Human Immunodeficiency Virus
Conditions
Keywords
Infection, Rilpivirine, CCR5 antagonists, Etravirine, Human Immunodeficiency Virus, Maraviroc, Safety and efficacy, Non nucleoside reverse transcriptase inhibitors (NNRTIs), Integrase inhibitors, Raltegravir, Kaletra
Brief summary
The purpose of this study is to investigate the tolerability of Kaletra (lopinavir/ritonavir) in combination with new substances such as integrase inhibitors (INIs), C-C chemokine receptor type 5 (CCR5) antagonists, and new non-nucleoside reverse transcriptase inhibitors (NNRTIs), as there are many reasons (intolerability, complex resistant patterns or even personal reasons) which may result in a change from the daily clinical routine and lead to the use of a newly approved antiretroviral agent in combination with Kaletra.
Detailed description
This study was designed as a non-interventional observational study. Kaletra was prescribed in the usual manner in accordance with the terms of the local market authorization with regards to dose, population and indication as well as local guidelines.
Interventions
None listed
Sponsors
AbbVie (prior sponsor, Abbott)
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
18 Years to 99 Years
Healthy volunteers
No
Inclusion criteria
* Patients ≥ 18years of age * Written informed consent (authorization to the investigator to use and/or disclose personal and/or health data before entry into the KALETRA® post marketing observational study) * HIV-1 infection * Patients treated with KALETRA®, independent from their participation in this study * Patients treated with novel antiretroviral therapy (for at least 8 weeks according to the study amendment), independent from their participation in this study
Exclusion criteria
* Hypersensitivity against Kaletra or other ingredients or INIs or NNRTIs or CCR5 antagonists * Severe liver insufficiency * No concommitant astemizole, terfenadine, oral midazolam, triazolam, cisapride, pimozide, amiodarone, ergotamine, dihydroergotamine, ergometrine, methylergometrine, vardenafil and/or St. John's wort
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Prevalence of Adverse Events (Weeks 0-144), Per Event | Weeks 0 to 144 | Percentage of overall number of adverse events experienced during Weeks 0-144 by adverse event type. Doctors asked participants for adverse events, grouped them into categories given in the electronic case report form (eCRF). The list of adverse events included in the eCRF were hypertriglyceridemia, hypercholesterolemia, low high density lipoprotein (HDL) cholesterol, high low density lipoprotein (LDL) cholesterol, hyperglycemia, hyperbilirubinemia, elevated aspartate aminotransferase (AST), elevated alanine aminotransferase (ALT), elevated gamma glutamyl transferase (γGT), elevated alkaline phosphatase, stomatitis, nausea, vomiting, diarrhea, abdominal pain, mood disorder, neurocerebellar disorder, headache, fatigue, fever, other (listed as 'not specified'). |
| Prevalence of Adverse Events (Weeks 0-144), Per Participant | Weeks 0 to 144 | Percentage of participants who experienced at least 1 adverse event during Weeks 0-144 by adverse event type. Doctors asked participants for adverse events, grouped them into categories given in the eCRF. The list of adverse events included in the eCRF were hypertriglyceridemia, hypercholesterolemia, low HDL cholesterol, high LDL cholesterol, hyperglycemia, hyperbilirubinemia, elevated AST, elevated ALT, elevated γGT, elevated alkaline phosphatase, stomatitis, nausea, vomiting, diarrhea, abdominal pain, mood disorder, neurocerebellar disorder, headache, fatigue, fever, other (listed as 'not specified'). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants Achieving Absolute CD4 Cell Count Increases From Baseline of ≥ 100 Cells/μL at All Time Points, Modified Intent-to-Treat Analysis | Baseline (Week 0) to Week 144 | Changes in participants' CD4 cell counts were assessed by measuring the number of CD4 cells at scheduled visits planned as part of routine care. |
| Percentage of Participants Achieving Absolute CD4 Cell Count Increases From Baseline of ≥ 100 Cells/μL at All Time Points, As Treated Analysis | Baseline (Week 0) to Week 144 | Changes in participants' CD4 cell counts were assessed by measuring the number of CD4 cells at scheduled visits planned as part of routine care. |
| Time to CD4 Cell Count Increase From Baseline of ≥ 100/ Cells/μL | From Week 0 to Week 144 | — |
| Number of Participants With Lopinavir (LPV) Resistance at Baseline | Baseline (Week 0) | Characterization of baseline resistance and development of resistance using the interpretation system HIV-Genotypic Resistance-Algorithm Deutschland (GRADE; available at www.hiv-grade.de. Genotypic interpretation was performed using the HIV-GRADE algorithm updated in December 2015). Susceptible indicates full susceptibility of a virus to a certain drug without any limitations in terms of resistance. Partial resistance is indicated if severe limitations in susceptibility have to be expected and the drug can not count for a fully active drug any more. However, these drugs can still be very useful in situations with generally limited options (salvage). Resistant indicates that high level drug resistance has to be expected. |
| Number of Participants With LPV Resistance During Follow-Up | up to Week 144 | Characterization of baseline resistance and development of resistance using the interpretation system HIV-GRADE (available at www.hiv-grade.de. Genotypic interpretation was performed using the HIV-GRADE algorithm updated in December 2015). Susceptible indicates full susceptibility of a virus to a certain drug without any limitations in terms of resistance. Partial resistance is indicated if severe limitations in susceptibility have to be expected and the drug can not count for a fully active drug any more. However, these drugs can still be very useful in situations with generally limited options (salvage). Resistant indicates that high level drug resistance has to be expected. |
| Number of Participants With Protease Inhibitor (PI) Resistance at Baseline | Baseline (Week 0) | Characterization of baseline resistance and development of resistance using the interpretation system HIV-Genotypic Resistance-Algorithm Deutschland (GRADE; available at www.hiv-grade.de. Genotypic interpretation was performed using the HIV-GRADE algorithm updated in December 2015). Susceptible indicates full susceptibility of a virus to a certain drug without any limitations in terms of resistance. Partial resistance is indicated if severe limitations in susceptibility have to be expected and the drug can not count for a fully active drug any more. However, these drugs can still be very useful in situations with generally limited options (salvage). Resistant indicates that high level drug resistance has to be expected. |
| Number of Participants With PI Resistance During Follow-Up | Up to Week 144 | Characterization of baseline resistance and development of resistance using the interpretation system HIV-GRADE (available at www.hiv-grade.de. Genotypic interpretation was performed using the HIV-GRADE algorithm updated in December 2015). Susceptible indicates full susceptibility of a virus to a certain drug without any limitations in terms of resistance. Partial resistance is indicated if severe limitations in susceptibility have to be expected and the drug can not count for a fully active drug any more. However, these drugs can still be very useful in situations with generally limited options (salvage). Resistant indicates that high level drug resistance has to be expected. |
| Number of Participants With INI Resistance During Follow-Up | up to Week 144 | Characterization of baseline resistance and development of resistance using the interpretation system HIV-GRADE (available at www.hiv-grade.de. Genotypic interpretation was performed using the HIV-GRADE algorithm updated in December 2015). Susceptible indicates full susceptibility of a virus to a certain drug without any limitations in terms of resistance. Partial resistance is indicated if severe limitations in susceptibility have to be expected and the drug can not count for a fully active drug any more. However, these drugs can still be very useful in situations with generally limited options (salvage). Resistant indicates that high level drug resistance has to be expected. |
| Number of Participants With NNRTI Resistance at Baseline | Baseline (Week 0) | Characterization of baseline resistance and development of resistance using the interpretation system HIV-GRADE (available at www.hiv-grade.de. Genotypic interpretation was performed using the HIV-GRADE algorithm updated in December 2015). Susceptible indicates full susceptibility of a virus to a certain drug without any limitations in terms of resistance. Partial resistance is indicated if severe limitations in susceptibility have to be expected and the drug can not count for a fully active drug any more. However, these drugs can still be very useful in situations with generally limited options (salvage). Resistant indicates that high level drug resistance has to be expected. |
| Number of Participants With NNRTI Resistance During Follow-Up | up to Week 144 | Characterization of baseline resistance and development of resistance using the interpretation system HIV-GRADE (available at www.hiv-grade.de. Genotypic interpretation was performed using the HIV-GRADE algorithm updated in December 2015). Susceptible indicates full susceptibility of a virus to a certain drug without any limitations in terms of resistance. Partial resistance is indicated if severe limitations in susceptibility have to be expected and the drug can not count for a fully active drug any more. However, these drugs can still be very useful in situations with generally limited options (salvage). Resistant indicates that high level drug resistance has to be expected. |
| Number of Participants With Nucleoside Analog Reverse-Transcriptase Inhibitor (NRTI) Resistance at Baseline | Baseline (Week 0) | Characterization of baseline resistance and development of resistance using the interpretation system HIV-GRADE (available at www.hiv-grade.de. Genotypic interpretation was performed using the HIV-GRADE algorithm updated in December 2015). Susceptible indicates full susceptibility of a virus to a certain drug without any limitations in terms of resistance. Partial resistance is indicated if severe limitations in susceptibility have to be expected and the drug can not count for a fully active drug any more. However, these drugs can still be very useful in situations with generally limited options (salvage). Resistant indicates that high level drug resistance has to be expected. |
| Number of Participants With NRTI Resistance During Follow-Up | up to Week 144 | Characterization of baseline resistance and development of resistance using the interpretation system HIV-GRADE (available at www.hiv-grade.de. Genotypic interpretation was performed using the HIV-GRADE algorithm updated in December 2015). Susceptible indicates full susceptibility of a virus to a certain drug without any limitations in terms of resistance. Partial resistance is indicated if severe limitations in susceptibility have to be expected and the drug can not count for a fully active drug any more. However, these drugs can still be very useful in situations with generally limited options (salvage). Resistant indicates that high level drug resistance has to be expected. |
| Number of Participants With HIV-1 Coreceptor Tropism at Baseline | Baseline (Week 0) | Participants with CCR5 tropic virus, CXC motif chemokine receptor 4 (CRCX4) tropic virus, or dual/mixed tropic virus at Baseline. |
| Number of Participants With HIV-1 Coreceptor Tropism During Follow-up | up to Week 144 | Participants with CCR5 tropic virus, CXC motif chemokine receptor 4 (CRCX4) tropic virus, or dual/mixed tropic virus at Follow-up. |
| Number of Participants With INI Resistance at Baseline | Baseline (Week 0) | Characterization of baseline resistance and development of resistance using the interpretation system HIV-GRADE (available at www.hiv-grade.de. Genotypic interpretation was performed using the HIV-GRADE algorithm updated in December 2015). Susceptible indicates full susceptibility of a virus to a certain drug without any limitations in terms of resistance. Partial resistance is indicated if severe limitations in susceptibility have to be expected and the drug can not count for a fully active drug any more. However, these drugs can still be very useful in situations with generally limited options (salvage). Resistant indicates that high level drug resistance has to be expected. |
| Change From Baseline in Absolute Cluster of Differentiation 4 (CD4) Cell Count | Baseline (Week 0) to Week 144 | Changes in participants' CD4 cell counts were assessed by measuring the change from Baseline in the number of CD4 cells at scheduled visits planned as part of routine care. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in HIV-1 Ribonucleic Acid (RNA) Viral Load | Baseline (Week 0) to Week 144 | Changes in participants' HIV-1 RNA viral load were assessed by measuring the change from Baseline at scheduled visits planned as part of routine care. |
| Time to Virologic Failure | Baseline (Week 0) to Week 144 | Time to virologic failure was defined by the earliest occurrence of: 1. HIV-1 RNA \> 400 copies/mL confirmed on 2 consecutive occasions after achieving at least 1 HIV-1 RNA \< 50 copies/mL, 2. HIV-1 RNA \> 400 copies/mL at the final on-study visit if the participant had previously experienced at least 1 HIV-1 RNA \< 50 copies/mL but subsequently did not have HIV-1 RNA \> 400 copies/mL on 2 consecutive occasions, or 3. Day 1 if the participant never achieved HIV-1 RNA \< 50 copies/mL during study participation. A participant who prematurely discontinued study drug with HIV-1 RNA \< 50 copies/mL was censored from analysis at the time of discontinuation provided that he/she did not previously experience either (a), (b) or (c). |
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| HIV-infected Participants HIV-infected participants on Kaletra and INIs or NNRTIs or CCR5 antagonists | 501 |
| Total | 501 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Withdrawal by Subject | 1 |
Baseline characteristics
| Characteristic | HIV-infected Participants |
|---|---|
| Age, Continuous | 45.4 years STANDARD_DEVIATION 11.1 |
| Sex: Female, Male Female | 70 Participants |
| Sex: Female, Male Male | 431 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 0 / 0 |
| serious Total, serious adverse events | 30 / 501 |
Outcome results
Primary
Prevalence of Adverse Events (Weeks 0-144), Per Event
Percentage of overall number of adverse events experienced during Weeks 0-144 by adverse event type. Doctors asked participants for adverse events, grouped them into categories given in the electronic case report form (eCRF). The list of adverse events included in the eCRF were hypertriglyceridemia, hypercholesterolemia, low high density lipoprotein (HDL) cholesterol, high low density lipoprotein (LDL) cholesterol, hyperglycemia, hyperbilirubinemia, elevated aspartate aminotransferase (AST), elevated alanine aminotransferase (ALT), elevated gamma glutamyl transferase (γGT), elevated alkaline phosphatase, stomatitis, nausea, vomiting, diarrhea, abdominal pain, mood disorder, neurocerebellar disorder, headache, fatigue, fever, other (listed as 'not specified').
Time frame: Weeks 0 to 144
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| HIV-infected Participants | Prevalence of Adverse Events (Weeks 0-144), Per Event | Hypertriglyceridemia | 13.8 percentage of adverse events |
| HIV-infected Participants | Prevalence of Adverse Events (Weeks 0-144), Per Event | Hypercholesterolemia | 19.3 percentage of adverse events |
| HIV-infected Participants | Prevalence of Adverse Events (Weeks 0-144), Per Event | Low HDL Cholesterol | 1.0 percentage of adverse events |
| HIV-infected Participants | Prevalence of Adverse Events (Weeks 0-144), Per Event | High LDL Cholesterol | 4.4 percentage of adverse events |
| HIV-infected Participants | Prevalence of Adverse Events (Weeks 0-144), Per Event | Hyperglycemia | 1.6 percentage of adverse events |
| HIV-infected Participants | Prevalence of Adverse Events (Weeks 0-144), Per Event | Hyperbilirubinemia | 1.8 percentage of adverse events |
| HIV-infected Participants | Prevalence of Adverse Events (Weeks 0-144), Per Event | Elevated AST | 3.4 percentage of adverse events |
| HIV-infected Participants | Prevalence of Adverse Events (Weeks 0-144), Per Event | Elevated ALT | 4.6 percentage of adverse events |
| HIV-infected Participants | Prevalence of Adverse Events (Weeks 0-144), Per Event | Elevated γGT | 6.3 percentage of adverse events |
| HIV-infected Participants | Prevalence of Adverse Events (Weeks 0-144), Per Event | Elevated Alkaline Phosphatase | 1.5 percentage of adverse events |
| HIV-infected Participants | Prevalence of Adverse Events (Weeks 0-144), Per Event | Stomatitis | 0.6 percentage of adverse events |
| HIV-infected Participants | Prevalence of Adverse Events (Weeks 0-144), Per Event | Nausea | 3.1 percentage of adverse events |
| HIV-infected Participants | Prevalence of Adverse Events (Weeks 0-144), Per Event | Vomiting | 1.2 percentage of adverse events |
| HIV-infected Participants | Prevalence of Adverse Events (Weeks 0-144), Per Event | Diarrhea | 14.9 percentage of adverse events |
| HIV-infected Participants | Prevalence of Adverse Events (Weeks 0-144), Per Event | Abdominal Pain | 3.1 percentage of adverse events |
| HIV-infected Participants | Prevalence of Adverse Events (Weeks 0-144), Per Event | Mood Disorder | 5.2 percentage of adverse events |
| HIV-infected Participants | Prevalence of Adverse Events (Weeks 0-144), Per Event | Neurocerebellar Disorder | 0.8 percentage of adverse events |
| HIV-infected Participants | Prevalence of Adverse Events (Weeks 0-144), Per Event | Headache | 1.3 percentage of adverse events |
| HIV-infected Participants | Prevalence of Adverse Events (Weeks 0-144), Per Event | Fatigue | 1.7 percentage of adverse events |
| HIV-infected Participants | Prevalence of Adverse Events (Weeks 0-144), Per Event | Fever | 1.2 percentage of adverse events |
| HIV-infected Participants | Prevalence of Adverse Events (Weeks 0-144), Per Event | Not Specified | 9.1 percentage of adverse events |
Primary
Prevalence of Adverse Events (Weeks 0-144), Per Participant
Percentage of participants who experienced at least 1 adverse event during Weeks 0-144 by adverse event type. Doctors asked participants for adverse events, grouped them into categories given in the eCRF. The list of adverse events included in the eCRF were hypertriglyceridemia, hypercholesterolemia, low HDL cholesterol, high LDL cholesterol, hyperglycemia, hyperbilirubinemia, elevated AST, elevated ALT, elevated γGT, elevated alkaline phosphatase, stomatitis, nausea, vomiting, diarrhea, abdominal pain, mood disorder, neurocerebellar disorder, headache, fatigue, fever, other (listed as 'not specified').
Time frame: Weeks 0 to 144
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| HIV-infected Participants | Prevalence of Adverse Events (Weeks 0-144), Per Participant | Hypertriglyceridemia | 14.8 percentage of participants |
| HIV-infected Participants | Prevalence of Adverse Events (Weeks 0-144), Per Participant | Hypercholesterolemia | 17.8 percentage of participants |
| HIV-infected Participants | Prevalence of Adverse Events (Weeks 0-144), Per Participant | Low HDL Cholesterol | 3.0 percentage of participants |
| HIV-infected Participants | Prevalence of Adverse Events (Weeks 0-144), Per Participant | High LDL Cholesterol | 7.2 percentage of participants |
| HIV-infected Participants | Prevalence of Adverse Events (Weeks 0-144), Per Participant | Hyperglycemia | 2.8 percentage of participants |
| HIV-infected Participants | Prevalence of Adverse Events (Weeks 0-144), Per Participant | Hyperbilirubinemia | 2.8 percentage of participants |
| HIV-infected Participants | Prevalence of Adverse Events (Weeks 0-144), Per Participant | Elevated AST | 5.0 percentage of participants |
| HIV-infected Participants | Prevalence of Adverse Events (Weeks 0-144), Per Participant | Elevated ALT | 6.4 percentage of participants |
| HIV-infected Participants | Prevalence of Adverse Events (Weeks 0-144), Per Participant | Elevated γGT | 7.8 percentage of participants |
| HIV-infected Participants | Prevalence of Adverse Events (Weeks 0-144), Per Participant | Elevated Alkaline Phosphatase | 3.2 percentage of participants |
| HIV-infected Participants | Prevalence of Adverse Events (Weeks 0-144), Per Participant | Stomatitis | 2.0 percentage of participants |
| HIV-infected Participants | Prevalence of Adverse Events (Weeks 0-144), Per Participant | Nausea | 8.6 percentage of participants |
| HIV-infected Participants | Prevalence of Adverse Events (Weeks 0-144), Per Participant | Vomiting | 4.0 percentage of participants |
| HIV-infected Participants | Prevalence of Adverse Events (Weeks 0-144), Per Participant | Diarrhea | 27.3 percentage of participants |
| HIV-infected Participants | Prevalence of Adverse Events (Weeks 0-144), Per Participant | Abdominal Pain | 7.8 percentage of participants |
| HIV-infected Participants | Prevalence of Adverse Events (Weeks 0-144), Per Participant | Mood Disorder | 9.8 percentage of participants |
| HIV-infected Participants | Prevalence of Adverse Events (Weeks 0-144), Per Participant | Neurocerebellar Disorder | 2.2 percentage of participants |
| HIV-infected Participants | Prevalence of Adverse Events (Weeks 0-144), Per Participant | Headache | 4.0 percentage of participants |
| HIV-infected Participants | Prevalence of Adverse Events (Weeks 0-144), Per Participant | Fatigue | 4.6 percentage of participants |
| HIV-infected Participants | Prevalence of Adverse Events (Weeks 0-144), Per Participant | Fever | 4.0 percentage of participants |
| HIV-infected Participants | Prevalence of Adverse Events (Weeks 0-144), Per Participant | Not Specified | 28.5 percentage of participants |
Secondary
Change From Baseline in Absolute Cluster of Differentiation 4 (CD4) Cell Count
Changes in participants' CD4 cell counts were assessed by measuring the change from Baseline in the number of CD4 cells at scheduled visits planned as part of routine care.
Time frame: Baseline (Week 0) to Week 144
Population: Participants with an assessment at Baseline. Number analyzed=participants with an assessment at given time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| HIV-infected Participants | Change From Baseline in Absolute Cluster of Differentiation 4 (CD4) Cell Count | Change at Week 4 | 54.0 cells/μL | Standard Deviation 161.7 |
| HIV-infected Participants | Change From Baseline in Absolute Cluster of Differentiation 4 (CD4) Cell Count | Change at Week 12 | 64.6 cells/μL | Standard Deviation 148.5 |
| HIV-infected Participants | Change From Baseline in Absolute Cluster of Differentiation 4 (CD4) Cell Count | Change at Week 24 | 78.8 cells/μL | Standard Deviation 195.3 |
| HIV-infected Participants | Change From Baseline in Absolute Cluster of Differentiation 4 (CD4) Cell Count | Change at Week 36 | 95.8 cells/μL | Standard Deviation 214.4 |
| HIV-infected Participants | Change From Baseline in Absolute Cluster of Differentiation 4 (CD4) Cell Count | Change at Week 48 | 107.4 cells/μL | Standard Deviation 213.2 |
| HIV-infected Participants | Change From Baseline in Absolute Cluster of Differentiation 4 (CD4) Cell Count | Change at Week 60 | 131.0 cells/μL | Standard Deviation 247.7 |
| HIV-infected Participants | Change From Baseline in Absolute Cluster of Differentiation 4 (CD4) Cell Count | Change at Week 72 | 125.3 cells/μL | Standard Deviation 216.1 |
| HIV-infected Participants | Change From Baseline in Absolute Cluster of Differentiation 4 (CD4) Cell Count | Change at Week 84 | 142.8 cells/μL | Standard Deviation 223.9 |
| HIV-infected Participants | Change From Baseline in Absolute Cluster of Differentiation 4 (CD4) Cell Count | Change at Week 96 | 143.3 cells/μL | Standard Deviation 207 |
| HIV-infected Participants | Change From Baseline in Absolute Cluster of Differentiation 4 (CD4) Cell Count | Change at Week 108 | 155.3 cells/μL | Standard Deviation 219.8 |
| HIV-infected Participants | Change From Baseline in Absolute Cluster of Differentiation 4 (CD4) Cell Count | Change at Week 120 | 170.9 cells/μL | Standard Deviation 233 |
| HIV-infected Participants | Change From Baseline in Absolute Cluster of Differentiation 4 (CD4) Cell Count | Change at Week 132 | 180.3 cells/μL | Standard Deviation 243.3 |
| HIV-infected Participants | Change From Baseline in Absolute Cluster of Differentiation 4 (CD4) Cell Count | Change at Week 144 | 190.0 cells/μL | Standard Deviation 252.9 |
Secondary
Number of Participants With HIV-1 Coreceptor Tropism at Baseline
Participants with CCR5 tropic virus, CXC motif chemokine receptor 4 (CRCX4) tropic virus, or dual/mixed tropic virus at Baseline.
Time frame: Baseline (Week 0)
Population: Participants with an assessment at Baseline
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| HIV-infected Participants | Number of Participants With HIV-1 Coreceptor Tropism at Baseline | CCR5 tropic | 74 Participants |
| HIV-infected Participants | Number of Participants With HIV-1 Coreceptor Tropism at Baseline | CRCX4 tropic | 21 Participants |
| HIV-infected Participants | Number of Participants With HIV-1 Coreceptor Tropism at Baseline | Dual/mixed tropic | 13 Participants |
Secondary
Number of Participants With HIV-1 Coreceptor Tropism During Follow-up
Participants with CCR5 tropic virus, CXC motif chemokine receptor 4 (CRCX4) tropic virus, or dual/mixed tropic virus at Follow-up.
Time frame: up to Week 144
Population: Since this was an observational study, resistance testing was performed at the discretion of the treating physician. No follow-up data on tropism was collected.
Secondary
Number of Participants With INI Resistance at Baseline
Characterization of baseline resistance and development of resistance using the interpretation system HIV-GRADE (available at www.hiv-grade.de. Genotypic interpretation was performed using the HIV-GRADE algorithm updated in December 2015). Susceptible indicates full susceptibility of a virus to a certain drug without any limitations in terms of resistance. Partial resistance is indicated if severe limitations in susceptibility have to be expected and the drug can not count for a fully active drug any more. However, these drugs can still be very useful in situations with generally limited options (salvage). Resistant indicates that high level drug resistance has to be expected.
Time frame: Baseline (Week 0)
Population: Participants with an assessment at Baseline
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| HIV-infected Participants | Number of Participants With INI Resistance at Baseline | Susceptible | 8 Participants |
| HIV-infected Participants | Number of Participants With INI Resistance at Baseline | Resistance/Partial Resistance | 1 Participants |
Secondary
Number of Participants With INI Resistance During Follow-Up
Characterization of baseline resistance and development of resistance using the interpretation system HIV-GRADE (available at www.hiv-grade.de. Genotypic interpretation was performed using the HIV-GRADE algorithm updated in December 2015). Susceptible indicates full susceptibility of a virus to a certain drug without any limitations in terms of resistance. Partial resistance is indicated if severe limitations in susceptibility have to be expected and the drug can not count for a fully active drug any more. However, these drugs can still be very useful in situations with generally limited options (salvage). Resistant indicates that high level drug resistance has to be expected.
Time frame: up to Week 144
Population: Participants with an assessment at follow-up (neither had available Baseline testing); since this was an observational study, resistance testing was performed at the discretion of the treating physician.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| HIV-infected Participants | Number of Participants With INI Resistance During Follow-Up | Susceptible | 0 Participants |
| HIV-infected Participants | Number of Participants With INI Resistance During Follow-Up | Resistance/Partial Resistance | 2 Participants |
Secondary
Number of Participants With Lopinavir (LPV) Resistance at Baseline
Characterization of baseline resistance and development of resistance using the interpretation system HIV-Genotypic Resistance-Algorithm Deutschland (GRADE; available at www.hiv-grade.de. Genotypic interpretation was performed using the HIV-GRADE algorithm updated in December 2015). Susceptible indicates full susceptibility of a virus to a certain drug without any limitations in terms of resistance. Partial resistance is indicated if severe limitations in susceptibility have to be expected and the drug can not count for a fully active drug any more. However, these drugs can still be very useful in situations with generally limited options (salvage). Resistant indicates that high level drug resistance has to be expected.
Time frame: Baseline (Week 0)
Population: Participants with an assessment at Baseline
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| HIV-infected Participants | Number of Participants With Lopinavir (LPV) Resistance at Baseline | Susceptible | 155 Participants |
| HIV-infected Participants | Number of Participants With Lopinavir (LPV) Resistance at Baseline | Resistance/Partial Resistance | 4 Participants |
Secondary
Number of Participants With LPV Resistance During Follow-Up
Characterization of baseline resistance and development of resistance using the interpretation system HIV-GRADE (available at www.hiv-grade.de. Genotypic interpretation was performed using the HIV-GRADE algorithm updated in December 2015). Susceptible indicates full susceptibility of a virus to a certain drug without any limitations in terms of resistance. Partial resistance is indicated if severe limitations in susceptibility have to be expected and the drug can not count for a fully active drug any more. However, these drugs can still be very useful in situations with generally limited options (salvage). Resistant indicates that high level drug resistance has to be expected.
Time frame: up to Week 144
Population: Participants with an assessment during follow-up; since this was an observational study, resistance testing was performed at the discretion of the treating physician.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| HIV-infected Participants | Number of Participants With LPV Resistance During Follow-Up | Susceptible | 5 Participants |
| HIV-infected Participants | Number of Participants With LPV Resistance During Follow-Up | Resistance/Partial Resistance | 1 Participants |
Secondary
Number of Participants With NNRTI Resistance at Baseline
Characterization of baseline resistance and development of resistance using the interpretation system HIV-GRADE (available at www.hiv-grade.de. Genotypic interpretation was performed using the HIV-GRADE algorithm updated in December 2015). Susceptible indicates full susceptibility of a virus to a certain drug without any limitations in terms of resistance. Partial resistance is indicated if severe limitations in susceptibility have to be expected and the drug can not count for a fully active drug any more. However, these drugs can still be very useful in situations with generally limited options (salvage). Resistant indicates that high level drug resistance has to be expected.
Time frame: Baseline (Week 0)
Population: Participants with an assessment at Baseline
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| HIV-infected Participants | Number of Participants With NNRTI Resistance at Baseline | Susceptible | 113 Participants |
| HIV-infected Participants | Number of Participants With NNRTI Resistance at Baseline | Resistance/Partial Resistance | 46 Participants |
Secondary
Number of Participants With NNRTI Resistance During Follow-Up
Characterization of baseline resistance and development of resistance using the interpretation system HIV-GRADE (available at www.hiv-grade.de. Genotypic interpretation was performed using the HIV-GRADE algorithm updated in December 2015). Susceptible indicates full susceptibility of a virus to a certain drug without any limitations in terms of resistance. Partial resistance is indicated if severe limitations in susceptibility have to be expected and the drug can not count for a fully active drug any more. However, these drugs can still be very useful in situations with generally limited options (salvage). Resistant indicates that high level drug resistance has to be expected.
Time frame: up to Week 144
Population: Participants with an assessment at follow-up; since this was an observational study, resistance testing was performed at the discretion of the treating physician.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| HIV-infected Participants | Number of Participants With NNRTI Resistance During Follow-Up | Susceptible | 5 Participants |
| HIV-infected Participants | Number of Participants With NNRTI Resistance During Follow-Up | Resistance/Partial Resistance | 1 Participants |
Secondary
Number of Participants With NRTI Resistance During Follow-Up
Characterization of baseline resistance and development of resistance using the interpretation system HIV-GRADE (available at www.hiv-grade.de. Genotypic interpretation was performed using the HIV-GRADE algorithm updated in December 2015). Susceptible indicates full susceptibility of a virus to a certain drug without any limitations in terms of resistance. Partial resistance is indicated if severe limitations in susceptibility have to be expected and the drug can not count for a fully active drug any more. However, these drugs can still be very useful in situations with generally limited options (salvage). Resistant indicates that high level drug resistance has to be expected.
Time frame: up to Week 144
Population: Participants with an assessment at follow-up; since this was an observational study, resistance testing was performed at the discretion of the treating physician.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| HIV-infected Participants | Number of Participants With NRTI Resistance During Follow-Up | Susceptible | 4 Participants |
| HIV-infected Participants | Number of Participants With NRTI Resistance During Follow-Up | Resistance/Partial Resistance | 2 Participants |
Secondary
Number of Participants With Nucleoside Analog Reverse-Transcriptase Inhibitor (NRTI) Resistance at Baseline
Characterization of baseline resistance and development of resistance using the interpretation system HIV-GRADE (available at www.hiv-grade.de. Genotypic interpretation was performed using the HIV-GRADE algorithm updated in December 2015). Susceptible indicates full susceptibility of a virus to a certain drug without any limitations in terms of resistance. Partial resistance is indicated if severe limitations in susceptibility have to be expected and the drug can not count for a fully active drug any more. However, these drugs can still be very useful in situations with generally limited options (salvage). Resistant indicates that high level drug resistance has to be expected.
Time frame: Baseline (Week 0)
Population: Participants with an assessment at Baseline
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| HIV-infected Participants | Number of Participants With Nucleoside Analog Reverse-Transcriptase Inhibitor (NRTI) Resistance at Baseline | Susceptible | 96 Participants |
| HIV-infected Participants | Number of Participants With Nucleoside Analog Reverse-Transcriptase Inhibitor (NRTI) Resistance at Baseline | Resistance/Partial Resistance | 63 Participants |
Secondary
Number of Participants With PI Resistance During Follow-Up
Characterization of baseline resistance and development of resistance using the interpretation system HIV-GRADE (available at www.hiv-grade.de. Genotypic interpretation was performed using the HIV-GRADE algorithm updated in December 2015). Susceptible indicates full susceptibility of a virus to a certain drug without any limitations in terms of resistance. Partial resistance is indicated if severe limitations in susceptibility have to be expected and the drug can not count for a fully active drug any more. However, these drugs can still be very useful in situations with generally limited options (salvage). Resistant indicates that high level drug resistance has to be expected.
Time frame: Up to Week 144
Population: Participants with an assessment during follow-up; since this was an observational study, resistance testing was performed at the discretion of the treating physician.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| HIV-infected Participants | Number of Participants With PI Resistance During Follow-Up | Susceptible | 5 Participants |
| HIV-infected Participants | Number of Participants With PI Resistance During Follow-Up | Resistance/Partial Resistance | 1 Participants |
Secondary
Number of Participants With Protease Inhibitor (PI) Resistance at Baseline
Characterization of baseline resistance and development of resistance using the interpretation system HIV-Genotypic Resistance-Algorithm Deutschland (GRADE; available at www.hiv-grade.de. Genotypic interpretation was performed using the HIV-GRADE algorithm updated in December 2015). Susceptible indicates full susceptibility of a virus to a certain drug without any limitations in terms of resistance. Partial resistance is indicated if severe limitations in susceptibility have to be expected and the drug can not count for a fully active drug any more. However, these drugs can still be very useful in situations with generally limited options (salvage). Resistant indicates that high level drug resistance has to be expected.
Time frame: Baseline (Week 0)
Population: Participants with an assessment at Baseline
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| HIV-infected Participants | Number of Participants With Protease Inhibitor (PI) Resistance at Baseline | Susceptible | 142 Participants |
| HIV-infected Participants | Number of Participants With Protease Inhibitor (PI) Resistance at Baseline | Resistance/Partial Resistance | 17 Participants |
Secondary
Percentage of Participants Achieving Absolute CD4 Cell Count Increases From Baseline of ≥ 100 Cells/μL at All Time Points, As Treated Analysis
Changes in participants' CD4 cell counts were assessed by measuring the number of CD4 cells at scheduled visits planned as part of routine care.
Time frame: Baseline (Week 0) to Week 144
Population: 'As treated' analyses: participants with an assessment, missing data excluded. Number analyzed=participants with an assessment at given time point.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| HIV-infected Participants | Percentage of Participants Achieving Absolute CD4 Cell Count Increases From Baseline of ≥ 100 Cells/μL at All Time Points, As Treated Analysis | Week 96 | 55.8 percentage of participants |
| HIV-infected Participants | Percentage of Participants Achieving Absolute CD4 Cell Count Increases From Baseline of ≥ 100 Cells/μL at All Time Points, As Treated Analysis | Week 108 | 60.1 percentage of participants |
| HIV-infected Participants | Percentage of Participants Achieving Absolute CD4 Cell Count Increases From Baseline of ≥ 100 Cells/μL at All Time Points, As Treated Analysis | Week 4 | 32.2 percentage of participants |
| HIV-infected Participants | Percentage of Participants Achieving Absolute CD4 Cell Count Increases From Baseline of ≥ 100 Cells/μL at All Time Points, As Treated Analysis | Week 12 | 32.5 percentage of participants |
| HIV-infected Participants | Percentage of Participants Achieving Absolute CD4 Cell Count Increases From Baseline of ≥ 100 Cells/μL at All Time Points, As Treated Analysis | Week 24 | 37.9 percentage of participants |
| HIV-infected Participants | Percentage of Participants Achieving Absolute CD4 Cell Count Increases From Baseline of ≥ 100 Cells/μL at All Time Points, As Treated Analysis | Week 36 | 43.8 percentage of participants |
| HIV-infected Participants | Percentage of Participants Achieving Absolute CD4 Cell Count Increases From Baseline of ≥ 100 Cells/μL at All Time Points, As Treated Analysis | Week 48 | 48.0 percentage of participants |
| HIV-infected Participants | Percentage of Participants Achieving Absolute CD4 Cell Count Increases From Baseline of ≥ 100 Cells/μL at All Time Points, As Treated Analysis | Week 60 | 50.5 percentage of participants |
| HIV-infected Participants | Percentage of Participants Achieving Absolute CD4 Cell Count Increases From Baseline of ≥ 100 Cells/μL at All Time Points, As Treated Analysis | Week 72 | 50.3 percentage of participants |
| HIV-infected Participants | Percentage of Participants Achieving Absolute CD4 Cell Count Increases From Baseline of ≥ 100 Cells/μL at All Time Points, As Treated Analysis | Week 84 | 54.5 percentage of participants |
| HIV-infected Participants | Percentage of Participants Achieving Absolute CD4 Cell Count Increases From Baseline of ≥ 100 Cells/μL at All Time Points, As Treated Analysis | Week 120 | 58.0 percentage of participants |
| HIV-infected Participants | Percentage of Participants Achieving Absolute CD4 Cell Count Increases From Baseline of ≥ 100 Cells/μL at All Time Points, As Treated Analysis | Week 132 | 58.0 percentage of participants |
| HIV-infected Participants | Percentage of Participants Achieving Absolute CD4 Cell Count Increases From Baseline of ≥ 100 Cells/μL at All Time Points, As Treated Analysis | Week 144 | 61.3 percentage of participants |
Secondary
Percentage of Participants Achieving Absolute CD4 Cell Count Increases From Baseline of ≥ 100 Cells/μL at All Time Points, Modified Intent-to-Treat Analysis
Changes in participants' CD4 cell counts were assessed by measuring the number of CD4 cells at scheduled visits planned as part of routine care.
Time frame: Baseline (Week 0) to Week 144
Population: Modified 'intent-to-treat' analysis: missing values were replaced by the last observed value of that variable (last observation carried forward method).
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| HIV-infected Participants | Percentage of Participants Achieving Absolute CD4 Cell Count Increases From Baseline of ≥ 100 Cells/μL at All Time Points, Modified Intent-to-Treat Analysis | Week 4 | 23.8 percentage of participants |
| HIV-infected Participants | Percentage of Participants Achieving Absolute CD4 Cell Count Increases From Baseline of ≥ 100 Cells/μL at All Time Points, Modified Intent-to-Treat Analysis | Week 12 | 36.5 percentage of participants |
| HIV-infected Participants | Percentage of Participants Achieving Absolute CD4 Cell Count Increases From Baseline of ≥ 100 Cells/μL at All Time Points, Modified Intent-to-Treat Analysis | Week 24 | 45.7 percentage of participants |
| HIV-infected Participants | Percentage of Participants Achieving Absolute CD4 Cell Count Increases From Baseline of ≥ 100 Cells/μL at All Time Points, Modified Intent-to-Treat Analysis | Week 36 | 53.1 percentage of participants |
| HIV-infected Participants | Percentage of Participants Achieving Absolute CD4 Cell Count Increases From Baseline of ≥ 100 Cells/μL at All Time Points, Modified Intent-to-Treat Analysis | Week 48 | 58.1 percentage of participants |
| HIV-infected Participants | Percentage of Participants Achieving Absolute CD4 Cell Count Increases From Baseline of ≥ 100 Cells/μL at All Time Points, Modified Intent-to-Treat Analysis | Week 60 | 62.7 percentage of participants |
| HIV-infected Participants | Percentage of Participants Achieving Absolute CD4 Cell Count Increases From Baseline of ≥ 100 Cells/μL at All Time Points, Modified Intent-to-Treat Analysis | Week 72 | 65.1 percentage of participants |
| HIV-infected Participants | Percentage of Participants Achieving Absolute CD4 Cell Count Increases From Baseline of ≥ 100 Cells/μL at All Time Points, Modified Intent-to-Treat Analysis | Week 84 | 67.7 percentage of participants |
| HIV-infected Participants | Percentage of Participants Achieving Absolute CD4 Cell Count Increases From Baseline of ≥ 100 Cells/μL at All Time Points, Modified Intent-to-Treat Analysis | Week 96 | 70.5 percentage of participants |
| HIV-infected Participants | Percentage of Participants Achieving Absolute CD4 Cell Count Increases From Baseline of ≥ 100 Cells/μL at All Time Points, Modified Intent-to-Treat Analysis | Week 108 | 72.3 percentage of participants |
| HIV-infected Participants | Percentage of Participants Achieving Absolute CD4 Cell Count Increases From Baseline of ≥ 100 Cells/μL at All Time Points, Modified Intent-to-Treat Analysis | Week 120 | 72.5 percentage of participants |
| HIV-infected Participants | Percentage of Participants Achieving Absolute CD4 Cell Count Increases From Baseline of ≥ 100 Cells/μL at All Time Points, Modified Intent-to-Treat Analysis | Week 132 | 73.1 percentage of participants |
| HIV-infected Participants | Percentage of Participants Achieving Absolute CD4 Cell Count Increases From Baseline of ≥ 100 Cells/μL at All Time Points, Modified Intent-to-Treat Analysis | Week 144 | 73.7 percentage of participants |
Secondary
Time to CD4 Cell Count Increase From Baseline of ≥ 100/ Cells/μL
Time frame: From Week 0 to Week 144
Population: Participants with an assessment
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| HIV-infected Participants | Time to CD4 Cell Count Increase From Baseline of ≥ 100/ Cells/μL | 56.1 weeks | Standard Error 2.8 |
Other Pre-specified
Change From Baseline in HIV-1 Ribonucleic Acid (RNA) Viral Load
Changes in participants' HIV-1 RNA viral load were assessed by measuring the change from Baseline at scheduled visits planned as part of routine care.
Time frame: Baseline (Week 0) to Week 144
Population: Participants with an assessment at Baseline. Number analyzed=participants with an assessment at given time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| HIV-infected Participants | Change From Baseline in HIV-1 Ribonucleic Acid (RNA) Viral Load | Change at Week 4 | -1.37 log copies/mL | Standard Deviation 1.4 |
| HIV-infected Participants | Change From Baseline in HIV-1 Ribonucleic Acid (RNA) Viral Load | Change at Week 12 | -1.53 log copies/mL | Standard Deviation 1.63 |
| HIV-infected Participants | Change From Baseline in HIV-1 Ribonucleic Acid (RNA) Viral Load | Change at Week 24 | -1.45 log copies/mL | Standard Deviation 1.7 |
| HIV-infected Participants | Change From Baseline in HIV-1 Ribonucleic Acid (RNA) Viral Load | Change at Week 36 | -1.49 log copies/mL | Standard Deviation 1.69 |
| HIV-infected Participants | Change From Baseline in HIV-1 Ribonucleic Acid (RNA) Viral Load | Change at Week 48 | -1.46 log copies/mL | Standard Deviation 1.68 |
| HIV-infected Participants | Change From Baseline in HIV-1 Ribonucleic Acid (RNA) Viral Load | Change at Week 60 | -1.27 log copies/mL | Standard Deviation 1.62 |
| HIV-infected Participants | Change From Baseline in HIV-1 Ribonucleic Acid (RNA) Viral Load | Change at Week 72 | -1.32 log copies/mL | Standard Deviation 1.65 |
| HIV-infected Participants | Change From Baseline in HIV-1 Ribonucleic Acid (RNA) Viral Load | Change at Week 84 | -1.34 log copies/mL | Standard Deviation 1.64 |
| HIV-infected Participants | Change From Baseline in HIV-1 Ribonucleic Acid (RNA) Viral Load | Change at Week 96 | -1.36 log copies/mL | Standard Deviation 1.59 |
| HIV-infected Participants | Change From Baseline in HIV-1 Ribonucleic Acid (RNA) Viral Load | Change at Week 108 | -1.32 log copies/mL | Standard Deviation 1.67 |
| HIV-infected Participants | Change From Baseline in HIV-1 Ribonucleic Acid (RNA) Viral Load | Change at Week 120 | -1.29 log copies/mL | Standard Deviation 1.73 |
| HIV-infected Participants | Change From Baseline in HIV-1 Ribonucleic Acid (RNA) Viral Load | Change at Week 132 | -1.33 log copies/mL | Standard Deviation 1.65 |
| HIV-infected Participants | Change From Baseline in HIV-1 Ribonucleic Acid (RNA) Viral Load | Change at Week 144 | -1.38 log copies/mL | Standard Deviation 1.68 |
Other Pre-specified
Time to Virologic Failure
Time to virologic failure was defined by the earliest occurrence of: 1. HIV-1 RNA \> 400 copies/mL confirmed on 2 consecutive occasions after achieving at least 1 HIV-1 RNA \< 50 copies/mL, 2. HIV-1 RNA \> 400 copies/mL at the final on-study visit if the participant had previously experienced at least 1 HIV-1 RNA \< 50 copies/mL but subsequently did not have HIV-1 RNA \> 400 copies/mL on 2 consecutive occasions, or 3. Day 1 if the participant never achieved HIV-1 RNA \< 50 copies/mL during study participation. A participant who prematurely discontinued study drug with HIV-1 RNA \< 50 copies/mL was censored from analysis at the time of discontinuation provided that he/she did not previously experience either (a), (b) or (c).
Time frame: Baseline (Week 0) to Week 144
Population: Participants with an assessment
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| HIV-infected Participants | Time to Virologic Failure | 194.4 weeks | Standard Error 6.2 |