MERIT: Trial of Maraviroc (UK-427,857) in Combination With Zidovudine/Lamivudine Versus Efavirenz in Combination With Zidovudine/Lamivudine

• Sponsor: ViiV Healthcare (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00098293
• Collaborator: Pfizer (Industry)
• Enrollment: 916
• Locations: 144
• Arms: 3
• Duration (Months): 97
• Patients Per Site: 6.4
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

Maraviroc (UK-427,857), a selective and reversible CCR5 coreceptor antagonist, has been shown to be active in vitro against a wide range of clinical isolates (including those resistant to existing classes). In HIV-1 infected patients, maraviroc (UK-427,857) given as monotherapy for 10 days reduced HIV-1 viral load by up to 1.6 log, consistent with currently available agents. Safety and toleration have been studied in over 400 subjects for up to 28 days at 300 mg twice daily. No significant effects were seen on the QTc interval. The goal of this study is to compare the safety and efficacy of maraviroc (UK-427,857) versus efavirenz, when each are combined with two other antiretroviral agents, in patients who are previously naive to antiretroviral therapy. This study will involve approximately 200 centers from around the world to achieve a total randomized subject population of 1071 subjects. Patients will be randomly assigned to one of three groups: maraviroc (UK-427,857) 300 mg once daily added to zidovudine/lamivudine (300 mg/150 mg twice daily), Maraviroc (UK-427,857) 300 mg twice daily added to zidovudine/lamivudine (300 mg/150 mg twice daily) or efavirenz (600 mg once daily) added to zidovudine/lamivudine (300 mg/150 mg twice daily). The study will enroll over approximately an 18 month period (5 months Phase 2b run-in, 13 months Phase 3) with 96 weeks of treatment. This may be extended for an additional 3 years depending on the results at 96 weeks. Physical examinations will be performed at study entry, weeks 4, 8, 12, 16, 20, 24, 32, 40, 48, 60, 72, 84 and 96. Blood samples will also be taken at study entry, weeks 2, 4, 8, 12, 16, 20, 24, 32, 40, 48, 60, 72, 84 and 96. Additionally, blood samples will be drawn twice, at least 30 minutes apart, at weeks 2 and 48 for maraviroc (UK-427,857) pharmacokinetic analysis. As part of this clinical study a blood sample will be taken for non-anonymized pharmacogenetic analysis. Patients will undergo a 12-lead electrocardiogram at study entry, weeks 24, 48 and 96. A computerized tomography (CT) scan will also be performed, at selected centers, at study entry and week 96. Patients will be asked to complete a symptom distress questionnaire at study entry, weeks 12, 24, 48 and 96.

Condition or Disease	Intervention/Treatment	Phase
HIV-1	Drug: Maraviroc + Zidovudine/Lamivudine; Drug: Efavirenz + Zidovudine/Lamivudine; Drug: Maraviroc (UK-427,857) + Zidovudine/Lamivudine	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 916 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Multicenter, Randomized, Double-Blind, Comparative Trial Of A Novel CCR5 Antagonist, UK-427,857, In Combination With Zidovudine/Lamivudine Versus Efavirenz In Combination With Zidovudine/Lamivudine For The Treatment Of Antiretroviral-Naive HIV-1 Infected Subjects
• Study Start Date: Nov 1, 2004
• Actual Primary Completion Date: Apr 1, 2007
• Actual Study Completion Date: Dec 1, 2012

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 1	Drug: Maraviroc + Zidovudine/Lamivudine; maraviroc (UK-427,857) 300 mg once daily added to zidovudine/lamivudine (300 mg/150 mg twice daily)
Active Comparator: 3	Drug: Efavirenz + Zidovudine/Lamivudine; efavirenz (600 mg once daily) added to zidovudine/lamivudine (300 mg/150 mg twice daily)
Experimental: 2 Following a review of the interim analysis data, the DSMB recommended to terminate the UK-427,857 300 mg QD arm based on pre-specified protocol non-inferiority criteria not being met for the QD arm versus efavirenz	Drug: Maraviroc (UK-427,857) + Zidovudine/Lamivudine; maraviroc (UK-427,857) 300 mg twice daily added to zidovudine/lamivudine (300 mg/150 mg twice daily)

Outcome Measures

Primary Outcome Measures

1. Percentage of Participants With Viral Load of Less Than 400 Copies/Milliliter [Copies/mL] and Less Than 50 Copies/mL of Human Immunodeficiency Virus (HIV)-1 Ribonucleic Acid (RNA) at Week 48 for Full Analysis Set (FAS) Population [Week 48]

2. Percentage of Participants With Viral Load of Less Than 400 Copies/mL and Less Than 50 Copies/mL of HIV-1 RNA at Week 48 for Per Protocol (PP) Population [Week 48]

   Percentage of participants with viral load of less than 400 copies/mL and less than 50 copies/mL of HIV-1 RNA were not analyzed for participants originally randomized to maraviroc once daily arm since after termination, focus was shifted from efficacy and safety to only safety as reflected in the abbreviated set of efficacy measures noted in the amended planned analysis.

Secondary Outcome Measures

1. Percentage of Participants With HIV-1 RNA Levels of Less Than 400 Copies/mL and Less Than 50 Copies/mL at Week 48 Analyzed Using Logistic Regression [Week 48]

2. Percentage of Participants With HIV-1 RNA Levels of Less Than 400 Copies/mL and Less Than 50 Copies/mL at Week 96 Analyzed Using Logistic Regression [Week 96]

3. Change From Baseline in Log 10-transformed Plasma Viral Load (HIV-1 RNA) Levels at Week 48 and 96 [Baseline, Week 48, Week 96]

   Change from baseline in log 10-transformed plasma viral load (HIV-1 RNA) levels (log10 copies/mL). Baseline value calculated as average of pre-dose measurements collected at screening, randomization, and immediately pre-dose.

4. Time-Averaged Difference (TAD) in log10-transformed HIV-1 RNA Levels [Baseline up to Week 48 and Week 96]

   TAD from baseline was calculated as area under the curve (AUC) of HIV-1 RNA load (log10 copies/mL) divided by time period minus baseline HIV-1 RNA load (log10 copies/mL). Baseline value calculated as average of pre-dose measurements collected at screening, randomization, and immediately pre-dose. Data not analyzed for participants originally randomized to maraviroc once daily arm since after termination, focus was shifted from efficacy and safety to only safety as reflected in the abbreviated set of efficacy measures noted in the amended planned analysis.

5. Change From Baseline in Lymphocyte Cluster of Differentiation 4 (CD4) Count at Week 48 and 96 [Baseline, Week 48, Week 96]

   Baseline value calculated as the average of pre-dose measurements collected at screening and immediately pre-dose.

6. Change From Baseline in Lymphocyte Cluster of Differentiation 8 (CD8) Count at Week 48 and 96 [Baseline, Week 48, Week 96]

   Baseline value calculated as the average of pre-dose measurements collected at screening and immediately pre-dose. Change from baseline in lymphocyte CD8 count at Week 48 and 96 was not analyzed for participants originally randomized to maraviroc once daily arm since after termination, focus was shifted from efficacy and safety to only safety as reflected in the abbreviated set of efficacy measures noted in the amended planned analysis.

7. Time to Virologic Failure [Week 48, Week 96]

   Time to virologic failure based on observed HIV-1 RNA levels and failure events (death;permanent discontinuation of drug;lost to follow-up [LTFU];new anti-retroviral drug added [except background drug change to drug of same class];or on open label for early non-response or rebound). Failure:at Time 0 if level not <400 copies/mL(2 consecutive visits) before events or last available visit;at time of earliest event if level <400 copies/mL(2 consecutive visits);failure if level >=400 copies/mL(2 consecutive visits) or 1 visit >=400 copies/mL followed by permanent discontinuation of drug or LTFU.

8. Number of Participants Per Tropism Status at Baseline and at the Time of Treatment Failure Through Week 48 [Baseline, time of failure through Week 48]

   Number of participants per tropism status (C-X-C chemokine receptor 5 {CCR5} [R5], C-X-C chemokine receptor type 4 {CXCR4} [X4], Dual/mixed [DM], or Non-reportable/Non-phenotypable [NR/NP]) at baseline and time of treatment failure analyzed through week 48 visit. Treatment failure: discontinuation due to insufficient clinical response. Tropism result was censored for participants with viral load <500 copies/mL at time of treatment failure categorized as below lower limit of quantification (BLQ). The assessment for time of treatment failure was defined as last on treatment assessment.

9. Number of Participants Per Tropism Status at Baseline and at the Time of Treatment Failure Through Week 96 [Baseline, time of failure through Week 96]

   Number of participants per tropism status (R5, X4, DM, or NR/NP) at baseline and time of treatment failure analyzed through week 96 visit. Treatment failure defined as insufficient clinical response. Tropism result was censored for participants with viral load <500 copies/mL at time of treatment failure categorized as BLQ. The assessment for time of treatment failure was defined as last on treatment assessment.

10. Number of Participants With Phenotypic Resistance at Time of Treatment Failure Through Week 48 and 96 [Screening, time of failure through Week 48, Week 96]

    Phenotypic resistance to nucleoside reverse transcriptase inhibitors (NRTIs) and non-nucleoside reverse transcriptase inhibitors (NNRTIs) assessed at screening by Monogram Bioscience PhenoSense genotype (MBPSGT) assay, repeated if viral load >500 copies/mL at treatment failure through week 48, 96. Phenotypic resistance to maraviroc was assumed in maraviroc treatment failures with X4-using virus and in R5 maraviroc treatment failures using Monogram Bioscience PhenoSense Entry Assay. Phenotypic resistance to zidovudine, lamivudine, efavirenz and maraviroc at time of failure was summarized.

11. Number of Participants With NRTI Associated Mutations at Time of Treatment Failure Through Week 48 and 96 [Screening, time of failure through Week 48, Week 96]

    Genotypic resistance to NRTIs was assessed by identification of relevant mutations at screening using MBPSGT assay and repeated for all participants with HIV-1 viral load more than 500 copies/mL at treatment failure through week 48 and week 96. Following mutations associated with NRTIs were summarized at time of failure: Any zidovudine/lamivudine (Zid/Lam), Any thymidine analogue-associated mutation (TAM), methionine (M) to valine/isoleucine (V/I) substitution at residue (r) 184 (M184V/I), lysine (K) to arginine (R) substitution at residue 65 (K65R) and any other NRTI mutations.

12. Number of Participants With Efavirenz Associated Mutations at Time of Treatment Failure Through Week 48 and 96 [Screening, time of failure through Week 48, Week 96]

    Genotypic resistance: mutations at screening by MBPSGT assay, repeated if viral load >500 copies/mL at treatment failure through week 48, 96. Efavirenz mutation:lysine to aspargine at r103(K103N);tyrosine to cysteine/isoleucine at r181(Y181C/I);tyrosine to cysteine/leucine/histidine at r188(Y188C/L/H);glycine to alanine/serine at r190(G190A/S);valine to alanine to r106(V106A);leucine to isoleucine at r100(L100I);alanine to glycine at r98(A98G);lysine to glutamic acid at r101(K101E);valine to isoleucine at r108(V108I);proline to histidine at r225(P225H);methionine to leucine at r230(M230L).

13. Percentage of Participants With HIV-1 RNA Levels Less Than 50 Copies/mL at Week 48 and Week 96 by Overall Susceptibility Score (OSS) at Screening [Baseline, Week 48, Week 96]

    Association between baseline resistance and virological response was assessed as percentage of participants with HIV-1RNA levels less than 50 copies/mL by OSS at screening. OSS categorized as 0, 1, 2, >3 (maximum value of 6) and calculated as the sum of the net assessment of in-vitro phenotypic and genotypic susceptibility using a binary scoring system (0= resistant, 1= sensitive or susceptible) for each antiretroviral agent in OBT. Higher scores indicate greater susceptibility.

Other Outcome Measures

1. Percentage of Participants With Viral Load of Less Than 400 Copies/mL and Less Than 50 Copies/mL of HIV-1 RNA at Week 96 [Week 96]

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• Men or women at least 16 years of age (or minimum age as determined by local regulatory authorities)

• HIV-1 RNA viral load of greater than or equal to 2, 000 copies/mL

• A negative urine pregnancy test at the baseline visit for Women of Child Bearing Potential (WOCBP)

• Effective barrier contraception for WOCBP and males

Exclusion Criteria:

• Suspected or documented active, untreated HIV-1 related opportunistic infection (OI) or other condition requiring acute therapy

• Treatment for an active opportunistic infection, or unexplained temperature >38.5 degrees Celsius for 7 consecutive days

• Prior treatment with efavirenz, zidovudine or lamivudine or with any other antiretroviral therapy for more than 14 days at any time

• Active alcohol or substance abuse sufficient, in the Investigator's judgment, to prevent adherence to study medication and/or follow up

• Lactating women, or planned pregnancy during the trial period

• Suspected primary (acute) HIV-1 infection

• Previous therapy with a potentially myelosuppressive, neurotoxic, hepatotoxic and/or cytotoxic agent within 30 days prior to randomization or the expected need for such therapy during the study period

• Documented or suspected acute hepatitis or pancreatitis within 30 days prior to randomization

• Significantly elevated liver enzymes or cirrhosis

• Significant neutropenia, anemia or thrombocytopenia

• Malabsorption or an inability to tolerate oral medications

• Symptomatic postural hypotension or severe cardiovascular or cerebrovascular disease

• Certain medications

• Genotypic or phenotypic resistance to efavirenz, zidovudine or lamivudine

• X4- or dual/mixed-tropic virus or repeated assay failure

• Any other clinical condition that, in the Investigator's judgement, would potentially compromise study compliance or the ability to evaluate safety/efficacy

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Pfizer Investigational Site	Birmingham	Alabama	United States	35233
2	Pfizer Investigational Site	Birmingham	Alabama	United States	35294-2050
3	Pfizer Investigational Site	Beverly Hills	California	United States	90211
4	Pfizer Investigational Site	Los Angeles	California	United States	90022
5	Pfizer Investigational Site	Los Angeles	California	United States	90048
6	Pfizer Investigational Site	Los Angeles	California	United States	90069
7	Pfizer Investigational Site	Newport Beach	California	United States	92663
8	Pfizer Investigational Site	Oakland	California	United States	94602
9	Pfizer Investigational Site	Sacramento	California	United States	95825
10	Pfizer Investigational Site	San Francisco	California	United States	94115-3029
11	Pfizer Investigational Site	San Francisco	California	United States	94115
12	Pfizer Investigational Site	Aurora	Colorado	United States	80045
13	Pfizer Investigational Site	Jacksonville	Florida	United States	32209
14	Pfizer Investigational Site	Miami Beach	Florida	United States	33139
15	Pfizer Investigational Site	Miami	Florida	United States	33133
16	Pfizer Investigational Site	Miami	Florida	United States	33136
17	Pfizer Investigational Site	Orlando	Florida	United States	32803
18	Pfizer Investigational Site	Sarasota	Florida	United States	34243
19	Pfizer Investigational Site	Tampa	Florida	United States	33614
20	Pfizer Investigational Site	Atlanta	Georgia	United States	30308
21	Pfizer Investigational Site	Chicago	Illinois	United States	60611
22	Pfizer Investigational Site	Indianapolis	Indiana	United States	46202
23	Pfizer Investigational Site	Baltimore	Maryland	United States	21201
24	Pfizer Investigational Site	Boston	Massachusetts	United States	02111
25	Pfizer Investigational Site	Boston	Massachusetts	United States	02118-2393
26	Pfizer Investigational Site	Boston	Massachusetts	United States	02215
27	Pfizer Investigational Site	Springfield	Massachusetts	United States	01107
28	Pfizer Investigational Site	Omaha	Nebraska	United States	68106
29	Pfizer Investigational Site	Albany	New York	United States	12208
30	Pfizer Investigational Site	Brooklyn	New York	United States	11203
31	Pfizer Investigational Site	Flushing	New York	United States	11355
32	Pfizer Investigational Site	Manhasset	New York	United States	11030
33	Pfizer Investigational Site	New York	New York	United States	10016
34	Pfizer Investigational Site	Huntersville	North Carolina	United States	28078
35	Pfizer Investigational Site	Cincinnati	Ohio	United States	45267-0405
36	Pfizer Investigational Site	Oklahoma City	Oklahoma	United States	73104-5068
37	Pfizer Investigational Site	Oklahoma City	Oklahoma	United States	73104
38	Pfizer Investigational Site	Philadelphia	Pennsylvania	United States	19104
39	Pfizer Investigational Site	Columbia	South Carolina	United States	29206
40	Pfizer Investigational Site	Dallas	Texas	United States	75208
41	Pfizer Investigational Site	Dallas	Texas	United States	75246
42	Pfizer Investigational Site	Houston	Texas	United States	77006
43	Pfizer Investigational Site	Houston	Texas	United States	77098
44	Pfizer Investigational Site	Annandale	Virginia	United States	22003
45	Pfizer Investigational Site	Puyallup	Washington	United States	98372
46	Pfizer Investigational Site	Tacoma	Washington	United States	98405
47	Pfizer Investigational Site	El Palomar	Provincia de Buenos Aires	Argentina	1684
48	Pfizer Investigational Site	Neuquen	Provincia de Neuquen	Argentina	Q8300PMB
49	Pfizer Investigational Site	Buenos Aires		Argentina
50	Pfizer Investigational Site	Ciudad de Buenos Aires		Argentina	C1202ABB
51	Pfizer Investigational Site	Ciudad de Buenos Aires		Argentina	C1406FWY
52	Pfizer Investigational Site	Ciudad de Buenos		Argentina	C1282AEN
53	Pfizer Investigational Site	Provincia de Buenos Aires		Argentina
54	Pfizer Investigational Site	Provincia de Santa Fe		Argentina
55	Pfizer Investigational Site	Burwood	New South Wales	Australia	2134
56	Pfizer Investigational Site	Darlinghurst	New South Wales	Australia	2010
57	Pfizer Investigational Site	Surrey Hills	New South Wales	Australia	2010
58	Pfizer Investigational Site	Wentworthville	New South Wales	Australia	2145
59	Pfizer Investigational Site	Herston	Queensland	Australia	4029
60	Pfizer Investigational Site	Miami	Queensland	Australia	4220
61	Pfizer Investigational Site	Melbourne	Victoria	Australia	3004
62	Pfizer Investigational Site	North Fitzroy	Victoria	Australia	3068
63	Pfizer Investigational Site	South Yarra	Victoria	Australia	3141
64	Pfizer Investigational Site	Brussels		Belgium	1000
65	Pfizer Investigational Site	Brussels		Belgium	1200
66	Pfizer Investigational Site	Gent		Belgium	9000
67	Pfizer Investigational Site	Leuven		Belgium	B-3000 Leuven
68	Pfizer Investigational Site	Rio de Janeiro	RJ	Brazil	20210-030
69	Pfizer Investigational Site	Calgary	Alberta	Canada	T2R0X7
70	Pfizer Investigational Site	Edmonton	Alberta	Canada	T6G 2B7
71	Pfizer Investigational Site	Edmonton	Alberta	Canada	T6G 2C8
72	Pfizer Investigational Site	Vancouver	British Columbia	Canada	V6B 1R3
73	Pfizer Investigational Site	Vancouver	British Columbia	Canada	V6Z 1Y6
74	Pfizer Investigational Site	Vancouver	British Columbia	Canada	V6Z 2C7
75	Pfizer Investigational Site	Vancouver	British Columbia	Canada	V6Z 2T1
76	Pfizer Investigational Site	Winnipeg	Manitoba	Canada	R3A 1R9
77	Pfizer Investigational Site	Halifax	Nova Scotia	Canada	B3H 1V7
78	Pfizer Investigational Site	Hamilton	Ontario	Canada	L8N 3Z5
79	Pfizer Investigational Site	Ottawa	Ontario	Canada	K1H 8L6
80	Pfizer Investigational Site	Toronto	Ontario	Canada	M4N 3M5
81	Pfizer Investigational Site	Toronto	Ontario	Canada	M5B 1W8
82	Pfizer Investigational Site	Toronto	Ontario	Canada	M5G 2N2
83	Pfizer Investigational Site	Montreal	Quebec	Canada	H2L 4M1
84	Pfizer Investigational Site	Montreal	Quebec	Canada	H2L 4P9
85	Pfizer Investigational Site	Montreal	Quebec	Canada	H2L 5B1
86	Pfizer Investigational Site	Montreal	Quebec	Canada	H2W 1T8
87	Pfizer Investigational Site	Montreal	Quebec	Canada	H2X 2P4
88	Pfizer Investigational Site	Montreal	Quebec	Canada	H3G 1A4
89	Pfizer Investigational Site	Sainte-Foy	Quebec	Canada	G1V 4G2
90	Pfizer Investigational Site	Antella (FI)		Italy	50011
91	Pfizer Investigational Site	Brescia		Italy	25123
92	Pfizer Investigational Site	Milano		Italy	20127
93	Pfizer Investigational Site	Modena		Italy	41100
94	Pfizer Investigational Site	Roma		Italy	00161
95	Pfizer Investigational Site	Roma		Italy	00185
96	Pfizer Investigational Site	Torino		Italy	10149
97	Pfizer Investigational Site	Del. Tlalpan C.P.	Mexico City	Mexico	14050
98	Pfizer Investigational Site	Del. Tlalpan, C.P.	Mexico D.F.	Mexico	14000
99	Pfizer Investigational Site	Del. Tlalpan, C.P.	Mexico D.F.	Mexico	14080
100	Pfizer Investigational Site	Delegacion Tlalpan C. P	Mexico D.F.	Mexico	14080
101	Pfizer Investigational Site	Amsterdam		Netherlands	1091 AC
102	Pfizer Investigational Site	Rotterdam		Netherlands	3015 GD
103	Pfizer Investigational Site	Utrecht		Netherlands	3584 CX
104	Pfizer Investigational Site	Bialystok		Poland	15-540
105	Pfizer Investigational Site	Bydgoszcz		Poland	85-030
106	Pfizer Investigational Site	Chorzow		Poland	41-500
107	Pfizer Investigational Site	Gdansk		Poland	80-214
108	Pfizer Investigational Site	Krakow		Poland	31-531
109	Pfizer Investigational Site	Szczecin		Poland	71-455
110	Pfizer Investigational Site	Warszawa		Poland	01-201
111	Pfizer Investigational Site	Ponce		Puerto Rico	00731
112	Pfizer Investigational Site	Rio Piedras		Puerto Rico	00935
113	Pfizer Investigational Site	San Juan		Puerto Rico	00909
114	Pfizer Investigational Site	San Juan		Puerto Rico	00935
115	Pfizer Investigational Site	Port Elizabeth	Eastern Cape	South Africa	6065
116	Pfizer Investigational Site	Bloemfontein	Free State	South Africa	9300
117	Pfizer Investigational Site	Johannesburg	Gauteng	South Africa	2092
118	Pfizer Investigational Site	Pretoria	Gauteng	South Africa	0083
119	Pfizer Investigational Site	Dundee	KwaZulu Natal	South Africa	3000
120	Pfizer Investigational Site	Bloomfontein		South Africa
121	Pfizer Investigational Site	Cape Town		South Africa	7405
122	Pfizer Investigational Site	Cape Town		South Africa	7550
123	Pfizer Investigational Site	Cape Town		South Africa	7705
124	Pfizer Investigational Site	Cape Town		South Africa	7780
125	Pfizer Investigational Site	Johannesburg		South Africa	2047
126	Pfizer Investigational Site	Pretoria North		South Africa	0182
127	Pfizer Investigational Site	Pretoria		South Africa	0132
128	Pfizer Investigational Site	Soweto, Johannesburg		South Africa	2013
129	Pfizer Investigational Site	Basel		Switzerland	4031
130	Pfizer Investigational Site	Bern		Switzerland	3010
131	Pfizer Investigational Site	Genève		Switzerland	1211
132	Pfizer Investigational Site	Lugano		Switzerland	6900
133	Pfizer Investigational Site	St. Gallen		Switzerland	9007
134	Pfizer Investigational Site	Zürich		Switzerland	8038
135	Pfizer Investigational Site	Zürich		Switzerland	8091
136	Pfizer Investigational Site	Edinburgh	Loth	United Kingdom	ED4 2XU
137	Pfizer Investigational Site	Birmingham		United Kingdom	B9 5SS
138	Pfizer Investigational Site	Brighton		United Kingdom	BN2 1ES
139	Pfizer Investigational Site	Edinburgh		United Kingdom	EH4 2XU
140	Pfizer Investigational Site	London		United Kingdom	NW3 2QG
141	Pfizer Investigational Site	London		United Kingdom	SE5 9RS
142	Pfizer Investigational Site	London		United Kingdom	SW10 9NH
143	Pfizer Investigational Site	London		United Kingdom	W2 1NY
144	Pfizer Investigational Site	Manchester		United Kingdom	M8 5RB

Sponsors and Collaborators

• ViiV Healthcare
• Pfizer

Investigators

• Study Director: Pfizer CT.gov Call Center, Pfizer

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• To obtain contact information for a study center near you, click here.

Publications

None provided.

• Responsible Party: ViiV Healthcare
• ClinicalTrials.gov Identifier: NCT00098293
• Other Study ID Numbers: A4001026
• First Posted: Dec 7, 2004
• Last Update Posted: Oct 9, 2013
• Last Verified: Aug 1, 2013

• Keywords provided by ViiV Healthcare: Aids; HIV
• Additional relevant MeSH terms: Lamivudine; Zidovudine; Efavirenz; Maraviroc

Study Results

Participant Flow

Pre-assignment Detail	Data Safety Monitoring Board (DSMB) recommended termination of maraviroc once daily treatment after interim analysis at nominal week 16, 130 participants of 177 randomized were switched to open-label (OL) maraviroc twice daily.

Arm/Group Title	Maraviroc Once Daily + CBV (DB)	Maraviroc Twice Daily + CBV (DB and OL)	Efavirenz Once Daily + CBV (DB and OL)	Maraviroc Twice Daily + CBV (OL)	Maraviroc Twice Daily + CBV (SP)
Arm/Group Description	Maraviroc 300 milligram (mg) tablet orally once daily in the evening along with placebo matched to maraviroc 300 mg tablet orally once daily in the morning and placebo matched to efavirenz 600 mg tablet orally once daily in the evening co-administered with combination therapy containing zidovudine 300 mg and lamivudine 150 mg (combivir [CBV]) tablet orally twice daily, during the double-blind (DB) phase prior to the termination of the treatment arm based on the recommendation of the DSMB following a planned interim analysis. DB phase nominally ended at last participant's Week 96 visit.	Maraviroc 300 mg tablet orally twice daily and placebo matched to efavirenz 600 mg tablet orally once daily in the evening co-administered with combination therapy containing zidovudine 300 mg and lamivudine 150 mg (combivir [CBV]) tablet orally twice daily, during the DB phase. DB phase nominally ended at last participant's Week 96 visit. Maraviroc 300 mg tablet orally twice daily co-administered with combination therapy containing zidovudine 300 mg and lamivudine 150 mg (combivir [CBV]) tablet orally twice daily, during the open-label (OL) phase. OL phase continued for at least 3 years after DB phase.	Placebo matched to maraviroc 300 mg tablet orally twice daily and efavirenz 600 mg tablet orally once daily in the evening co-administered with combination therapy containing zidovudine 300 mg and lamivudine 150 mg (combivir [CBV]) tablet orally twice daily, during the DB phase. DB phase nominally ended at last participant's Week 96 visit. Efavirenz 600 mg tablet orally once daily in the evening co-administered with combination therapy containing zidovudine 300 mg and lamivudine 150 mg (combivir [CBV]) tablet orally twice daily, during the OL phase. OL phase continued for at least 3 years after DB phase.	Participants who received maraviroc 300 mg tablet orally once daily treatment during the DB phase and who were eligible based on safety criteria and virologic response, switched to OL maraviroc 300 mg tablet orally twice daily co-administered with combination therapy containing zidovudine 300 mg and lamivudine 150 mg (combivir [CBV]) tablet orally twice daily, following the DSMB recommendation to terminate the maraviroc once daily treatment arm after planned interim analysis. OL phase continued for at least 3 years after DB phase.	Participants who remained on mararviroc until their open-label phase End-of-Study visit and for whom maraviroc was commercially or otherwise unavailable entered an additional supplemental phase (SP) (initially planned for 6 months and subsequently extended for another 6 months) which consisted of study visits at 3-month intervals and received maraviroc 300 mg tablet orally twice daily co-administered with combination therapy containing zidovudine 300 mg and lamivudine 150 mg (combivir [CBV]) tablet orally twice daily until maraviroc was commercially or otherwise available.
Period Title: Double-blind (DB) Phase
STARTED	177	368	372	0	0
Treated	174	360	361	0	0
COMPLETED	0	202	202	0	0
NOT COMPLETED	177	166	170	0	0
Period Title: Double-blind (DB) Phase
STARTED	0	202	202	0	0
COMPLETED	0	202	199	0	0
NOT COMPLETED	0	0	3	0	0
Period Title: Double-blind (DB) Phase
STARTED	0	202	199	130	0
COMPLETED	0	177	158	65	0
NOT COMPLETED	0	25	41	65	0
Period Title: Double-blind (DB) Phase
STARTED	0	0	0	0	127
COMPLETED	0	0	0	0	94
NOT COMPLETED	0	0	0	0	33

Baseline Characteristics

Arm/Group Title	Maraviroc Once Daily + CBV (DB)	Maraviroc Twice Daily + CBV (DB and OL)	Efavirenz Once Daily + CBV (DB and OL)	Total
Arm/Group Description	Maraviroc 300 milligram (mg) tablet orally once daily in the evening along with placebo matched to maraviroc 300 mg tablet orally once daily in the morning and placebo matched to efavirenz 600 mg tablet orally once daily in the evening co-administered with combination therapy containing zidovudine 300 mg and lamivudine 150 mg (combivir [CBV]) tablet orally twice daily, during the double-blind (DB) phase prior to the termination of the treatment arm based on the recommendation of the DSMB following a planned interim analysis. DB phase nominally ended at last participant's Week 96 visit.	Maraviroc 300 mg tablet orally twice daily and placebo matched to efavirenz 600 mg tablet orally once daily in the evening co-administered with combination therapy containing zidovudine 300 mg and lamivudine 150 mg (combivir [CBV]) tablet orally twice daily, during the DB phase. DB phase nominally ended at last participant's Week 96 visit. Maraviroc 300 mg tablet orally twice daily co-administered with combination therapy containing zidovudine 300 mg and lamivudine 150 mg (combivir [CBV]) tablet orally twice daily, during the open-label (OL) phase. OL phase continued for at least 3 years after DB phase.	Placebo matched to maraviroc 300 mg tablet orally twice daily and efavirenz 600 mg tablet orally once daily in the evening co-administered with combination therapy containing zidovudine 300 mg and lamivudine 150 mg (combivir [CBV]) tablet orally twice daily, up to week 96 in DB phase. Efavirenz 600 mg tablet orally once daily in the evening co-administered with combination therapy containing zidovudine 300 mg and lamivudine 150 mg (combivir [CBV]) tablet orally twice daily from Week 97 up to Week 240 in open-label (OL) phase.	Total of all reporting groups
Overall Participants	174	360	361	895
Age, Customized (participants) [Number]
Less than 18 years	0 0%	0 0%	0 0%	0 0%
18 to 24 years	17 9.8%	24 6.7%	25 6.9%	66 7.4%
25 to 34 years	47 27%	147 40.8%	120 33.2%	314 35.1%
35 to 44 years	73 42%	117 32.5%	141 39.1%	331 37%
45 to 54 years	29 16.7%	56 15.6%	55 15.2%	140 15.6%
55 to 64 years	7 4%	14 3.9%	15 4.2%	36 4%
Greater than or equal to 65 years	1 0.6%	2 0.6%	5 1.4%	8 0.9%
Sex: Female, Male (Count of Participants)
Female	44 25.3%	104 28.9%	102 28.3%	250 27.9%
Male	130 74.7%	256 71.1%	259 71.7%	645 72.1%

Outcome Measures

1. Primary Outcome

Title	Percentage of Participants With Viral Load of Less Than 400 Copies/Milliliter [Copies/mL] and Less Than 50 Copies/mL of Human Immunodeficiency Virus (HIV)-1 Ribonucleic Acid (RNA) at Week 48 for Full Analysis Set (FAS) Population
Time Frame	Week 48

Outcome Measure Data

Analysis Population Description

FAS population included all the randomized participants who had taken at least 1 dose of the study medication. Missing data (MD) imputed as failure (F); that is, participants with missing data classified as not achieving the viral load criterion (MD=F).

Arm/Group Title	Maraviroc Once Daily + CBV (DB), Then Twice Daily + CBV (OL)	Maraviroc Twice Daily + CBV (DB)	Efavirenz Once Daily + CBV (DB)
Arm/Group Description	Maraviroc 300 milligram (mg) tablet orally once daily in the evening along with placebo matched to maraviroc 300 mg tablet orally once daily in the morning and placebo matched to efavirenz 600 mg tablet orally once daily in the evening co-administered with combination therapy containing zidovudine 300 mg and lamivudine 150 mg (combivir [CBV]) tablet orally twice daily, during the DB phase prior to the termination of the treatment arm based on the recommendation of the DSMB following a planned interim analysis. Eligible participants then switched to open-label maraviroc 300 mg tablet orally twice daily co-administered with combination therapy containing zidovudine 300 mg and lamivudine 150 mg (combivir [CBV]) tablet orally twice daily for the remainder of the study.	Maraviroc 300 mg tablet orally twice daily and placebo matched to efavirenz 600 mg tablet orally once daily in the evening co-administered with combination therapy containing zidovudine 300 mg and lamivudine 150 mg (combivir [CBV]) tablet orally twice daily, during the DB phase.	Placebo matched to maraviroc 300 mg tablet orally twice daily and efavirenz 600 mg tablet orally once daily in the evening co-administered with combination therapy containing zidovudine 300 mg and lamivudine 150 mg (combivir [CBV]) tablet orally twice daily, during the DB phase.
Measure Participants	174	360	361
Less than 400 copies/mL	61.5 35.3%	70.6 19.6%	73.1 20.2%
Less than 50 copies/mL	55.8 32.1%	65.3 18.1%	69.3 19.2%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Maraviroc Twice Daily + CBV (DB), Efavirenz Once Daily + CBV (DB)
	Comments	Less than 400 copies/mL: Treatment difference in percentages stratified by randomization strata (screening viral load and geographic region) was presented along with the lower bound of the 1-sided 97.5% confidence interval (CI) based on the normal approximation to the binomial distribution. Positive value would favor maraviroc. Step down procedure used to control for multiple comparisons.
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	Non-inferiority was to be concluded if the lower bound of the 1-sided 97.5% CI was greater than (>) -10%.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Difference in Percentage
	Estimated Value	-3.0
	Confidence Interval	(1-Sided) 97.5%; -9.5 to
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Maraviroc Twice Daily + CBV (DB), Efavirenz Once Daily + CBV (DB)
	Comments	Less than 50 copies/mL: Treatment difference in percentages stratified by randomization strata (screening viral load and geographic region) was presented along with the lower bound of the 1-sided 97.5% CI based on the normal approximation to the binomial distribution. Positive value would favor maraviroc. Step down procedure used to control for multiple comparisons.
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	Non-inferiority was to be concluded if the lower bound of the 1-sided 97.5% CI was > -10%.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Difference in Percentage
	Estimated Value	-4.2
	Confidence Interval	(1-Sided) 97.5%; -10.9 to
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Primary Outcome

Title	Percentage of Participants With Viral Load of Less Than 400 Copies/mL and Less Than 50 Copies/mL of HIV-1 RNA at Week 48 for Per Protocol (PP) Population
Description	Percentage of participants with viral load of less than 400 copies/mL and less than 50 copies/mL of HIV-1 RNA were not analyzed for participants originally randomized to maraviroc once daily arm since after termination, focus was shifted from efficacy and safety to only safety as reflected in the abbreviated set of efficacy measures noted in the amended planned analysis.
Time Frame	Week 48

Outcome Measure Data

Analysis Population Description

Per protocol (PP) population included all randomized participants who had taken at least 1 dose of study medication, were treated for at least 14 days or discontinued before this time due to treatment failure, were >80% compliant with randomized treatment and had no violation of any inclusion or exclusion criteria, which affected efficacy. MD=F.

Arm/Group Title	Maraviroc Twice Daily + CBV (DB)	Efavirenz Once Daily + CBV (DB)
Arm/Group Description	Maraviroc 300 mg tablet orally twice daily and placebo matched to efavirenz 600 mg tablet orally once daily in the evening co-administered with combination therapy containing zidovudine 300 mg and lamivudine 150 mg (combivir [CBV]) tablet orally twice daily, during the DB phase.	Placebo matched to maraviroc 300 mg tablet orally twice daily and efavirenz 600 mg tablet orally once daily in the evening co-administered with combination therapy containing zidovudine 300 mg and lamivudine 150 mg (combivir [CBV]) tablet orally twice daily, during the DB phase.
Measure Participants	360	361
Less than 400 copies/mL	75.00 43.1%	78.27 21.7%
Less than 50 copies/mL	70.00 40.2%	74.44 20.7%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Maraviroc Once Daily + CBV (DB), Then Twice Daily + CBV (OL), Maraviroc Twice Daily + CBV (DB)
	Comments	Less than 400 copies/mL: Treatment difference in percentage stratified by randomization strata (screening viral load and geographic region) was presented along with the lower bound of the 1-sided 97.5% CI based on the normal approximation to the binomial distribution. Positive value would favor maraviroc. Step down procedure used to control for multiple comparisons.
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	Non-inferiority was to be concluded if the lower bound of the 1-sided 97.5% CI was > -10%.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Difference in Percentage
	Estimated Value	-4.1
	Confidence Interval	(1-Sided) 97.5%; -10.5 to
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Maraviroc Once Daily + CBV (DB), Then Twice Daily + CBV (OL), Maraviroc Twice Daily + CBV (DB)
	Comments	Less than 50 copies/mL: Treatment difference in percentage stratified by randomization strata (screening viral load and geographic region) was presented along with the lower bound of the 1-sided 97.5% CI based on the normal approximation to the binomial distribution. Positive value would favor maraviroc. Step down procedure used to control for multiple comparisons.
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	Non-inferiority was to be concluded if the lower bound of the 1-sided 97.5% CI was > -10%.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Difference in Percentage
	Estimated Value	-4.4
	Confidence Interval	(1-Sided) 97.5%; -11.2 to
	Parameter Dispersion	Type: Value:
	Estimation Comments

3. Secondary Outcome

Title	Percentage of Participants With HIV-1 RNA Levels of Less Than 400 Copies/mL and Less Than 50 Copies/mL at Week 48 Analyzed Using Logistic Regression
Time Frame	Week 48

Outcome Measure Data

Analysis Population Description

FAS population included all the randomized participants who had taken at least 1 dose of the study medication. Missing data (MD) imputed as failure (F); that is, participants with missing data classified as not achieving the viral load criterion (MD=F).

Arm/Group Title	Maraviroc Once Daily + CBV (DB), Then Twice Daily + CBV (OL)	Maraviroc Twice Daily + CBV (DB)	Efavirenz Once Daily + CBV (DB)
Arm/Group Description	Maraviroc 300 milligram (mg) tablet orally once daily in the evening along with placebo matched to maraviroc 300 mg tablet orally once daily in the morning and placebo matched to efavirenz 600 mg tablet orally once daily in the evening co-administered with combination therapy containing zidovudine 300 mg and lamivudine 150 mg (combivir [CBV]) tablet orally twice daily, during the DB phase prior to the termination of the treatment arm based on the recommendation of the DSMB following a planned interim analysis. Eligible participants then switched to open-label maraviroc 300 mg tablet orally twice daily co-administered with combination therapy containing zidovudine 300 mg and lamivudine 150 mg (combivir [CBV]) tablet orally twice daily for the remainder of the study.	Maraviroc 300 mg tablet orally twice daily and placebo matched to efavirenz 600 mg tablet orally once daily in the evening co-administered with combination therapy containing zidovudine 300 mg and lamivudine 150 mg (combivir [CBV]) tablet orally twice daily, during the DB phase.	Placebo matched to maraviroc 300 mg tablet orally twice daily and efavirenz 600 mg tablet orally once daily in the evening co-administered with combination therapy containing zidovudine 300 mg and lamivudine 150 mg (combivir [CBV]) tablet orally twice daily, during the DB phase.
Measure Participants	174	360	361
Less than 400 copies/mL	61.5 35.3%	70.6 19.6%	73.1 20.2%
Less than 50 copies/mL	55.8 32.1%	65.3 18.1%	69.3 19.2%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Maraviroc Twice Daily + CBV (DB), Efavirenz Once Daily + CBV (DB)
	Comments	Less than 400 copies/mL: Two-sided 95% CI was presented for the odds ratio between treatment groups. CIs were calculated using the Wald-approximation. Logistic model with treatment, screening HIV concentrations (<100,000 or >=100,000), geographic region (Northern or Southern Hemisphere) as covariates was used. Odds ratio > 1 would favor maraviroc.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.4485
	Comments
	Method	Regression, Logistic
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	0.88
	Confidence Interval	(2-Sided) 95%; 0.64 to 1.22
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Maraviroc Twice Daily + CBV (DB), Efavirenz Once Daily + CBV (DB)
	Comments	Less than 50 copies/mL: Two-sided 95% CI was presented for the odds ratio between treatment groups. CIs were calculated using the Wald-approximation. Logistic model with treatment, screening HIV concentrations (<100,000 or >=100,000), geographic region (Northern or Southern Hemisphere) as covariates were used. Odds ratio > 1 would favor maraviroc.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.2724
	Comments
	Method	Regression, Logistic
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	0.84
	Confidence Interval	(2-Sided) 95%; 0.61 to 1.15
	Parameter Dispersion	Type: Value:
	Estimation Comments

4. Secondary Outcome

Title	Percentage of Participants With HIV-1 RNA Levels of Less Than 400 Copies/mL and Less Than 50 Copies/mL at Week 96 Analyzed Using Logistic Regression
Time Frame	Week 96

Outcome Measure Data

Analysis Population Description

FAS population included all the randomized participants who had taken at least 1 dose of the study medication. Missing data (MD) imputed as failure (F); that is, participants with missing data classified as not achieving the viral load criterion (MD=F).

Arm/Group Title	Maraviroc Once Daily + CBV (DB), Then Twice Daily + CBV (OL)	Maraviroc Twice Daily + CBV (DB)	Efavirenz Once Daily + CBV (DB)
Arm/Group Description	Maraviroc 300 milligram (mg) tablet orally once daily in the evening along with placebo matched to maraviroc 300 mg tablet orally once daily in the morning and placebo matched to efavirenz 600 mg tablet orally once daily in the evening co-administered with combination therapy containing zidovudine 300 mg and lamivudine 150 mg (combivir [CBV]) tablet orally twice daily, during the DB phase prior to the termination of the treatment arm based on the recommendation of the DSMB following a planned interim analysis. Eligible participants then switched to open-label maraviroc 300 mg tablet orally twice daily co-administered with combination therapy containing zidovudine 300 mg and lamivudine 150 mg (combivir [CBV]) tablet orally twice daily for the remainder of the study.	Maraviroc 300 mg tablet orally twice daily and placebo matched to efavirenz 600 mg tablet orally once daily in the evening co-administered with combination therapy containing zidovudine 300 mg and lamivudine 150 mg (combivir [CBV]) tablet orally twice daily, during the DB phase.	Placebo matched to maraviroc 300 mg tablet orally twice daily and efavirenz 600 mg tablet orally once daily in the evening co-administered with combination therapy containing zidovudine 300 mg and lamivudine 150 mg (combivir [CBV]) tablet orally twice daily, during the DB phase.
Measure Participants	174	360	361
Less than 400 copies/mL	52.9 30.4%	61.4 17.1%	64.5 17.9%
Less than 50 copies/mL	48.3 27.8%	56.9 15.8%	62.6 17.3%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Maraviroc Twice Daily + CBV (DB), Efavirenz Once Daily + CBV (DB)
	Comments	Less than 400 copies/mL: Two-sided 95% CI was presented for the odds ratio between treatment groups. CIs were calculated using the Wald-approximation. Logistic model with treatment, screening HIV concentrations (<100,000 or >=100,000), geographic region (Northern or Southern Hemisphere) as covariates were used. Odds ratio > 1 would favor maraviroc.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.3943
	Comments
	Method	Regression, Logistic
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	0.88
	Confidence Interval	(2-Sided) 95%; 0.65 to 1.19
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Maraviroc Twice Daily + CBV (DB), Efavirenz Once Daily + CBV (DB)
	Comments	Less than 50 copies/mL: Two-sided 95% CI was presented for the odds ratio between treatment groups. CIs were calculated using the Wald-approximation. Logistic model with treatment, screening HIV concentrations (<100,000 or >=100,000), geographic region (Northern or Southern Hemisphere) as covariates were used. Odds ratio > 1 would favor maraviroc.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.1289
	Comments
	Method	Regression, Logistic
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	0.79
	Confidence Interval	(2-Sided) 95%; 0.59 to 1.07
	Parameter Dispersion	Type: Value:
	Estimation Comments

5. Secondary Outcome

Title	Change From Baseline in Log 10-transformed Plasma Viral Load (HIV-1 RNA) Levels at Week 48 and 96
Description	Change from baseline in log 10-transformed plasma viral load (HIV-1 RNA) levels (log10 copies/mL). Baseline value calculated as average of pre-dose measurements collected at screening, randomization, and immediately pre-dose.
Time Frame	Baseline, Week 48, Week 96

Outcome Measure Data

Analysis Population Description

FAS population. Missing values for viral load at week 48 and 96 were imputed as baseline value for participants who discontinued and as last observation carried forward (LOCF) for participants who did not discontinue for maraviroc twice daily and efavirenz once daily arm and as LOCF for participants randomized to maraviroc once daily arm.

Arm/Group Title	Maraviroc Once Daily + CBV (DB), Then Twice Daily + CBV (OL)	Maraviroc Twice Daily + CBV (DB)	Efavirenz Once Daily + CBV (DB)
Arm/Group Description	Maraviroc 300 milligram (mg) tablet orally once daily in the evening along with placebo matched to maraviroc 300 mg tablet orally once daily in the morning and placebo matched to efavirenz 600 mg tablet orally once daily in the evening co-administered with combination therapy containing zidovudine 300 mg and lamivudine 150 mg (combivir [CBV]) tablet orally twice daily, during the DB phase prior to the termination of the treatment arm based on the recommendation of the DSMB following a planned interim analysis. Eligible participants then switched to open-label maraviroc 300 mg tablet orally twice daily co-administered with combination therapy containing zidovudine 300 mg and lamivudine 150 mg (combivir [CBV]) tablet orally twice daily for the remainder of the study.	Maraviroc 300 mg tablet orally twice daily and placebo matched to efavirenz 600 mg tablet orally once daily in the evening co-administered with combination therapy containing zidovudine 300 mg and lamivudine 150 mg (combivir [CBV]) tablet orally twice daily, during the DB phase.	Placebo matched to maraviroc 300 mg tablet orally twice daily and efavirenz 600 mg tablet orally once daily in the evening co-administered with combination therapy containing zidovudine 300 mg and lamivudine 150 mg (combivir [CBV]) tablet orally twice daily, during the DB phase.
Measure Participants	174	360	361
Baseline	4.899 (0.6273)	4.851 (0.6511)	4.857 (0.6156)
Change at Week 48	-2.665 (0.9454)	-2.240 (1.484)	-2.347 (1.455)
Change at Week 96	-2.565 (0.9731)	-1.961 (1.575)	-2.053 (1.564)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Maraviroc Twice Daily + CBV (DB), Efavirenz Once Daily + CBV (DB)
	Comments	Change at week 48: P-value was calculated using Analysis of Covariance (ANCOVA) with the model including treatment arm and, as covariates, the randomization strata (screening viral load and geographic region). The difference between the treatment least squares means (LS means) adjusted for the covariates was presented in addition to 2-sided 95% CI. Negative value would favor maraviroc.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.2741
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	0.118
	Confidence Interval	(2-Sided) 95%; -0.094 to 0.329
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.1077
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Maraviroc Twice Daily + CBV (DB), Efavirenz Once Daily + CBV (DB)
	Comments	Change at week 96: P-value was calculated using ANCOVA with the model including treatment arm and, as covariates, the randomization strata (screening viral load and geographic region). The difference between the treatment LS means adjusted for the covariates was presented in addition to 2-sided 95% CI. Negative value would favor maraviroc.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.3899
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	0.100
	Confidence Interval	(2-Sided) 95%; -0.128 to 0.328
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.1162
	Estimation Comments

6. Secondary Outcome

Title	Time-Averaged Difference (TAD) in log10-transformed HIV-1 RNA Levels
Description	TAD from baseline was calculated as area under the curve (AUC) of HIV-1 RNA load (log10 copies/mL) divided by time period minus baseline HIV-1 RNA load (log10 copies/mL). Baseline value calculated as average of pre-dose measurements collected at screening, randomization, and immediately pre-dose. Data not analyzed for participants originally randomized to maraviroc once daily arm since after termination, focus was shifted from efficacy and safety to only safety as reflected in the abbreviated set of efficacy measures noted in the amended planned analysis.
Time Frame	Baseline up to Week 48 and Week 96

Outcome Measure Data

Analysis Population Description

FAS population included all the randomized participants who had taken at least 1 dose of the study medication. TAD imputed as 0 for participants who discontinued. TAD calculated using the last non-missing value prior to the analysis time point for participants with a missing value at the analysis time point but who had not discontinued.

Arm/Group Title	Maraviroc Twice Daily + CBV (DB)	Efavirenz Once Daily + CBV (DB)
Arm/Group Description	Maraviroc 300 mg tablet orally twice daily and placebo matched to efavirenz 600 mg tablet orally once daily in the evening co-administered with combination therapy containing zidovudine 300 mg and lamivudine 150 mg (combivir [CBV]) tablet orally twice daily, during the DB phase.	Placebo matched to maraviroc 300 mg tablet orally twice daily and efavirenz 600 mg tablet orally once daily in the evening co-administered with combination therapy containing zidovudine 300 mg and lamivudine 150 mg (combivir [CBV]) tablet orally twice daily, during the DB phase.
Measure Participants	360	361
Week 48	-2.152 (0.0713)	-2.262 (0.0714)
Week 96	-1.945 (0.0798)	-2.034 (0.0800)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Maraviroc Once Daily + CBV (DB), Then Twice Daily + CBV (OL), Maraviroc Twice Daily + CBV (DB)
	Comments	Week 48: P-value was calculated using ANCOVA with the model including treatment arm and, as covariates, the randomization strata (screening viral load and geographic region). The difference between the treatment LS means adjusted for the covariates was presented in addition to 2-sided 95% CI. Negative value would favor maraviroc.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.2693
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	0.111
	Confidence Interval	(2-Sided) 95%; -0.086 to 0.307
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.1002
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Maraviroc Once Daily + CBV (DB), Then Twice Daily + CBV (OL), Maraviroc Twice Daily + CBV (DB)
	Comments	Week 96: P-value was calculated using ANCOVA with the model including treatment arm and, as covariates, the randomization strata (screening viral load and geographic region). The difference between the treatment LS means adjusted for the covariates was presented in addition to 2-sided 95% CI. Negative value would favor maraviroc.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.4270
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	0.089
	Confidence Interval	(2-Sided) 95%; -0.131 to 0.309
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.1121
	Estimation Comments

7. Secondary Outcome

Title	Change From Baseline in Lymphocyte Cluster of Differentiation 4 (CD4) Count at Week 48 and 96
Description	Baseline value calculated as the average of pre-dose measurements collected at screening and immediately pre-dose.
Time Frame	Baseline, Week 48, Week 96

Outcome Measure Data

Analysis Population Description

FAS population included all the randomized participants who had taken at least 1 dose of the study medication. 'N' (number of participants analyzed) signifies participants evaluable for this measure. Missing values were imputed using LOCF.

Arm/Group Title	Maraviroc Once Daily + CBV (DB), Then Twice Daily + CBV (OL)	Maraviroc Twice Daily + CBV (DB)	Efavirenz Once Daily + CBV (DB)
Arm/Group Description	Maraviroc 300 milligram (mg) tablet orally once daily in the evening along with placebo matched to maraviroc 300 mg tablet orally once daily in the morning and placebo matched to efavirenz 600 mg tablet orally once daily in the evening co-administered with combination therapy containing zidovudine 300 mg and lamivudine 150 mg (combivir [CBV]) tablet orally twice daily, during the DB phase prior to the termination of the treatment arm based on the recommendation of the DSMB following a planned interim analysis. Eligible participants then switched to open-label maraviroc 300 mg tablet orally twice daily co-administered with combination therapy containing zidovudine 300 mg and lamivudine 150 mg (combivir [CBV]) tablet orally twice daily for the remainder of the study.	Maraviroc 300 mg tablet orally twice daily and placebo matched to efavirenz 600 mg tablet orally once daily in the evening co-administered with combination therapy containing zidovudine 300 mg and lamivudine 150 mg (combivir [CBV]) tablet orally twice daily, during the DB phase.	Placebo matched to maraviroc 300 mg tablet orally twice daily and efavirenz 600 mg tablet orally once daily in the evening co-administered with combination therapy containing zidovudine 300 mg and lamivudine 150 mg (combivir [CBV]) tablet orally twice daily, during the DB phase.
Measure Participants	174	360	360
Baseline	274.1 (175.45)	264.70 (153.508)	271.87 (133.491)
Change at Week 48	172.50 (205.561)	169.53 (134.409)	143.52 (124.931)
Change at Week 96	183.75 (166.454)	206.31 (152.682)	171.50 (149.163)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Maraviroc Twice Daily + CBV (DB), Efavirenz Once Daily + CBV (DB)
	Comments	Change at Week 48: P-value was calculated using ANCOVA with the model including treatment arm and, as covariates, baseline CD4 count and the randomization strata (screening viral load and geographic region). The difference between the treatment LS means adjusted for the covariates was presented in addition to 2-sided 95% CI. Positive value would favor maraviroc.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0075
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	26.34
	Confidence Interval	(2-Sided) 95%; 7.04 to 45.63
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 9.827
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Maraviroc Twice Daily + CBV (DB), Efavirenz Once Daily + CBV (DB)
	Comments	Change at Week 96: P-value was calculated using ANCOVA with the model including treatment arm and, as covariates, baseline CD4 count and the randomization strata (screening viral load and geographic region). The difference between the treatment LS means adjusted for the covariates was presented in addition to 2-sided 95% CI. Positive value would favor maraviroc.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0020
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	35.44
	Confidence Interval	(2-Sided) 95%; 13.02 to 57.86
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 11.419
	Estimation Comments

8. Secondary Outcome

Title	Change From Baseline in Lymphocyte Cluster of Differentiation 8 (CD8) Count at Week 48 and 96
Description	Baseline value calculated as the average of pre-dose measurements collected at screening and immediately pre-dose. Change from baseline in lymphocyte CD8 count at Week 48 and 96 was not analyzed for participants originally randomized to maraviroc once daily arm since after termination, focus was shifted from efficacy and safety to only safety as reflected in the abbreviated set of efficacy measures noted in the amended planned analysis.
Time Frame	Baseline, Week 48, Week 96

Outcome Measure Data

Analysis Population Description

FAS population included all the randomized participants who had taken at least 1 dose of the study medication. 'N' (number of participants analyzed) signifies participants evaluable for this measure. Missing values were imputed using LOCF.

Arm/Group Title	Maraviroc Twice Daily + CBV (DB)	Efavirenz Once Daily + CBV (DB)
Arm/Group Description	Maraviroc 300 mg tablet orally twice daily and placebo matched to efavirenz 600 mg tablet orally once daily in the evening co-administered with combination therapy containing zidovudine 300 mg and lamivudine 150 mg (combivir [CBV]) tablet orally twice daily, during the DB phase.	Placebo matched to maraviroc 300 mg tablet orally twice daily and efavirenz 600 mg tablet orally once daily in the evening co-administered with combination therapy containing zidovudine 300 mg and lamivudine 150 mg (combivir [CBV]) tablet orally twice daily, during the DB phase.
Measure Participants	360	360
Baseline	938.80 (503.392)	935.78 (476.607)
Change at Week 48	38.34 (397.503)	-126.83 (374.494)
Change at Week 96	20.74 (412.081)	-150.27 (389.996)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Maraviroc Once Daily + CBV (DB), Then Twice Daily + CBV (OL), Maraviroc Twice Daily + CBV (DB)
	Comments	Change at Week 48: P-value was calculated using ANCOVA with the model including treatment arm and, as covariates, baseline CD8 count and the randomization strata (screening viral load and geographic region). The difference between the treatment LS means adjusted for the covariates was presented in addition to 2-sided 95% CI. Positive value would favor maraviroc.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	166.29
	Confidence Interval	(2-Sided) 95%; 117.13 to 215.46
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 25.040
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Maraviroc Once Daily + CBV (DB), Then Twice Daily + CBV (OL), Maraviroc Twice Daily + CBV (DB)
	Comments	Change at Week 96: P-value was calculated using ANCOVA with the model including treatment arm and, as covariates, baseline CD8 count and the randomization strata (screening viral load and geographic region). The difference between the treatment LS means adjusted for the covariates was presented in addition to 2-sided 95% CI. Positive value would favor maraviroc.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	172.22
	Confidence Interval	(2-Sided) 95%; 122.21 to 222.23
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 25.471
	Estimation Comments

9. Secondary Outcome

Title	Time to Virologic Failure
Description	Time to virologic failure based on observed HIV-1 RNA levels and failure events (death;permanent discontinuation of drug;lost to follow-up [LTFU];new anti-retroviral drug added [except background drug change to drug of same class];or on open label for early non-response or rebound). Failure:at Time 0 if level not <400 copies/mL(2 consecutive visits) before events or last available visit;at time of earliest event if level <400 copies/mL(2 consecutive visits);failure if level >=400 copies/mL(2 consecutive visits) or 1 visit >=400 copies/mL followed by permanent discontinuation of drug or LTFU.
Time Frame	Week 48, Week 96

Outcome Measure Data

Analysis Population Description

FAS population; Data not analyzed for participants originally randomized to maraviroc once daily arm since after termination, focus was shifted from efficacy and safety to only safety as reflected in the abbreviated set of efficacy measures noted in the amended planned analysis.

Arm/Group Title	Maraviroc Twice Daily + CBV (DB)	Efavirenz Once Daily + CBV (DB)
Arm/Group Description	Maraviroc 300 mg tablet orally twice daily and placebo matched to efavirenz 600 mg tablet orally once daily in the evening co-administered with combination therapy containing zidovudine 300 mg and lamivudine 150 mg (combivir [CBV]) tablet orally twice daily, during the DB phase.	Placebo matched to maraviroc 300 mg tablet orally twice daily and efavirenz 600 mg tablet orally once daily in the evening co-administered with combination therapy containing zidovudine 300 mg and lamivudine 150 mg (combivir [CBV]) tablet orally twice daily, during the DB phase.
Measure Participants	360	361
Week 48	NA	NA
Week 96	NA	NA

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Maraviroc Once Daily + CBV (DB), Then Twice Daily + CBV (OL), Maraviroc Twice Daily + CBV (DB)
	Comments	Week 48: P-value was calculated using Log rank test controlling for the effect of the randomization strata. Hazard ratio was calculated by fitting a Cox proportional hazards model including treatment group and the two randomization strata, HIV-1 RNA at screening and geographic region. Hazard ratio < 1 would favor maraviroc.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.5874
	Comments
	Method	Log Rank
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	1.10
	Confidence Interval	(2-Sided) 95%; 0.83 to 1.45
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Maraviroc Once Daily + CBV (DB), Then Twice Daily + CBV (OL), Maraviroc Twice Daily + CBV (DB)
	Comments	Week 96: P-value was calculated using Log rank test controlling for the effect of the randomization strata. Hazard ratio was calculated by fitting a Cox proportional hazards model including treatment group and the two randomization strata, HIV-1 RNA at screening and geographic region. Hazard ratio < 1 would favor maraviroc.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.4811
	Comments
	Method	Log Rank
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	1.10
	Confidence Interval	(2-Sided) 95%; 0.86 to 1.40
	Parameter Dispersion	Type: Value:
	Estimation Comments

10. Secondary Outcome

Title	Number of Participants Per Tropism Status at Baseline and at the Time of Treatment Failure Through Week 48
Description	Number of participants per tropism status (C-X-C chemokine receptor 5 {CCR5} [R5], C-X-C chemokine receptor type 4 {CXCR4} [X4], Dual/mixed [DM], or Non-reportable/Non-phenotypable [NR/NP]) at baseline and time of treatment failure analyzed through week 48 visit. Treatment failure: discontinuation due to insufficient clinical response. Tropism result was censored for participants with viral load <500 copies/mL at time of treatment failure categorized as below lower limit of quantification (BLQ). The assessment for time of treatment failure was defined as last on treatment assessment.
Time Frame	Baseline, time of failure through Week 48

Outcome Measure Data

Analysis Population Description

FAS population included all the randomized participants who had taken at least 1 dose of the study medication. 'N' (number of participants analyzed) is signifying those participants who experienced treatment failure, defined as discontinuation due to insufficient response and had tropism assessment at baseline.

Arm/Group Title	Maraviroc Once Daily + CBV (DB), Then Twice Daily + CBV (OL)	Maraviroc Twice Daily + CBV (DB)	Efavirenz Once Daily + CBV (DB)
Arm/Group Description	Maraviroc 300 milligram (mg) tablet orally once daily in the evening along with placebo matched to maraviroc 300 mg tablet orally once daily in the morning and placebo matched to efavirenz 600 mg tablet orally once daily in the evening co-administered with combination therapy containing zidovudine 300 mg and lamivudine 150 mg (combivir [CBV]) tablet orally twice daily, during the DB phase prior to the termination of the treatment arm based on the recommendation of the DSMB following a planned interim analysis. Eligible participants then switched to open-label maraviroc 300 mg tablet orally twice daily co-administered with combination therapy containing zidovudine 300 mg and lamivudine 150 mg (combivir [CBV]) tablet orally twice daily for the remainder of the study.	Maraviroc 300 mg tablet orally twice daily and placebo matched to efavirenz 600 mg tablet orally once daily in the evening co-administered with combination therapy containing zidovudine 300 mg and lamivudine 150 mg (combivir [CBV]) tablet orally twice daily, during the DB phase.	Placebo matched to maraviroc 300 mg tablet orally twice daily and efavirenz 600 mg tablet orally once daily in the evening co-administered with combination therapy containing zidovudine 300 mg and lamivudine 150 mg (combivir [CBV]) tablet orally twice daily, during the DB phase.
Measure Participants	20	42	15
Baseline: R5; Treatment failure: R5	5 2.9%	11 3.1%	6 1.7%
Baseline: R5; Treatment failure: X4	0 0%	0 0%	0 0%
Baseline: R5; Treatment failure: DM	3 1.7%	10 2.8%	0 0%
Baseline: R5; Treatment failure: NR/NP	5 2.9%	5 1.4%	4 1.1%
Baseline: DM; Treatment failure: R5	0 0%	1 0.3%	0 0%
Baseline: DM; Treatment failure: X4	0 0%	2 0.6%	0 0%
Baseline: DM; Treatment failure: DM	5 2.9%	4 1.1%	0 0%
Baseline: DM; Treatment failure: NR/NP	0 0%	0 0%	0 0%

11. Secondary Outcome

Title	Number of Participants Per Tropism Status at Baseline and at the Time of Treatment Failure Through Week 96
Description	Number of participants per tropism status (R5, X4, DM, or NR/NP) at baseline and time of treatment failure analyzed through week 96 visit. Treatment failure defined as insufficient clinical response. Tropism result was censored for participants with viral load <500 copies/mL at time of treatment failure categorized as BLQ. The assessment for time of treatment failure was defined as last on treatment assessment.
Time Frame	Baseline, time of failure through Week 96

Outcome Measure Data

Analysis Population Description

FAS population included all the randomized participants who had taken at least 1 dose of the study medication. 'N' (number of participants analyzed) is signifying those participants who experienced treatment failure, defined as discontinuation due to insufficient response and had tropism assessment at baseline.

Arm/Group Title	Maraviroc Once Daily + CBV (DB), Then Twice Daily + CBV (OL)	Maraviroc Twice Daily + CBV (DB)	Efavirenz Once Daily + CBV (DB)
Arm/Group Description	Maraviroc 300 milligram (mg) tablet orally once daily in the evening along with placebo matched to maraviroc 300 mg tablet orally once daily in the morning and placebo matched to efavirenz 600 mg tablet orally once daily in the evening co-administered with combination therapy containing zidovudine 300 mg and lamivudine 150 mg (combivir [CBV]) tablet orally twice daily, during the DB phase prior to the termination of the treatment arm based on the recommendation of the DSMB following a planned interim analysis. Eligible participants then switched to open-label maraviroc 300 mg tablet orally twice daily co-administered with combination therapy containing zidovudine 300 mg and lamivudine 150 mg (combivir [CBV]) tablet orally twice daily for the remainder of the study.	Maraviroc 300 mg tablet orally twice daily and placebo matched to efavirenz 600 mg tablet orally once daily in the evening co-administered with combination therapy containing zidovudine 300 mg and lamivudine 150 mg (combivir [CBV]) tablet orally twice daily, during the DB phase.	Placebo matched to maraviroc 300 mg tablet orally twice daily and efavirenz 600 mg tablet orally once daily in the evening co-administered with combination therapy containing zidovudine 300 mg and lamivudine 150 mg (combivir [CBV]) tablet orally twice daily, during the DB phase.
Measure Participants	27	54	23
Baseline: R5; Treatment failure: R5	9 5.2%	14 3.9%	10 2.8%
Baseline: R5; Treatment failure: X4	0 0%	1 0.3%	0 0%
Baseline: R5; Treatment failure: DM	4 2.3%	11 3.1%	0 0%
Baseline: R5; Treatment failure: NR/NP	6 3.4%	7 1.9%	5 1.4%
Baseline: DM; Treatment failure: R5	0 0%	1 0.3%	1 0.3%
Baseline: DM; Treatment failure: X4	0 0%	2 0.6%	0 0%
Baseline: DM; Treatment failure: DM	5 2.9%	4 1.1%	0 0%
Baseline: DM; Treatment failure: NR/NP	0 0%	0 0%	0 0%
Baseline: NR/NP; Treatment failure: R5	0 0%	1 0.3%	0 0%
Baseline: NR/NP; Treatment failure: X4	0 0%	0 0%	0 0%
Baseline: NR/NP; Treatment failure: DM	0 0%	0 0%	0 0%
Baseline: NR/NP; Treatment failure: NR/NP	0 0%	1 0.3%	0 0%

12. Secondary Outcome

Title	Number of Participants With Phenotypic Resistance at Time of Treatment Failure Through Week 48 and 96
Description	Phenotypic resistance to nucleoside reverse transcriptase inhibitors (NRTIs) and non-nucleoside reverse transcriptase inhibitors (NNRTIs) assessed at screening by Monogram Bioscience PhenoSense genotype (MBPSGT) assay, repeated if viral load >500 copies/mL at treatment failure through week 48, 96. Phenotypic resistance to maraviroc was assumed in maraviroc treatment failures with X4-using virus and in R5 maraviroc treatment failures using Monogram Bioscience PhenoSense Entry Assay. Phenotypic resistance to zidovudine, lamivudine, efavirenz and maraviroc at time of failure was summarized.
Time Frame	Screening, time of failure through Week 48, Week 96

Outcome Measure Data

Analysis Population Description

FAS population included all the randomized participants who had taken at least 1 dose of the study medication. 'n' is signifying those participants who experienced treatment failure, defined as discontinuation due to insufficient response at specified time points for each arm group respectively.

Arm/Group Title	Maraviroc Once Daily + CBV (DB), Then Twice Daily + CBV (OL)	Maraviroc Twice Daily + CBV (DB)	Efavirenz Once Daily + CBV (DB)
Arm/Group Description	Maraviroc 300 milligram (mg) tablet orally once daily in the evening along with placebo matched to maraviroc 300 mg tablet orally once daily in the morning and placebo matched to efavirenz 600 mg tablet orally once daily in the evening co-administered with combination therapy containing zidovudine 300 mg and lamivudine 150 mg (combivir [CBV]) tablet orally twice daily, during the DB phase prior to the termination of the treatment arm based on the recommendation of the DSMB following a planned interim analysis. Eligible participants then switched to open-label maraviroc 300 mg tablet orally twice daily co-administered with combination therapy containing zidovudine 300 mg and lamivudine 150 mg (combivir [CBV]) tablet orally twice daily for the remainder of the study.	Maraviroc 300 mg tablet orally twice daily and placebo matched to efavirenz 600 mg tablet orally once daily in the evening co-administered with combination therapy containing zidovudine 300 mg and lamivudine 150 mg (combivir [CBV]) tablet orally twice daily, during the DB phase.	Placebo matched to maraviroc 300 mg tablet orally twice daily and efavirenz 600 mg tablet orally once daily in the evening co-administered with combination therapy containing zidovudine 300 mg and lamivudine 150 mg (combivir [CBV]) tablet orally twice daily, during the DB phase.
Measure Participants	174	360	361
Resistance to Zidovudine: Week 48 (n= 20, 43, 15)	0 0%	0 0%	0 0%
Resistance to Lamivudine: Week 48 (n= 20, 43, 15)	14 8%	27 7.5%	3 0.8%
Resistance to Efavirenz: Week 48 (n= 20, 43, 15)	0 0%	0 0%	7 1.9%
Resistance to Maraviroc: Week 48 (n= 20, 43, 15)	NA NaN	12 3.3%	NA NaN
Resistance to Zidovudine: Week 96 (n= 27, 55, 23)	0 0%	0 0%	0 0%
Resistance to Lamivudine: Week 96 (n= 27, 55, 23)	20 11.5%	33 9.2%	8 2.2%
Resistance to Efavirenz: Week 96 (n= 27, 55, 23)	0 0%	0 0%	13 3.6%
Resistance to Maraviroc: Week 96 (n= 27, 55, 23)	NA NaN	NA NaN	NA NaN

13. Secondary Outcome

Title	Number of Participants With NRTI Associated Mutations at Time of Treatment Failure Through Week 48 and 96
Description	Genotypic resistance to NRTIs was assessed by identification of relevant mutations at screening using MBPSGT assay and repeated for all participants with HIV-1 viral load more than 500 copies/mL at treatment failure through week 48 and week 96. Following mutations associated with NRTIs were summarized at time of failure: Any zidovudine/lamivudine (Zid/Lam), Any thymidine analogue-associated mutation (TAM), methionine (M) to valine/isoleucine (V/I) substitution at residue (r) 184 (M184V/I), lysine (K) to arginine (R) substitution at residue 65 (K65R) and any other NRTI mutations.
Time Frame	Screening, time of failure through Week 48, Week 96

Outcome Measure Data

Analysis Population Description

FAS population included all the randomized participants who had taken at least 1 dose of the study medication. 'n' is signifying those participants who experienced treatment failure, defined as discontinuation due to insufficient response at specified time points for each arm group respectively.

Arm/Group Title	Maraviroc Once Daily + CBV (DB), Then Twice Daily + CBV (OL)	Maraviroc Twice Daily + CBV (DB)	Efavirenz Once Daily + CBV (DB)
Arm/Group Description	Maraviroc 300 milligram (mg) tablet orally once daily in the evening along with placebo matched to maraviroc 300 mg tablet orally once daily in the morning and placebo matched to efavirenz 600 mg tablet orally once daily in the evening co-administered with combination therapy containing zidovudine 300 mg and lamivudine 150 mg (combivir [CBV]) tablet orally twice daily, during the DB phase prior to the termination of the treatment arm based on the recommendation of the DSMB following a planned interim analysis. Eligible participants then switched to open-label maraviroc 300 mg tablet orally twice daily co-administered with combination therapy containing zidovudine 300 mg and lamivudine 150 mg (combivir [CBV]) tablet orally twice daily for the remainder of the study.	Maraviroc 300 mg tablet orally twice daily and placebo matched to efavirenz 600 mg tablet orally once daily in the evening co-administered with combination therapy containing zidovudine 300 mg and lamivudine 150 mg (combivir [CBV]) tablet orally twice daily, during the DB phase.	Placebo matched to maraviroc 300 mg tablet orally twice daily and efavirenz 600 mg tablet orally once daily in the evening co-administered with combination therapy containing zidovudine 300 mg and lamivudine 150 mg (combivir [CBV]) tablet orally twice daily, during the DB phase.
Measure Participants	174	360	361
Any Zid/Lam Mutation: Week 48 (n= 20, 43, 15)	14 8%	27 7.5%	3 0.8%
Any TAM Mutation: Week 48 (n= 20, 43, 15)	1 0.6%	6 1.7%	0 0%
K65R Mutation: Week 48 (n= 20, 43, 15)	0 0%	1 0.3%	0 0%
M184V/I Mutation: Week 48 (n= 20, 43, 15)	14 8%	27 7.5%	3 0.8%
Other NRTI Mutation: Week 48 (n= 20, 43, 15)	0 0%	1 0.3%	0 0%
Any Zid/Lam Mutation: Week 96 (n= 27, 55, 23)	20 11.5%	33 9.2%	8 2.2%
Any TAM Mutation: Week 96 (n= 27, 55, 23)	3 1.7%	6 1.7%	2 0.6%
K65R Mutation: Week 96 (n= 27, 55, 23)	0 0%	1 0.3%	0 0%
M184V/I Mutation: Week 96 (n= 27, 55, 23)	20 11.5%	33 9.2%	8 2.2%
Other NRTI Mutation: Week 96 (n= 27, 55, 23)	0 0%	1 0.3%	0 0%

14. Secondary Outcome

Title	Number of Participants With Efavirenz Associated Mutations at Time of Treatment Failure Through Week 48 and 96
Description	Genotypic resistance: mutations at screening by MBPSGT assay, repeated if viral load >500 copies/mL at treatment failure through week 48, 96. Efavirenz mutation:lysine to aspargine at r103(K103N);tyrosine to cysteine/isoleucine at r181(Y181C/I);tyrosine to cysteine/leucine/histidine at r188(Y188C/L/H);glycine to alanine/serine at r190(G190A/S);valine to alanine to r106(V106A);leucine to isoleucine at r100(L100I);alanine to glycine at r98(A98G);lysine to glutamic acid at r101(K101E);valine to isoleucine at r108(V108I);proline to histidine at r225(P225H);methionine to leucine at r230(M230L).
Time Frame	Screening, time of failure through Week 48, Week 96

Outcome Measure Data

Analysis Population Description

FAS population; n=participants with treatment failure at specified time points for each arm group respectively. Data not analyzed for participants originally randomized to maraviroc once daily arm since after termination focus shifted from efficacy, safety to only safety as reflected in abbreviated set of efficacy noted in amended planned analysis.

Arm/Group Title	Maraviroc Twice Daily + CBV (DB)	Efavirenz Once Daily + CBV (DB)
Arm/Group Description	Maraviroc 300 mg tablet orally twice daily and placebo matched to efavirenz 600 mg tablet orally once daily in the evening co-administered with combination therapy containing zidovudine 300 mg and lamivudine 150 mg (combivir [CBV]) tablet orally twice daily, during the DB phase.	Placebo matched to maraviroc 300 mg tablet orally twice daily and efavirenz 600 mg tablet orally once daily in the evening co-administered with combination therapy containing zidovudine 300 mg and lamivudine 150 mg (combivir [CBV]) tablet orally twice daily, during the DB phase.
Measure Participants	360	361
L100I Mutation: Week 48 (n= 43, 15)	0 0%	0 0%
K103N Mutation: Week 48 (n= 43, 15)	0 0%	6 1.7%
V106M Mutation: Week 48 (n= 43, 15)	0 0%	0 0%
V108I Mutation: Week 48 (n= 43, 15)	1 0.6%	0 0%
Y181C/I Mutation: Week 48 (n= 43, 15)	0 0%	0 0%
Y188L Mutation: Week 48 (n= 43, 15)	0 0%	0 0%
G190S/A Mutation: Week 48 (n= 43, 15)	0 0%	1 0.3%
P225H Mutation: Week 48 (n= 43, 15)	0 0%	0 0%
L100I Mutation: Week 96 (n= 55, 23)	0 0%	0 0%
K103N Mutation: Week 96 (n= 55, 23)	0 0%	12 3.3%
V106M Mutation: Week 96 (n= 55, 23)	0 0%	1 0.3%
V108I Mutation: Week 96 (n= 55, 23)	1 0.6%	1 0.3%
Y181C/I Mutation: Week 96 (n= 55, 23)	0 0%	0 0%
Y188L Mutation: Week 96 (n= 55, 23)	0 0%	0 0%
G190S/A Mutation: Week 96 (n= 55, 23)	0 0%	2 0.6%
P225H Mutation: Week 96 (n= 55, 23)	0 0%	1 0.3%

15. Secondary Outcome

Title	Percentage of Participants With HIV-1 RNA Levels Less Than 50 Copies/mL at Week 48 and Week 96 by Overall Susceptibility Score (OSS) at Screening
Description	Association between baseline resistance and virological response was assessed as percentage of participants with HIV-1RNA levels less than 50 copies/mL by OSS at screening. OSS categorized as 0, 1, 2, >3 (maximum value of 6) and calculated as the sum of the net assessment of in-vitro phenotypic and genotypic susceptibility using a binary scoring system (0= resistant, 1= sensitive or susceptible) for each antiretroviral agent in OBT. Higher scores indicate greater susceptibility.
Time Frame	Baseline, Week 48, Week 96

Outcome Measure Data

Analysis Population Description

Data not analyzed because of insufficient diversity amongst participants with respect to baseline resistance due to the study entry criteria regarding baseline resistance.

Arm/Group Title	Maraviroc Once Daily + CBV (DB), Then Twice Daily + CBV (OL)	Maraviroc Twice Daily + CBV (DB)	Efavirenz Once Daily + CBV (DB)
Arm/Group Description	Maraviroc 300 milligram (mg) tablet orally once daily in the evening along with placebo matched to maraviroc 300 mg tablet orally once daily in the morning and placebo matched to efavirenz 600 mg tablet orally once daily in the evening co-administered with combination therapy containing zidovudine 300 mg and lamivudine 150 mg (combivir [CBV]) tablet orally twice daily, during the DB phase prior to the termination of the treatment arm based on the recommendation of the DSMB following a planned interim analysis. Eligible participants then switched to open-label maraviroc 300 mg tablet orally twice daily co-administered with combination therapy containing zidovudine 300 mg and lamivudine 150 mg (combivir [CBV]) tablet orally twice daily for the remainder of the study.	Maraviroc 300 mg tablet orally twice daily and placebo matched to efavirenz 600 mg tablet orally once daily in the evening co-administered with combination therapy containing zidovudine 300 mg and lamivudine 150 mg (combivir [CBV]) tablet orally twice daily, during the DB phase.	Placebo matched to maraviroc 300 mg tablet orally twice daily and efavirenz 600 mg tablet orally once daily in the evening co-administered with combination therapy containing zidovudine 300 mg and lamivudine 150 mg (combivir [CBV]) tablet orally twice daily, during the DB phase.
Measure Participants	0	0	0

16. Other Pre-specified Outcome

Title	Percentage of Participants With Viral Load of Less Than 400 Copies/mL and Less Than 50 Copies/mL of HIV-1 RNA at Week 96
Time Frame	Week 96

Outcome Measure Data

Analysis Population Description

FAS population included all the randomized participants who had taken at least 1 dose of the study medication. Missing data (MD) imputed as failure (F); that is, participants with missing data classified as not achieving the viral load criterion (MD=F).

Arm/Group Title	Maraviroc Once Daily + CBV (DB), Then Twice Daily + CBV (OL)	Maraviroc Twice Daily + CBV (DB)	Efavirenz Once Daily + CBV (DB)
Arm/Group Description	Maraviroc 300 milligram (mg) tablet orally once daily in the evening along with placebo matched to maraviroc 300 mg tablet orally once daily in the morning and placebo matched to efavirenz 600 mg tablet orally once daily in the evening co-administered with combination therapy containing zidovudine 300 mg and lamivudine 150 mg (combivir [CBV]) tablet orally twice daily, during the DB phase prior to the termination of the treatment arm based on the recommendation of the DSMB following a planned interim analysis. Eligible participants then switched to open-label maraviroc 300 mg tablet orally twice daily co-administered with combination therapy containing zidovudine 300 mg and lamivudine 150 mg (combivir [CBV]) tablet orally twice daily for the remainder of the study.	Maraviroc 300 mg tablet orally twice daily and placebo matched to efavirenz 600 mg tablet orally once daily in the evening co-administered with combination therapy containing zidovudine 300 mg and lamivudine 150 mg (combivir [CBV]) tablet orally twice daily, during the DB phase.	Placebo matched to maraviroc 300 mg tablet orally twice daily and efavirenz 600 mg tablet orally once daily in the evening co-administered with combination therapy containing zidovudine 300 mg and lamivudine 150 mg (combivir [CBV]) tablet orally twice daily, during the DB phase.
Measure Participants	174	360	361
Less than 400 copies/mL	52.9 30.4%	61.4 17.1%	64.5 17.9%
Less than 50 copies/mL	48.3 27.8%	56.9 15.8%	62.6 17.3%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Maraviroc Twice Daily + CBV (DB), Efavirenz Once Daily + CBV (DB)
	Comments	Less than 400 copies/mL: Treatment difference in percentage stratified by randomization strata was presented along with the lower bound of the 1-sided 97.5% CI based on the normal approximation to the binomial distribution. Positive value would favor maraviroc. Step down procedure used to control for multiple comparisons.
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	Non-inferiority was to be concluded if the lower bound of the 1-sided 97.5% CI was greater than (>) -10%.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Difference in Percentage
	Estimated Value	-3.2
	Confidence Interval	(1-Sided) 97.5%; -10.2 to
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Maraviroc Twice Daily + CBV (DB), Efavirenz Once Daily + CBV (DB)
	Comments	Less than 50 copies/mL: Treatment difference in percentage stratified by randomization strata was presented along with the lower bound of the 1-sided 97.5% CI based on the normal approximation to the binomial distribution. Positive value would favor maraviroc. Step down procedure used to control for multiple comparisons.
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	Non-inferiority was to be concluded if the lower bound of the 1-sided 97.5% CI was > -10%.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Difference in Percentage
	Estimated Value	-5.8
	Confidence Interval	(1-Sided) 97.5%; -12.8 to
	Parameter Dispersion	Type: Value:
	Estimation Comments

17. Post-Hoc Outcome

Title	Percentage of Participants With HIV-1 RNA Levels of Less Than 400 Copies/mL and Less Than 50 Copies/mL at Week 48 for Enhanced Sensitivity Trofile Assay (ESTA) R5 Participants
Description	Percentage of participants with HIV-1 RNA levels of less than 400 copies/mL and less than 50 copies/mL were not analyzed for maraviroc once daily, then twice daily arm in order to avoid misinterpretation due to possible bias due to the fact that only a non-random sample of participants in the terminated arm were re-assayed with ESTA.
Time Frame	Week 48

Outcome Measure Data

Analysis Population Description

FAS population; 'N' number of participants analyzed included ESTA R5 participants who had R5 tropic virus by ESTA at screening. Missing data (MD) imputed as failure (F); that is, participants with missing data classified as not achieving the viral load criterion (MD=F).

Arm/Group Title	Maraviroc Twice Daily + CBV (DB)	Efavirenz Once Daily + CBV (DB)
Arm/Group Description	Maraviroc 300 mg tablet orally twice daily and placebo matched to efavirenz 600 mg tablet orally once daily in the evening co-administered with combination therapy containing zidovudine 300 mg and lamivudine 150 mg (combivir [CBV]) tablet orally twice daily, during the DB phase.	Placebo matched to maraviroc 300 mg tablet orally twice daily and efavirenz 600 mg tablet orally once daily in the evening co-administered with combination therapy containing zidovudine 300 mg and lamivudine 150 mg (combivir [CBV]) tablet orally twice daily, during the DB phase.
Measure Participants	311	303
Less than 400 copies/mL	73.3 42.1%	72.3 20.1%
Less than 50 copies/mL	68.5 39.4%	68.3 19%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Maraviroc Once Daily + CBV (DB), Then Twice Daily + CBV (OL), Maraviroc Twice Daily + CBV (DB)
	Comments	Less than 400 copies/mL: Treatment difference in percentage stratified by randomization strata was presented along with the lower bound of the 1-sided 97.5% CI based on the normal approximation to the binomial distribution. Positive value would favor maraviroc. Due to its post-hoc nature, this analysis was considered descriptive only rather than inferential.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Difference in Percentage
	Estimated Value	0.6
	Confidence Interval	(1-Sided) 97.5%; -6.4 to
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Maraviroc Once Daily + CBV (DB), Then Twice Daily + CBV (OL), Maraviroc Twice Daily + CBV (DB)
	Comments	Less than 50 copies/mL: Treatment difference in percentage stratified by randomization strata was presented along with the lower bound of the 1-sided 97.5% CI based on the normal approximation to the binomial distribution. Positive value would favor maraviroc. Due to its post-hoc nature, this analysis was considered descriptive only rather than inferential.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Difference in Percentage
	Estimated Value	-0.2
	Confidence Interval	(1-Sided) 97.5%; -7.4 to
	Parameter Dispersion	Type: Value:
	Estimation Comments

18. Post-Hoc Outcome

Title	Percentage of Participants With HIV-1 RNA Levels of Less Than 400 Copies/mL and Less Than 50 Copies/mL at Week 96 for Enhanced Sensitivity Trofile Assay (ESTA) R5 Participants
Description	Percentage of participants with HIV-1 RNA levels of less than 400 copies/mL and less than 50 copies/mL were not analyzed for maraviroc once daily, then twice daily arm in order to avoid misinterpretation due to possible bias due to the fact that only a non-random sample of participants in the terminated arm were re-assayed with ESTA.
Time Frame	Week 96

Outcome Measure Data

Analysis Population Description

FAS population; 'N' number of participants analyzed included ESTA R5 participants who had R5 tropic virus by ESTA at screening. Missing data (MD) imputed as failure (F); that is, participants with missing data classified as not achieving the viral load criterion (MD=F).

Arm/Group Title	Maraviroc Twice Daily + CBV (DB)	Efavirenz Once Daily + CBV (DB)
Arm/Group Description	Maraviroc 300 mg tablet orally twice daily and placebo matched to efavirenz 600 mg tablet orally once daily in the evening co-administered with combination therapy containing zidovudine 300 mg and lamivudine 150 mg (combivir [CBV]) tablet orally twice daily, during the DB phase.	Placebo matched to maraviroc 300 mg tablet orally twice daily and efavirenz 600 mg tablet orally once daily in the evening co-administered with combination therapy containing zidovudine 300 mg and lamivudine 150 mg (combivir [CBV]) tablet orally twice daily, during the DB phase.
Measure Participants	311	303
Less than 400 copies/mL	64.0 36.8%	64.4 17.9%
Less than 50 copies/mL	58.8 33.8%	62.7 17.4%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Maraviroc Once Daily + CBV (DB), Then Twice Daily + CBV (OL), Maraviroc Twice Daily + CBV (DB)
	Comments	Less than 400 copies/mL: Treatment difference in percentage stratified by randomization strata was presented along with the lower bound of the 1-sided 97.5% CI based on the normal approximation to the binomial distribution. Positive value would favor maraviroc. Due to its post-hoc nature, this analysis was considered descriptive only rather than inferential.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Difference in Percentage
	Estimated Value	-0.4
	Confidence Interval	(1-Sided) 97.5%; -7.9 to
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Maraviroc Once Daily + CBV (DB), Then Twice Daily + CBV (OL), Maraviroc Twice Daily + CBV (DB)
	Comments	Less than 50 copies/mL: Treatment difference in percentage stratified by randomization strata was presented along with the lower bound of the 1-sided 97.5% CI based on the normal approximation to the binomial distribution. Positive value would favor maraviroc. Due to its post-hoc nature, this analysis was considered descriptive only rather than inferential.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Difference in Percentage
	Estimated Value	-3.9
	Confidence Interval	(1-Sided) 97.5%; -11.5 to
	Parameter Dispersion	Type: Value:
	Estimation Comments

Adverse Events

Adverse Event Reporting Description	The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Arm/Group Title	Maraviroc Once Daily + CBV (DB), Then Twice Daily + CBV (OL)		Maraviroc Twice Daily + CBV (DB and OL)		Efavirenz Once Daily + CBV (DB and OL)		Maraviroc Twice Daily + CBV (SP)
Arm/Group Description	Maraviroc 300 milligram (mg) tablet orally once daily in the evening along with placebo matched to maraviroc 300 mg tablet orally once daily in the morning and placebo matched to efavirenz 600 mg tablet orally once daily in the evening co-administered with combination therapy containing zidovudine 300 mg and lamivudine 150 mg (combivir [CBV]) tablet orally twice daily, during the DB phase prior to the termination of the treatment arm based on the recommendation of the DSMB following a planned interim analysis. Eligible participants then switched to open-label maraviroc 300 mg tablet orally twice daily co-administered with combination therapy containing zidovudine 300 mg and lamivudine 150 mg (combivir [CBV]) tablet orally twice daily for the remainder of the study.		Maraviroc 300 mg tablet orally twice daily and placebo matched to efavirenz 600 mg tablet orally once daily in the evening co-administered with combination therapy containing zidovudine 300 mg and lamivudine 150 mg (combivir [CBV]) tablet orally twice daily, during the DB phase. DB phase nominally ended at last participant's Week 96 visit. Maraviroc 300 mg tablet orally twice daily co-administered with combination therapy containing zidovudine 300 mg and lamivudine 150 mg (combivir [CBV]) tablet orally twice daily, during the open-label (OL) phase. OL phase continued for at least 3 years after DB phase.		Placebo matched to maraviroc 300 mg tablet orally twice daily and efavirenz 600 mg tablet orally once daily in the evening co-administered with combination therapy containing zidovudine 300 mg and lamivudine 150 mg (combivir [CBV]) tablet orally twice daily, during the DB phase. DB phase nominally ended at last participant's Week 96 visit. Efavirenz 600 mg tablet orally once daily in the evening co-administered with combination therapy containing zidovudine 300 mg and lamivudine 150 mg (combivir [CBV]) tablet orally twice daily, during the OL phase. OL phase continued for at least 3 years after DB phase.		Participants who remained on mararviroc until their open-label phase End-of-Study visit and for whom maraviroc was commercially or otherwise unavailable entered an additional supplemental phase (SP) (initially planned for 6 months and subsequently extended for another 6 months) which consisted of study visits at 3-month intervals and received maraviroc 300 mg tablet orally twice daily co-administered with combination therapy containing zidovudine 300 mg and lamivudine 150 mg (combivir [CBV]) tablet orally twice daily until maraviroc was commercially or otherwise available.
All Cause Mortality
	Maraviroc Once Daily + CBV (DB), Then Twice Daily + CBV (OL)		Maraviroc Twice Daily + CBV (DB and OL)		Efavirenz Once Daily + CBV (DB and OL)		Maraviroc Twice Daily + CBV (SP)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Maraviroc Once Daily + CBV (DB), Then Twice Daily + CBV (OL)		Maraviroc Twice Daily + CBV (DB and OL)		Efavirenz Once Daily + CBV (DB and OL)		Maraviroc Twice Daily + CBV (SP)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	47/174 (27%)		77/360 (21.4%)		82/361 (22.7%)		4/127 (3.1%)
Blood and lymphatic system disorders
Anaemia	6/174 (3.4%)		7/360 (1.9%)		6/361 (1.7%)		0/127 (0%)
Leukocytosis	0/174 (0%)		0/360 (0%)		1/361 (0.3%)		0/127 (0%)
Neutropenia	3/174 (1.7%)		2/360 (0.6%)		2/361 (0.6%)		0/127 (0%)
Pancytopenia	0/174 (0%)		0/360 (0%)		2/361 (0.6%)		0/127 (0%)
Cardiac disorders
Acute myocardial infarction	0/174 (0%)		1/360 (0.3%)		2/361 (0.6%)		0/127 (0%)
Angina unstable	1/174 (0.6%)		1/360 (0.3%)		1/361 (0.3%)		0/127 (0%)
Cardiopulmonary failure	0/174 (0%)		0/360 (0%)		1/361 (0.3%)		0/127 (0%)
Myocardial infarciton	0/174 (0%)		2/360 (0.6%)		1/361 (0.3%)		0/127 (0%)
Pericardial effusion	1/174 (0.6%)		0/360 (0%)		0/361 (0%)		0/127 (0%)
Pulseless electrical activity	0/174 (0%)		1/360 (0.3%)		0/361 (0%)		0/127 (0%)
Congenital, familial and genetic disorders
Bicuspid aortic valve	0/174 (0%)		0/360 (0%)		1/361 (0.3%)		0/127 (0%)
Tinnitus	1/174 (0.6%)		0/360 (0%)		0/361 (0%)		0/127 (0%)
Vertigo	1/174 (0.6%)		0/360 (0%)		0/361 (0%)		0/127 (0%)
Ear and labyrinth disorders
Haematotympanum	1/174 (0.6%)		0/360 (0%)		0/361 (0%)		0/127 (0%)
Eye disorders
Diabetic eye disease	0/174 (0%)		1/360 (0.3%)		0/361 (0%)		0/127 (0%)
Uveitis	0/174 (0%)		1/360 (0.3%)		0/361 (0%)		0/127 (0%)
Gastrointestinal disorders
Abdominal pain	1/174 (0.6%)		4/360 (1.1%)		1/361 (0.3%)		0/127 (0%)
Abdominal pain lower	1/174 (0.6%)		0/360 (0%)		0/361 (0%)		0/127 (0%)
Anal fistula	0/174 (0%)		1/360 (0.3%)		2/361 (0.6%)		0/127 (0%)
Ascites	1/174 (0.6%)		0/360 (0%)		0/361 (0%)		0/127 (0%)
Colitis	0/174 (0%)		0/360 (0%)		1/361 (0.3%)		0/127 (0%)
Diarrhoea	2/174 (1.1%)		2/360 (0.6%)		0/361 (0%)		0/127 (0%)
Duodenal ulcer	1/174 (0.6%)		0/360 (0%)		0/361 (0%)		0/127 (0%)
Gastric ulcer	0/174 (0%)		0/360 (0%)		1/361 (0.3%)		0/127 (0%)
Gastritis	0/174 (0%)		1/360 (0.3%)		1/361 (0.3%)		0/127 (0%)
Gastrointestinal haemorrhage	1/174 (0.6%)		0/360 (0%)		0/361 (0%)		0/127 (0%)
Haemorrhoids	1/174 (0.6%)		1/360 (0.3%)		0/361 (0%)		0/127 (0%)
Ileus	0/174 (0%)		0/360 (0%)		1/361 (0.3%)		0/127 (0%)
Inguinal hernia	0/174 (0%)		0/360 (0%)		1/361 (0.3%)		0/127 (0%)
Mesenteric vein thrombosis	0/174 (0%)		0/360 (0%)		1/361 (0.3%)		0/127 (0%)
Nausea	0/174 (0%)		1/360 (0.3%)		0/361 (0%)		0/127 (0%)
Pancreatitis	0/174 (0%)		1/360 (0.3%)		1/361 (0.3%)		0/127 (0%)
Rectal haemorrhage	0/174 (0%)		0/360 (0%)		1/361 (0.3%)		0/127 (0%)
Rectal polyp	1/174 (0.6%)		0/360 (0%)		0/361 (0%)		0/127 (0%)
Small intestinal obstruction	0/174 (0%)		1/360 (0.3%)		0/361 (0%)		0/127 (0%)
Vomiting	0/174 (0%)		2/360 (0.6%)		0/361 (0%)		0/127 (0%)
Umbilical hernia	0/174 (0%)		0/360 (0%)		0/361 (0%)		1/127 (0.8%)
General disorders
Asthenia	1/174 (0.6%)		0/360 (0%)		0/361 (0%)		0/127 (0%)
Chest pain	2/174 (1.1%)		0/360 (0%)		0/361 (0%)		0/127 (0%)
Influenza like illness	0/174 (0%)		0/360 (0%)		2/361 (0.6%)		0/127 (0%)
Pyrexia	4/174 (2.3%)		4/360 (1.1%)		5/361 (1.4%)		0/127 (0%)
Sudden cardiac death	0/174 (0%)		0/360 (0%)		1/361 (0.3%)		0/127 (0%)
Hepatobiliary disorders
Biliary colic	0/174 (0%)		0/360 (0%)		1/361 (0.3%)		0/127 (0%)
Cholelithiasis	0/174 (0%)		2/360 (0.6%)		2/361 (0.6%)		0/127 (0%)
Hepatitis	0/174 (0%)		0/360 (0%)		1/361 (0.3%)		0/127 (0%)
Hepatitis toxic	1/174 (0.6%)		0/360 (0%)		0/361 (0%)		0/127 (0%)
Hypertransaminasaemia	0/174 (0%)		1/360 (0.3%)		0/361 (0%)		0/127 (0%)
Immune system disorders
Anaphylactic shock	1/174 (0.6%)		0/360 (0%)		0/361 (0%)		0/127 (0%)
Drug hypersensitivity	0/174 (0%)		1/360 (0.3%)		0/361 (0%)		0/127 (0%)
Hypersensitivity	0/174 (0%)		0/360 (0%)		1/361 (0.3%)		0/127 (0%)
Infections and infestations
Anal abscess	0/174 (0%)		0/360 (0%)		1/361 (0.3%)		0/127 (0%)
Anal fistula infection	0/174 (0%)		1/360 (0.3%)		0/361 (0%)		0/127 (0%)
Anogenital warts	1/174 (0.6%)		1/360 (0.3%)		0/361 (0%)		0/127 (0%)
Appendicitis	0/174 (0%)		3/360 (0.8%)		3/361 (0.8%)		0/127 (0%)
Appendicitis perforated	0/174 (0%)		0/360 (0%)		1/361 (0.3%)		0/127 (0%)
Bronchitis	1/174 (0.6%)		0/360 (0%)		2/361 (0.6%)		1/127 (0.8%)
Bronchopneumonia	1/174 (0.6%)		1/360 (0.3%)		1/361 (0.3%)		0/127 (0%)
Cellulitis	0/174 (0%)		1/360 (0.3%)		1/361 (0.3%)		0/127 (0%)
Cryptosporidiosis infection	1/174 (0.6%)		0/360 (0%)		0/361 (0%)		0/127 (0%)
Disseminated tuberculosis	1/174 (0.6%)		0/360 (0%)		0/361 (0%)		0/127 (0%)
Diverticulitis	0/174 (0%)		0/360 (0%)		1/361 (0.3%)		0/127 (0%)
Hepatitis A	0/174 (0%)		1/360 (0.3%)		0/361 (0%)		0/127 (0%)
Hepatitis C	0/174 (0%)		1/360 (0.3%)		0/361 (0%)		0/127 (0%)
Herpes zoster	0/174 (0%)		0/360 (0%)		1/361 (0.3%)		0/127 (0%)
Intervertebral discitis	1/174 (0.6%)		0/360 (0%)		0/361 (0%)		0/127 (0%)
Lobar pneumonia	0/174 (0%)		2/360 (0.6%)		2/361 (0.6%)		0/127 (0%)
Localised infection	1/174 (0.6%)		0/360 (0%)		0/361 (0%)		0/127 (0%)
Lower respiratory tract infection	0/174 (0%)		1/360 (0.3%)		1/361 (0.3%)		0/127 (0%)
Meningitis	0/174 (0%)		1/360 (0.3%)		0/361 (0%)		0/127 (0%)
Meningitis bacterial	0/174 (0%)		1/360 (0.3%)		0/361 (0%)		0/127 (0%)
Neurosyphilis	0/174 (0%)		1/360 (0.3%)		1/361 (0.3%)		0/127 (0%)
Orchitis	1/174 (0.6%)		0/360 (0%)		0/361 (0%)		0/127 (0%)
Osteomyelitis	0/174 (0%)		0/360 (0%)		1/361 (0.3%)		0/127 (0%)
Parasitic gastroenteritis	1/174 (0.6%)		0/360 (0%)		0/361 (0%)		0/127 (0%)
Pelvic inflamatory disease	0/174 (0%)		0/360 (0%)		1/361 (0.3%)		0/127 (0%)
Penile infection	0/174 (0%)		1/360 (0.3%)		0/361 (0%)		0/127 (0%)
Peritoneal abscess	0/174 (0%)		0/360 (0%)		1/361 (0.3%)		0/127 (0%)
Pneumocystis jiroveci infection	1/174 (0.6%)		0/360 (0%)		0/361 (0%)		0/127 (0%)
Pneumocystis jiroveci pneumonia	1/174 (0.6%)		1/360 (0.3%)		0/361 (0%)		0/127 (0%)
Pneumonia	1/174 (0.6%)		3/360 (0.8%)		5/361 (1.4%)		0/127 (0%)
Pneumonia staphylococcal	0/174 (0%)		0/360 (0%)		1/361 (0.3%)		0/127 (0%)
Pulmonary tuberculosis	0/174 (0%)		2/360 (0.6%)		3/361 (0.8%)		0/127 (0%)
Sepsis	0/174 (0%)		0/360 (0%)		1/361 (0.3%)		0/127 (0%)
Sinobronchitis	0/174 (0%)		1/360 (0.3%)		0/361 (0%)		0/127 (0%)
Sinusitis	0/174 (0%)		1/360 (0.3%)		0/361 (0%)		0/127 (0%)
Staphylococcal bacteraemia	1/174 (0.6%)		0/360 (0%)		0/361 (0%)		0/127 (0%)
Staphylococcal infection	1/174 (0.6%)		0/360 (0%)		0/361 (0%)		0/127 (0%)
Subcutaneous abscess	0/174 (0%)		0/360 (0%)		2/361 (0.6%)		0/127 (0%)
Syphilis	0/174 (0%)		2/360 (0.6%)		0/361 (0%)		0/127 (0%)
Upper respiratory tract infection	0/174 (0%)		0/360 (0%)		1/361 (0.3%)		0/127 (0%)
Urinary tract infection	0/174 (0%)		0/360 (0%)		1/361 (0.3%)		0/127 (0%)
Injury, poisoning and procedural complications
Ankle fracture	1/174 (0.6%)		1/360 (0.3%)		1/361 (0.3%)		0/127 (0%)
Chest injury	0/174 (0%)		0/360 (0%)		1/361 (0.3%)		0/127 (0%)
Concussion	0/174 (0%)		0/360 (0%)		1/361 (0.3%)		0/127 (0%)
Femoral neck fracture	0/174 (0%)		1/360 (0.3%)		0/361 (0%)		0/127 (0%)
Head injury	0/174 (0%)		2/360 (0.6%)		0/361 (0%)		0/127 (0%)
Heart injury	0/174 (0%)		0/360 (0%)		1/361 (0.3%)		0/127 (0%)
Hip fracture	0/174 (0%)		1/360 (0.3%)		0/361 (0%)		0/127 (0%)
Human bite	0/174 (0%)		0/360 (0%)		1/361 (0.3%)		0/127 (0%)
Injury	0/174 (0%)		1/360 (0.3%)		0/361 (0%)		0/127 (0%)
Jaw fracture	2/174 (1.1%)		0/360 (0%)		0/361 (0%)		0/127 (0%)
Laceration	0/174 (0%)		0/360 (0%)		2/361 (0.6%)		0/127 (0%)
Limb injury	0/174 (0%)		1/360 (0.3%)		0/361 (0%)		0/127 (0%)
Multiple fracture	0/174 (0%)		1/360 (0.3%)		1/361 (0.3%)		0/127 (0%)
Overdose	0/174 (0%)		0/360 (0%)		2/361 (0.6%)		1/127 (0.8%)
Pubis fracture	0/174 (0%)		1/360 (0.3%)		0/361 (0%)		0/127 (0%)
Rib fracture	1/174 (0.6%)		0/360 (0%)		0/361 (0%)		0/127 (0%)
Skull fracture	1/174 (0.6%)		0/360 (0%)		0/361 (0%)		0/127 (0%)
Soft tissue injury	0/174 (0%)		0/360 (0%)		1/361 (0.3%)		0/127 (0%)
Spinal compression fracture	0/174 (0%)		1/360 (0.3%)		0/361 (0%)		0/127 (0%)
Tendon rupture	0/174 (0%)		1/360 (0.3%)		0/361 (0%)		0/127 (0%)
Whiplash injury	0/174 (0%)		0/360 (0%)		1/361 (0.3%)		0/127 (0%)
Injury	0/174 (0%)		0/360 (0%)		0/361 (0%)		1/127 (0.8%)
Back injury	0/174 (0%)		0/360 (0%)		0/361 (0%)		1/127 (0.8%)
Investigations
Alanine aminotransferase increased	1/174 (0.6%)		1/360 (0.3%)		1/361 (0.3%)		0/127 (0%)
Aspartate aminotransferase increased	0/174 (0%)		1/360 (0.3%)		2/361 (0.6%)		0/127 (0%)
Blood creatine phosphokinase increased	1/174 (0.6%)		2/360 (0.6%)		3/361 (0.8%)		0/127 (0%)
Blood lactate dehydrogenase increased	0/174 (0%)		0/360 (0%)		1/361 (0.3%)		0/127 (0%)
Blood sodium decreased	0/174 (0%)		0/360 (0%)		1/361 (0.3%)		0/127 (0%)
Gama-glutamytransferase increased	1/174 (0.6%)		0/360 (0%)		2/361 (0.6%)		0/127 (0%)
Haemoglobin decreased	0/174 (0%)		1/360 (0.3%)		0/361 (0%)		0/127 (0%)
Hepatic enzyme increased	1/174 (0.6%)		0/360 (0%)		1/361 (0.3%)		0/127 (0%)
Transaminases increased	0/174 (0%)		1/360 (0.3%)		1/361 (0.3%)		0/127 (0%)
Metabolism and nutrition disorders
Decreased appetite	1/174 (0.6%)		1/360 (0.3%)		0/361 (0%)		0/127 (0%)
Dehydration	0/174 (0%)		0/360 (0%)		1/361 (0.3%)		0/127 (0%)
Hyperkalaemia	0/174 (0%)		1/360 (0.3%)		0/361 (0%)		0/127 (0%)
Musculoskeletal and connective tissue disorders
Arthralgia	1/174 (0.6%)		0/360 (0%)		0/361 (0%)		0/127 (0%)
Back pain	0/174 (0%)		2/360 (0.6%)		0/361 (0%)		0/127 (0%)
Flank pain	0/174 (0%)		0/360 (0%)		1/361 (0.3%)		0/127 (0%)
Myalgia	1/174 (0.6%)		0/360 (0%)		0/361 (0%)		0/127 (0%)
Osteoarthritis	0/174 (0%)		1/360 (0.3%)		0/361 (0%)		0/127 (0%)
Pain in extremity	0/174 (0%)		1/360 (0.3%)		0/361 (0%)		0/127 (0%)
Rhabdomyolysis	1/174 (0.6%)		0/360 (0%)		0/361 (0%)		0/127 (0%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Basal cell carcinoma	0/174 (0%)		0/360 (0%)		1/361 (0.3%)		0/127 (0%)
Breast cancer in situ	1/174 (0.6%)		0/360 (0%)		0/361 (0%)		0/127 (0%)
Castleman's disease	0/174 (0%)		0/360 (0%)		1/361 (0.3%)		0/127 (0%)
Diffuse large B-cell lymphoma	0/174 (0%)		1/360 (0.3%)		0/361 (0%)		0/127 (0%)
Fibroma	1/174 (0.6%)		0/360 (0%)		0/361 (0%)		0/127 (0%)
Hoadgkin's disease	0/174 (0%)		2/360 (0.6%)		3/361 (0.8%)		0/127 (0%)
Kaposi's sarcoma	1/174 (0.6%)		0/360 (0%)		0/361 (0%)		0/127 (0%)
Metastases to bone	0/174 (0%)		1/360 (0.3%)		0/361 (0%)		0/127 (0%)
Metastatic neoplasm	0/174 (0%)		0/360 (0%)		1/361 (0.3%)		0/127 (0%)
Multiple myeloma	1/174 (0.6%)		0/360 (0%)		0/361 (0%)		0/127 (0%)
Nasopharyngeal cancer	0/174 (0%)		1/360 (0.3%)		0/361 (0%)		0/127 (0%)
Neoplasm	0/174 (0%)		1/360 (0.3%)		0/361 (0%)		0/127 (0%)
Non-Hodgkin's lymphoma	1/174 (0.6%)		0/360 (0%)		1/361 (0.3%)		0/127 (0%)
Non-small cell lung cancer	0/174 (0%)		0/360 (0%)		1/361 (0.3%)		0/127 (0%)
Rectal cancer	0/174 (0%)		0/360 (0%)		1/361 (0.3%)		0/127 (0%)
Squamous cell carcinoma	1/174 (0.6%)		0/360 (0%)		0/361 (0%)		0/127 (0%)
Thyroid cancer	0/174 (0%)		1/360 (0.3%)		0/361 (0%)		0/127 (0%)
Thyroid neoplasm	0/174 (0%)		1/360 (0.3%)		0/361 (0%)		0/127 (0%)
Vulval neoplasm	0/174 (0%)		0/360 (0%)		0/361 (0%)		0/127 (0%)
Nervous system disorders
Ataxia	0/174 (0%)		0/360 (0%)		2/361 (0.6%)		0/127 (0%)
Balance disorder	0/174 (0%)		0/360 (0%)		1/361 (0.3%)		0/127 (0%)
Cerebrovascular accident	0/174 (0%)		1/360 (0.3%)		0/361 (0%)		0/127 (0%)
Convulsion	1/174 (0.6%)		1/360 (0.3%)		2/361 (0.6%)		0/127 (0%)
Cranial nerve paralysis	0/174 (0%)		0/360 (0%)		1/361 (0.3%)		0/127 (0%)
Dysarthria	0/174 (0%)		1/360 (0.3%)		1/361 (0.3%)		0/127 (0%)
Dyspraxia	1/174 (0.6%)		0/360 (0%)		0/361 (0%)		0/127 (0%)
Encephalitis	1/174 (0.6%)		0/360 (0%)		0/361 (0%)		0/127 (0%)
Grand mal convulsion	0/174 (0%)		0/360 (0%)		1/361 (0.3%)		0/127 (0%)
Headache	1/174 (0.6%)		1/360 (0.3%)		1/361 (0.3%)		0/127 (0%)
Ischaemic stroke	0/174 (0%)		1/360 (0.3%)		0/361 (0%)		0/127 (0%)
Loss of consciousness	0/174 (0%)		2/360 (0.6%)		0/361 (0%)		0/127 (0%)
Monoparesis	0/174 (0%)		1/360 (0.3%)		0/361 (0%)		0/127 (0%)
Syncope	1/174 (0.6%)		1/360 (0.3%)		0/361 (0%)		0/127 (0%)
Thoracic outlet syndrome	0/174 (0%)		1/360 (0.3%)		0/361 (0%)		0/127 (0%)
Transient ischaemic attack	1/174 (0.6%)		0/360 (0%)		0/361 (0%)		0/127 (0%)
Vascular demetia	0/174 (0%)		1/360 (0.3%)		0/361 (0%)		0/127 (0%)
Pregnancy, puerperium and perinatal conditions
Abortion	0/174 (0%)		0/360 (0%)		1/361 (0.3%)		0/127 (0%)
Abortion spontaneous	0/174 (0%)		0/360 (0%)		1/361 (0.3%)		0/127 (0%)
Pregnancy	3/174 (1.7%)		5/360 (1.4%)		8/361 (2.2%)		0/127 (0%)
Psychiatric disorders
Completed suicide	1/174 (0.6%)		0/360 (0%)		0/361 (0%)		0/127 (0%)
Depression	1/174 (0.6%)		2/360 (0.6%)		0/361 (0%)		0/127 (0%)
Depression suicidal	1/174 (0.6%)		0/360 (0%)		0/361 (0%)		0/127 (0%)
Drug abuse	0/174 (0%)		1/360 (0.3%)		0/361 (0%)		0/127 (0%)
Drug dependence	1/174 (0.6%)		0/360 (0%)		0/361 (0%)		0/127 (0%)
Intentional self-injury	0/174 (0%)		1/360 (0.3%)		1/361 (0.3%)		0/127 (0%)
Major depression	0/174 (0%)		1/360 (0.3%)		0/361 (0%)		0/127 (0%)
Mental status changes	1/174 (0.6%)		0/360 (0%)		0/361 (0%)		0/127 (0%)
Post-traumatic stress disorder	0/174 (0%)		1/360 (0.3%)		0/361 (0%)		0/127 (0%)
Suicidal ideation	1/174 (0.6%)		0/360 (0%)		0/361 (0%)		0/127 (0%)
Suicide attempt	2/174 (1.1%)		0/360 (0%)		2/361 (0.6%)		0/127 (0%)
Renal and urinary disorders
Calculus bladder	0/174 (0%)		0/360 (0%)		1/361 (0.3%)		0/127 (0%)
Haematuria	0/174 (0%)		0/360 (0%)		1/361 (0.3%)		0/127 (0%)
Nephrolithiasis	1/174 (0.6%)		0/360 (0%)		0/361 (0%)		0/127 (0%)
Renal failure	0/174 (0%)		0/360 (0%)		1/361 (0.3%)		0/127 (0%)
Renal failure acute	1/174 (0.6%)		0/360 (0%)		1/361 (0.3%)		0/127 (0%)
Reproductive system and breast disorders
Cervix haemorrhage uterine	1/174 (0.6%)		0/360 (0%)		0/361 (0%)		0/127 (0%)
Epididymitis	0/174 (0%)		1/360 (0.3%)		0/361 (0%)		0/127 (0%)
Ovarian cyst	0/174 (0%)		0/360 (0%)		1/361 (0.3%)		0/127 (0%)
Testicular pain	0/174 (0%)		1/360 (0.3%)		0/361 (0%)		0/127 (0%)
Uterine cervical laceration	1/174 (0.6%)		0/360 (0%)		0/361 (0%)		0/127 (0%)
Respiratory, thoracic and mediastinal disorders
Atelectasis	1/174 (0.6%)		0/360 (0%)		0/361 (0%)		0/127 (0%)
Haemoptysis	1/174 (0.6%)		0/360 (0%)		0/361 (0%)		0/127 (0%)
Pleural effusion	1/174 (0.6%)		0/360 (0%)		0/361 (0%)		0/127 (0%)
Pneumothorax	0/174 (0%)		0/360 (0%)		1/361 (0.3%)		0/127 (0%)
Pulmonary embolism	1/174 (0.6%)		3/360 (0.8%)		0/361 (0%)		0/127 (0%)
Skin and subcutaneous tissue disorders
Dermal cyst	0/174 (0%)		0/360 (0%)		1/361 (0.3%)		0/127 (0%)
Drug eruption	0/174 (0%)		1/360 (0.3%)		0/361 (0%)		0/127 (0%)
Penile ulceration	0/174 (0%)		1/360 (0.3%)		0/361 (0%)		0/127 (0%)
Rash	1/174 (0.6%)		0/360 (0%)		1/361 (0.3%)		0/127 (0%)
Rash erythematous	1/174 (0.6%)		0/360 (0%)		0/361 (0%)		0/127 (0%)
Rash pruritic	0/174 (0%)		0/360 (0%)		1/361 (0.3%)		0/127 (0%)
Stevens-Johnson syndrome	1/174 (0.6%)		0/360 (0%)		0/361 (0%)		0/127 (0%)
Social circumstances
Drug abuser	1/174 (0.6%)		0/360 (0%)		0/361 (0%)		0/127 (0%)
Pregnancy of partner	0/174 (0%)		1/360 (0.3%)		0/361 (0%)		0/127 (0%)
Surgical and medical procedures
Cholecystectomy	0/174 (0%)		1/360 (0.3%)		0/361 (0%)		0/127 (0%)
Finger amputation	0/174 (0%)		1/360 (0.3%)		0/361 (0%)		0/127 (0%)
Vascular disorders
Deep vein thrombosis	0/174 (0%)		1/360 (0.3%)		1/361 (0.3%)		0/127 (0%)
Hypertension	1/174 (0.6%)		0/360 (0%)		0/361 (0%)		0/127 (0%)
Other (Not Including Serious) Adverse Events
	Maraviroc Once Daily + CBV (DB), Then Twice Daily + CBV (OL)		Maraviroc Twice Daily + CBV (DB and OL)		Efavirenz Once Daily + CBV (DB and OL)		Maraviroc Twice Daily + CBV (SP)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	151/174 (86.8%)		319/360 (88.6%)		327/361 (90.6%)		0/127 (0%)
Blood and lymphatic system disorders
Anaemia	12/174 (6.9%)		27/360 (7.5%)		18/361 (5%)		0/127 (0%)
Eye disorders
Conjunctivitis	11/174 (6.3%)		11/360 (3.1%)		25/361 (6.9%)		0/127 (0%)
Gastrointestinal disorders
Abdominal distension	12/174 (6.9%)		21/360 (5.8%)		20/361 (5.5%)		0/127 (0%)
Abdominal pain	30/174 (17.2%)		53/360 (14.7%)		53/361 (14.7%)		0/127 (0%)
Abdominal pain upper	7/174 (4%)		22/360 (6.1%)		23/361 (6.4%)		0/127 (0%)
Constipation	13/174 (7.5%)		37/360 (10.3%)		20/361 (5.5%)		0/127 (0%)
Diarrhoea	46/174 (26.4%)		90/360 (25%)		111/361 (30.7%)		0/127 (0%)
Dyspepsia	9/174 (5.2%)		26/360 (7.2%)		38/361 (10.5%)		0/127 (0%)
Flatulence	10/174 (5.7%)		26/360 (7.2%)		13/361 (3.6%)		0/127 (0%)
Gastritis	5/174 (2.9%)		16/360 (4.4%)		22/361 (6.1%)		0/127 (0%)
Haemorrhoids	6/174 (3.4%)		25/360 (6.9%)		16/361 (4.4%)		0/127 (0%)
Nausea	60/174 (34.5%)		138/360 (38.3%)		132/361 (36.6%)		0/127 (0%)
Vomiting	28/174 (16.1%)		53/360 (14.7%)		61/361 (16.9%)		0/127 (0%)
General disorders
Asthenia	17/174 (9.8%)		29/360 (8.1%)		40/361 (11.1%)		0/127 (0%)
Chest pain	6/174 (3.4%)		17/360 (4.7%)		25/361 (6.9%)		0/127 (0%)
Fatigue	37/174 (21.3%)		64/360 (17.8%)		60/361 (16.6%)		0/127 (0%)
Influenza like illness	14/174 (8%)		21/360 (5.8%)		22/361 (6.1%)		0/127 (0%)
Pyrexia	16/174 (9.2%)		21/360 (5.8%)		30/361 (8.3%)		0/127 (0%)
Infections and infestations
Bronchitis	28/174 (16.1%)		64/360 (17.8%)		49/361 (13.6%)		0/127 (0%)
Gastroenteritis	10/174 (5.7%)		27/360 (7.5%)		33/361 (9.1%)		0/127 (0%)
Herpes zoster	4/174 (2.3%)		18/360 (5%)		16/361 (4.4%)		0/127 (0%)
Influenza	15/174 (8.6%)		56/360 (15.6%)		50/361 (13.9%)		0/127 (0%)
Nasopharyngitis	24/174 (13.8%)		70/360 (19.4%)		48/361 (13.3%)		0/127 (0%)
Pharyngitis	15/174 (8.6%)		24/360 (6.7%)		33/361 (9.1%)		0/127 (0%)
Sinusitis	4/174 (2.3%)		29/360 (8.1%)		28/361 (7.8%)		0/127 (0%)
Syphilis	10/174 (5.7%)		16/360 (4.4%)		13/361 (3.6%)		0/127 (0%)
Upper respiratory tract infection	32/174 (18.4%)		82/360 (22.8%)		78/361 (21.6%)		0/127 (0%)
Urinary tract infection	7/174 (4%)		15/360 (4.2%)		25/361 (6.9%)		0/127 (0%)
Investigations
Alanine aminotransferase increased	15/174 (8.6%)		20/360 (5.6%)		11/361 (3%)		0/127 (0%)
Aspartate aminotransferase increased	12/174 (6.9%)		13/360 (3.6%)		12/361 (3.3%)		0/127 (0%)
Metabolism and nutrition disorders
Decreased appetite	18/174 (10.3%)		34/360 (9.4%)		36/361 (10%)		0/127 (0%)
Musculoskeletal and connective tissue disorders
Arthralgia	17/174 (9.8%)		37/360 (10.3%)		30/361 (8.3%)		0/127 (0%)
Back pain	18/174 (10.3%)		44/360 (12.2%)		44/361 (12.2%)		0/127 (0%)
Muscle spasms	9/174 (5.2%)		16/360 (4.4%)		22/361 (6.1%)		0/127 (0%)
Myalgia	14/174 (8%)		29/360 (8.1%)		28/361 (7.8%)		0/127 (0%)
Pain in extremity	15/174 (8.6%)		27/360 (7.5%)		23/361 (6.4%)		0/127 (0%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Skin papilloma	10/174 (5.7%)		6/360 (1.7%)		14/361 (3.9%)		0/127 (0%)
Nervous system disorders
Dizziness	25/174 (14.4%)		62/360 (17.2%)		116/361 (32.1%)		0/127 (0%)
Dysgeusia	10/174 (5.7%)		10/360 (2.8%)		11/361 (3%)		0/127 (0%)
Headache	44/174 (25.3%)		109/360 (30.3%)		105/361 (29.1%)		0/127 (0%)
Paraesthesia	7/174 (4%)		19/360 (5.3%)		13/361 (3.6%)		0/127 (0%)
Somnolence	6/174 (3.4%)		18/360 (5%)		13/361 (3.6%)		0/127 (0%)
Psychiatric disorders
Abnormal dreams	20/174 (11.5%)		22/360 (6.1%)		46/361 (12.7%)		0/127 (0%)
Anxiety	8/174 (4.6%)		21/360 (5.8%)		26/361 (7.2%)		0/127 (0%)
Depression	18/174 (10.3%)		40/360 (11.1%)		28/361 (7.8%)		0/127 (0%)
Insomnia	20/174 (11.5%)		48/360 (13.3%)		44/361 (12.2%)		0/127 (0%)
Sleep disorder	7/174 (4%)		12/360 (3.3%)		19/361 (5.3%)		0/127 (0%)
Respiratory, thoracic and mediastinal disorders
Cough	22/174 (12.6%)		51/360 (14.2%)		66/361 (18.3%)		0/127 (0%)
Oropharyngeal pain	9/174 (5.2%)		30/360 (8.3%)		21/361 (5.8%)		0/127 (0%)
Skin and subcutaneous tissue disorders
Eczema	6/174 (3.4%)		9/360 (2.5%)		22/361 (6.1%)		0/127 (0%)
Lipodystrophy acquired	7/174 (4%)		12/360 (3.3%)		21/361 (5.8%)		0/127 (0%)
Pruritus	9/174 (5.2%)		8/360 (2.2%)		26/361 (7.2%)		0/127 (0%)
Rash	25/174 (14.4%)		38/360 (10.6%)		56/361 (15.5%)		0/127 (0%)
Vascular disorders
Hypertension	6/174 (3.4%)		25/360 (6.9%)		23/361 (6.4%)		0/127 (0%)

Limitations/Caveats

Following DSMB decision to discontinue maraviroc 300 mg once daily, inferential statistical analyses was performed between maraviroc 300 mg twice daily and efavirenz 600 mg once daily only. Data at Week 24 was not analyzed as planned in protocol.

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

Pfizer has the right to review disclosures, requesting a delay of less than 60 days. Investigator will postpone single center publications until after disclosure of pooled data (all sites), less than 12 months from study completion/termination at all participating sites. Investigator may not disclose previously undisclosed confidential information other than study results.