AIDS
Conditions
Brief summary
A pilot 24-week open-label, randomized, controlled clinical trial to assess the safety, tolerability and efficacy of dual therapy with Raltegravir/Lamivudine combination when replacing standard combination therapy in HIV-infected patients with prolonged virological suppression
Interventions
DRUGRAL plus ABC/3TC
DRUGOther ART regimens
DRUGRaltegravir/3TC
MK0518B (Raltegravir/3TC) (300mg/150mg) twice daily, administered orally in the 300/150 mg film-coated tablets according to instructions in the prescribing information.
DRUGEFV/TDF/FTC
standard combination therapy
DRUGATV/r + TDF/FTC or DRV/r + TDF/FTC
DRUGDTG+ABC/3TC DTG+TDF/FTC EVG/cobi/TDF/FTC RAL+TDF/FTC
DRUGEFV plus ABC/3TC or RPV/TDF/FTC
DRUGATV/r plus ABC/3TC
DRUGDRV/r + ABC/3TC or LPV/r + ABC/3TC or LPV/r + TDF/FTC
Sponsors
Juan A. Arnaiz
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Eligible patients will be males or females at least 18 years of age. Women of childbearing potential must have a negative pregnancy test within 10 days prior to randomization into the study. 2. Patients seropositive for HIV-1 using standard diagnostic criteria. 3. Patients virologically suppressed during at least 12 months prior to inclusion (viral load \<50 copies/mL). 4. Patients on combination antiretroviral therapy (at least 2 antiretroviral drugs) for at least 12 months before being randomized in this study. 5. Patients who are clinically stable in the opinion of the investigator at study entry (clinical status and chronic medication must not have not been modified at least 14 days prior to randomization). 6. Patients who have signed informed consent to participate in the study.
Exclusion criteria
1. Pregnancy, lactation, or planned pregnancy during the study period. 2. Previous failure to an integrase inhibitor-containing regimen. 3. Previous failure to a 3TC or FTC-containing regimen. 4. Resistance mutations to 3TC or integrase inhibitor if any resistance test had been previously performed. 5. Any disease or history of disease which, in the opinion of the investigator, might confound the results of the study or pose additional risk to patient treatment. 6. Chronic hepatitis B.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Proportion of Patients Free of Therapeutic Failure | 24 weeks | Proportion of patients free of therapeutic failure at week 24. Therapeutic failure includes virological failure, change in treatment for any reason, consent withdrawal, loss to follow-up or death |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Changes in Peripheral Mononuclear Blood Cells HIV-1 Reservoir | 24 weeks | — |
| Changes in Insulin Resistance (HOMA-IR) | 24 weeks | Composite measure |
| Changes in Body Fat Composition | 24 weeks | Composite measure |
| Changes in Plasma 25-OH Vitamin D Levels | 24 weeks | — |
| Changes in Estimated Glomerular Filtration Rate (CKD-EPI) | 24 weeks | Composite measure |
| Changes in CD38 | 24 weeks | — |
| Changes in IL-6 | 24 weeks | — |
| Changes in Sleep Quality (Pittsburgh Sleep Quality Index) | 24 weeks | The Pittsburgh Quality Index (PSQI) is an effective instrument used to measure the quality and patterns of sleep in adults. It differentiates poor from good sleep quality by measuring seven áreas (components): subjective sleep quality, sleep latency, sleep duration, habitual sleep efficiency, sleep disturbances, use of sleeping medications, and daytime dysfunction over the last month. The posible range of the scale is from 0 to 21 points. The greater the score the poorest is the sleep quality. |
| Changes in Adherence in Both Treatment Arms (Morisky-Green Test) | 24 weeks | Patients were asked to complete the Morisky-Green questionnaire: Some people forget to take their medication as prescribed. How often does it happen to you? (Always/often/sometimes/rarely/never) Some people forget some taking of the medication or change the prescribed schedule / take to adapt it to their own needs. How often do you do it? (Always/often/sometimes/rarely/never) Some people stop taking their medications as prescribed when they feel better. How often do you do it? (Always/often/sometimes/rarely/never) Some people stop taking their medications as prescribed when they feel worse. How often do you do it? (Always/often/sometimes/rarely/never) Only if patients answered never to each four questions, they were considered adherent; if not, non adherent. |
| Efficacy in Virological Suppression Assessed With Ultrasensitive HIV-1 RNA Detection (Limit of Detection 1 Copy/mL) | 24 weeks | — |
| Changes in HDL Cholesterol | 24 weeks | — |
| Changes in LDL Cholesterol | 24 weeks | — |
| Changes in Triglycerides | 24 weeks | — |
| Changes in Bone Mineral Density | 24 weeks | DEXA |
| Changes in Urine Beta-2-microglobulin/Creatinine Ratio | 24 weeks | — |
| Changes in HLA-DR | 24 weeks | — |
| Changes in High Sensitivity C-reactive Protein | 24 weeks | — |
| Changes in Mononuclear Activation SD-14 | 24 weeks | — |
| Changes in Mononuclear Activation SD-163 | 24 weeks | — |
| Changes in Total Cholesterol | 24 weeks | — |
Countries
Spain
Participant flow
Pre-assignment details
A total of 75 participants were enrolled and randomized. One participant assigned to the Raltegravir/Lamivudine arm withdrew consent before starting treatment and was excluded from the analysis. As a result, 74 participants initiated treatment.
Participants by arm
| Arm | Count |
|---|---|
| Group 1 Raltegravir / 3TC (MK0518B) Raltegravir / 3TC (MK0518B )
Raltegravir/3TC: MK0518B (Raltegravir/3TC) (300mg/150mg) twice daily, administered orally in the 300/150 mg film-coated tablets according to instructions in the prescribing information. | 49 |
| Group 2 Standard Combination Therapy NNRTI-Based Regimen:
• EFV/TDF/FTC
PI-Based Regimens:
ATV/r + TDF/FTC or DRV/r + TDF/FTC
INSTI-Based Regimens:
DTG+ABC/3TC DTG+TDF/FTC EVG/cobi/TDF/FTC RAL+TDF/FTC
NNRTI-Based Regimens:
EFV plus ABC/3TC or RPV/TDF/FTC
PI-Based Regimen:
ATV/r plus ABC/3TC
PI-Based Regimens:
DRV/r + ABC/3TC or LPV/r + ABC/3TC or LPV/r + TDF/FTC
INSTI-Based Regimen:
RAL plus ABC/3TC
And other ART regimens
EFV/TDF/FTC: standard combination therapy
ATV/r + TDF/FTC or DRV/r + TDF/FTC
DTG+ABC/3TC DTG+TDF/FTC EVG/cobi/TDF/FTC RAL+TDF/FTC
EFV plus ABC/3TC or RPV/TDF/FTC
ATV/r plus ABC/3TC
DRV/r + ABC/3TC or LPV/r + ABC/3TC or LPV/r + TDF/FTC
RAL plus ABC/3TC
Other ART regimens | 25 |
| Total | 74 |
Baseline characteristics
| Characteristic | Group 2 Standard Combination Therapy | Total | Group 1 Raltegravir / 3TC (MK0518B) |
|---|---|---|---|
| Age, Continuous | 50 years STANDARD_DEVIATION 13 | 50 years STANDARD_DEVIATION 12 | 50 years STANDARD_DEVIATION 12 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 24 Participants | 73 Participants | 49 Participants |
| Sex: Female, Male Female | 4 Participants | 16 Participants | 12 Participants |
| Sex: Female, Male Male | 21 Participants | 58 Participants | 37 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 1 / 49 | 0 / 25 |
| other Total, other adverse events | 12 / 49 | 10 / 25 |
| serious Total, serious adverse events | 3 / 49 | 3 / 25 |
Outcome results
Primary
Proportion of Patients Free of Therapeutic Failure
Proportion of patients free of therapeutic failure at week 24. Therapeutic failure includes virological failure, change in treatment for any reason, consent withdrawal, loss to follow-up or death
Time frame: 24 weeks
Population: A total of 75 subjects were randomized. However, in the RAL/3TC group (n=50), one subject was excluded due to consent withdrawal prior to the initiation of medication and therefore did not complete the Baseline (randomization) visit.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Group 1 Raltegravir / 3TC (MK0518B | Proportion of Patients Free of Therapeutic Failure | No events | 47 Participants |
| Group 1 Raltegravir / 3TC (MK0518B | Proportion of Patients Free of Therapeutic Failure | Lost to follow up | 0 Participants |
| Group 1 Raltegravir / 3TC (MK0518B | Proportion of Patients Free of Therapeutic Failure | Pregnancy | 1 Participants |
| Group 1 Raltegravir / 3TC (MK0518B | Proportion of Patients Free of Therapeutic Failure | Stops treatment | 0 Participants |
| Group 1 Raltegravir / 3TC (MK0518B | Proportion of Patients Free of Therapeutic Failure | Virological faiulure | 0 Participants |
| Group 1 Raltegravir / 3TC (MK0518B | Proportion of Patients Free of Therapeutic Failure | Stops study medical decision | 1 Participants |
| Group 2 Standard Combination Therapy | Proportion of Patients Free of Therapeutic Failure | Virological faiulure | 1 Participants |
| Group 2 Standard Combination Therapy | Proportion of Patients Free of Therapeutic Failure | No events | 20 Participants |
| Group 2 Standard Combination Therapy | Proportion of Patients Free of Therapeutic Failure | Stops treatment | 2 Participants |
| Group 2 Standard Combination Therapy | Proportion of Patients Free of Therapeutic Failure | Lost to follow up | 2 Participants |
| Group 2 Standard Combination Therapy | Proportion of Patients Free of Therapeutic Failure | Stops study medical decision | 0 Participants |
| Group 2 Standard Combination Therapy | Proportion of Patients Free of Therapeutic Failure | Pregnancy | 0 Participants |
Secondary
Changes in Adherence in Both Treatment Arms (Morisky-Green Test)
Patients were asked to complete the Morisky-Green questionnaire: Some people forget to take their medication as prescribed. How often does it happen to you? (Always/often/sometimes/rarely/never) Some people forget some taking of the medication or change the prescribed schedule / take to adapt it to their own needs. How often do you do it? (Always/often/sometimes/rarely/never) Some people stop taking their medications as prescribed when they feel better. How often do you do it? (Always/often/sometimes/rarely/never) Some people stop taking their medications as prescribed when they feel worse. How often do you do it? (Always/often/sometimes/rarely/never) Only if patients answered never to each four questions, they were considered adherent; if not, non adherent.
Time frame: 24 weeks
Population: Some patients did not complete the questionnaire
| Arm | Measure | Group | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|---|
| Group 1 Raltegravir / 3TC (MK0518B | Changes in Adherence in Both Treatment Arms (Morisky-Green Test) | Baseline | Adherent | 19 Participants |
| Group 1 Raltegravir / 3TC (MK0518B | Changes in Adherence in Both Treatment Arms (Morisky-Green Test) | Baseline | Non adherent | 29 Participants |
| Group 1 Raltegravir / 3TC (MK0518B | Changes in Adherence in Both Treatment Arms (Morisky-Green Test) | Baseline | Not evaluated/ Lost follow Up | 1 Participants |
| Group 1 Raltegravir / 3TC (MK0518B | Changes in Adherence in Both Treatment Arms (Morisky-Green Test) | Week 24 | Adherent | 19 Participants |
| Group 1 Raltegravir / 3TC (MK0518B | Changes in Adherence in Both Treatment Arms (Morisky-Green Test) | Week 24 | Non adherent | 27 Participants |
| Group 1 Raltegravir / 3TC (MK0518B | Changes in Adherence in Both Treatment Arms (Morisky-Green Test) | Week 24 | Not evaluated/ Lost follow Up | 3 Participants |
| Group 2 Standard Combination Therapy | Changes in Adherence in Both Treatment Arms (Morisky-Green Test) | Week 24 | Non adherent | 5 Participants |
| Group 2 Standard Combination Therapy | Changes in Adherence in Both Treatment Arms (Morisky-Green Test) | Baseline | Adherent | 11 Participants |
| Group 2 Standard Combination Therapy | Changes in Adherence in Both Treatment Arms (Morisky-Green Test) | Week 24 | Adherent | 14 Participants |
| Group 2 Standard Combination Therapy | Changes in Adherence in Both Treatment Arms (Morisky-Green Test) | Baseline | Non adherent | 13 Participants |
| Group 2 Standard Combination Therapy | Changes in Adherence in Both Treatment Arms (Morisky-Green Test) | Week 24 | Not evaluated/ Lost follow Up | 6 Participants |
| Group 2 Standard Combination Therapy | Changes in Adherence in Both Treatment Arms (Morisky-Green Test) | Baseline | Not evaluated/ Lost follow Up | 1 Participants |
Secondary
Changes in Body Fat Composition
Composite measure
Time frame: 24 weeks
Population: Some patients were not performed a DEXA during the study
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Group 1 Raltegravir / 3TC (MK0518B | Changes in Body Fat Composition | Baseline extremities fat percentage | 54.13 percentage of fat weight | Standard Deviation 19.44 |
| Group 1 Raltegravir / 3TC (MK0518B | Changes in Body Fat Composition | Baseline total fat percentage | 28.50 percentage of fat weight | Standard Deviation 7.62 |
| Group 1 Raltegravir / 3TC (MK0518B | Changes in Body Fat Composition | Week 24 extremities fat percentage | 54.09 percentage of fat weight | Standard Deviation 17.68 |
| Group 1 Raltegravir / 3TC (MK0518B | Changes in Body Fat Composition | Week 24 total fat percentage | 28.84 percentage of fat weight | Standard Deviation 7.23 |
| Group 2 Standard Combination Therapy | Changes in Body Fat Composition | Week 24 total fat percentage | 28.78 percentage of fat weight | Standard Deviation 9.55 |
| Group 2 Standard Combination Therapy | Changes in Body Fat Composition | Baseline extremities fat percentage | 49.43 percentage of fat weight | Standard Deviation 21.26 |
| Group 2 Standard Combination Therapy | Changes in Body Fat Composition | Week 24 extremities fat percentage | 50.21 percentage of fat weight | Standard Deviation 23.77 |
| Group 2 Standard Combination Therapy | Changes in Body Fat Composition | Baseline total fat percentage | 27.54 percentage of fat weight | Standard Deviation 8.75 |
Secondary
Changes in Bone Mineral Density
DEXA
Time frame: 24 weeks
Population: Not all the patients performed the DEXA
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Group 1 Raltegravir / 3TC (MK0518B | Changes in Bone Mineral Density | Baseline | 1166.1 gr/cm^2 | Standard Deviation 100.9 |
| Group 1 Raltegravir / 3TC (MK0518B | Changes in Bone Mineral Density | Week 24 | 1183.0 gr/cm^2 | Standard Deviation 98.5 |
| Group 2 Standard Combination Therapy | Changes in Bone Mineral Density | Baseline | 1211.6 gr/cm^2 | Standard Deviation 79.6 |
| Group 2 Standard Combination Therapy | Changes in Bone Mineral Density | Week 24 | 1247.4 gr/cm^2 | Standard Deviation 80.9 |
Secondary
Changes in CD38
Time frame: 24 weeks
Secondary
Changes in Estimated Glomerular Filtration Rate (CKD-EPI)
Composite measure
Time frame: 24 weeks
Secondary
Changes in HDL Cholesterol
Time frame: 24 weeks
Population: Some patients did not performed all the determinations
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Group 1 Raltegravir / 3TC (MK0518B | Changes in HDL Cholesterol | Baseline | 48 mg/dl | Standard Deviation 15 |
| Group 1 Raltegravir / 3TC (MK0518B | Changes in HDL Cholesterol | Week 24 | 49 mg/dl | Standard Deviation 14 |
| Group 2 Standard Combination Therapy | Changes in HDL Cholesterol | Baseline | 46 mg/dl | Standard Deviation 13 |
| Group 2 Standard Combination Therapy | Changes in HDL Cholesterol | Week 24 | 45 mg/dl | Standard Deviation 15 |
Secondary
Changes in High Sensitivity C-reactive Protein
Time frame: 24 weeks
Secondary
Changes in HLA-DR
Time frame: 24 weeks
Secondary
Changes in IL-6
Time frame: 24 weeks
Secondary
Changes in Insulin Resistance (HOMA-IR)
Composite measure
Time frame: 24 weeks
Secondary
Changes in LDL Cholesterol
Time frame: 24 weeks
Population: Some patients did not perform all the determinations
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Group 1 Raltegravir / 3TC (MK0518B | Changes in LDL Cholesterol | Baseline | 120 mg/dl | Standard Deviation 39 |
| Group 1 Raltegravir / 3TC (MK0518B | Changes in LDL Cholesterol | Week 24 | 119 mg/dl | Standard Deviation 40 |
| Group 2 Standard Combination Therapy | Changes in LDL Cholesterol | Baseline | 115 mg/dl | Standard Deviation 29 |
| Group 2 Standard Combination Therapy | Changes in LDL Cholesterol | Week 24 | 118 mg/dl | Standard Deviation 33 |
Secondary
Changes in Mononuclear Activation SD-14
Time frame: 24 weeks
Secondary
Changes in Mononuclear Activation SD-163
Time frame: 24 weeks
Secondary
Changes in Peripheral Mononuclear Blood Cells HIV-1 Reservoir
Time frame: 24 weeks
Secondary
Changes in Plasma 25-OH Vitamin D Levels
Time frame: 24 weeks
Population: Some patients vitamine D determination was not available
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Group 1 Raltegravir / 3TC (MK0518B | Changes in Plasma 25-OH Vitamin D Levels | Baseline | 17.4 ng/mL | Standard Deviation 9 |
| Group 1 Raltegravir / 3TC (MK0518B | Changes in Plasma 25-OH Vitamin D Levels | week 24 | 29.5 ng/mL | Standard Deviation 15.1 |
| Group 2 Standard Combination Therapy | Changes in Plasma 25-OH Vitamin D Levels | Baseline | 16.7 ng/mL | Standard Deviation 9.6 |
| Group 2 Standard Combination Therapy | Changes in Plasma 25-OH Vitamin D Levels | week 24 | 26.5 ng/mL | Standard Deviation 17.2 |
Secondary
Changes in Sleep Quality (Pittsburgh Sleep Quality Index)
The Pittsburgh Quality Index (PSQI) is an effective instrument used to measure the quality and patterns of sleep in adults. It differentiates poor from good sleep quality by measuring seven áreas (components): subjective sleep quality, sleep latency, sleep duration, habitual sleep efficiency, sleep disturbances, use of sleeping medications, and daytime dysfunction over the last month. The posible range of the scale is from 0 to 21 points. The greater the score the poorest is the sleep quality.
Time frame: 24 weeks
Population: Some patients did not complete the questionnaire
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Group 1 Raltegravir / 3TC (MK0518B | Changes in Sleep Quality (Pittsburgh Sleep Quality Index) | Baseline score | 5 score on a scale | Standard Deviation 3.5 |
| Group 1 Raltegravir / 3TC (MK0518B | Changes in Sleep Quality (Pittsburgh Sleep Quality Index) | Week 24 score | 4.8 score on a scale | Standard Deviation 3.1 |
| Group 2 Standard Combination Therapy | Changes in Sleep Quality (Pittsburgh Sleep Quality Index) | Baseline score | 4.7 score on a scale | Standard Deviation 3.1 |
| Group 2 Standard Combination Therapy | Changes in Sleep Quality (Pittsburgh Sleep Quality Index) | Week 24 score | 5.1 score on a scale | Standard Deviation 3.5 |
Secondary
Changes in Total Cholesterol
Time frame: 24 weeks
Population: Some patients have not performed all the protocol determinations
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Group 1 Raltegravir / 3TC (MK0518B | Changes in Total Cholesterol | Baseline | 189 mg/dl | Standard Deviation 46 |
| Group 1 Raltegravir / 3TC (MK0518B | Changes in Total Cholesterol | Week 24 | 190 mg/dl | Standard Deviation 45 |
| Group 2 Standard Combination Therapy | Changes in Total Cholesterol | Baseline | 187 mg/dl | Standard Deviation 44 |
| Group 2 Standard Combination Therapy | Changes in Total Cholesterol | Week 24 | 186 mg/dl | Standard Deviation 37 |
Secondary
Changes in Triglycerides
Time frame: 24 weeks
Population: All patients did not perform all the determinations
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Group 1 Raltegravir / 3TC (MK0518B | Changes in Triglycerides | Baseline | 98.5 mg/dl | Standard Deviation 49.9 |
| Group 1 Raltegravir / 3TC (MK0518B | Changes in Triglycerides | Week 24 | 97.7 mg/dl | Standard Deviation 44.8 |
| Group 2 Standard Combination Therapy | Changes in Triglycerides | Baseline | 112.0 mg/dl | Standard Deviation 53 |
| Group 2 Standard Combination Therapy | Changes in Triglycerides | Week 24 | 100.9 mg/dl | Standard Deviation 37.3 |
Secondary
Changes in Urine Beta-2-microglobulin/Creatinine Ratio
Time frame: 24 weeks
Population: Some patients did not performed this determination
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Group 1 Raltegravir / 3TC (MK0518B | Changes in Urine Beta-2-microglobulin/Creatinine Ratio | Baseline | 672.8 mg/g | Standard Deviation 773.3 |
| Group 1 Raltegravir / 3TC (MK0518B | Changes in Urine Beta-2-microglobulin/Creatinine Ratio | Week 24 | 275.7 mg/g | Standard Deviation 227.2 |
| Group 2 Standard Combination Therapy | Changes in Urine Beta-2-microglobulin/Creatinine Ratio | Week 24 | 788.5 mg/g | Standard Deviation 1587.3 |
| Group 2 Standard Combination Therapy | Changes in Urine Beta-2-microglobulin/Creatinine Ratio | Baseline | 595.3 mg/g | Standard Deviation 948.7 |
Secondary
Efficacy in Virological Suppression Assessed With Ultrasensitive HIV-1 RNA Detection (Limit of Detection 1 Copy/mL)
Time frame: 24 weeks