HIV-1 Infection
Conditions
Keywords
HIV, antiretroviral, human immunodeficiency virus, Raltegravir, Adults with HIV-1 infection
Brief summary
This is an observational, non-comparative, multicenter, open-label study. Participants will be treated with Raltegravir according to standard clinical practice, and monitored over a total period of 96 weeks. In an extension to the study (Amendment 1), a new cohort of aging participants (≥ 50 years) will be recruited and monitored over a total period of 48 weeks. Participants who stop taking Raltegravir before the end of the 96-week period or 48-week period, respectively, will be followed up for 3 months after discontinuing the drug. The primary objective is to determine the proportion of participants with a human immunodeficiency virus (HIV)-1 viral load \< 50 copies/mL after 48 weeks of treatment with Raltegravir.
Interventions
DRUGRaltegravir
Raltegravir, 400 mg, per oral (p.o.) twice daily (b.i.d.) for 48 or 144 weeks
Sponsors
Merck Sharp & Dohme LLC
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
The prospective participant must meet, at least, all of the criteria below to be eligible for study participation. The participant: * Is a minimum age of 18 years (adults) or 50 years (aging participants); * Is male or female; * Has confirmed infection with HIV-1 (positive HIV test according to appropriate standard practice); * Has commenced antiretroviral treatment with Raltegravir according to the recommendations made in the Summary of Product Characteristics at the time of enrollment on the study, or a maximum 6 months prior to enrollment on the study; * Has any cluster of differentiation (CD4) cell (specialized white blood cell) count upon enrollment on the study.
Exclusion criteria
If the prospective participant meets any of the criteria below (among others determined by the study staff) they will NOT be eligible for study participation. The participant: * For which Raltegravir, or its ingredients, are contraindicated; * Has intolerance to Raltegravir, or its ingredients; * If female, is pregnant, breastfeeding, or is planning a pregnancy or egg donation during the study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With an HIV-1 Viral Load <50 Copies/mL After 48 Weeks of Raltegravir Treatment | Baseline and 48 weeks | The percentage of participants with an HIV-1 viral load \<50 copies/mL of HIV-1 RNA after 48 weeks of raltegravir treatment was determined. |
| Percentage of Aging Participants With an HIV-1 Viral Load <50 Copies/mL After 48 Weeks of Raltegravir Treatment | Baseline and 48 weeks | The percentage of aging participants (\>=50 years old at initiation of raltegravir treatment) with an HIV-1 viral load \<50 copies/mL of HIV-1 RNA after 48 weeks of raltegravir treatment was determined. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in CD4+ T-cell Counts After 96 Weeks of Raltegravir Treatment | Baseline and 96 weeks | Mean CD4+ T-cell counts were determined at baseline and after 96 weeks of raltegravir treatment. A positive change from baseline indicates an increase in CD4+ T-cell count. |
| HIV-1 Viral Load in Aging Participants After 48 Weeks of Raltegravir Treatment | Baseline and 48 weeks | The HIV-1 viral load (log10 copies/mL of HIV-1 RNA) was determined in aging participants (\>=50 years old at initiation of raltegravir treatment) at Baseline and after 48 weeks of raltegravir treatment. |
| Change From Baseline in CD4+ T-cell Counts in Aging Participants After 48 Weeks of Raltegravir Treatment | Baseline and 48 weeks | Mean CD4+ T-cell counts were determined in aging participants (\>=50 years old at initiation of raltegravir treatment) at baseline and after 48 weeks of raltegravir treatment was determined. A positive change from baseline indicates an increase in CD4+ T-cell count. |
| Percentage of Participants With an HIV-1 Viral Load <50 Copies/mL After 96 Weeks of Raltegravir Treatment | Baseline and 96 weeks | The percentage of participants with an HIV-1 viral load \<50 copies/mL of HIV-1 RNA after 96 weeks of raltegravir treatment was determined. |
| Change From Baseline in Mean D:A:D Risk Score for the 5-Year Cardiovascular Risk in Aging Participants After 48 Weeks of Raltegravir Treatment | Baseline and 48 weeks | Mean Data Collection on Adverse Events of Anti-HIV Drugs (D:A:D) Risk Score for 5-year cardiovascular risk was determined in aging participants (\>=50 years old at initiation of raltegravir treatment) at Baseline and after 48 weeks of raltegravir treatment. The score included the following 8 risk factors: sex, age, systolic blood pressure, family cardiovascular disease history, current smoking, previous cigarette smoker, diabetes, total cholesterol, high-density lipoprotein, currently on indinavir, currently on lopinavir, currently on abacavir, duration and current use of indinavir and duration and current use of lopinavir. The D:A:D Risk Score is interpreted as low: \<1%; moderate: 1-5%; high: 5-10%; and very high: \>10%. The change from baseline was calculated as Week 48 minus Baseline; a positive change indicates increased risk. This Outcome Measure was added with Amendment 1 and applies only to aging participants. |
| Percentage of Aging Participants With Concomitant Diseases at Baseline | Baseline | The percentage of aging participants with Baseline comorbidities was reported. This Outcome Measure was added with Amendment 1 and applies only to aging participants. |
| Percentage of Aging Participants Taking Concomitant Medications at Baseline | Baseline | The percentage of aging participants taking concomitant medication in addition to their other antiretroviral therapy was reported. This Outcome Measure was added with Amendment 1 and applies only to aging participants. |
| Change From Baseline in Mean Framingham Risk Score for the 10-Year Cardiovascular Risk in Aging Participants After 48 Weeks of Raltegravir Treatment | Baseline and 48 weeks | Mean Framingham Risk for 10-year cardiovascular risk was determined in aging participants (\>=50 years old at initiation of raltegravir treatment). Points were allotted for each of following 8 risk factors : sex, age, systolic blood pressure, treatment for hypertension, smoking, diabetes, total cholesterol, and high-density lipoprotein. The sum of the points for each participant was assigned a percent 10-year cardiovascular risk on a lookup table, and could range from 0% to 100%. The mean Framingham Risk for 10-year cardiovascular risk was then calculated for the analysis population. The change from baseline was calculated as Baseline minus Week 48; a positive change indicates reduced risk. This Outcome Measure was added with Amendment 1 and applies only to aging participants. |
| HIV-1 Viral Load After 96 Weeks of Raltegravir Treatment | Baseline and 96 weeks | The HIV-1 viral load (log10 copies/mL of HIV-1 RNA) was determined at Baseline and after 96 weeks of raltegravir treatment. |
Participant flow
Recruitment details
The Initial Cohort included participants \>=18 years old to receive treatment for 96 weeks. With the amendment, participants in the initial cohort \>=50 years old could continue for an additional 48-weeks observation (Prolonged Cohort), and participants \>=50 years old were newly enrolled to receive treatment for 48 weeks (Amendment Cohort).
Participants by arm
| Arm | Count |
|---|---|
| Overall Participants HIV-1 infected participants received raltegravir 400 mg tablet orally twice daily for 96 weeks (Initial Cohort), 144 weeks (Prolonged Cohort) or 48 weeks (Amendment Cohort) in combination with other antiretroviral drugs under conditions representative of standard of clinical practice for HIV-1 patients in Germany. | 451 |
| Total | 451 |
Baseline characteristics
| Characteristic | Overall Participants |
|---|---|
| Age, Continuous | 50.8 Years STANDARD_DEVIATION 11.5 |
| Sex: Female, Male Female | 69 Participants |
| Sex: Female, Male Male | 382 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 0 / 451 | 0 / 272 | 0 / 227 |
| serious Total, serious adverse events | 34 / 451 | 25 / 272 | 17 / 227 |
Outcome results
Primary
Percentage of Aging Participants With an HIV-1 Viral Load <50 Copies/mL After 48 Weeks of Raltegravir Treatment
The percentage of aging participants (\>=50 years old at initiation of raltegravir treatment) with an HIV-1 viral load \<50 copies/mL of HIV-1 RNA after 48 weeks of raltegravir treatment was determined.
Time frame: Baseline and 48 weeks
Population: The analysis set included aging participants (Prolonged Participants and Newly Enrolled Participants) who received at least one dose of raltegravir during the observation period.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Overall Participants | Percentage of Aging Participants With an HIV-1 Viral Load <50 Copies/mL After 48 Weeks of Raltegravir Treatment | Baseline | 62.1 Percentage of participants |
| Overall Participants | Percentage of Aging Participants With an HIV-1 Viral Load <50 Copies/mL After 48 Weeks of Raltegravir Treatment | 48 weeks | 77.5 Percentage of participants |
Primary
Percentage of Participants With an HIV-1 Viral Load <50 Copies/mL After 48 Weeks of Raltegravir Treatment
The percentage of participants with an HIV-1 viral load \<50 copies/mL of HIV-1 RNA after 48 weeks of raltegravir treatment was determined.
Time frame: Baseline and 48 weeks
Population: The analysis set included all participants who received at least one dose of raltegravir during the observation period.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Overall Participants | Percentage of Participants With an HIV-1 Viral Load <50 Copies/mL After 48 Weeks of Raltegravir Treatment | Baseline | 50.8 Percentage of participants |
| Overall Participants | Percentage of Participants With an HIV-1 Viral Load <50 Copies/mL After 48 Weeks of Raltegravir Treatment | 48 weeks | 74.7 Percentage of participants |
Secondary
Change From Baseline in CD4+ T-cell Counts After 96 Weeks of Raltegravir Treatment
Mean CD4+ T-cell counts were determined at baseline and after 96 weeks of raltegravir treatment. A positive change from baseline indicates an increase in CD4+ T-cell count.
Time frame: Baseline and 96 weeks
Population: The analysis set included participants in the Initial Cohort who received at least one dose of raltegravir during the observation period.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Overall Participants | Change From Baseline in CD4+ T-cell Counts After 96 Weeks of Raltegravir Treatment | Baseline | 461.9 CD4+ T-cells/µL | Standard Deviation 286.35 |
| Overall Participants | Change From Baseline in CD4+ T-cell Counts After 96 Weeks of Raltegravir Treatment | Change from Baseline at 96 weeks: n=216 | 161.7 CD4+ T-cells/µL | Standard Deviation 225.98 |
Secondary
Change From Baseline in CD4+ T-cell Counts in Aging Participants After 48 Weeks of Raltegravir Treatment
Mean CD4+ T-cell counts were determined in aging participants (\>=50 years old at initiation of raltegravir treatment) at baseline and after 48 weeks of raltegravir treatment was determined. A positive change from baseline indicates an increase in CD4+ T-cell count.
Time frame: Baseline and 48 weeks
Population: The analysis set included aging participants (Prolonged Participants and Newly Enrolled Participants) who received at least one dose of raltegravir during the observation period.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Overall Participants | Change From Baseline in CD4+ T-cell Counts in Aging Participants After 48 Weeks of Raltegravir Treatment | Baseline | 534.4 CD4+ T-cells/µL | Standard Deviation 297.48 |
| Overall Participants | Change From Baseline in CD4+ T-cell Counts in Aging Participants After 48 Weeks of Raltegravir Treatment | Change from Baseline at 48 weeks: n=202 | 63.2 CD4+ T-cells/µL | Standard Deviation 183.43 |
Secondary
Change From Baseline in Mean D:A:D Risk Score for the 5-Year Cardiovascular Risk in Aging Participants After 48 Weeks of Raltegravir Treatment
Mean Data Collection on Adverse Events of Anti-HIV Drugs (D:A:D) Risk Score for 5-year cardiovascular risk was determined in aging participants (\>=50 years old at initiation of raltegravir treatment) at Baseline and after 48 weeks of raltegravir treatment. The score included the following 8 risk factors: sex, age, systolic blood pressure, family cardiovascular disease history, current smoking, previous cigarette smoker, diabetes, total cholesterol, high-density lipoprotein, currently on indinavir, currently on lopinavir, currently on abacavir, duration and current use of indinavir and duration and current use of lopinavir. The D:A:D Risk Score is interpreted as low: \<1%; moderate: 1-5%; high: 5-10%; and very high: \>10%. The change from baseline was calculated as Week 48 minus Baseline; a positive change indicates increased risk. This Outcome Measure was added with Amendment 1 and applies only to aging participants.
Time frame: Baseline and 48 weeks
Population: The analysis set included aging participants (Prolonged Participants and Newly Enrolled Participants) who received at least one dose of raltegravir during the observation period and had evaluable results.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Overall Participants | Change From Baseline in Mean D:A:D Risk Score for the 5-Year Cardiovascular Risk in Aging Participants After 48 Weeks of Raltegravir Treatment | Score at Baseline | 9.4 Percentage risk | Standard Deviation 8.7 |
| Overall Participants | Change From Baseline in Mean D:A:D Risk Score for the 5-Year Cardiovascular Risk in Aging Participants After 48 Weeks of Raltegravir Treatment | Change from Baseline at 48 weeks: n=57 | 4.2 Percentage risk | Standard Deviation 9.5 |
Secondary
Change From Baseline in Mean Framingham Risk Score for the 10-Year Cardiovascular Risk in Aging Participants After 48 Weeks of Raltegravir Treatment
Mean Framingham Risk for 10-year cardiovascular risk was determined in aging participants (\>=50 years old at initiation of raltegravir treatment). Points were allotted for each of following 8 risk factors : sex, age, systolic blood pressure, treatment for hypertension, smoking, diabetes, total cholesterol, and high-density lipoprotein. The sum of the points for each participant was assigned a percent 10-year cardiovascular risk on a lookup table, and could range from 0% to 100%. The mean Framingham Risk for 10-year cardiovascular risk was then calculated for the analysis population. The change from baseline was calculated as Baseline minus Week 48; a positive change indicates reduced risk. This Outcome Measure was added with Amendment 1 and applies only to aging participants.
Time frame: Baseline and 48 weeks
Population: The analysis set included aging participants (Prolonged Participants and Newly Enrolled Participants) who received at least one dose of raltegravir during the observation period and had evaluable results.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Overall Participants | Change From Baseline in Mean Framingham Risk Score for the 10-Year Cardiovascular Risk in Aging Participants After 48 Weeks of Raltegravir Treatment | Score at Baseline | 24.1 Percentage risk | Standard Deviation 17.5 |
| Overall Participants | Change From Baseline in Mean Framingham Risk Score for the 10-Year Cardiovascular Risk in Aging Participants After 48 Weeks of Raltegravir Treatment | Change from Baseline at 48 weeks: n=65 | 1.1 Percentage risk | Standard Deviation 10.9 |
Secondary
HIV-1 Viral Load After 96 Weeks of Raltegravir Treatment
The HIV-1 viral load (log10 copies/mL of HIV-1 RNA) was determined at Baseline and after 96 weeks of raltegravir treatment.
Time frame: Baseline and 96 weeks
Population: The analysis set included participants in the Initial Cohort who received at least one dose of raltegravir during the observation period.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Overall Participants | HIV-1 Viral Load After 96 Weeks of Raltegravir Treatment | Baseline | 2.90 Log10 Copies/mL | Standard Deviation 1.65 |
| Overall Participants | HIV-1 Viral Load After 96 Weeks of Raltegravir Treatment | 96 weeks | 1.52 Log10 Copies/mL | Standard Deviation 0.43 |
Secondary
HIV-1 Viral Load in Aging Participants After 48 Weeks of Raltegravir Treatment
The HIV-1 viral load (log10 copies/mL of HIV-1 RNA) was determined in aging participants (\>=50 years old at initiation of raltegravir treatment) at Baseline and after 48 weeks of raltegravir treatment.
Time frame: Baseline and 48 weeks
Population: The analysis set included aging participants (Prolonged Participants and Newly Enrolled Participants) who received at least one dose of raltegravir during the observation period.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Overall Participants | HIV-1 Viral Load in Aging Participants After 48 Weeks of Raltegravir Treatment | Baseline | 2.28 Log10 Copies/mL | Standard Deviation 1.43 |
| Overall Participants | HIV-1 Viral Load in Aging Participants After 48 Weeks of Raltegravir Treatment | 48 weeks | 1.50 Log10 Copies/mL | Standard Deviation 0.45 |
Secondary
Percentage of Aging Participants Taking Concomitant Medications at Baseline
The percentage of aging participants taking concomitant medication in addition to their other antiretroviral therapy was reported. This Outcome Measure was added with Amendment 1 and applies only to aging participants.
Time frame: Baseline
Population: The analysis set included aging participants (Prolonged Participants and Newly Enrolled Participants) who received at least one dose of raltegravir during the observation period.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Overall Participants | Percentage of Aging Participants Taking Concomitant Medications at Baseline | 74.9 Percentage of participants |
Secondary
Percentage of Aging Participants With Concomitant Diseases at Baseline
The percentage of aging participants with Baseline comorbidities was reported. This Outcome Measure was added with Amendment 1 and applies only to aging participants.
Time frame: Baseline
Population: The analysis set included aging participants (Prolonged Participants and Newly Enrolled Participants) who received at least one dose of raltegravir during the observation period.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Overall Participants | Percentage of Aging Participants With Concomitant Diseases at Baseline | 93.8 Percentage of participants |
Secondary
Percentage of Participants With an HIV-1 Viral Load <50 Copies/mL After 96 Weeks of Raltegravir Treatment
The percentage of participants with an HIV-1 viral load \<50 copies/mL of HIV-1 RNA after 96 weeks of raltegravir treatment was determined.
Time frame: Baseline and 96 weeks
Population: The analysis set included participants in the Initial Cohort who received at least one dose of raltegravir during the observation period.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Overall Participants | Percentage of Participants With an HIV-1 Viral Load <50 Copies/mL After 96 Weeks of Raltegravir Treatment | Baseline | 43.8 Percentage of participants |
| Overall Participants | Percentage of Participants With an HIV-1 Viral Load <50 Copies/mL After 96 Weeks of Raltegravir Treatment | 96 weeks | 68.0 Percentage of participants |