Analysis Population Description

Full Analysis Set (FAS) defined as all randomized and treated patients but numbers are reduced as indicated due to empty cells in analyses adjusting for baseline categories

Arm/Group Title	Nevirapine QD	Nevirapine BID	Nevirapine QD+BID	Atazanvir/Ritonavir
Arm/Group Description	Nevirapine (NVP) 400mg QD on a background of the fixed combination Truvada® (emitricitabine 200mg QD and tenofovir 300mg QD)	NVP 200mg BID on a background of the fixed combination Truvada®	NVP 400mg QD or 200mg BID on a background of the fixed combination Truvada®	ATZ/r on a background of the fixed combination Truvada®
Measure Participants	188	188	376	193
Median (Inter-Quartile Range) [weeks]	143.86	143.21	143.71	143.00

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Nevirapine QD+BID, Atazanvir/Ritonavir
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0444
	Comments
	Method	Regression, Cox
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.731
	Confidence Interval	() 95%; 0.539 to 0.992
	Parameter Dispersion	Type: Value:
	Estimation Comments

25. Secondary Outcome

Title	Change in the Calculated Glomerular Filtration Rate (GFR) at Week 48, 96 and 144
Description	Calculations based on the MDRD algorithm.
Time Frame	From baseline to Week 48, 96, 144

Outcome Measure Data

Analysis Population Description

Full Analysis Set (FAS) defined as all randomized and treated patients but numbers are reduced as indicated due to empty cells in analyses adjusting for baseline categories

Arm/Group Title	Nevirapine QD	Nevirapine BID	Nevirapine QD+BID	Atazanvir/Ritonavir
Arm/Group Description	Nevirapine (NVP) 400mg QD on a background of the fixed combination Truvada® (emitricitabine 200mg QD and tenofovir 300mg QD)	NVP 200mg BID on a background of the fixed combination Truvada®	NVP 400mg QD or 200mg BID on a background of the fixed combination Truvada®	ATZ/r on a background of the fixed combination Truvada®
Measure Participants	188	188	376	193
change baseline to week 48 (N=143, 128, 271, 173)	-3.91 (13.93)	-5.92 (17.11)	-4.86 (15.52)	-7.18 (15.19)
change baseline to week 96 (N=130, 122, 252, 157)	-6.93 (14.33)	-10.02 (17.37)	-8.42 (15.92)	-11.53 (15.59)
change baseline to week 144 (N=163, 168, 331, 174)	-3.27 (20.65)	-6.33 (17.30)	-4.82 (19.06)	-9.56 (17.47)

26. Secondary Outcome

Title	Proportion of Patients With >= DAIDS Grade 2 Laboratory Abnormalities
Time Frame	week 148

Outcome Measure Data

Analysis Population Description

Full Analysis Set (FAS) defined as all randomized and treated patients.

Arm/Group Title	Nevirapine QD	Nevirapine BID	Atazanvir/Ritonavir
Arm/Group Description	NVP 400mg QD on a background of the fixed combination Truvada®	NVP 200mg BID on a background of the fixed combination Truvada®	ATZ/r on a background of the fixed combination Truvada®
Measure Participants	188	188	193
DAIDS 2 moderate	74 39.4%	84 44.7%	72 37.3%
DAIDS 3 severe	30 16%	28 14.9%	39 20.2%
DAIDS 4 potential lifethreatening	9 4.8%	15 8%	9 4.7%

27. Secondary Outcome

Title	Proportion of Patients Reporting Rash of Any Severity
Description	Proportion of Patients reporting rash of any severity
Time Frame	week 148

Outcome Measure Data

Analysis Population Description

Full Analysis Set (FAS) defined as all randomized and treated patients.

Arm/Group Title	Nevirapine QD	Nevirapine BID	Atazanvir/Ritonavir
Arm/Group Description	NVP 400mg QD on a background of the fixed combination Truvada®	NVP 200mg BID on a background of the fixed combination Truvada®	ATZ/r on a background of the fixed combination Truvada®
Measure Participants	188	188	193
Number [participants]	75 39.9%	64 34%	74 38.3%

28. Secondary Outcome

Title	Proportion of Patients Reporting Hepatic Events of Any Severity
Description	Proportion of Patients reporting hepatic events of any severity
Time Frame	week 148

Outcome Measure Data

Analysis Population Description

Full Analysis Set (FAS) defined as all randomized and treated patients.

Arm/Group Title	Nevirapine QD	Nevirapine BID	Atazanvir/Ritonavir
Arm/Group Description	NVP 400mg QD on a background of the fixed combination Truvada®	NVP 200mg BID on a background of the fixed combination Truvada®	ATZ/r on a background of the fixed combination Truvada®
Measure Participants	188	188	193
Number [participants]	26 13.8%	24 12.8%	92 47.7%

29. Secondary Outcome

Title	Proportion of Patients Reporting CNS (Central Nervous System) Side Effects of Any Severity
Description	Proportion of Patients reporting CNS (central nervous system) side effects of any severity
Time Frame	week 148

Outcome Measure Data

Analysis Population Description

Full Analysis Set (FAS) defined as all randomized and treated patients.

Arm/Group Title	Nevirapine QD	Nevirapine BID	Atazanvir/Ritonavir
Arm/Group Description	NVP 400mg QD on a background of the fixed combination Truvada®	NVP 200mg BID on a background of the fixed combination Truvada®	ATZ/r on a background of the fixed combination Truvada®
Measure Participants	188	188	193
Number [participants]	41 21.8%	41 21.8%	37 19.2%

30. Secondary Outcome

Title	Change of Cholesterol Values From Baseline to Week 48, 96, 144
Description	Changes frombaseline in total cholesterol, LDL-cholesterol(LDL-c) and HDL
Time Frame	baseline to week 48, 96, 144

Outcome Measure Data

Analysis Population Description

FAS, where only patients with corresponding laboratory values for the considered time point are considered

Arm/Group Title	Nevirapine QD	Nevirapine BID	Atazanvir/Ritonavir
Arm/Group Description	NVP 400mg QD on a background of the fixed combination Truvada®	NVP 200mg BID on a background of the fixed combination Truvada®	ATZ/r on a background of the fixed combination Truvada®
Measure Participants	188	188	193
total cholesterol, week 48 (N=138,122,164)	29.28 (30.64)	29.54 (27.33)	20.84 (30.46)
total cholesterol, week 96 (N=124,114,147)	39.17 (33.67)	36.87 (30.60)	29.99 (31.93)
total cholesterol, week 144 (N=154,155,160)	33.12 (32.77)	30.66 (33.24)	28.13 (32.06)
LDL-c, week 48 (N=136,117,159)	16.54 (24.44)	17.70 (22.16)	10.58 (26.07)
LDL-c, week 96 (N=119,110,145)	21.93 (23.44)	21.66 (25.14)	19.19 (25.49)
LDL-c, week 144 (N=151,150,157)	21.42 (26.61)	17.95 (26.04)	17.61 (28.33)
HDL, week 48(N=138,122,164)	12.06 (9.72)	11.59 (10.95)	3.49 (9.44)
HDL, week 96 (N=124,114,147)	13.86 (10.95)	13.33 (12.00)	4.74 (10.62)
HDL, week 144(N=154,155,160)	12.61 (13.64)	10.47 (15.35)	5.73 (11.14)

31. Secondary Outcome

Title	Changes of Apolipoprotein Values From Baseline to Week 48, 96, 144
Description	Changes frombaseline apolipoprotein A1 & B
Time Frame	baseline to week 48, 96, 144

Outcome Measure Data

Analysis Population Description

FAS, where only patients with corresponding laboratory values for the considered time point are considered

Arm/Group Title	Nevirapine QD	Nevirapine BID	Atazanvir/Ritonavir
Arm/Group Description	NVP 400mg QD on a background of the fixed combination Truvada®	NVP 200mg BID on a background of the fixed combination Truvada®	ATZ/r on a background of the fixed combination Truvada®
Measure Participants	188	188	193
apolipoprotein A1, week 48 (N=134,121,156)	0.23 (0.22)	0.23 (0.24)	0.08 (0.21)
apolipoprotein A1, week 96 (N=115,106,141)	0.23 (0.24)	0.23 (0.25)	0.07 (0.22)
apolipoprotein A1, week 144 (N=144,140,148)	0.16 (0.24)	0.14 (0.26)	0.06 (0.23)
apolipoprotein B, week 48 (N=134,120,156)	0.00 (0.17)	0.03 (0.16)	0.03 (0.16)
apolipoprotein B, week 96 (N=115,106,141)	0.00 (0.16)	-0.00 (0.17)	0.03 (0.17)
apolipoprotein B, week 144 (N=144,139,148)	0.01 (0.16)	0.05 (0.18)	0.03 (0.17)

32. Secondary Outcome

Title	Change of hsCRP From Baseline to Week 48, 96, 144
Description	Change of hsCRP from baseline to week 48, 96, 144
Time Frame	baseline to week 48, 96, 144

Outcome Measure Data

Analysis Population Description

FAS, where only patients with corresponding laboratory values for the considered time point are considered

Arm/Group Title	Nevirapine QD	Nevirapine BID	Atazanvir/Ritonavir
Arm/Group Description	NVP 400mg QD on a background of the fixed combination Truvada®	NVP 200mg BID on a background of the fixed combination Truvada®	ATZ/r on a background of the fixed combination Truvada®
Measure Participants	188	188	193
hsCRP, week 48 (N=142,126,173)	-1.01 (12.53)	-0.67 (12.71)	-0.70 (8.61)
hsCRP, week 96 (N=128,120,157)	-1.54 (11.21)	-0.79 (21.32)	0.35 (15.19)
hsCRP, week 144 (N=160,164,174)	-0.09 (14.34)	-0.02 (12.76)	0.04 (8.20)

33. Secondary Outcome

Title	Change of Total Triglycerides From Baseline to Week 48, 96, 144
Description	Change of total triglycerides from baseline to week 48, 96, 144
Time Frame	baseline to week 48, 96, 144

Outcome Measure Data

Analysis Population Description

FAS, where only patients with corresponding laboratory values for the considered time point are considered

Arm/Group Title	Nevirapine QD	Nevirapine BID	Atazanvir/Ritonavir
Arm/Group Description	NVP 400mg QD on a background of the fixed combination Truvada®	NVP 200mg BID on a background of the fixed combination Truvada®	ATZ/r on a background of the fixed combination Truvada®
Measure Participants	188	188	193
total triglycerides, week 48 (N=138,120,164)	0.08 (92.39)	1.67 (99.31)	36.28 (80.24)
total triglycerides, week 96 (N=124,113,147)	9.34 (95.66)	5.35 (84.92)	30.45 (94.99)
total triglycerides, week 144 (N=153,153,159)	-3.46 (77.97)	6.11 (80.82)	27.11 (85.97)

34. Secondary Outcome

Title	Change of Total Cholesterol to HDL-cholesterol Ratio From Baseline to Week 48, 96, 144
Description	Change of Total cholesterol to HDL-cholesterol ratio from baseline to week 48, 96, 144
Time Frame	baseline to week 48, 96, 144

Outcome Measure Data

Analysis Population Description

FAS, where only patients with corresponding laboratory values for the considered time point are considered

Arm/Group Title	Nevirapine QD	Nevirapine BID	Atazanvir/Ritonavir
Arm/Group Description	NVP 400mg QD on a background of the fixed combination Truvada®	NVP 200mg BID on a background of the fixed combination Truvada®	ATZ/r on a background of the fixed combination Truvada®
Measure Participants	188	188	193
total triglycerides, week 48 (N=138,122,164)	-0.37 (0.95)	-0.33 (1.05)	0.20 (0.99)
total triglycerides, week 96 (N=124,114,147)	-0.22 (0.93)	-0.25 (1.03)	0.28 (1.05)
total triglycerides, week 144 (N=154,155,160)	-0.24 (0.96)	-0.07 (1.45)	0.17 (1.05)

Adverse Events

Time Frame	148 weeks
Arm/Group Title	Nevirapine QD		Nevirapine BID		Atazanvir/Ritonavir
Arm/Group Description	NVP 400mg QD on a background of the fixed combination Truvada®		NVP 200mg BID on a background of the fixed combination Truvada®		ATZ/r on a background of the fixed combination Truvada®
All Cause Mortality
	Nevirapine QD		Nevirapine BID		Atazanvir/Ritonavir
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Nevirapine QD		Nevirapine BID		Atazanvir/Ritonavir
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	25/188 (13.3%)		31/188 (16.5%)		27/193 (14%)
Blood and lymphatic system disorders
Anaemia	0/188 (0%)		2/188 (1.1%)		0/193 (0%)
Neutropenia	0/188 (0%)		1/188 (0.5%)		0/193 (0%)
Cardiac disorders
Acute myocardial infarction	0/188 (0%)		0/188 (0%)		1/193 (0.5%)
Angina pectoris	0/188 (0%)		1/188 (0.5%)		0/193 (0%)
Angina unstable	0/188 (0%)		1/188 (0.5%)		0/193 (0%)
Cardiac failure	0/188 (0%)		0/188 (0%)		1/193 (0.5%)
Myocardial infarction	0/188 (0%)		0/188 (0%)		1/193 (0.5%)
Myopericarditis	0/188 (0%)		1/188 (0.5%)		0/193 (0%)
Endocrine disorders
Goitre	1/188 (0.5%)		0/188 (0%)		0/193 (0%)
Eye disorders
Retinal detachment	0/188 (0%)		0/188 (0%)		1/193 (0.5%)
Gastrointestinal disorders
Constipation	1/188 (0.5%)		0/188 (0%)		0/193 (0%)
Inguinal hernia	1/188 (0.5%)		0/188 (0%)		0/193 (0%)
Peritonitis	0/188 (0%)		1/188 (0.5%)		0/193 (0%)
General disorders
Asthenia	0/188 (0%)		1/188 (0.5%)		0/193 (0%)
Fatigue	0/188 (0%)		1/188 (0.5%)		0/193 (0%)
Multi-organ failure	1/188 (0.5%)		0/188 (0%)		0/193 (0%)
Pain	0/188 (0%)		1/188 (0.5%)		0/193 (0%)
Puncture site haemorrhage	1/188 (0.5%)		0/188 (0%)		0/193 (0%)
Pyrexia	1/188 (0.5%)		3/188 (1.6%)		0/193 (0%)
Hepatobiliary disorders
Cholecystitis	0/188 (0%)		0/188 (0%)		1/193 (0.5%)
Cholecystitis acute	1/188 (0.5%)		0/188 (0%)		0/193 (0%)
Cholelithiasis	0/188 (0%)		3/188 (1.6%)		0/193 (0%)
Cholestasis	1/188 (0.5%)		0/188 (0%)		0/193 (0%)
Immune system disorders
Drug hypersensitivity	1/188 (0.5%)		0/188 (0%)		0/193 (0%)
Infections and infestations
Abscess jaw	1/188 (0.5%)		0/188 (0%)		0/193 (0%)
Anal abscess	1/188 (0.5%)		0/188 (0%)		0/193 (0%)
Anogenital warts	0/188 (0%)		0/188 (0%)		5/193 (2.6%)
Appendicitis	0/188 (0%)		1/188 (0.5%)		0/193 (0%)
Candida pneumonia	0/188 (0%)		1/188 (0.5%)		0/193 (0%)
Cerebral toxoplasmosis	1/188 (0.5%)		0/188 (0%)		0/193 (0%)
Cryptococcosis	1/188 (0.5%)		0/188 (0%)		0/193 (0%)
Cytomegalovirus infection	0/188 (0%)		0/188 (0%)		1/193 (0.5%)
Gastroenteritis	0/188 (0%)		0/188 (0%)		1/193 (0.5%)
H1N1 influenza	1/188 (0.5%)		0/188 (0%)		0/193 (0%)
HIV infection	0/188 (0%)		1/188 (0.5%)		0/193 (0%)
Hepatitis A	0/188 (0%)		0/188 (0%)		2/193 (1%)
Herpes zoster	1/188 (0.5%)		0/188 (0%)		0/193 (0%)
Meningitis viral	0/188 (0%)		0/188 (0%)		1/193 (0.5%)
Neurosyphilis	1/188 (0.5%)		0/188 (0%)		0/193 (0%)
Orchitis	0/188 (0%)		0/188 (0%)		1/193 (0.5%)
Papilloma viral infection	0/188 (0%)		1/188 (0.5%)		0/193 (0%)
Pneumocystis jiroveci pneumonia	1/188 (0.5%)		0/188 (0%)		0/193 (0%)
Pneumonia	2/188 (1.1%)		0/188 (0%)		3/193 (1.6%)
Postoperative wound infection	1/188 (0.5%)		0/188 (0%)		0/193 (0%)
Pulmonary tuberculosis	1/188 (0.5%)		0/188 (0%)		0/193 (0%)
Salpingitis	0/188 (0%)		0/188 (0%)		1/193 (0.5%)
Sepsis	0/188 (0%)		1/188 (0.5%)		0/193 (0%)
Sinusitis	0/188 (0%)		0/188 (0%)		1/193 (0.5%)
Subcutaneous abscess	0/188 (0%)		0/188 (0%)		1/193 (0.5%)
Tuberculosis	0/188 (0%)		1/188 (0.5%)		0/193 (0%)
Urinary tract infection	0/188 (0%)		0/188 (0%)		1/193 (0.5%)
Injury, poisoning and procedural complications
Drug exposure during pregnancy	1/188 (0.5%)		0/188 (0%)		0/193 (0%)
Fall	1/188 (0.5%)		1/188 (0.5%)		0/193 (0%)
Fracture of penis	0/188 (0%)		0/188 (0%)		1/193 (0.5%)
Meniscus lesion	1/188 (0.5%)		0/188 (0%)		0/193 (0%)
Multiple injuries	0/188 (0%)		1/188 (0.5%)		0/193 (0%)
Rib fracture	0/188 (0%)		0/188 (0%)		1/193 (0.5%)
Subdural haematoma	0/188 (0%)		1/188 (0.5%)		0/193 (0%)
Upper limb fracture	1/188 (0.5%)		2/188 (1.1%)		0/193 (0%)
Investigations
Alanine aminotransferase increased	0/188 (0%)		1/188 (0.5%)		1/193 (0.5%)
Aspartate aminotransferase increased	0/188 (0%)		1/188 (0.5%)		0/193 (0%)
Blood bilirubin increased	0/188 (0%)		1/188 (0.5%)		1/193 (0.5%)
Blood creatine phosphokinase increased	0/188 (0%)		0/188 (0%)		1/193 (0.5%)
Gamma-glutamyltransferase increased	0/188 (0%)		1/188 (0.5%)		0/193 (0%)
Haemoglobin decreased	1/188 (0.5%)		0/188 (0%)		0/193 (0%)
Transaminases increased	0/188 (0%)		1/188 (0.5%)		0/193 (0%)
Musculoskeletal and connective tissue disorders
Arthralgia	0/188 (0%)		1/188 (0.5%)		0/193 (0%)
Back pain	1/188 (0.5%)		0/188 (0%)		0/193 (0%)
Flank pain	1/188 (0.5%)		0/188 (0%)		0/193 (0%)
Musculoskeletal stiffness	1/188 (0.5%)		0/188 (0%)		0/193 (0%)
Myalgia	1/188 (0.5%)		0/188 (0%)		0/193 (0%)
Neck pain	1/188 (0.5%)		0/188 (0%)		0/193 (0%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Basal cell carcinoma	0/188 (0%)		1/188 (0.5%)		0/193 (0%)
Bladder neoplasm	0/188 (0%)		1/188 (0.5%)		0/193 (0%)
Bone neoplasm	0/188 (0%)		1/188 (0.5%)		0/193 (0%)
Hodgkin's disease	2/188 (1.1%)		2/188 (1.1%)		0/193 (0%)
Kaposi's sarcoma	0/188 (0%)		1/188 (0.5%)		0/193 (0%)
Lung carcinoma cell type unspecified recurrent	0/188 (0%)		0/188 (0%)		1/193 (0.5%)
Lung neoplasm malignant	0/188 (0%)		0/188 (0%)		1/193 (0.5%)
Lymphoma	0/188 (0%)		1/188 (0.5%)		0/193 (0%)
Myelodysplastic syndrome	0/188 (0%)		1/188 (0.5%)		0/193 (0%)
Non-Hodgkin's lymphoma	0/188 (0%)		2/188 (1.1%)		0/193 (0%)
Pancreatic carcinoma	1/188 (0.5%)		0/188 (0%)		0/193 (0%)
Nervous system disorders
Carpal tunnel syndrome	1/188 (0.5%)		0/188 (0%)		0/193 (0%)
Cerebellar syndrome	1/188 (0.5%)		0/188 (0%)		0/193 (0%)
Cerebrovascular accident	0/188 (0%)		2/188 (1.1%)		0/193 (0%)
Convulsion	0/188 (0%)		1/188 (0.5%)		0/193 (0%)
Epilepsy	0/188 (0%)		1/188 (0.5%)		0/193 (0%)
Headache	1/188 (0.5%)		0/188 (0%)		1/193 (0.5%)
Hypoaesthesia	1/188 (0.5%)		0/188 (0%)		0/193 (0%)
Neuralgia	1/188 (0.5%)		0/188 (0%)		0/193 (0%)
Neuropathy peripheral	0/188 (0%)		1/188 (0.5%)		0/193 (0%)
Psychiatric disorders
Alcohol abuse	1/188 (0.5%)		0/188 (0%)		0/193 (0%)
Depression	1/188 (0.5%)		0/188 (0%)		0/193 (0%)
Schizophrenia	0/188 (0%)		1/188 (0.5%)		0/193 (0%)
Suicide attempt	1/188 (0.5%)		0/188 (0%)		0/193 (0%)
Renal and urinary disorders
Renal failure	0/188 (0%)		0/188 (0%)		1/193 (0.5%)
Renal failure acute	1/188 (0.5%)		1/188 (0.5%)		0/193 (0%)
Reproductive system and breast disorders
Cervical dysplasia	1/188 (0.5%)		0/188 (0%)		0/193 (0%)
Ovarian cyst ruptured	1/188 (0.5%)		0/188 (0%)		0/193 (0%)
Respiratory, thoracic and mediastinal disorders
Asthma	0/188 (0%)		1/188 (0.5%)		0/193 (0%)
Chronic obstructive pulmonary disease	0/188 (0%)		0/188 (0%)		1/193 (0.5%)
Cough	0/188 (0%)		1/188 (0.5%)		0/193 (0%)
Dyspnoea	0/188 (0%)		1/188 (0.5%)		0/193 (0%)
Interstitial lung disease	1/188 (0.5%)		0/188 (0%)		0/193 (0%)
Pleural effusion	0/188 (0%)		1/188 (0.5%)		0/193 (0%)
Pleurisy	0/188 (0%)		0/188 (0%)		1/193 (0.5%)
Pulmonary oedema	1/188 (0.5%)		0/188 (0%)		0/193 (0%)
Skin and subcutaneous tissue disorders
Rash	1/188 (0.5%)		0/188 (0%)		0/193 (0%)
Surgical and medical procedures
Breast prosthesis implantation	0/188 (0%)		1/188 (0.5%)		0/193 (0%)
Mastoidectomy	0/188 (0%)		0/188 (0%)		1/193 (0.5%)
Tympanoplasty	0/188 (0%)		0/188 (0%)		1/193 (0.5%)
Other (Not Including Serious) Adverse Events
	Nevirapine QD		Nevirapine BID		Atazanvir/Ritonavir
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	136/188 (72.3%)		141/188 (75%)		161/193 (83.4%)
Eye disorders
Ocular icterus	0/188 (0%)		0/188 (0%)		14/193 (7.3%)
Gastrointestinal disorders
Abdominal pain	5/188 (2.7%)		10/188 (5.3%)		15/193 (7.8%)
Abdominal pain upper	9/188 (4.8%)		14/188 (7.4%)		13/193 (6.7%)
Diarrhoea	29/188 (15.4%)		33/188 (17.6%)		47/193 (24.4%)
Flatulence	9/188 (4.8%)		10/188 (5.3%)		9/193 (4.7%)
Nausea	22/188 (11.7%)		21/188 (11.2%)		21/193 (10.9%)
Vomiting	13/188 (6.9%)		15/188 (8%)		8/193 (4.1%)
General disorders
Fatigue	11/188 (5.9%)		11/188 (5.9%)		12/193 (6.2%)
Influenza like illness	10/188 (5.3%)		6/188 (3.2%)		9/193 (4.7%)
Pyrexia	14/188 (7.4%)		13/188 (6.9%)		9/193 (4.7%)
Hepatobiliary disorders
Hyperbilirubinaemia	0/188 (0%)		0/188 (0%)		15/193 (7.8%)
Jaundice	0/188 (0%)		0/188 (0%)		40/193 (20.7%)
Infections and infestations
Bronchitis	28/188 (14.9%)		19/188 (10.1%)		19/193 (9.8%)
Gastroenteritis	8/188 (4.3%)		14/188 (7.4%)		8/193 (4.1%)
Gonorrhoea	11/188 (5.9%)		3/188 (1.6%)		4/193 (2.1%)
Herpes zoster	16/188 (8.5%)		12/188 (6.4%)		7/193 (3.6%)
Influenza	21/188 (11.2%)		18/188 (9.6%)		16/193 (8.3%)
Nasopharyngitis	41/188 (21.8%)		36/188 (19.1%)		40/193 (20.7%)
Pharyngitis	10/188 (5.3%)		10/188 (5.3%)		12/193 (6.2%)
Rhinitis	8/188 (4.3%)		7/188 (3.7%)		13/193 (6.7%)
Sinusitis	13/188 (6.9%)		9/188 (4.8%)		10/193 (5.2%)
Upper respiratory tract infection	6/188 (3.2%)		8/188 (4.3%)		14/193 (7.3%)
Investigations
Blood bilirubin increased	0/188 (0%)		1/188 (0.5%)		33/193 (17.1%)
Musculoskeletal and connective tissue disorders
Arthralgia	14/188 (7.4%)		8/188 (4.3%)		11/193 (5.7%)
Back pain	14/188 (7.4%)		13/188 (6.9%)		17/193 (8.8%)
Myalgia	12/188 (6.4%)		10/188 (5.3%)		9/193 (4.7%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Skin papilloma	1/188 (0.5%)		0/188 (0%)		11/193 (5.7%)
Nervous system disorders
Headache	27/188 (14.4%)		24/188 (12.8%)		35/193 (18.1%)
Psychiatric disorders
Depression	16/188 (8.5%)		9/188 (4.8%)		18/193 (9.3%)
Respiratory, thoracic and mediastinal disorders
Cough	18/188 (9.6%)		22/188 (11.7%)		21/193 (10.9%)
Oropharyngeal pain	6/188 (3.2%)		4/188 (2.1%)		12/193 (6.2%)
Skin and subcutaneous tissue disorders
Rash	25/188 (13.3%)		31/188 (16.5%)		23/193 (11.9%)
Vascular disorders
Hypertension	10/188 (5.3%)		9/188 (4.8%)		9/193 (4.7%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

Other - Any publication of the result of this trial must be consistent with the Boehringer Ingelheim publication policy. The rights of the investigator and of the sponsor with regard to publication of the results of this trial are described in the investigator contract.