HIV-1 Infections
Conditions
Keywords
HIV
Brief summary
The objective of this study is to monitor Health Outcomes of Interest (HOI) in participants with human immunodeficiency virus-1 (HIV-1) infection following treatment with Raltegravir.
Detailed description
Study participants contributed data to one or more of 3 cohorts: 1) Historical Cohort: HIV-infected participants treated with antiretroviral therapy in the course of ordinary clinical practice at the clinics and medical centers of Kaiser Permanente (KP) between 1 January 2000 and 12 October 2007 (date of market authorization for raltegravir in USA), 2) Concurrent Cohort: HIV-infected participant treated with a new non-raltegravir antiretroviral therapy in the course of ordinary clinical practice at the clinics and medical centers of KP on or after 12 October 2007, and 3) Raltegravir Cohort: HIV-infected participant treated with raltegravir in the course of ordinary clinical practice at the clinics and medical centers of KP on or after 12 October 2007. Participants could contribute data to more than one cohort, but no overlap in follow-up time was allowed.
Interventions
None listed
Sponsors
Kaiser Permanente
Merck Sharp & Dohme LLC
Study design
Observational model
COHORT
Time perspective
RETROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Historical Cohort: HIV-infected participant treated with antiretroviral therapy in the course of ordinary clinical practice at the clinics and medical centers of Kaiser Permanente (KP) between 1 January 2000 and 12 October 2007 (date of market authorization for raltegravir in USA) * Raltegravir Cohort: HIV-infected participant treated with raltegravir in the course of ordinary clinical practice at the clinics and medical centers of KP on or after 12 October 2007 * Concurrent Cohort: HIV-infected participant treated with a new non-raltegravir antiretroviral therapy in the course of ordinary clinical practice at the clinics and medical centers of KP on or after 12 October 2007 * All participants must have at least one year of continuous membership with KP prior to date when the participant received the first dispensed prescription for study drug (index date) to allow for the assessment of medical and treatment history
Exclusion criteria
* Less than 18 years of age * Do not receive their medications through the KP pharmacy system * Do not receive their laboratory examinations through the KP system * Participating in the raltegravir phase III or expanded access program
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of Clinically Important Hepatic Events | Historical Cohort: up to 33 months (January 2005 to October 2007); Raltegravir and Concurrent Cohorts: up to 69 months (October 2007 to June 2013) | Hepatic events occurring during the risk period were identified through computer-stored records of laboratory values, outpatient visits, Emergency Department visits, and hospitalizations. Significant hepatic events were identified based on algorithms utilizing a combination of diagnoses, procedures, and laboratory results. Incidence is reported as unadjusted, crude rates. |
| Incidence of Clinically Important Muscle Events | Historical Cohort: up to 33 months (January 2005 to October 2007); Raltegravir and Concurrent Cohorts: up to 69 months (October 2007 to June 2013) | Significant muscle events (e.g. rhabdomyolysis) occurring during the risk period were identified through the use of computer-stored records of laboratory values, outpatient visits, Emergency Department visits and hospitalizations. The identification of potential significant muscle events was based on algorithms utilizing a combination of diagnoses, procedures and/or laboratory results for creatinine kinase. The number of muscle events did not meet the threshold for statistical analysis per protocol. Incidence is reported as unadjusted, crude rates. |
| Incidence of Lipodystrophy | Historical Cohort: up to 33 months (January 2005 to October 2007); Raltegravir and Concurrent Cohorts: up to 69 months (October 2007 to June 2013) | Lipodystrophy (e.g. lipoatrophy, facial wasting) occurring during the risk period was identified through the use of computer-stored records of outpatient visits, Emergency Department visits and hospitalizations. The identification of potential lipodystrophy was based on two coded diagnoses codes indicative of lipodystrophy appearing at least 6 months apart over the course of patient care, the identification of interventions to treat such conditions (e.g. sculptra therapy), or procedural codes for Computerized Tomography indicating incident neck or abdominal lipoaccumulation. Incidence is reported as unadjusted, crude rates. |
| Incidence of AIDS-defining and Non-AIDS-defining Malignancy | Historical Cohort: up to 33 months (January 2005 to October 2007); Raltegravir and Concurrent Cohorts: up to 69 months (October 2007 to June 2013) | All new malignancies occurring during the risk period, including Acquired Immune Deficiency Syndrome (AIDS)-defining and non-AIDS-defining malignancies, were identified through the Kaiser Permanente cancer registries. The registry data was supplemented by the use of computer-stored records of outpatient visits, Emergency Department visits and hospitalizations to identify cancers that would not be captured through the cancer registries (e.g. cutaneous Kaposi's sarcoma).The AIDS-defining malignancies reported for any cohort were invasive cervical cancer, Kaposi's sarcoma, and non-Hodgkin lymphoma. Incidence is reported as unadjusted, crude rates. |
| Incidence of Clinically Important Skin Events | Historical Cohort: up to 33 months (January 2005 to October 2007); Raltegravir and Concurrent Cohorts: up to 69 months (October 2007 to June 2013) | Significant skin events (e.g. Stevens-Johnson syndrome and toxic epidermal necrolysis) occurring during the risk period were identified through the use of computer-stored records of outpatient visits, Emergency Department visits and hospitalizations. The identification of potential significant skin events was based on algorithms utilizing a combination of diagnoses, procedures and/or medications. Surveillance of outpatient visits was limited to rashes coded as drug-related and requiring use of steroid (e.g. prednisone) administration. Incidence is reported as unadjusted, crude rates. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of All-cause Mortality | Historical Cohort: up to 33 months (January 2005 to October 2007); Raltegravir and Concurrent Cohorts: up to 69 months (October 2007 to June 2013) | All-cause mortality occurring during the risk period was identified through the use of computer-stored records of Emergency Department visits, hospitalizations, and state death certificates. Deaths were identified from administrative Kaiser Permanente databases, including Kaiser Permanente regional research and respective state(s) mortality files as well as the Social Security Administrative files. Incidence is reported as unadjusted, crude rates. |
| Incidence of Clinically Important Cardiovascular Events | Historical Cohort: up to 33 months (January 2005 to October 2007); Raltegravir and Concurrent Cohorts: up to 69 months (October 2007 to June 2013) | Significant cardiovascular events occurring during the risk period were identified through the use of computer-stored records and defined as inpatient events based on algorithms that utilize a combination of diagnosis and/or procedure codes. The identification of potential significant cardiovascular events was based on the occurrence of major adverse cardiovascular events (MACE) which include acute myocardial infarction (MI), ischemic stroke, unstable angina, revascularization (e.g. percutaneous coronary intervention (PCI) and coronary bypass graft surgery (CABG)), and cardiovascular death. Incidence is reported as unadjusted, crude rates. |
Participant flow
Pre-assignment details
The analyses in this study are based on data collected from a cohort of human immunodeficiency virus (HIV-1)-infected participants in a setting of routine clinical care at the Kaiser Permanente medical centers in California, United States. Participants could contribute data to more than one cohort, but no overlap in follow-up time was allowed.
Participants by arm
| Arm | Count |
|---|---|
| Raltegravir Cohort Only Participants with HIV-1 infection who received raltegravir (RAL) on or after 12 October 2007 (the market authorization date in the United States) (Raltegravir Cohort). These participants contributed data to the Raltegravir Cohort only. | 1,041 |
| Historical and Raltegravir Cohorts Only Participants with HIV-1 infection who 1) received antiretroviral therapy (non-RAL) between 1 January 2005 and 11 October 2007 (Historical Cohort), and 2) received RAL on or after 12 October 2007 (Raltegravir Cohort). These participants contributed data to the Historical and Raltegravir Cohorts only. | 405 |
| Historical Cohort Only Participants with HIV-1 infection who received antiretroviral therapy (non-RAL) between 1 January 2005 and 11 October 2007 (Historical Cohort). These participants contributed data to the Historical Cohort only. | 1,963 |
| Historical and Concurrent Cohorts Only Participants with HIV-1 infection who 1) received antiretroviral therapy (non-RAL) between 1 January 2005 and 11 October 2007 (Historical Cohort), and 2) received therapy with a new non-RAL antiretroviral therapy after 12 October 2007 (Concurrent Cohort). These participants contributed data to the Historical and Concurrent Cohorts only. | 152 |
| Concurrent Cohort Only Participants with HIV-1 infection who received therapy with a new non-RAL antiretroviral therapy after 12 October 2007 (Concurrent Cohort). These participants contributed data to the Concurrent Cohort only. | 3,310 |
| Concurrent and Raltegravir Cohorts Only Participants with HIV-1 infection who 1) received therapy with a new non-RAL antiretroviral therapy on or after 12 October 2007 (Concurrent Cohort), and 2) received RAL after 12 October 2007 (Raltegravir Cohort). These participants contributed data to the Concurrent and Raltegravir Cohorts only. | 231 |
| Historical, Concurrent and Raltegravir Cohorts Participants with HIV-1 infection who 1) received antiretroviral therapy (non-RAL) between 1 January 2005 and 11 October 2007 (Historical Cohort), 2) received therapy with a new non-RAL antiretroviral therapy on or after 12 October 2007 (Concurrent Cohort), and 3) received RAL after 12 October 2007 (Raltegravir Cohort). These participants contributed data to all three cohorts. | 22 |
| Total | 7,124 |
Baseline characteristics
| Characteristic | Raltegravir Cohort Only | Historical and Raltegravir Cohorts Only | Historical Cohort Only | Historical and Concurrent Cohorts Only | Concurrent Cohort Only | Concurrent and Raltegravir Cohorts Only | Historical, Concurrent and Raltegravir Cohorts | Total |
|---|---|---|---|---|---|---|---|---|
| Age, Continuous | 48.2 Years STANDARD_DEVIATION 10.7 | 49.2 Years STANDARD_DEVIATION 10 | 45.8 Years STANDARD_DEVIATION 10.1 | 44.9 Years STANDARD_DEVIATION 9.9 | 43.0 Years STANDARD_DEVIATION 11.5 | 46.8 Years STANDARD_DEVIATION 12.4 | 45.5 Years STANDARD_DEVIATION 9.9 | 45.0 Years STANDARD_DEVIATION 11.1 |
| Sex: Female, Male Female | 121 Participants | 41 Participants | 195 Participants | 23 Participants | 340 Participants | 33 Participants | 4 Participants | 757 Participants |
| Sex: Female, Male Male | 920 Participants | 364 Participants | 1768 Participants | 129 Participants | 2970 Participants | 198 Participants | 18 Participants | 6367 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 / 0 | 0 / 0 | 0 / 0 |
| serious Total, serious adverse events | 0 / 0 | 0 / 0 | 0 / 0 |
Outcome results
Primary
Incidence of AIDS-defining and Non-AIDS-defining Malignancy
All new malignancies occurring during the risk period, including Acquired Immune Deficiency Syndrome (AIDS)-defining and non-AIDS-defining malignancies, were identified through the Kaiser Permanente cancer registries. The registry data was supplemented by the use of computer-stored records of outpatient visits, Emergency Department visits and hospitalizations to identify cancers that would not be captured through the cancer registries (e.g. cutaneous Kaposi's sarcoma).The AIDS-defining malignancies reported for any cohort were invasive cervical cancer, Kaposi's sarcoma, and non-Hodgkin lymphoma. Incidence is reported as unadjusted, crude rates.
Time frame: Historical Cohort: up to 33 months (January 2005 to October 2007); Raltegravir and Concurrent Cohorts: up to 69 months (October 2007 to June 2013)
Population: The analysis includes all eligible participants.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Raltegravir Cohort | Incidence of AIDS-defining and Non-AIDS-defining Malignancy | AIDS-defining Malignancy | 13.0 Events per 1000 person-years of followup |
| Raltegravir Cohort | Incidence of AIDS-defining and Non-AIDS-defining Malignancy | Non-AIDS-defining Malignancy | 18.2 Events per 1000 person-years of followup |
| Historical Cohort | Incidence of AIDS-defining and Non-AIDS-defining Malignancy | AIDS-defining Malignancy | 8.9 Events per 1000 person-years of followup |
| Historical Cohort | Incidence of AIDS-defining and Non-AIDS-defining Malignancy | Non-AIDS-defining Malignancy | 9.1 Events per 1000 person-years of followup |
| Concurrent Cohort | Incidence of AIDS-defining and Non-AIDS-defining Malignancy | AIDS-defining Malignancy | 9.3 Events per 1000 person-years of followup |
| Concurrent Cohort | Incidence of AIDS-defining and Non-AIDS-defining Malignancy | Non-AIDS-defining Malignancy | 10.3 Events per 1000 person-years of followup |
Comparison: AIDS-defining malignanciesp-value: 0.00295% CI: [1.344, 3.875]Poisson Regression
Comparison: AIDS-defining malignanciesp-value: <0.0595% CI: [1.621, 4.977]Cox Proportional Hazard Regression
Comparison: AIDS-defining malignanciesp-value: 0.00595% CI: [1.207, 2.899]Poisson Regression
Comparison: AIDS-defining malignanciesp-value: 0.00495% CI: [1.227, 2.879]Cox Proportional Hazard Regression
Comparison: Non-AIDS-defining malignanciesp-value: 0.00895% CI: [1.191, 3.168]Poisson Regression
Comparison: Non-AIDS-defining malignanciesp-value: 0.00195% CI: [1.454, 4.159]Cox Proportional Hazard Regression
Comparison: Non-AIDS-defining malignanciesp-value: 0.00495% CI: [1.199, 2.631]Poisson Regression
Comparison: Non-AIDS-defining malignanciesp-value: 0.00195% CI: [1.274, 2.717]Cox Proportional Hazard Regression
Primary
Incidence of Clinically Important Hepatic Events
Hepatic events occurring during the risk period were identified through computer-stored records of laboratory values, outpatient visits, Emergency Department visits, and hospitalizations. Significant hepatic events were identified based on algorithms utilizing a combination of diagnoses, procedures, and laboratory results. Incidence is reported as unadjusted, crude rates.
Time frame: Historical Cohort: up to 33 months (January 2005 to October 2007); Raltegravir and Concurrent Cohorts: up to 69 months (October 2007 to June 2013)
Population: The analysis includes all eligible participants.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Raltegravir Cohort | Incidence of Clinically Important Hepatic Events | 19.0 Events per 1000 person-years of followup |
| Historical Cohort | Incidence of Clinically Important Hepatic Events | 25.0 Events per 1000 person-years of followup |
| Concurrent Cohort | Incidence of Clinically Important Hepatic Events | 17.1 Events per 1000 person-years of followup |
p-value: 0.25595% CI: [0.557, 1.168]Poisson regression
p-value: 0.64695% CI: [0.597, 1.376]Cox Proportional Hazard Regression
p-value: 0.18295% CI: [0.895, 1.795]Poisson Regression
p-value: 0.18895% CI: [0.894, 1.768]Cox Proportional Hazard Regression
Primary
Incidence of Clinically Important Muscle Events
Significant muscle events (e.g. rhabdomyolysis) occurring during the risk period were identified through the use of computer-stored records of laboratory values, outpatient visits, Emergency Department visits and hospitalizations. The identification of potential significant muscle events was based on algorithms utilizing a combination of diagnoses, procedures and/or laboratory results for creatinine kinase. The number of muscle events did not meet the threshold for statistical analysis per protocol. Incidence is reported as unadjusted, crude rates.
Time frame: Historical Cohort: up to 33 months (January 2005 to October 2007); Raltegravir and Concurrent Cohorts: up to 69 months (October 2007 to June 2013)
Population: The analysis includes all eligible participants.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Raltegravir Cohort | Incidence of Clinically Important Muscle Events | 3.4 Events per 1000 person-years of followup |
| Historical Cohort | Incidence of Clinically Important Muscle Events | 3.3 Events per 1000 person-years of followup |
| Concurrent Cohort | Incidence of Clinically Important Muscle Events | 1.5 Events per 1000 person-years of followup |
Primary
Incidence of Clinically Important Skin Events
Significant skin events (e.g. Stevens-Johnson syndrome and toxic epidermal necrolysis) occurring during the risk period were identified through the use of computer-stored records of outpatient visits, Emergency Department visits and hospitalizations. The identification of potential significant skin events was based on algorithms utilizing a combination of diagnoses, procedures and/or medications. Surveillance of outpatient visits was limited to rashes coded as drug-related and requiring use of steroid (e.g. prednisone) administration. Incidence is reported as unadjusted, crude rates.
Time frame: Historical Cohort: up to 33 months (January 2005 to October 2007); Raltegravir and Concurrent Cohorts: up to 69 months (October 2007 to June 2013)
Population: The analysis includes all eligible participants.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Raltegravir Cohort | Incidence of Clinically Important Skin Events | 40.6 Events per 1000 person-years of followup |
| Historical Cohort | Incidence of Clinically Important Skin Events | 69.8 Events per 1000 person-years of followup |
| Concurrent Cohort | Incidence of Clinically Important Skin Events | 63.6 Events per 1000 person-years of followup |
p-value: 0.89795% CI: [0.796, 1.297]Poisson Regression
p-value: 0.0795% CI: [0.98, 1.69]Cox Proportional Hazard Regression
p-value: 0.57595% CI: [0.85, 1.339]Poisson Regression
p-value: 0.62695% CI: [0.847, 1.319]Cox Proportional Hazard Regression
Primary
Incidence of Lipodystrophy
Lipodystrophy (e.g. lipoatrophy, facial wasting) occurring during the risk period was identified through the use of computer-stored records of outpatient visits, Emergency Department visits and hospitalizations. The identification of potential lipodystrophy was based on two coded diagnoses codes indicative of lipodystrophy appearing at least 6 months apart over the course of patient care, the identification of interventions to treat such conditions (e.g. sculptra therapy), or procedural codes for Computerized Tomography indicating incident neck or abdominal lipoaccumulation. Incidence is reported as unadjusted, crude rates.
Time frame: Historical Cohort: up to 33 months (January 2005 to October 2007); Raltegravir and Concurrent Cohorts: up to 69 months (October 2007 to June 2013)
Population: The analysis includes all eligible participants.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Raltegravir Cohort | Incidence of Lipodystrophy | 20.6 Events per 1000 person-years of followup |
| Historical Cohort | Incidence of Lipodystrophy | 35.6 Events per 1000 person-years of followup |
| Concurrent Cohort | Incidence of Lipodystrophy | 9.2 Events per 1000 person-years of followup |
p-value: <0.000195% CI: [0.274, 0.551]Poisson Regression
p-value: <0.0595% CI: [0.314, 0.707]Cox Proportional Hazard Regression
p-value: 0.01595% CI: [1.102, 2.47]Poisson Regression
p-value: 0.01895% CI: [1.085, 2.425]Cox Proportional Hazard Regression
Secondary
Incidence of All-cause Mortality
All-cause mortality occurring during the risk period was identified through the use of computer-stored records of Emergency Department visits, hospitalizations, and state death certificates. Deaths were identified from administrative Kaiser Permanente databases, including Kaiser Permanente regional research and respective state(s) mortality files as well as the Social Security Administrative files. Incidence is reported as unadjusted, crude rates.
Time frame: Historical Cohort: up to 33 months (January 2005 to October 2007); Raltegravir and Concurrent Cohorts: up to 69 months (October 2007 to June 2013)
Population: The analysis includes all eligible participants.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Raltegravir Cohort | Incidence of All-cause Mortality | 16.9 Events per 1000 person-years of followup |
| Historical Cohort | Incidence of All-cause Mortality | 18.4 Events per 1000 person-years of followup |
| Concurrent Cohort | Incidence of All-cause Mortality | 7.7 Events per 1000 person-years of followup |
p-value: 0.10995% CI: [0.464, 1.08]Poisson Regression
p-value: 0.35695% CI: [0.486, 1.296]Cox Proportional Hazard Regression
p-value: 0.03995% CI: [1.022, 2.37]Poisson Regression
p-value: 0.03395% CI: [1.036, 2.361]Cox Proportional Hazard Regression
p-value: 0.12595% CI: [0.861, 3.437]Cox Proportional Hazard Regression
p-value: 0.88195% CI: [0.517, 2.155]Cox Proportional Hazard Regression
p-value: 0.10795% CI: [0.854, 5.05]Cox Proportional Hazard Regression
Secondary
Incidence of Clinically Important Cardiovascular Events
Significant cardiovascular events occurring during the risk period were identified through the use of computer-stored records and defined as inpatient events based on algorithms that utilize a combination of diagnosis and/or procedure codes. The identification of potential significant cardiovascular events was based on the occurrence of major adverse cardiovascular events (MACE) which include acute myocardial infarction (MI), ischemic stroke, unstable angina, revascularization (e.g. percutaneous coronary intervention (PCI) and coronary bypass graft surgery (CABG)), and cardiovascular death. Incidence is reported as unadjusted, crude rates.
Time frame: Historical Cohort: up to 33 months (January 2005 to October 2007); Raltegravir and Concurrent Cohorts: up to 69 months (October 2007 to June 2013)
Population: The analysis includes all eligible participants.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Raltegravir Cohort | Incidence of Clinically Important Cardiovascular Events | 6.7 Events per 1000 person-years of followup |
| Historical Cohort | Incidence of Clinically Important Cardiovascular Events | 6.4 Events per 1000 person-years of followup |
| Concurrent Cohort | Incidence of Clinically Important Cardiovascular Events | 4.0 Events per 1000 person-years of followup |
p-value: 0.42395% CI: [0.37, 1.517]Poisson Regression
p-value: 0.63195% CI: [0.559, 2.612]Cox Proportional Hazard Regression
p-value: 0.59295% CI: [0.458, 1.561]Poisson Regression
p-value: 0.94395% CI: [0.565, 1.85]Cox Proportional Hazard Regression