Trial Outcomes & Findings for Raltegravir + Lopinavir/Ritonavir Versus Efavirenz + Tenofovir + Emtricitabine in Treatment Naive Patients (NCT NCT00752856)

Results Overview

Repeated HIV RNA measured at different time points (baseline, days 2, 7, 10, 14) will be treated as the outcome variable in a linear mixed-effects model. The primary fixed effects will include time, treatment group, treatment group-by-time interaction; random effects will include both intercept and slope allowing each subject to have individual baseline viral load and viral decay (rate of decrease in viral load following initiation of antiretroviral therapy). The treatment group-by- time interaction term in the model will indicate the difference in viral decay rates between the two treatment groups. Baseline covariate adjustment will be included if necessary.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

51 participants

Primary outcome timeframe

Baseline, days 2, 7, 10, 14

Results posted on

2020-07-22

Participant Flow

Participant milestones

Participant milestones
Measure	1 - Kaletra + Isentress Taken Twice Daily Kaletra (lopinavir/ritonavir 400/100 mg) + Isentress (Raltegravir 400 mg) twice-daily Kaletra + Isentress: kaletra 2 tabs twice a day + Raltegravir 1 tab twice a day	2 - Atripla Taken Once Daily Sustiva (EFV 600 mg), Viread (TDF 300 mg) and Emtriva (FTC 200 mg) taken as Atripla® once-daily Atripla: Atripla 1 tab once a day
Overall Study STARTED	26	25
Overall Study COMPLETED	26	24
Overall Study NOT COMPLETED	0	1

Reasons for withdrawal

Reasons for withdrawal
Measure	1 - Kaletra + Isentress Taken Twice Daily Kaletra (lopinavir/ritonavir 400/100 mg) + Isentress (Raltegravir 400 mg) twice-daily Kaletra + Isentress: kaletra 2 tabs twice a day + Raltegravir 1 tab twice a day	2 - Atripla Taken Once Daily Sustiva (EFV 600 mg), Viread (TDF 300 mg) and Emtriva (FTC 200 mg) taken as Atripla® once-daily Atripla: Atripla 1 tab once a day
Overall Study randomized but did not do viral kinetics	0	1

Baseline Characteristics

Raltegravir + Lopinavir/Ritonavir Versus Efavirenz + Tenofovir + Emtricitabine in Treatment Naive Patients

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	1 - Kaletra + Isentress Taken Twice Daily n=26 Participants Kaletra (lopinavir/ritonavir 400/100 mg) + Isentress (Raltegravir 400 mg) twice-daily Kaletra + Isentress: kaletra 2 tabs twice a day + Raltegravir 1 tab twice a day	2 - Atripla Taken Once Daily n=25 Participants Sustiva (EFV 600 mg), Viread (TDF 300 mg) and Emtriva (FTC 200 mg) taken as Atripla® once-daily Atripla: Atripla 1 tab once a day	Total n=51 Participants Total of all reporting groups
Age, Continuous	40 years n=5 Participants	43 years n=7 Participants	43 years n=5 Participants
Sex: Female, Male Female	1 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants
Sex: Female, Male Male	25 Participants n=5 Participants	24 Participants n=7 Participants	49 Participants n=5 Participants
Race/Ethnicity, Customized White	21 Participants n=5 Participants	22 Participants n=7 Participants	43 Participants n=5 Participants
Race/Ethnicity, Customized Black	5 Participants n=5 Participants	0 Participants n=7 Participants	5 Participants n=5 Participants
Race/Ethnicity, Customized Asian	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Race/Ethnicity, Customized Other	0 Participants n=5 Participants	2 Participants n=7 Participants	2 Participants n=5 Participants
Race/Ethnicity, Customized Hispanic	12 Participants n=5 Participants	14 Participants n=7 Participants	26 Participants n=5 Participants
Race/Ethnicity, Customized Non-Hispanic	14 Participants n=5 Participants	11 Participants n=7 Participants	25 Participants n=5 Participants

PRIMARY outcome

Timeframe: Baseline, days 2, 7, 10, 14

Repeated HIV RNA measured at different time points (baseline, days 2, 7, 10, 14) will be treated as the outcome variable in a linear mixed-effects model. The primary fixed effects will include time, treatment group, treatment group-by-time interaction; random effects will include both intercept and slope allowing each subject to have individual baseline viral load and viral decay (rate of decrease in viral load following initiation of antiretroviral therapy). The treatment group-by- time interaction term in the model will indicate the difference in viral decay rates between the two treatment groups. Baseline covariate adjustment will be included if necessary.

Outcome measures

Outcome measures
Measure	1 - Kaletra + Isentress Taken Twice Daily n=26 Participants Kaletra (lopinavir/ritonavir 400/100 mg) + Isentress (Raltegravir 400 mg) twice-daily Kaletra + Isentress: kaletra 2 tabs twice a day + Raltegravir 1 tab twice a day	2 - Atripla Taken Once Daily n=24 Participants Sustiva (EFV 600 mg), Viread (TDF 300 mg) and Emtriva (FTC 200 mg) taken as Atripla® once-daily Atripla: Atripla 1 tab once a day
To Compare the Phase 1 Viral Decay Rates Between LPV/r + RAL vs. EFV/TDF/FTC Treatment Combinations.	0.47 log(10)/day Interval 0.42 to 0.52	0.55 log(10)/day Interval 0.52 to 0.58

SECONDARY outcome

Timeframe: 48 weeks

To determine the antiviral efficacy of LPV/r + RAL compared to EFV/TDF/FTC after 48 weeks of treatment by achieving undetectable viral load

Outcome measures

Outcome measures
Measure	1 - Kaletra + Isentress Taken Twice Daily n=26 Participants Kaletra (lopinavir/ritonavir 400/100 mg) + Isentress (Raltegravir 400 mg) twice-daily Kaletra + Isentress: kaletra 2 tabs twice a day + Raltegravir 1 tab twice a day	2 - Atripla Taken Once Daily n=24 Participants Sustiva (EFV 600 mg), Viread (TDF 300 mg) and Emtriva (FTC 200 mg) taken as Atripla® once-daily Atripla: Atripla 1 tab once a day
Viral Suppression Efficacy at 48 Weeks	86 percentage of participants	87.5 percentage of participants

SECONDARY outcome

Timeframe: Baseline to Week 4

Population: Participants who achieved viral suppression at week 24 and maintained it at week 48 were included in this analysis.

To compare early (baseline to Week 4) activated CD4+ T-cell recovery rates between treatment regimens.

Outcome measures

Outcome measures
Measure	1 - Kaletra + Isentress Taken Twice Daily n=12 Participants Kaletra (lopinavir/ritonavir 400/100 mg) + Isentress (Raltegravir 400 mg) twice-daily Kaletra + Isentress: kaletra 2 tabs twice a day + Raltegravir 1 tab twice a day	2 - Atripla Taken Once Daily n=16 Participants Sustiva (EFV 600 mg), Viread (TDF 300 mg) and Emtriva (FTC 200 mg) taken as Atripla® once-daily Atripla: Atripla 1 tab once a day
Compare Early Activated CD4+ T-cell Recovery Rates From Baseline to Week 4.	-3.81 cells/mm^3 Interval -6.12 to -1.51	-1.18 cells/mm^3 Interval -3.17 to 0.08

SECONDARY outcome

Timeframe: 48 weeks

Population: Participants who achieved viral suppression at week 24 and maintained it at week 48 were included in this analysis.

To compare late (baseline to Week 48) activated CD4+ T-cell recovery rates between treatment regimens.

Outcome measures

Outcome measures
Measure	1 - Kaletra + Isentress Taken Twice Daily n=12 Participants Kaletra (lopinavir/ritonavir 400/100 mg) + Isentress (Raltegravir 400 mg) twice-daily Kaletra + Isentress: kaletra 2 tabs twice a day + Raltegravir 1 tab twice a day	2 - Atripla Taken Once Daily n=16 Participants Sustiva (EFV 600 mg), Viread (TDF 300 mg) and Emtriva (FTC 200 mg) taken as Atripla® once-daily Atripla: Atripla 1 tab once a day
Compare Late Activated CD4+ T-cell Recovery Rates Between Treatment Regimens From Baseline to Week 48	-2.24 cells/mm^3 Interval -5.83 to 1.36	-5.65 cells/mm^3 Interval -8.76 to -2.54

Adverse Events

1 - Kaletra + Isentress Taken Twice Daily

Serious events: 0 serious events

Other events: 13 other events

Deaths: 0 deaths

2 - Atripla Taken Once Daily

Serious events: 0 serious events

Other events: 15 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure	1 - Kaletra + Isentress Taken Twice Daily n=26 participants at risk Kaletra (lopinavir/ritonavir 400/100 mg) + Isentress (Raltegravir 400 mg) twice-daily Kaletra + Isentress: kaletra 2 tabs twice a day + Raltegravir 1 tab twice a day	2 - Atripla Taken Once Daily n=25 participants at risk Sustiva (EFV 600 mg), Viread (TDF 300 mg) and Emtriva (FTC 200 mg) taken as Atripla® once-daily Atripla: Atripla 1 tab once a day
General disorders Generalized Symptoms	11.5% 3/26 • Number of events 4	16.0% 4/25 • Number of events 4
Gastrointestinal disorders GI Symptoms	50.0% 13/26 • Number of events 14	16.0% 4/25 • Number of events 4
Musculoskeletal and connective tissue disorders Pain, Aches & Muscle Discomfort	15.4% 4/26 • Number of events 4	20.0% 5/25 • Number of events 5
Nervous system disorders Any CNS Symptoms	11.5% 3/26 • Number of events 3	56.0% 14/25 • Number of events 14
Skin and subcutaneous tissue disorders Rash	11.5% 3/26 • Number of events 3	32.0% 8/25 • Number of events 8

Additional Information

Sheldon Morris

UCSD

Phone: 8583364088

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place