HIV Infections
Conditions
Keywords
HIV infections, HIV-1, HIV-2, Acquired Immunodeficiency Syndrome, AIDS, Anti-Retroviral Agents, Raltegravir, Integrase Inhibitors, multiple-experienced HIV infected patients
Brief summary
The purpose of this study is to evaluate the efficacy of raltegravir with optimized background therapy (OBT) in multiple-experienced HIV infected patients, measured by the proportion of patients with undetectable viral load and the mean increase of CD4 cells count at week 24 and 48. It is also intended to evaluate: * viral load suppression and the mean increase of CD4 cells count at week 24 and 48 in patients who needed to change antiretroviral (ARV) therapy due to inacceptable toxicity, as determined by the investigator, including patients who needed to replace T20. * efficacy of raltegravir with OBT in HIV-2 infected patients that were included in this cohort, measured by the percentage of patients with undetectable viral load and the mean change of CD4 cells count at week 24 and 48. Study hypotheses: * Raltegravir with OBT is effective in achieving and maintaining a long term virologic suppression along with a significant increase on CD4 cells count in both HIV-1 and HIV-2 infected patients. * Patients who replaced T20 by raltegravir, due to intolerance, are able to maintain long term virologic suppression.
Detailed description
Considering its novel mechanism of action, potency, safety and tolerability, and pharmacokinetic profile, raltegravir has been used in several clinical scenarios. Since its initial clinical use in multiresistant patients throughout the Expanded Access and Compassionate Use Program (started in March 2007) raltegravir has been used successfully in other clinical scenarios, including but not limited to: enfuvirtide-related serious adverse events and intolerance, nucleoside analogue inhibitors' toxicity, ritonavir and protease inhibitor intolerance and to avoid significant drug-drug interactions. Early access to raltegravir was basically focused on patients on therapeutic failure and triple-class resistance and due to enfuvirtide intolerance. In order to achieve a better understanding of the efficacy and safety profile of raltegravir in the clinical setting, it is intended to evaluate retrospectively HIV patients treated in Portugal with raltegravir since the Early Access and Compassionate Use Program (EAP) was implemented. This is a national, multicenter, observational, clinical cohort study with retrospective collection of data. Each site will include patients who had started treatment with raltegravir under the EAP.
Interventions
None listed
Sponsors
Merck Sharp & Dohme LLC
Eurotrials Brasil Consultores Cientificos Ltda
Doroana, Maria Manuela, M.D.
Study design
Observational model
COHORT
Time perspective
RETROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Male or female patients, aged 18 years or older 2. ARV multi-experienced patients (i.e. experienced at least two prior regimens) with need to change current ARV therapy, including: * HIV-1 infected patients with documented therapeutic failure, * HIV-2 infected patients with documented therapeutic failure * HIV infected patients in virologic suppression who needed to change ARV due to inacceptable toxicity, as determined by the investigator, including patients who needed to replace T20 3. Raltegravir-naïve patients who initiated raltegravir since the EAP Program, with optimized background therapy(OBT) 4. Patient who has been followed at the same clinical site since the start of raltegravir
Exclusion criteria
1. Acute or decompensated chronic hepatitis. Patients with serum aminotransferase levels 10 times the upper limit of the normal range or higher (grade 4) 2. Patients who presented resistance to drugs included in OBT (namely, etravirine, darunavir or maraviroc) 3. Non-existing medical records for viral load and TCD4 at baseline, week 24 and 48
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| HIV-RNA Levels | Baseline | Patients with undetectable viral load (confirmed HIV RNA \< 50 copies/mL) at baseline. |
| CD4 Cells Count | Baseline | CD4 cells count at baseline. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| HIV-RNA Levels | Baseline | For patients in whom T20 was replaced by raltegravir it will be determined the number of patients that presented undetectable viral load (confirmed HIV RNA \< 50 copies/mL) at baseline. |
| CD4 Cells Count | Baseline | For patients in whom T20 was replaced by raltegravir CD4 cells count will be assessed. |
| Adverse Drug Reactions | Week 48 | Number of participants that suffered clinical and laboratory-associated adverse events, including events that lead to discontinuations or death. Investigator will collect all drug-related adverse events, i.e. judged by the investigator to be definitely, probably, or possibly related to the study drug. |
Participant flow
Recruitment details
Retrospective collection of data took place in 11 portuguese public hospitals. Each site included patients who started treatment with raltegravir from March 2007 until December 2008.
Pre-assignment details
197 patients were included in the database. However, only 151 patients were included in the analysis, as 46 did not meet inclusion/exclusion criteria
Participants by arm
| Arm | Count |
|---|---|
| HIV-1 at Virologic Failure Adult multiple-experienced HIV-1 infected patients at virologic failure (patients under treatment with RNA HIV \>1000 cop/mL) | 107 |
| HIV With Need for Therapy Change Adult HIV infected patients at virologic suppression (with RNA HIV \<40 cop/mL), who needed to change antiretroviral therapy due to inacceptable toxicity, as determined by the investigator (including patients who needed to replace T20) | 24 |
| HIV-2 With Therapeutic Failure Adult HIV-2 infected patients with therapeutic failure (including those at virologic suppression but with decreasing immunological response with prior treatment) | 20 |
| Total | 151 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Death | 3 | 0 | 0 |
| Overall Study | Lost to Follow-up | 2 | 0 | 0 |
| Overall Study | Therapeutic Failure | 12 | 0 | 1 |
Baseline characteristics
| Characteristic | HIV-1 at Virologic Failure | HIV With Need for Therapy Change | HIV-2 With Therapeutic Failure | Total |
|---|---|---|---|---|
| Age Continuous | 44.0 years FULL_RANGE 10.2 | 45.5 years FULL_RANGE 12.7 | 52.5 years FULL_RANGE 11.6 | 45.0 years FULL_RANGE 10.9 |
| Sex: Female, Male Female | 22 Participants | 5 Participants | 10 Participants | 37 Participants |
| Sex: Female, Male Male | 85 Participants | 19 Participants | 10 Participants | 114 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 | 7 / 107 | 1 / 24 | 1 / 20 |
| serious Total, serious adverse events | 3 / 107 | 0 / 24 | 0 / 20 |
Outcome results
Primary
CD4 Cells Count
CD4 cells count at baseline.
Time frame: Baseline
| Arm | Measure | Value (MEDIAN) | Dispersion |
|---|---|---|---|
| HIV-1 at Virologic Failure | CD4 Cells Count | 166.00 cells/mm^3 | Full Range 203.57 |
| HIV With Need for Therapy Change | CD4 Cells Count | 391 cells/mm^3 | Full Range 200.77 |
| HIV-2 With Therapeutic Failure | CD4 Cells Count | 120 cells/mm^3 | Full Range 104.66 |
Comparison: Comparison between the 3 study groups, in order to determine if there are statistically significant differences concerning CD4 cells count at baselinep-value: <0.001Kruskal-Wallis
Primary
CD4 Cells Count
CD4 cells count at week 24.
Time frame: week 24
| Arm | Measure | Value (MEDIAN) | Dispersion |
|---|---|---|---|
| HIV-1 at Virologic Failure | CD4 Cells Count | 299.50 cells/mm^3 | Full Range 272.28 |
| HIV With Need for Therapy Change | CD4 Cells Count | 389.00 cells/mm^3 | Full Range 183.18 |
| HIV-2 With Therapeutic Failure | CD4 Cells Count | 190.00 cells/mm^3 | Full Range 156.83 |
Comparison: Comparison between the 3 study groups, in order to determine if there are statistically significant differences concerning CD4 cells count at week 24p-value: 0.007Kruskal-Wallis
Primary
CD4 Cells Count
CD4 cells count at week 48.
Time frame: week 48
| Arm | Measure | Value (MEDIAN) | Dispersion |
|---|---|---|---|
| HIV-1 at Virologic Failure | CD4 Cells Count | 336.50 cells/mm^3 | Full Range 3108.8 |
| HIV With Need for Therapy Change | CD4 Cells Count | 452.00 cells/mm^3 | Full Range 174.25 |
| HIV-2 With Therapeutic Failure | CD4 Cells Count | 180.00 cells/mm^3 | Full Range 160.26 |
Comparison: Comparison between the 3 study groups, in order to determine if there are statistically significant differences concerning CD4 cells count at week 48p-value: 0.001Kruskal-Wallis
Primary
HIV-RNA Levels
Patients with undetectable viral load (confirmed HIV RNA \< 50 copies/mL) at baseline.
Time frame: Baseline
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| HIV-1 at Virologic Failure | HIV-RNA Levels | >= 50 copies/mL | 107 participants |
| HIV-1 at Virologic Failure | HIV-RNA Levels | < 50 copies/mL | 0 participants |
| HIV With Need for Therapy Change | HIV-RNA Levels | < 50 copies/mL | 24 participants |
| HIV With Need for Therapy Change | HIV-RNA Levels | >= 50 copies/mL | 0 participants |
| HIV-2 With Therapeutic Failure | HIV-RNA Levels | < 50 copies/mL | 10 participants |
| HIV-2 With Therapeutic Failure | HIV-RNA Levels | >= 50 copies/mL | 10 participants |
Comparison: Comparison between the 3 study groups, in order to determine if there are statistically significant differences concerning HIV-RNA levels at baselinep-value: <0.001Chi-squared
Primary
HIV-RNA Levels
Patients achieving undetectable viral load (confirmed HIV RNA \< 50 copies/mL) at week 24.
Time frame: week 24
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| HIV-1 at Virologic Failure | HIV-RNA Levels | >= 50 copies / mL | 27 participants |
| HIV-1 at Virologic Failure | HIV-RNA Levels | < 50 copies / mL | 75 participants |
| HIV-1 at Virologic Failure | HIV-RNA Levels | Missing value | 5 participants |
| HIV With Need for Therapy Change | HIV-RNA Levels | >= 50 copies / mL | 0 participants |
| HIV With Need for Therapy Change | HIV-RNA Levels | < 50 copies / mL | 24 participants |
| HIV With Need for Therapy Change | HIV-RNA Levels | Missing value | 0 participants |
| HIV-2 With Therapeutic Failure | HIV-RNA Levels | < 50 copies / mL | 17 participants |
| HIV-2 With Therapeutic Failure | HIV-RNA Levels | Missing value | 1 participants |
| HIV-2 With Therapeutic Failure | HIV-RNA Levels | >= 50 copies / mL | 2 participants |
Primary
HIV-RNA Levels
Patients achieving undetectable viral load (confirmed HIV RNA \< 50 copies/mL) at week 48.
Time frame: week 48
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| HIV-1 at Virologic Failure | HIV-RNA Levels | >= 50 copies/mL | 18 participants |
| HIV-1 at Virologic Failure | HIV-RNA Levels | < 50 copies/mL | 74 participants |
| HIV-1 at Virologic Failure | HIV-RNA Levels | Missing value | 15 participants |
| HIV With Need for Therapy Change | HIV-RNA Levels | >= 50 copies/mL | 0 participants |
| HIV With Need for Therapy Change | HIV-RNA Levels | < 50 copies/mL | 24 participants |
| HIV With Need for Therapy Change | HIV-RNA Levels | Missing value | 0 participants |
| HIV-2 With Therapeutic Failure | HIV-RNA Levels | < 50 copies/mL | 16 participants |
| HIV-2 With Therapeutic Failure | HIV-RNA Levels | Missing value | 1 participants |
| HIV-2 With Therapeutic Failure | HIV-RNA Levels | >= 50 copies/mL | 3 participants |
Secondary
Adverse Drug Reactions
Number of participants that suffered clinical and laboratory-associated adverse events, including events that lead to discontinuations or death. Investigator will collect all drug-related adverse events, i.e. judged by the investigator to be definitely, probably, or possibly related to the study drug.
Time frame: Week 48
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| HIV-1 at Virologic Failure | Adverse Drug Reactions | At least one adverse reaction | 12 participants |
| HIV-1 at Virologic Failure | Adverse Drug Reactions | At least one non serious adverse reaction | 9 participants |
| HIV-1 at Virologic Failure | Adverse Drug Reactions | At least one serious adverse reaction | 3 participants |
| HIV-1 at Virologic Failure | Adverse Drug Reactions | Patients that discontinued due to adverse reaction | 0 participants |
Secondary
CD4 Cells Count
For patients in whom T20 was replaced by raltegravir it will be assessed the median changes of CD4 cells count at week 24.
Time frame: Week 24
| Arm | Measure | Value (MEDIAN) | Dispersion |
|---|---|---|---|
| HIV-1 at Virologic Failure | CD4 Cells Count | 378.00 cells/mm^3 | Full Range 171 |
Secondary
CD4 Cells Count
For the HIV-2 infected patients CD4 cells count will be assessed at baseline.
Time frame: Baseline
| Arm | Measure | Value (MEDIAN) | Dispersion |
|---|---|---|---|
| HIV-1 at Virologic Failure | CD4 Cells Count | 120.00 cells/mm^3 | Full Range 104.66 |
Secondary
CD4 Cells Count
For the HIV-2 infected patients CD4 cells count will be assessed at week 24.
Time frame: Week 24
| Arm | Measure | Value (MEDIAN) | Dispersion |
|---|---|---|---|
| HIV-1 at Virologic Failure | CD4 Cells Count | 190.00 cells/mm^3 | Full Range 156.83 |
Secondary
CD4 Cells Count
For the HIV-2 infected patients CD4 cells count will be assessed at week 48.
Time frame: Week 48
| Arm | Measure | Value (MEDIAN) | Dispersion |
|---|---|---|---|
| HIV-1 at Virologic Failure | CD4 Cells Count | 180.00 cells/mm^3 | Full Range 160 |
Secondary
CD4 Cells Count
For patients in whom T20 was replaced by raltegravir CD4 cells count will be assessed.
Time frame: Baseline
| Arm | Measure | Value (MEDIAN) | Dispersion |
|---|---|---|---|
| HIV-1 at Virologic Failure | CD4 Cells Count | 400.50 cells/mm^3 | Full Range 193.5 |
Secondary
CD4 Cells Count
For patients in whom T20 was replaced by raltegravir it will be assessed the median changes of CD4 cells count at week 48.
Time frame: Week 48
| Arm | Measure | Value (MEDIAN) | Dispersion |
|---|---|---|---|
| HIV-1 at Virologic Failure | CD4 Cells Count | 452.00 cells/mm^3 | Full Range 181.99 |
Secondary
HIV-RNA Levels
For patients in whom T20 was replaced by raltegravir it will be determined the number of patients that maintain undetectable viral load (confirmed HIV RNA \< 50 copies/mL) at week 24.
Time frame: Week 24
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| HIV-1 at Virologic Failure | HIV-RNA Levels | < 50 copies/mL | 20 participants |
| HIV-1 at Virologic Failure | HIV-RNA Levels | >= 50 copies/mL | 0 participants |
Secondary
HIV-RNA Levels
For the HIV-2 infected patients it will be determined the number of patients that achieve or maintain undetectable viral load (confirmed HIV RNA \< 50 copies/mL) at week 48.
Time frame: Week 48
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| HIV-1 at Virologic Failure | HIV-RNA Levels | < 50 copies/mL | 16 participants |
| HIV-1 at Virologic Failure | HIV-RNA Levels | >= 50 copies/mL | 3 participants |
| HIV-1 at Virologic Failure | HIV-RNA Levels | Missing value | 1 participants |
Secondary
HIV-RNA Levels
For patients in whom T20 was replaced by raltegravir it will be determined the number of patients that presented undetectable viral load (confirmed HIV RNA \< 50 copies/mL) at baseline.
Time frame: Baseline
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| HIV-1 at Virologic Failure | HIV-RNA Levels | < 50 copies/mL | 20 participants |
| HIV-1 at Virologic Failure | HIV-RNA Levels | >= 50 copies/mL | 0 participants |
Secondary
HIV-RNA Levels
For the HIV-2 infected patients it will be determined the number of patients that achieve or maintain undetectable viral load (confirmed HIV RNA \< 50 copies/mL) at week 24.
Time frame: Week 24
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| HIV-1 at Virologic Failure | HIV-RNA Levels | < 50 copies/mL | 17 participants |
| HIV-1 at Virologic Failure | HIV-RNA Levels | >= 50 copies/mL | 2 participants |
| HIV-1 at Virologic Failure | HIV-RNA Levels | Missing value | 1 participants |
Secondary
HIV-RNA Levels
For patients in whom T20 was replaced by raltegravir it will be determined the number of patients that maintain undetectable viral load (confirmed HIV RNA \< 50 copies/mL) at week 48.
Time frame: Week 48
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| HIV-1 at Virologic Failure | HIV-RNA Levels | < 50 copies/mL | 20 participants |
| HIV-1 at Virologic Failure | HIV-RNA Levels | >= 50 copies/mL | 0 participants |
Secondary
HIV-RNA Levels
For the HIV-2 infected patients it will be determined the number of patients with undetectable viral load (confirmed HIV RNA \< 50 copies/mL) at baseline.
Time frame: Baseline
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| HIV-1 at Virologic Failure | HIV-RNA Levels | < 50 copies/mL | 10 participants |
| HIV-1 at Virologic Failure | HIV-RNA Levels | >= 50 copies/mL | 10 participants |