Raltegravir With Optimized Background Therapy (OBT) in Multiple Experienced HIV-infected Patients

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

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.

Study Overview

• Status: Completed
• Conditions: HIV Infections

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.

• Study Type: Observational
• Enrollment (Actual): 151

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• 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)

Description

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

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort
CohortHIV; Adult multiple-experienced HIV infected patients who needed to change their antiretroviral therapy and initiated raltegravir + optimized background therapy under the Early Access Program.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
HIV-RNA Levels	Patients with undetectable viral load (confirmed HIV RNA < 50 copies/mL) at baseline.	Baseline
HIV-RNA Levels	Patients achieving undetectable viral load (confirmed HIV RNA < 50 copies/mL) at week 24.	week 24
HIV-RNA Levels	Patients achieving undetectable viral load (confirmed HIV RNA < 50 copies/mL) at week 48.	week 48
CD4 Cells Count	CD4 cells count at baseline.	Baseline
CD4 Cells Count	CD4 cells count at week 24.	week 24
CD4 Cells Count	CD4 cells count at week 48.	week 48

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	Baseline
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.	Week 24
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.	Week 48
CD4 Cells Count	For patients in whom T20 was replaced by raltegravir CD4 cells count will be assessed.	Baseline
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.	Week 24
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.	Week 48
CD4 Cells Count	For the HIV-2 infected patients CD4 cells count will be assessed at baseline.	Baseline
CD4 Cells Count	For the HIV-2 infected patients CD4 cells count will be assessed at week 24.	Week 24
CD4 Cells Count	For the HIV-2 infected patients CD4 cells count will be assessed at week 48.	Week 48
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.	Baseline
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.	Week 24
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.	Week 48
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.	Week 48

Collaborators and Investigators

• Sponsor: Doroana, Maria Manuela, M.D.
• Collaborators: Merck Sharp & Dohme LLC; Eurotrials Brasil Consultores Cientificos Ltda
• Investigators: Principal Investigator: Manuela S Doroana, MD, Hospital de Santa Maria - Centro Hospitalar Lisboa Norte

Study record dates

Study Major Dates

• Study Start: April 1, 2010
• Primary Completion (Actual): July 1, 2010
• Study Completion (Actual): July 1, 2010

Study Registration Dates

• First Submitted: August 25, 2010
• First Submitted That Met QC Criteria: August 26, 2010
• First Posted (Estimate): August 27, 2010

Study Record Updates

• Last Update Posted (Estimate): May 19, 2011
• Last Update Submitted That Met QC Criteria: April 20, 2011
• Last Verified: April 1, 2011

More Information

Terms related to this study

• Keywords: HIV-1; HIV infections; Acquired Immunodeficiency Syndrome; AIDS; Anti-Retroviral Agents; Raltegravir; HIV-2; Integrase Inhibitors; multiple-experienced HIV infected patients
• Additional Relevant MeSH Terms: RNA Virus Infections; Virus Diseases; Infections; Blood-Borne Infections; Communicable Diseases; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; Immunologic Deficiency Syndromes; Immune System Diseases; HIV Infections
• Other Study ID Numbers: CohortHIV2008PT