Clinical trial NCT01190124: Raltegravir With Optimized Background Therapy (OBT) in Multiple Experienced HIV-infected Patients
Official title: Raltegravir With Optimized Background Therapy (OBT) in Multiple Experienced HIV-infected Patients: a Retrospective Analysis of a Portuguese Cohort Treated Within the Expanded Access Program
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: HIV Infections
Keywords: HIV infections
HIV-1
HIV-2
Acquired Immunodeficiency Syndrome
AIDS
Anti-Retroviral Agents
Raltegravir
Integrase Inhibitors
multiple-experienced HIV infected patients
Lead sponsor: Doroana, Maria Manuela, M.D.
Sponsor class: INDIV
Collaborators: name: Merck Sharp & Dohme LLC
name: Eurotrials Brasil Consultores Cientificos Ltda
First posted: 2010-08-27
Enrollment: 151
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: RETROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: HIV-infected adult portuguese patients who started treatment with raltegravir since the Early Access Program and Compassionate Use Program (from March 2007 to December 2008)

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.

Eligibility criteria: 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

Primary outcomes:
measure: HIV-RNA Levels
timeFrame: Baseline
measure: HIV-RNA Levels
timeFrame: week 24
measure: HIV-RNA Levels
timeFrame: week 48
measure: CD4 Cells Count
timeFrame: Baseline
measure: CD4 Cells Count
timeFrame: week 24
measure: CD4 Cells Count
timeFrame: week 48
Secondary outcomes:
measure: HIV-RNA Levels
timeFrame: Baseline
measure: HIV-RNA Levels
timeFrame: Week 24
measure: HIV-RNA Levels
timeFrame: Week 48
measure: CD4 Cells Count
timeFrame: Baseline
measure: CD4 Cells Count
timeFrame: Week 24
measure: CD4 Cells Count
timeFrame: Week 48
measure: CD4 Cells Count
timeFrame: Baseline
measure: CD4 Cells Count
timeFrame: Week 24
measure: CD4 Cells Count
timeFrame: Week 48
measure: HIV-RNA Levels
timeFrame: Baseline
measure: HIV-RNA Levels
timeFrame: Week 24
measure: HIV-RNA Levels
timeFrame: Week 48
measure: Adverse Drug Reactions
timeFrame: Week 48
Other outcomes:
Locations:
Study officials:
affiliation: Hospital de Santa Maria - Centro Hospitalar Lisboa Norte
name: Manuela S Doroana, MD
role: PRINCIPAL_INVESTIGATOR
References: