Trial Outcomes & Findings for Comparative Trial Of Maraviroc Versus Emtricitabine/Tenofovir Both With Darunavir/Ritonavir In Antiretroviral-Naive Patients Infected With CCR5 Tropic HIV 1 (NCT NCT01345630)

Last Updated: 2016-01-14

Results Overview

The proportion of participants who achieved HIV-1 RNA \<50 copies/mL at week 48 was assessed according to Food and Drug Administration's (FDA's) Missing, Switch, Discontinuation'=Failure (MSDF) Snapshot algorithm. The algorithm used the plasma HIV-1 RNA in the Week 48 visit window, followed the "virology-first principle" and considers a participant who has a missing plasma HIV-1 RNA, or switches to prohibited ARV regimen or discontinues from the study or study drug for any reason, or dies, as a failure.

Recruitment status

TERMINATED

Study phase

PHASE3

Target enrollment

813 participants

Primary outcome timeframe

Week 48

Results posted on

2016-01-14

Participant Flow

Overall, 1423 participants were screened and 813 participants randomized in the study. A total of 797 participants were treated (396 were treated in the maraviroc + darunavir/ritonavir \[MVC+DRV/r\] group and 401 in the emtricitabine/tenofovir + darunavir/ritonavir \[FTC/TDF+DRV/r\] group). The study was conducted in 138 sites in 18 countries.

Participants were randomized to undergo either genotype testing or enhanced Trofile assay (ESTA) in a 1:1 ratio. Among participants who were identified as being infected with R5 tropic HIV-1 by either testing methods, 813 were randomized in a 1:1 ratio to receive 96-week treatment either in the MVC+DRV/r arm or in the FTC/TDF+DRV/r arm.

Participant milestones

Participant milestones
Measure	MVC+DRV/r Participants infected with R5 HIV-1 received oral tablets of Maraviroc 150 mg once daily plus darunavir/ritonavir 800/100 mg once daily plus placebo for emtricitabine/tenofovir once daily.	FTC/TDF+DRV/r Participants infected with R5 HIV-1 received oral tablets of emtricitabine/tenofovir 200/300 mg once daily plus darunavir/ritonavir 800/100 mg once daily plus placebo for maraviroc once daily.
Overall Study STARTED	396	401
Overall Study COMPLETED	35	42
Overall Study NOT COMPLETED	361	359

Reasons for withdrawal

Reasons for withdrawal
Measure	MVC+DRV/r Participants infected with R5 HIV-1 received oral tablets of Maraviroc 150 mg once daily plus darunavir/ritonavir 800/100 mg once daily plus placebo for emtricitabine/tenofovir once daily.	FTC/TDF+DRV/r Participants infected with R5 HIV-1 received oral tablets of emtricitabine/tenofovir 200/300 mg once daily plus darunavir/ritonavir 800/100 mg once daily plus placebo for maraviroc once daily.
Overall Study Adverse Event	22	23
Overall Study Lost to Follow-up	17	16
Overall Study Protocol Violation	4	1
Overall Study Medication error without associated AE	0	1
Overall Study Study terminated by sponsor	254	285
Overall Study Other reasons	6	8
Overall Study Withdrawn due to pregnancy	1	2
Overall Study No longer willing to participate	9	12
Overall Study Insufficient clinical response	48	11

Baseline Characteristics

Comparative Trial Of Maraviroc Versus Emtricitabine/Tenofovir Both With Darunavir/Ritonavir In Antiretroviral-Naive Patients Infected With CCR5 Tropic HIV 1

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	MVC+DRV/r n=396 Participants Participants infected with R5 HIV-1 received oral tablets of Maraviroc 150 mg once daily plus darunavir/ritonavir 800/100 mg once daily plus placebo for emtricitabine/tenofovir once daily.	FTC/TDF+DRV/r n=401 Participants Participants infected with R5 HIV-1 received oral tablets of emtricitabine/tenofovir 200/300 mg once daily plus darunavir/ritonavir 800/100 mg once daily plus placebo for maraviroc once daily.	Total n=797 Participants Total of all reporting groups
Age, Continuous	37.9 Years STANDARD_DEVIATION 10.9 • n=5 Participants	36.2 Years STANDARD_DEVIATION 10.9 • n=7 Participants	37.1 Years STANDARD_DEVIATION 10.9 • n=5 Participants
Sex: Female, Male Female	36 Participants n=5 Participants	34 Participants n=7 Participants	70 Participants n=5 Participants
Sex: Female, Male Male	360 Participants n=5 Participants	367 Participants n=7 Participants	727 Participants n=5 Participants

PRIMARY outcome

Timeframe: Week 48

Population: The Full Analysis Set (FAS) consisted of all randomized participants who received at least one dose of the study drug. The missing value was imputed per FDA's MSDF Snapshot algorithm as described under "Outcome Measure Description" above.

Outcome measures

Outcome measures
Measure	MVC+DRV/r n=396 Participants Participants infected with R5 HIV-1 received oral tablets of Maraviroc 150 mg once daily plus darunavir/ritonavir 800/100 mg once daily plus placebo for emtricitabine/tenofovir once daily.	FTC/TDF+DRV/r n=401 Participants Participants infected with R5 HIV-1 received oral tablets of emtricitabine/tenofovir 200/300 mg once daily plus darunavir/ritonavir 800/100 mg once daily plus placebo for maraviroc once daily.	FTC/TDF+DRV/r - Baseline Participants infected with R5 HIV-1 received oral tablets of emtricitabine/tenofovir 200/300 mg once daily plus darunavir/ritonavir 800/100 mg once daily plus placebo for maraviroc once daily. Summary of tropism results by baseline.	FTC/TDF+DRV/r - Failure Participants infected with R5 HIV-1 received oral tablets of emtricitabine/tenofovir 200/300 mg once daily plus darunavir/ritonavir 800/100 mg once daily plus placebo for maraviroc once daily. Summary of tropism results corresponding to timepoint at or after PDTF.
Percentage of Participants With Plasma HIV-1 RNA <50 Copies/mL.	77.3 Percentage of participants	86.8 Percentage of participants	—	—

SECONDARY outcome

Timeframe: Week 96

Number of participants with treatment-emergent non serious AEs

Outcome measures

Outcome measures
Measure	MVC+DRV/r n=396 Participants Participants infected with R5 HIV-1 received oral tablets of Maraviroc 150 mg once daily plus darunavir/ritonavir 800/100 mg once daily plus placebo for emtricitabine/tenofovir once daily.	FTC/TDF+DRV/r n=401 Participants Participants infected with R5 HIV-1 received oral tablets of emtricitabine/tenofovir 200/300 mg once daily plus darunavir/ritonavir 800/100 mg once daily plus placebo for maraviroc once daily.	FTC/TDF+DRV/r - Baseline Participants infected with R5 HIV-1 received oral tablets of emtricitabine/tenofovir 200/300 mg once daily plus darunavir/ritonavir 800/100 mg once daily plus placebo for maraviroc once daily. Summary of tropism results by baseline.	FTC/TDF+DRV/r - Failure Participants infected with R5 HIV-1 received oral tablets of emtricitabine/tenofovir 200/300 mg once daily plus darunavir/ritonavir 800/100 mg once daily plus placebo for maraviroc once daily. Summary of tropism results corresponding to timepoint at or after PDTF.
Frequency of Adverse Events (AE).	360 participants	365 participants	—	—

SECONDARY outcome

Timeframe: Week 96

Number of participants with grade 3 or 4 AEs are presented here.

Outcome measures

Outcome measures
Measure	MVC+DRV/r n=396 Participants Participants infected with R5 HIV-1 received oral tablets of Maraviroc 150 mg once daily plus darunavir/ritonavir 800/100 mg once daily plus placebo for emtricitabine/tenofovir once daily.	FTC/TDF+DRV/r n=401 Participants Participants infected with R5 HIV-1 received oral tablets of emtricitabine/tenofovir 200/300 mg once daily plus darunavir/ritonavir 800/100 mg once daily plus placebo for maraviroc once daily.	FTC/TDF+DRV/r - Baseline Participants infected with R5 HIV-1 received oral tablets of emtricitabine/tenofovir 200/300 mg once daily plus darunavir/ritonavir 800/100 mg once daily plus placebo for maraviroc once daily. Summary of tropism results by baseline.	FTC/TDF+DRV/r - Failure Participants infected with R5 HIV-1 received oral tablets of emtricitabine/tenofovir 200/300 mg once daily plus darunavir/ritonavir 800/100 mg once daily plus placebo for maraviroc once daily. Summary of tropism results corresponding to timepoint at or after PDTF.
Number of Participants With Grade 3 or 4 AEs	65 participants	71 participants	—	—

SECONDARY outcome

Timeframe: Week 96

Number of participants who discontinued due to AEs are reported here. Three participants (two from the MVC+DRV/r arm and one from the FTC/TDF+DRV/r arm) were not considered as discontinued due to AE because other reasons for discontinuation were prioritized for these participants.

Outcome measures

Outcome measures
Measure	MVC+DRV/r n=396 Participants Participants infected with R5 HIV-1 received oral tablets of Maraviroc 150 mg once daily plus darunavir/ritonavir 800/100 mg once daily plus placebo for emtricitabine/tenofovir once daily.	FTC/TDF+DRV/r n=401 Participants Participants infected with R5 HIV-1 received oral tablets of emtricitabine/tenofovir 200/300 mg once daily plus darunavir/ritonavir 800/100 mg once daily plus placebo for maraviroc once daily.	FTC/TDF+DRV/r - Baseline Participants infected with R5 HIV-1 received oral tablets of emtricitabine/tenofovir 200/300 mg once daily plus darunavir/ritonavir 800/100 mg once daily plus placebo for maraviroc once daily. Summary of tropism results by baseline.	FTC/TDF+DRV/r - Failure Participants infected with R5 HIV-1 received oral tablets of emtricitabine/tenofovir 200/300 mg once daily plus darunavir/ritonavir 800/100 mg once daily plus placebo for maraviroc once daily. Summary of tropism results corresponding to timepoint at or after PDTF.
Number of Participants Who Discontinued Due to AEs	22 participants	23 participants	—	—

SECONDARY outcome

Timeframe: Week 96

Number of treatment-related AEs are presented here.

Outcome measures

Outcome measures
Measure	MVC+DRV/r n=396 Participants Participants infected with R5 HIV-1 received oral tablets of Maraviroc 150 mg once daily plus darunavir/ritonavir 800/100 mg once daily plus placebo for emtricitabine/tenofovir once daily.	FTC/TDF+DRV/r n=401 Participants Participants infected with R5 HIV-1 received oral tablets of emtricitabine/tenofovir 200/300 mg once daily plus darunavir/ritonavir 800/100 mg once daily plus placebo for maraviroc once daily.	FTC/TDF+DRV/r - Baseline Participants infected with R5 HIV-1 received oral tablets of emtricitabine/tenofovir 200/300 mg once daily plus darunavir/ritonavir 800/100 mg once daily plus placebo for maraviroc once daily. Summary of tropism results by baseline.	FTC/TDF+DRV/r - Failure Participants infected with R5 HIV-1 received oral tablets of emtricitabine/tenofovir 200/300 mg once daily plus darunavir/ritonavir 800/100 mg once daily plus placebo for maraviroc once daily. Summary of tropism results corresponding to timepoint at or after PDTF.
Number of Treatment-related AEs	316 events	361 events	—	—

SECONDARY outcome

Timeframe: Week 96

Total number of participants with treatment-emergent serious adverse events are reported

Outcome measures

Outcome measures
Measure	MVC+DRV/r n=396 Participants Participants infected with R5 HIV-1 received oral tablets of Maraviroc 150 mg once daily plus darunavir/ritonavir 800/100 mg once daily plus placebo for emtricitabine/tenofovir once daily.	FTC/TDF+DRV/r n=401 Participants Participants infected with R5 HIV-1 received oral tablets of emtricitabine/tenofovir 200/300 mg once daily plus darunavir/ritonavir 800/100 mg once daily plus placebo for maraviroc once daily.	FTC/TDF+DRV/r - Baseline Participants infected with R5 HIV-1 received oral tablets of emtricitabine/tenofovir 200/300 mg once daily plus darunavir/ritonavir 800/100 mg once daily plus placebo for maraviroc once daily. Summary of tropism results by baseline.	FTC/TDF+DRV/r - Failure Participants infected with R5 HIV-1 received oral tablets of emtricitabine/tenofovir 200/300 mg once daily plus darunavir/ritonavir 800/100 mg once daily plus placebo for maraviroc once daily. Summary of tropism results corresponding to timepoint at or after PDTF.
Number of Participants With Treatment-emergent Serious Adverse Events	41 participants	40 participants	—	—

SECONDARY outcome

Timeframe: Week 96

Population: Safety Analysis Set was the same as the FAS consisting of all randomized participants who received at least one dose of the study drug but analyzed as realized for tropism assay and treatment. One participant was not analyzed for laboratory data as the collection date for all lab data was less than the first active therapy date.

Number of participants with laboratory abnormalities are reported

Outcome measures

Outcome measures
Measure	MVC+DRV/r n=396 Participants Participants infected with R5 HIV-1 received oral tablets of Maraviroc 150 mg once daily plus darunavir/ritonavir 800/100 mg once daily plus placebo for emtricitabine/tenofovir once daily.	FTC/TDF+DRV/r n=400 Participants Participants infected with R5 HIV-1 received oral tablets of emtricitabine/tenofovir 200/300 mg once daily plus darunavir/ritonavir 800/100 mg once daily plus placebo for maraviroc once daily.	FTC/TDF+DRV/r - Baseline Participants infected with R5 HIV-1 received oral tablets of emtricitabine/tenofovir 200/300 mg once daily plus darunavir/ritonavir 800/100 mg once daily plus placebo for maraviroc once daily. Summary of tropism results by baseline.	FTC/TDF+DRV/r - Failure Participants infected with R5 HIV-1 received oral tablets of emtricitabine/tenofovir 200/300 mg once daily plus darunavir/ritonavir 800/100 mg once daily plus placebo for maraviroc once daily. Summary of tropism results corresponding to timepoint at or after PDTF.
Number of Participants With Abnormal Laboratory Values Normal Baseline	210 participants	205 participants	—	—
Number of Participants With Abnormal Laboratory Values Abnormal Baseline	111 participants	101 participants	—	—

SECONDARY outcome

Timeframe: Week 96

Number of participants who had clinically significant laboratory abnormalities of Grade 3 and Grade 4 according to DAIDS. Abnormality incidence of highest grade was reported for a labcode for each individual participant.

Outcome measures

Outcome measures
Measure	MVC+DRV/r n=396 Participants Participants infected with R5 HIV-1 received oral tablets of Maraviroc 150 mg once daily plus darunavir/ritonavir 800/100 mg once daily plus placebo for emtricitabine/tenofovir once daily.	FTC/TDF+DRV/r n=401 Participants Participants infected with R5 HIV-1 received oral tablets of emtricitabine/tenofovir 200/300 mg once daily plus darunavir/ritonavir 800/100 mg once daily plus placebo for maraviroc once daily.	FTC/TDF+DRV/r - Baseline Participants infected with R5 HIV-1 received oral tablets of emtricitabine/tenofovir 200/300 mg once daily plus darunavir/ritonavir 800/100 mg once daily plus placebo for maraviroc once daily. Summary of tropism results by baseline.	FTC/TDF+DRV/r - Failure Participants infected with R5 HIV-1 received oral tablets of emtricitabine/tenofovir 200/300 mg once daily plus darunavir/ritonavir 800/100 mg once daily plus placebo for maraviroc once daily. Summary of tropism results corresponding to timepoint at or after PDTF.
Severity of Abnormal Laboratory Values Total Bilirubin (n=396, 400)	3 participants	1 participants	—	—
Severity of Abnormal Laboratory Values Alanine Aminotransferase (ALT) (n=396, 400)	9 participants	6 participants	—	—
Severity of Abnormal Laboratory Values Alkaline Phosphatase (n=396, 400)	1 participants	0 participants	—	—
Severity of Abnormal Laboratory Values Amylase (n=396, 400)	5 participants	13 participants	—	—
Severity of Abnormal Laboratory Values Aspartate Aminotransferase (AST) (n=396, 400)	11 participants	7 participants	—	—
Severity of Abnormal Laboratory Values Blood Urea Nitrogen (BUN) (n=396, 400)	3 participants	5 participants	—	—
Severity of Abnormal Laboratory Values Calcium (n=396, 400)	7 participants	10 participants	—	—
Severity of Abnormal Laboratory Values Creatine Kinase (n=396, 400)	18 participants	22 participants	—	—
Severity of Abnormal Laboratory Values Hemoglobin (n=396, 400)	4 participants	2 participants	—	—
Severity of Abnormal Laboratory Values LDL Cholesterol (n=396, 400)	50 participants	24 participants	—	—
Severity of Abnormal Laboratory Values Lipase (n=116, 122)	3 participants	10 participants	—	—
Severity of Abnormal Laboratory Values Lymphocytes (Abs) (n=396, 400)	2 participants	2 participants	—	—
Severity of Abnormal Laboratory Values Phosphate (n=396, 400)	5 participants	12 participants	—	—
Severity of Abnormal Laboratory Values Platelets (n=396, 400)	5 participants	1 participants	—	—
Severity of Abnormal Laboratory Values Potassium (n=396, 400)	3 participants	2 participants	—	—
Severity of Abnormal Laboratory Values Sodium (n=396, 400)	2 participants	0 participants	—	—
Severity of Abnormal Laboratory Values Total Neutrophils (Abs) (n=396, 400)	6 participants	2 participants	—	—
Severity of Abnormal Laboratory Values Triglycerides (n=396, 400)	4 participants	6 participants	—	—
Severity of Abnormal Laboratory Values Uric Acid (n=396, 400)	0 participants	2 participants	—	—
Severity of Abnormal Laboratory Values White Blood Cell Count (n=396, 400)	1 participants	0 participants	—	—
Severity of Abnormal Laboratory Values Creatinine (n=396, 400)	0 participants	1 participants	—	—

SECONDARY outcome

Timeframe: Week 48

Population: The FAS consisted of all randomized participants who received at least one dose of the study drug.

The relationship of the proportion of participants achieving HIV-1 RNA \<50 copies/mL at Week 48 with the screening tropism test for the MVC containing regimen was analyzed. Virologic response for a participant at Week 48 was derived using the FDA's Snapshot MSDF algorithm. Difference in proportions of patients with plasma HIV-1 RNA \<50 copies/mL at week 48 between the maraviroc and the emtricitabine/tenofovir treatment arms, with two-sided 95% confidence interval, among patients who are R5 by genotype (including some who were originally randomized to ESTA and are R5 by genotype upon retesting), were calculated via the Maximum Likelihood method. The estimate was adjusted for the screening plasma HIV RNA level (\<100,000 vs. ≥100,000) copies/mL via the Mantel Haenszel (MH) method.

Outcome measures

Outcome measures
Measure	MVC+DRV/r n=396 Participants Participants infected with R5 HIV-1 received oral tablets of Maraviroc 150 mg once daily plus darunavir/ritonavir 800/100 mg once daily plus placebo for emtricitabine/tenofovir once daily.	FTC/TDF+DRV/r n=401 Participants Participants infected with R5 HIV-1 received oral tablets of emtricitabine/tenofovir 200/300 mg once daily plus darunavir/ritonavir 800/100 mg once daily plus placebo for maraviroc once daily.	FTC/TDF+DRV/r - Baseline Participants infected with R5 HIV-1 received oral tablets of emtricitabine/tenofovir 200/300 mg once daily plus darunavir/ritonavir 800/100 mg once daily plus placebo for maraviroc once daily. Summary of tropism results by baseline.	FTC/TDF+DRV/r - Failure Participants infected with R5 HIV-1 received oral tablets of emtricitabine/tenofovir 200/300 mg once daily plus darunavir/ritonavir 800/100 mg once daily plus placebo for maraviroc once daily. Summary of tropism results corresponding to timepoint at or after PDTF.
The Relationship Between the Proportion of Participants With Plasma HIV-1 RNA <50 Copies/mL at the Week 48 and the Screening Tropism Test (Genotype Test or ESTA).	0.8047 proportion of participants 0.0238	0.8797 proportion of participants 0.0187	—	—

SECONDARY outcome

Timeframe: Week 48

Population: The FAS consisted of all randomized participants who received at least one dose of the study drug. No imputation for missing values was performed for this endpoint. 'Evaluability' is determined by the on-treatment viral load (≥400 copies/mL at sample time point).

Per the protocol participants who meet the following criteria were regarded as PDTFs requiring a confirmatory plasma HIV-1 RNA determination: • Decrease in plasma HIV-1 RNA \<1 log10 from baseline after Week 4 unless plasma HIV-1 RNA is \<50 copies/mL, or • Plasma HIV-1 RNA \>1.0 log10 above the nadir value after Week 4 where the nadir is the lowest plasma HIV-1 RNA concentration, or • Plasma HIV-1 RNA ≥50 copies/mL at any time after Week 24, or • Plasma HIV-1 RNA ≥50 copies/mL after suppression to \<50 copies/mL on two consecutive visits, or • Decrease in plasma HIV-1 RNA ≤2 log10 from baseline on or after Week 12 unless plasma HIV-1 RNA is \<400 copies/mL. Decrease in plasma HIV-1 RNA ≤2 log10 from baseline on or after Week 12 unless plasma HIV-1 RNA is \<50 copies/mL (before August 30 2012) or \<400 copies/mL (after August 30 2012).

Outcome measures

Outcome measures
Measure	MVC+DRV/r n=396 Participants Participants infected with R5 HIV-1 received oral tablets of Maraviroc 150 mg once daily plus darunavir/ritonavir 800/100 mg once daily plus placebo for emtricitabine/tenofovir once daily.	FTC/TDF+DRV/r n=401 Participants Participants infected with R5 HIV-1 received oral tablets of emtricitabine/tenofovir 200/300 mg once daily plus darunavir/ritonavir 800/100 mg once daily plus placebo for maraviroc once daily.	FTC/TDF+DRV/r - Baseline Participants infected with R5 HIV-1 received oral tablets of emtricitabine/tenofovir 200/300 mg once daily plus darunavir/ritonavir 800/100 mg once daily plus placebo for maraviroc once daily. Summary of tropism results by baseline.	FTC/TDF+DRV/r - Failure Participants infected with R5 HIV-1 received oral tablets of emtricitabine/tenofovir 200/300 mg once daily plus darunavir/ritonavir 800/100 mg once daily plus placebo for maraviroc once daily. Summary of tropism results corresponding to timepoint at or after PDTF.
Virologic Outcomes at Week 48 Using Protocol-Defined Treatment Failure (PDTF). Confirmed PDTF	40 Number of participants	13 Number of participants	—	—
Virologic Outcomes at Week 48 Using Protocol-Defined Treatment Failure (PDTF). Evaluable PDTF	17 Number of participants	3 Number of participants	—	—

SECONDARY outcome

Timeframe: Week 48

Population: Number of Evaluable PDTF = Virology Analysis Population (VAP) 'Evaluability' is determined by the on-treatment viral load (≥400 copies/mL at sample time point).

For participants meeting the PDTF criteria, tropism was assessed using the original randomized and alternate assays (ie, both genotype testing and ESTA). Data reported here corresponds to the timepoint at or after PDTF.

Outcome measures

Outcome measures
Measure	MVC+DRV/r n=17 Participants Participants infected with R5 HIV-1 received oral tablets of Maraviroc 150 mg once daily plus darunavir/ritonavir 800/100 mg once daily plus placebo for emtricitabine/tenofovir once daily.	FTC/TDF+DRV/r n=17 Participants Participants infected with R5 HIV-1 received oral tablets of emtricitabine/tenofovir 200/300 mg once daily plus darunavir/ritonavir 800/100 mg once daily plus placebo for maraviroc once daily.	FTC/TDF+DRV/r - Baseline n=3 Participants Participants infected with R5 HIV-1 received oral tablets of emtricitabine/tenofovir 200/300 mg once daily plus darunavir/ritonavir 800/100 mg once daily plus placebo for maraviroc once daily. Summary of tropism results by baseline.	FTC/TDF+DRV/r - Failure n=3 Participants Participants infected with R5 HIV-1 received oral tablets of emtricitabine/tenofovir 200/300 mg once daily plus darunavir/ritonavir 800/100 mg once daily plus placebo for maraviroc once daily. Summary of tropism results corresponding to timepoint at or after PDTF.
Tropism Change Between Screening or Baseline and PDTF R5 (Alternate Assay)	10 participants	10 participants	3 participants	2 participants
Tropism Change Between Screening or Baseline and PDTF R5 (Randomized Assay)	14 participants	13 participants	2 participants	1 participants
Tropism Change Between Screening or Baseline and PDTF NON R5 (Randomized Assay)	1 participants	1 participants	0 participants	0 participants
Tropism Change Between Screening or Baseline and PDTF NR (Randomized Assay)	2 participants	3 participants	1 participants	2 participants
Tropism Change Between Screening or Baseline and PDTF NON R5 (Alternate Assay)	2 participants	3 participants	0 participants	1 participants
Tropism Change Between Screening or Baseline and PDTF NR (Alternate Assay)	5 participants	4 participants	0 participants	0 participants

SECONDARY outcome

Timeframe: Week 48

Population: The FAS consisted of all randomized participants who received at least one dose of the study drug.

For participants meeting the PDTF criteria, viral resistance to maraviroc for maraviroc treated participants was assessed in patients with R5 virus at failure. The resistance level is calculated by reference to a laboratory strain of virus that is analyzed in parallel with the clinical isolate to identify 50% inhibitory concentrations (IC50). The maximal percent inhibition is the percent inhibition that is achieved in a titration of the drug at high concentrations when the addition of more drug does not result in increased inhibition. Maximal percent inhibition is obtained in the same way as the titration for IC50, but the key measure is of the plateau height of percent inhibition, where increased concentration of maraviroc does not result in additional inhibition. This is consistent with the virus developing some ability to use maraviroc-bound CCR5 for entry. A significant change in IC50 is not required for this mechanism.

Outcome measures

Outcome measures
Measure	MVC+DRV/r n=17 Participants Participants infected with R5 HIV-1 received oral tablets of Maraviroc 150 mg once daily plus darunavir/ritonavir 800/100 mg once daily plus placebo for emtricitabine/tenofovir once daily.	FTC/TDF+DRV/r n=3 Participants Participants infected with R5 HIV-1 received oral tablets of emtricitabine/tenofovir 200/300 mg once daily plus darunavir/ritonavir 800/100 mg once daily plus placebo for maraviroc once daily.	FTC/TDF+DRV/r - Baseline Participants infected with R5 HIV-1 received oral tablets of emtricitabine/tenofovir 200/300 mg once daily plus darunavir/ritonavir 800/100 mg once daily plus placebo for maraviroc once daily. Summary of tropism results by baseline.	FTC/TDF+DRV/r - Failure Participants infected with R5 HIV-1 received oral tablets of emtricitabine/tenofovir 200/300 mg once daily plus darunavir/ritonavir 800/100 mg once daily plus placebo for maraviroc once daily. Summary of tropism results corresponding to timepoint at or after PDTF.
Number of Participants With Viral Resistance to Maraviroc (Maraviroc Treated Participants Only) in Participants Meeting PDTF Criteria. Not eligible for analysis (failed tropism test)	4 participants	1 participants	—	—
Number of Participants With Viral Resistance to Maraviroc (Maraviroc Treated Participants Only) in Participants Meeting PDTF Criteria. Not eligible for analysis (non-R5 tropism)	1 participants	1 participants	—	—
Number of Participants With Viral Resistance to Maraviroc (Maraviroc Treated Participants Only) in Participants Meeting PDTF Criteria. Eligible for analysis (R5 virus using ESTA)	12 participants	1 participants	—	—
Number of Participants With Viral Resistance to Maraviroc (Maraviroc Treated Participants Only) in Participants Meeting PDTF Criteria. Results reported	12 participants	1 participants	—	—
Number of Participants With Viral Resistance to Maraviroc (Maraviroc Treated Participants Only) in Participants Meeting PDTF Criteria. Maximal percent inhibition <95%	0 participants	0 participants	—	—
Number of Participants With Viral Resistance to Maraviroc (Maraviroc Treated Participants Only) in Participants Meeting PDTF Criteria. IC50 FC ≥3.0	0 participants	0 participants	—	—

SECONDARY outcome

Timeframe: Week 48

Population: The FAS consisted of all randomized participants who received at least one dose of the study drug. The assessment was performed using the overall (ie. net) susceptibility score provided using the PhenoSense GT assay. The number of participants with successful assessments were 15 for the MVC+DRV/r arm and 3 for the FTC/TDF+DRV/r arm.

For participants meeting the PDTF criteria, viral resistance (both genotypic and phenotypic) to NRTI, NNRTI, and PI's were assessed at Baseline and on-treatment. The assessment was performed using the overall (i.e. net) susceptibility score provided using the PhenoSense GT assay. The number of participants with successful assessments were 15/17 for the MVC+DRV/r arm and 3/3 for the FTC/TDF+DRV/r arm.

Outcome measures

Outcome measures
Measure	MVC+DRV/r n=15 Participants Participants infected with R5 HIV-1 received oral tablets of Maraviroc 150 mg once daily plus darunavir/ritonavir 800/100 mg once daily plus placebo for emtricitabine/tenofovir once daily.	FTC/TDF+DRV/r n=3 Participants Participants infected with R5 HIV-1 received oral tablets of emtricitabine/tenofovir 200/300 mg once daily plus darunavir/ritonavir 800/100 mg once daily plus placebo for maraviroc once daily.	FTC/TDF+DRV/r - Baseline Participants infected with R5 HIV-1 received oral tablets of emtricitabine/tenofovir 200/300 mg once daily plus darunavir/ritonavir 800/100 mg once daily plus placebo for maraviroc once daily. Summary of tropism results by baseline.	FTC/TDF+DRV/r - Failure Participants infected with R5 HIV-1 received oral tablets of emtricitabine/tenofovir 200/300 mg once daily plus darunavir/ritonavir 800/100 mg once daily plus placebo for maraviroc once daily. Summary of tropism results corresponding to timepoint at or after PDTF.
Number of Participants With Resistance to Nucleoside/Nucleotide Reverse Transcriptase Inhibitors (NRTI), Non-nucleoside Reverse Transcriptase Inhibitors (NNRTI), and Protease Inhibitors (PI) in Participants Meeting PDTF Criteria NRTI - All (Baseline, n=15, 3)	0 participants	0 participants	—	—
Number of Participants With Resistance to Nucleoside/Nucleotide Reverse Transcriptase Inhibitors (NRTI), Non-nucleoside Reverse Transcriptase Inhibitors (NNRTI), and Protease Inhibitors (PI) in Participants Meeting PDTF Criteria NNRTI Delavirdine (Baseline, n=15, 3)	1 participants	0 participants	—	—
Number of Participants With Resistance to Nucleoside/Nucleotide Reverse Transcriptase Inhibitors (NRTI), Non-nucleoside Reverse Transcriptase Inhibitors (NNRTI), and Protease Inhibitors (PI) in Participants Meeting PDTF Criteria NNRTI Nevirapine (Baseline, n=15, 3)	1 participants	0 participants	—	—
Number of Participants With Resistance to Nucleoside/Nucleotide Reverse Transcriptase Inhibitors (NRTI), Non-nucleoside Reverse Transcriptase Inhibitors (NNRTI), and Protease Inhibitors (PI) in Participants Meeting PDTF Criteria NNRTI Efavirenz (Baseline, n=15, 3)	1 participants	0 participants	—	—
Number of Participants With Resistance to Nucleoside/Nucleotide Reverse Transcriptase Inhibitors (NRTI), Non-nucleoside Reverse Transcriptase Inhibitors (NNRTI), and Protease Inhibitors (PI) in Participants Meeting PDTF Criteria PRI - All (Baseline, n=15, 3)	0 participants	0 participants	—	—
Number of Participants With Resistance to Nucleoside/Nucleotide Reverse Transcriptase Inhibitors (NRTI), Non-nucleoside Reverse Transcriptase Inhibitors (NNRTI), and Protease Inhibitors (PI) in Participants Meeting PDTF Criteria NRTI - All (PDTF, n=15, 3)	0 participants	0 participants	—	—
Number of Participants With Resistance to Nucleoside/Nucleotide Reverse Transcriptase Inhibitors (NRTI), Non-nucleoside Reverse Transcriptase Inhibitors (NNRTI), and Protease Inhibitors (PI) in Participants Meeting PDTF Criteria NNRTI Delavirdine (PDTF, n=15, 3)	1 participants	0 participants	—	—
Number of Participants With Resistance to Nucleoside/Nucleotide Reverse Transcriptase Inhibitors (NRTI), Non-nucleoside Reverse Transcriptase Inhibitors (NNRTI), and Protease Inhibitors (PI) in Participants Meeting PDTF Criteria NNRTI Nevirapine (PDTF, n=15, 3)	1 participants	0 participants	—	—
Number of Participants With Resistance to Nucleoside/Nucleotide Reverse Transcriptase Inhibitors (NRTI), Non-nucleoside Reverse Transcriptase Inhibitors (NNRTI), and Protease Inhibitors (PI) in Participants Meeting PDTF Criteria NNRTI Efavirenz (PDTF, n=15, 3)	1 participants	0 participants	—	—
Number of Participants With Resistance to Nucleoside/Nucleotide Reverse Transcriptase Inhibitors (NRTI), Non-nucleoside Reverse Transcriptase Inhibitors (NNRTI), and Protease Inhibitors (PI) in Participants Meeting PDTF Criteria PRI - All (PDTF, n=15, 3)	0 participants	0 participants	—	—

SECONDARY outcome

Timeframe: Baseline, Week 48

Population: The FAS consisted of all randomized participants who received at least one dose of the study drug. Missing values were imputed using LOCF approach. Baseline was calculated as the average of all the pre-dose measurements excluding the screening value. If all pre-dose values were missing, screening value was considered as the baseline.

The differences in the magnitude of changes in CD4+ at Baseline and at Week 48 for maraviroc versus emtricitabine/tenofovir were compared.

Outcome measures

Outcome measures
Measure	MVC+DRV/r n=396 Participants Participants infected with R5 HIV-1 received oral tablets of Maraviroc 150 mg once daily plus darunavir/ritonavir 800/100 mg once daily plus placebo for emtricitabine/tenofovir once daily.	FTC/TDF+DRV/r n=401 Participants Participants infected with R5 HIV-1 received oral tablets of emtricitabine/tenofovir 200/300 mg once daily plus darunavir/ritonavir 800/100 mg once daily plus placebo for maraviroc once daily.	FTC/TDF+DRV/r - Baseline Participants infected with R5 HIV-1 received oral tablets of emtricitabine/tenofovir 200/300 mg once daily plus darunavir/ritonavir 800/100 mg once daily plus placebo for maraviroc once daily. Summary of tropism results by baseline.	FTC/TDF+DRV/r - Failure Participants infected with R5 HIV-1 received oral tablets of emtricitabine/tenofovir 200/300 mg once daily plus darunavir/ritonavir 800/100 mg once daily plus placebo for maraviroc once daily. Summary of tropism results corresponding to timepoint at or after PDTF.
Absolute Change From Baseline in Immune Cell Function at Week 48: Lymphocyte Marker Cluster of Differentiation 4 (CD4, Cell/mm^3) Baseline (n=396, 401)	382.0 cell/mm^3 Standard Deviation 173.4	379.5 cell/mm^3 Standard Deviation 170.9	—	—
Absolute Change From Baseline in Immune Cell Function at Week 48: Lymphocyte Marker Cluster of Differentiation 4 (CD4, Cell/mm^3) Week 48 (n=394, 396)	576.9 cell/mm^3 Standard Deviation 226.0	574.6 cell/mm^3 Standard Deviation 232.1	—	—
Absolute Change From Baseline in Immune Cell Function at Week 48: Lymphocyte Marker Cluster of Differentiation 4 (CD4, Cell/mm^3) Change from Baseline at Week 48 (n=394, 396)	194.9 cell/mm^3 Standard Deviation 175.5	194.2 cell/mm^3 Standard Deviation 175.8	—	—

SECONDARY outcome

Timeframe: Baseline, Week 48

The differences in the magnitude of changes in CD4+ from Baseline through Week 48 for maraviroc versus emtricitabine/tenofovir were compared.

Outcome measures

Outcome measures
Measure	MVC+DRV/r n=396 Participants Participants infected with R5 HIV-1 received oral tablets of Maraviroc 150 mg once daily plus darunavir/ritonavir 800/100 mg once daily plus placebo for emtricitabine/tenofovir once daily.	FTC/TDF+DRV/r n=401 Participants Participants infected with R5 HIV-1 received oral tablets of emtricitabine/tenofovir 200/300 mg once daily plus darunavir/ritonavir 800/100 mg once daily plus placebo for maraviroc once daily.	FTC/TDF+DRV/r - Baseline Participants infected with R5 HIV-1 received oral tablets of emtricitabine/tenofovir 200/300 mg once daily plus darunavir/ritonavir 800/100 mg once daily plus placebo for maraviroc once daily. Summary of tropism results by baseline.	FTC/TDF+DRV/r - Failure Participants infected with R5 HIV-1 received oral tablets of emtricitabine/tenofovir 200/300 mg once daily plus darunavir/ritonavir 800/100 mg once daily plus placebo for maraviroc once daily. Summary of tropism results corresponding to timepoint at or after PDTF.
Percent Change From Baseline in Immune Cell Function at Week 48: Lymphocyte Activation Marker CD4 (%) Baseline (n=396, 401)	24.2 Percentage of lymphocytes Standard Deviation 7.9	24.5 Percentage of lymphocytes Standard Deviation 8.2	—	—
Percent Change From Baseline in Immune Cell Function at Week 48: Lymphocyte Activation Marker CD4 (%) Week 48 (n=394, 396)	31.3 Percentage of lymphocytes Standard Deviation 8.3	33.7 Percentage of lymphocytes Standard Deviation 8.6	—	—
Percent Change From Baseline in Immune Cell Function at Week 48: Lymphocyte Activation Marker CD4 (%) Change from Baseline at Week 48 (n=394, 396)	7.0 Percentage of lymphocytes Standard Deviation 5.7	9.2 Percentage of lymphocytes Standard Deviation 6.0	—	—

SECONDARY outcome

Timeframe: Baseline, Week 48

The differences in the magnitude of changes in CD8+ cell counts from baseline through Week 48 for maraviroc versus emtricitabine/tenofovir were compared.

Outcome measures

Outcome measures
Measure	MVC+DRV/r n=396 Participants Participants infected with R5 HIV-1 received oral tablets of Maraviroc 150 mg once daily plus darunavir/ritonavir 800/100 mg once daily plus placebo for emtricitabine/tenofovir once daily.	FTC/TDF+DRV/r n=401 Participants Participants infected with R5 HIV-1 received oral tablets of emtricitabine/tenofovir 200/300 mg once daily plus darunavir/ritonavir 800/100 mg once daily plus placebo for maraviroc once daily.	FTC/TDF+DRV/r - Baseline Participants infected with R5 HIV-1 received oral tablets of emtricitabine/tenofovir 200/300 mg once daily plus darunavir/ritonavir 800/100 mg once daily plus placebo for maraviroc once daily. Summary of tropism results by baseline.	FTC/TDF+DRV/r - Failure Participants infected with R5 HIV-1 received oral tablets of emtricitabine/tenofovir 200/300 mg once daily plus darunavir/ritonavir 800/100 mg once daily plus placebo for maraviroc once daily. Summary of tropism results corresponding to timepoint at or after PDTF.
Absolute Change From Baseline in Immune Cell Function at Week 48: Lymphocyte Marker Cluster of Differentiation 8 (CD8, Cell/mm^3) Baseline (n=396, 401)	954.4 cell/mm^3 Standard Deviation 502.1	914.5 cell/mm^3 Standard Deviation 473.0	—	—
Absolute Change From Baseline in Immune Cell Function at Week 48: Lymphocyte Marker Cluster of Differentiation 8 (CD8, Cell/mm^3) Week 48 (n=394, 396)	900.0 cell/mm^3 Standard Deviation 508.3	751.1 cell/mm^3 Standard Deviation 386.7	—	—
Absolute Change From Baseline in Immune Cell Function at Week 48: Lymphocyte Marker Cluster of Differentiation 8 (CD8, Cell/mm^3) Change from Baseline at Week 48 (n=394, 396)	-49.9 cell/mm^3 Standard Deviation 410.7	-157.9 cell/mm^3 Standard Deviation 444.0	—	—

SECONDARY outcome

Timeframe: Baseline, Week 48

The differences in the magnitude of changes in CD8+ cell counts from Baseline through Week 48 for maraviroc versus emtricitabine/tenofovir were compared.

Outcome measures

Outcome measures
Measure	MVC+DRV/r n=396 Participants Participants infected with R5 HIV-1 received oral tablets of Maraviroc 150 mg once daily plus darunavir/ritonavir 800/100 mg once daily plus placebo for emtricitabine/tenofovir once daily.	FTC/TDF+DRV/r n=401 Participants Participants infected with R5 HIV-1 received oral tablets of emtricitabine/tenofovir 200/300 mg once daily plus darunavir/ritonavir 800/100 mg once daily plus placebo for maraviroc once daily.	FTC/TDF+DRV/r - Baseline Participants infected with R5 HIV-1 received oral tablets of emtricitabine/tenofovir 200/300 mg once daily plus darunavir/ritonavir 800/100 mg once daily plus placebo for maraviroc once daily. Summary of tropism results by baseline.	FTC/TDF+DRV/r - Failure Participants infected with R5 HIV-1 received oral tablets of emtricitabine/tenofovir 200/300 mg once daily plus darunavir/ritonavir 800/100 mg once daily plus placebo for maraviroc once daily. Summary of tropism results corresponding to timepoint at or after PDTF.
Percent Change From Baseline in Immune Cell Function at Week 48: Lymphocyte Activation Marker CD8 (%) Baseline (n=396, 401)	57.0 Percentage of lymphocytes Standard Deviation 10.7	55.8 Percentage of lymphocytes Standard Deviation 10.5	—	—
Percent Change From Baseline in Immune Cell Function at Week 48: Lymphocyte Activation Marker CD8 (%) Week 48 (n=394, 396)	46.0 Percentage of lymphocytes Standard Deviation 10.4	43.0 Percentage of lymphocytes Standard Deviation 10.2	—	—
Percent Change From Baseline in Immune Cell Function at Week 48: Lymphocyte Activation Marker CD8 (%) Change from Baseline at Week 48 (n=394, 396)	-10.9 Percentage of lymphocytes Standard Deviation 7.2	-12.6 Percentage of lymphocytes Standard Deviation 8.1	—	—

SECONDARY outcome

Timeframe: Baseline, Week 48

The differences in the magnitude of changes in CD4+/CD8+ ratio from Baseline through Weeks 48 for maraviroc versus emtricitabine/tenofovir were compared.

Outcome measures

Outcome measures
Measure	MVC+DRV/r n=396 Participants Participants infected with R5 HIV-1 received oral tablets of Maraviroc 150 mg once daily plus darunavir/ritonavir 800/100 mg once daily plus placebo for emtricitabine/tenofovir once daily.	FTC/TDF+DRV/r n=401 Participants Participants infected with R5 HIV-1 received oral tablets of emtricitabine/tenofovir 200/300 mg once daily plus darunavir/ritonavir 800/100 mg once daily plus placebo for maraviroc once daily.	FTC/TDF+DRV/r - Baseline Participants infected with R5 HIV-1 received oral tablets of emtricitabine/tenofovir 200/300 mg once daily plus darunavir/ritonavir 800/100 mg once daily plus placebo for maraviroc once daily. Summary of tropism results by baseline.	FTC/TDF+DRV/r - Failure Participants infected with R5 HIV-1 received oral tablets of emtricitabine/tenofovir 200/300 mg once daily plus darunavir/ritonavir 800/100 mg once daily plus placebo for maraviroc once daily. Summary of tropism results corresponding to timepoint at or after PDTF.
Absolute Change in CD4+/CD8+ Ratio From Baseline to Week 48 Baseline (n=396, 401)	0.47 Ratio Standard Deviation 0.24	0.48 Ratio Standard Deviation 0.25	—	—
Absolute Change in CD4+/CD8+ Ratio From Baseline to Week 48 Week 48 (n=394, 396)	0.75 Ratio Standard Deviation 0.34	0.87 Ratio Standard Deviation 0.45	—	—
Absolute Change in CD4+/CD8+ Ratio From Baseline to Week 48 Change from Baseline at Week 48 (n=394, 396)	0.28 Ratio Standard Deviation 0.22	0.39 Ratio Standard Deviation 0.34	—	—

SECONDARY outcome

Timeframe: Week 48

A sub-study was conducted in which the participants underwent whole-body DEXA scans to evaluate peripheral fat tissue estimates for left and right arms and legs and truncal fat mass and truncal lean mass. Truncal abdominal fat were estimated from the DEXA scan field set on the torso. The effects on estimates of fat mass and lean mass were addressed by providing LSMs of change from baseline.

Outcome measures

Outcome measures
Measure	MVC+DRV/r n=52 Participants Participants infected with R5 HIV-1 received oral tablets of Maraviroc 150 mg once daily plus darunavir/ritonavir 800/100 mg once daily plus placebo for emtricitabine/tenofovir once daily.	FTC/TDF+DRV/r n=56 Participants Participants infected with R5 HIV-1 received oral tablets of emtricitabine/tenofovir 200/300 mg once daily plus darunavir/ritonavir 800/100 mg once daily plus placebo for maraviroc once daily.	FTC/TDF+DRV/r - Baseline Participants infected with R5 HIV-1 received oral tablets of emtricitabine/tenofovir 200/300 mg once daily plus darunavir/ritonavir 800/100 mg once daily plus placebo for maraviroc once daily. Summary of tropism results by baseline.	FTC/TDF+DRV/r - Failure Participants infected with R5 HIV-1 received oral tablets of emtricitabine/tenofovir 200/300 mg once daily plus darunavir/ritonavir 800/100 mg once daily plus placebo for maraviroc once daily. Summary of tropism results corresponding to timepoint at or after PDTF.
Changes in Peripheral Fat Distribution Using Dual Energy X-ray Absorptiometry [DEXA] Scan From Baseline and at Week 48.	-181.6 gram Standard Error 569.8	-257.5 gram Standard Error 556.9	—	—

SECONDARY outcome

Timeframe: Week 48

Outcome measures

Outcome measures
Measure	MVC+DRV/r n=52 Participants Participants infected with R5 HIV-1 received oral tablets of Maraviroc 150 mg once daily plus darunavir/ritonavir 800/100 mg once daily plus placebo for emtricitabine/tenofovir once daily.	FTC/TDF+DRV/r n=56 Participants Participants infected with R5 HIV-1 received oral tablets of emtricitabine/tenofovir 200/300 mg once daily plus darunavir/ritonavir 800/100 mg once daily plus placebo for maraviroc once daily.	FTC/TDF+DRV/r - Baseline Participants infected with R5 HIV-1 received oral tablets of emtricitabine/tenofovir 200/300 mg once daily plus darunavir/ritonavir 800/100 mg once daily plus placebo for maraviroc once daily. Summary of tropism results by baseline.	FTC/TDF+DRV/r - Failure Participants infected with R5 HIV-1 received oral tablets of emtricitabine/tenofovir 200/300 mg once daily plus darunavir/ritonavir 800/100 mg once daily plus placebo for maraviroc once daily. Summary of tropism results corresponding to timepoint at or after PDTF.
Changes in Trunk to Limb Fat Distribution Using DEXA Scan From Baseline and at Week 48	0.017 ratio Standard Error 0.048	-0.014 ratio Standard Error 0.048	—	—

SECONDARY outcome

Timeframe: Week 48

Bone mineral density was evaluated by DEXA scan in a subset of participants who consented to these evaluations. The effects on BMD were addressed by providing LSMs of change from baseline bone mineral density of the lumbar spine (L1-L4), left total hip and femoral neck as measured by the DEXA scan.

Outcome measures

Outcome measures
Measure	MVC+DRV/r n=47 Participants Participants infected with R5 HIV-1 received oral tablets of Maraviroc 150 mg once daily plus darunavir/ritonavir 800/100 mg once daily plus placebo for emtricitabine/tenofovir once daily.	FTC/TDF+DRV/r n=57 Participants Participants infected with R5 HIV-1 received oral tablets of emtricitabine/tenofovir 200/300 mg once daily plus darunavir/ritonavir 800/100 mg once daily plus placebo for maraviroc once daily.	FTC/TDF+DRV/r - Baseline Participants infected with R5 HIV-1 received oral tablets of emtricitabine/tenofovir 200/300 mg once daily plus darunavir/ritonavir 800/100 mg once daily plus placebo for maraviroc once daily. Summary of tropism results by baseline.	FTC/TDF+DRV/r - Failure Participants infected with R5 HIV-1 received oral tablets of emtricitabine/tenofovir 200/300 mg once daily plus darunavir/ritonavir 800/100 mg once daily plus placebo for maraviroc once daily. Summary of tropism results corresponding to timepoint at or after PDTF.
Changes in Bone Mineral Density (Using DEXA Scan and Serum Markers) From Baseline and at Week 48 - Total Hip BMD	-0.014 g/cm^2 Standard Error 0.005	-0.028 g/cm^2 Standard Error 0.005	—	—

SECONDARY outcome

Timeframe: Week 48

Bone mineral density was evaluated by DEXA scan in a subset of participants who consented to these evaluations. The effects on BMD were addressed by providing LSMs of change from Baseline bone mineral density femoral neck as measured by the DEXA scan.

Outcome measures

Outcome measures
Measure	MVC+DRV/r n=47 Participants Participants infected with R5 HIV-1 received oral tablets of Maraviroc 150 mg once daily plus darunavir/ritonavir 800/100 mg once daily plus placebo for emtricitabine/tenofovir once daily.	FTC/TDF+DRV/r n=57 Participants Participants infected with R5 HIV-1 received oral tablets of emtricitabine/tenofovir 200/300 mg once daily plus darunavir/ritonavir 800/100 mg once daily plus placebo for maraviroc once daily.	FTC/TDF+DRV/r - Baseline Participants infected with R5 HIV-1 received oral tablets of emtricitabine/tenofovir 200/300 mg once daily plus darunavir/ritonavir 800/100 mg once daily plus placebo for maraviroc once daily. Summary of tropism results by baseline.	FTC/TDF+DRV/r - Failure Participants infected with R5 HIV-1 received oral tablets of emtricitabine/tenofovir 200/300 mg once daily plus darunavir/ritonavir 800/100 mg once daily plus placebo for maraviroc once daily. Summary of tropism results corresponding to timepoint at or after PDTF.
Changes in Bone Mineral Density (Using DEXA Scan and Serum Markers) From Baseline and at Week 48 - Femoral Neck BMD	-0.021 g/cm^2 Standard Error 0.007	-0.029 g/cm^2 Standard Error 0.007	—	—

SECONDARY outcome

Timeframe: Week 48

Outcome measures

Outcome measures
Measure	MVC+DRV/r n=54 Participants Participants infected with R5 HIV-1 received oral tablets of Maraviroc 150 mg once daily plus darunavir/ritonavir 800/100 mg once daily plus placebo for emtricitabine/tenofovir once daily.	FTC/TDF+DRV/r n=60 Participants Participants infected with R5 HIV-1 received oral tablets of emtricitabine/tenofovir 200/300 mg once daily plus darunavir/ritonavir 800/100 mg once daily plus placebo for maraviroc once daily.	FTC/TDF+DRV/r - Baseline Participants infected with R5 HIV-1 received oral tablets of emtricitabine/tenofovir 200/300 mg once daily plus darunavir/ritonavir 800/100 mg once daily plus placebo for maraviroc once daily. Summary of tropism results by baseline.	FTC/TDF+DRV/r - Failure Participants infected with R5 HIV-1 received oral tablets of emtricitabine/tenofovir 200/300 mg once daily plus darunavir/ritonavir 800/100 mg once daily plus placebo for maraviroc once daily. Summary of tropism results corresponding to timepoint at or after PDTF.
Changes in Bone Mineral Density (Using DEXA Scan and Serum Markers) From Baseline and at Week 48 - AP Lumbar Spine (L1 - L4) BMD	-0.020 g/cm^2 Standard Error 0.006	-0.025 g/cm^2 Standard Error 0.006	—	—

SECONDARY outcome

Timeframe: Week 48

Bone turnover marker, osteocalcin, was collected in the subset of participants participating in the DEXA scan sub-study.

Outcome measures

Outcome measures
Measure	MVC+DRV/r n=52 Participants Participants infected with R5 HIV-1 received oral tablets of Maraviroc 150 mg once daily plus darunavir/ritonavir 800/100 mg once daily plus placebo for emtricitabine/tenofovir once daily.	FTC/TDF+DRV/r n=61 Participants Participants infected with R5 HIV-1 received oral tablets of emtricitabine/tenofovir 200/300 mg once daily plus darunavir/ritonavir 800/100 mg once daily plus placebo for maraviroc once daily.	FTC/TDF+DRV/r - Baseline Participants infected with R5 HIV-1 received oral tablets of emtricitabine/tenofovir 200/300 mg once daily plus darunavir/ritonavir 800/100 mg once daily plus placebo for maraviroc once daily. Summary of tropism results by baseline.	FTC/TDF+DRV/r - Failure Participants infected with R5 HIV-1 received oral tablets of emtricitabine/tenofovir 200/300 mg once daily plus darunavir/ritonavir 800/100 mg once daily plus placebo for maraviroc once daily. Summary of tropism results corresponding to timepoint at or after PDTF.
Change in Bone Turnover Markers From Baseline and at Week 48 - Blood Osteocalcin	5.61 ng/mL Standard Deviation 8.02	6.77 ng/mL Standard Deviation 8.31	—	—

SECONDARY outcome

Timeframe: Week 48

Bone turnover marker, C-telopeptide of type 1 collagen (CTx), was collected in the subset of participants participating in the DEXA scan sub-study.

Outcome measures

Outcome measures
Measure	MVC+DRV/r n=53 Participants Participants infected with R5 HIV-1 received oral tablets of Maraviroc 150 mg once daily plus darunavir/ritonavir 800/100 mg once daily plus placebo for emtricitabine/tenofovir once daily.	FTC/TDF+DRV/r n=62 Participants Participants infected with R5 HIV-1 received oral tablets of emtricitabine/tenofovir 200/300 mg once daily plus darunavir/ritonavir 800/100 mg once daily plus placebo for maraviroc once daily.	FTC/TDF+DRV/r - Baseline Participants infected with R5 HIV-1 received oral tablets of emtricitabine/tenofovir 200/300 mg once daily plus darunavir/ritonavir 800/100 mg once daily plus placebo for maraviroc once daily. Summary of tropism results by baseline.	FTC/TDF+DRV/r - Failure Participants infected with R5 HIV-1 received oral tablets of emtricitabine/tenofovir 200/300 mg once daily plus darunavir/ritonavir 800/100 mg once daily plus placebo for maraviroc once daily. Summary of tropism results corresponding to timepoint at or after PDTF.
Change in Bone Turnover Markers From Baseline and at Week 48 - Type 1 Collagen Peptide (CTX-1)	121.13 pg/mL Standard Deviation 243.03	223.52 pg/mL Standard Deviation 293.03	—	—

Adverse Events

MVC+DRV/r

Serious events: 41 serious events

Other events: 257 other events

Deaths: 0 deaths

FTC/TDF+DRV/r

Serious events: 40 serious events

Other events: 285 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

Pfizer ClinicalTrials.gov Call Center

Pfizer, Inc.

Phone: 1-800-718-1021

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee 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.
Publication restrictions are in place

Restriction type: OTHER

Measure	MVC+DRV/r n=396 participants at risk Participants infected with R5 HIV-1 received oral tablets of Maraviroc 150 mg once daily plus darunavir/ritonavir 800/100 mg once daily plus placebo for emtricitabine/tenofovir once daily.	FTC/TDF+DRV/r n=401 participants at risk Participants infected with R5 HIV-1 received oral tablets of emtricitabine/tenofovir 200/300 mg once daily plus darunavir/ritonavir 800/100 mg once daily plus placebo for maraviroc once daily.
Gastrointestinal disorders Diarrhoea	22.2% 88/396 • From the day the first dose of the study drug was administered to 28 days after the last dose of the study drug was administered. 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 participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	33.7% 135/401 • From the day the first dose of the study drug was administered to 28 days after the last dose of the study drug was administered. 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 participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Gastrointestinal disorders Nausea	8.6% 34/396 • From the day the first dose of the study drug was administered to 28 days after the last dose of the study drug was administered. 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 participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	11.2% 45/401 • From the day the first dose of the study drug was administered to 28 days after the last dose of the study drug was administered. 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 participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
General disorders Fatigue	6.8% 27/396 • From the day the first dose of the study drug was administered to 28 days after the last dose of the study drug was administered. 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 participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	11.5% 46/401 • From the day the first dose of the study drug was administered to 28 days after the last dose of the study drug was administered. 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 participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Infections and infestations Bronchitis	6.3% 25/396 • From the day the first dose of the study drug was administered to 28 days after the last dose of the study drug was administered. 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 participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	6.0% 24/401 • From the day the first dose of the study drug was administered to 28 days after the last dose of the study drug was administered. 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 participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Infections and infestations Gastroenteritis	5.8% 23/396 • From the day the first dose of the study drug was administered to 28 days after the last dose of the study drug was administered. 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 participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	4.0% 16/401 • From the day the first dose of the study drug was administered to 28 days after the last dose of the study drug was administered. 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 participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Infections and infestations Nasopharyngitis	12.1% 48/396 • From the day the first dose of the study drug was administered to 28 days after the last dose of the study drug was administered. 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 participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	13.7% 55/401 • From the day the first dose of the study drug was administered to 28 days after the last dose of the study drug was administered. 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 participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Infections and infestations Upper respiratory tract infection	10.1% 40/396 • From the day the first dose of the study drug was administered to 28 days after the last dose of the study drug was administered. 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 participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	11.2% 45/401 • From the day the first dose of the study drug was administered to 28 days after the last dose of the study drug was administered. 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 participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Musculoskeletal and connective tissue disorders Back pain	5.6% 22/396 • From the day the first dose of the study drug was administered to 28 days after the last dose of the study drug was administered. 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 participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	5.7% 23/401 • From the day the first dose of the study drug was administered to 28 days after the last dose of the study drug was administered. 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 participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Nervous system disorders Headache	6.8% 27/396 • From the day the first dose of the study drug was administered to 28 days after the last dose of the study drug was administered. 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 participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	11.7% 47/401 • From the day the first dose of the study drug was administered to 28 days after the last dose of the study drug was administered. 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 participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Psychiatric disorders Depression	6.6% 26/396 • From the day the first dose of the study drug was administered to 28 days after the last dose of the study drug was administered. 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 participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	7.2% 29/401 • From the day the first dose of the study drug was administered to 28 days after the last dose of the study drug was administered. 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 participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Psychiatric disorders Insomnia	3.8% 15/396 • From the day the first dose of the study drug was administered to 28 days after the last dose of the study drug was administered. 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 participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	6.2% 25/401 • From the day the first dose of the study drug was administered to 28 days after the last dose of the study drug was administered. 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 participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Respiratory, thoracic and mediastinal disorders Cough	6.8% 27/396 • From the day the first dose of the study drug was administered to 28 days after the last dose of the study drug was administered. 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 participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	7.5% 30/401 • From the day the first dose of the study drug was administered to 28 days after the last dose of the study drug was administered. 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 participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Skin and subcutaneous tissue disorders Rash	9.3% 37/396 • From the day the first dose of the study drug was administered to 28 days after the last dose of the study drug was administered. 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 participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	7.5% 30/401 • From the day the first dose of the study drug was administered to 28 days after the last dose of the study drug was administered. 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 participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Gastrointestinal disorders Abdominal distension	2.3% 9/396 • From the day the first dose of the study drug was administered to 28 days after the last dose of the study drug was administered. 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 participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	5.5% 22/401 • From the day the first dose of the study drug was administered to 28 days after the last dose of the study drug was administered. 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 participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Infections and infestations Influenza	5.6% 22/396 • From the day the first dose of the study drug was administered to 28 days after the last dose of the study drug was administered. 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 participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	5.0% 20/401 • From the day the first dose of the study drug was administered to 28 days after the last dose of the study drug was administered. 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 participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Infections and infestations Syphilis	3.8% 15/396 • From the day the first dose of the study drug was administered to 28 days after the last dose of the study drug was administered. 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 participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	5.7% 23/401 • From the day the first dose of the study drug was administered to 28 days after the last dose of the study drug was administered. 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 participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Investigations Blood cholesterol increased	5.6% 22/396 • From the day the first dose of the study drug was administered to 28 days after the last dose of the study drug was administered. 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 participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	2.5% 10/401 • From the day the first dose of the study drug was administered to 28 days after the last dose of the study drug was administered. 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 participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Investigations Low density lipoprotein increased	5.6% 22/396 • From the day the first dose of the study drug was administered to 28 days after the last dose of the study drug was administered. 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 participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	2.7% 11/401 • From the day the first dose of the study drug was administered to 28 days after the last dose of the study drug was administered. 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 participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.