Clinical trial NCT02708342: Observational, Retrospective Analysis in HIV-1 Infected Patients. (ORASWIRAL)
Official title: Observational, Retrospective Analysis to Evaluate Switching to Raltegravir Plus Abacavir/Lamivudine in HIV-1-Infected Patients. ORASWIRAL Study
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: HIV
Lead sponsor: IRCCS San Raffaele
Sponsor class: OTHER
Collaborators: name: Merck Sharp & Dohme LLC
First posted: 2016-03-15
Enrollment: 100
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: OTHER
Time perspective: RETROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: patient HIV-1 positive treated with raltegravir plus abacavir and lamivudine

Brief summary: RESEARCH METHODS Study Design Observational, Retrospective, Single-center, Single-arm Study of patients treated with raltegravir plus abacavir and lamivudine.

Detailed description: Adult, male and female HIV-1 infected subjects, who started an antiretroviral regimen of RALTEGRAVIR plus ABACAVIR and LAMIVUDINE after a different antiretroviral regimen.

Subject Selection: Inclusion Criteria

All consecutive patients fulfilling the following inclusion criteria will be considered:

* HIV-1 infected patients,
* age \> 18 years,
* Human leukocyte antigen (HLA) B5701-negative
* treatment-experienced patients with viral suppression (HIV-RNA \<50 copies/mL), who switched from any antiretroviral drug to raltegravir plus abacavir and lamivudine because of toxicity, convenience or other reasons
* switch from Protease Inhibitor to Raltegravir in patients on Abacavir and lamivudine, switch from any Nucleoside analog reverse-transcriptase inhibitors (NRTI) combination to abacavir and lamivudine in patients on raltegravir, switch to raltegravir plus abacavir and lamivudine from any other combination will all allow the inclusion in the study
* At least one viral load assessed before and at least once after starting the study regimen.

Subject Selection: Exclusion Criteria

* Documented drug-resistance or virological failure to integrase inhibitors, abacavir or lamivudine before starting the study regimen.
* Pregnancy at the start of the study regimen.
* HBsAg positive.

Definitions

Treatment Failure will be defined as the occurrence of Virological Failure or change in any component of the study regimen for any reason or treatment discontinuation at any time after the start of the considered treatment.

Virological failure will be defined by the occurrence of two consecutive (confirmed ) viral loads \>50 copies/mL at any time during follow-up.

Variables/Information

The following information will be extracted from the Hospital database of the Department:

* demographics (age, sex, race)
* smoking
* risk factors for HIV infection
* time from HIV-1 diagnosis (years)
* history of AIDS diagnosis
* hepatitis C virus (HCV) co-infection
* hepatitis B virus (HBV) co-infection
* presence of co-morbidities (including diabetes, hypertension, Cardio Vascular Diseases, Chronic kidney disease, cancer, etc)
* reasons for switching to raltegravir + abacavir/lamivudine
* time with HIV-1 RNA \< 50 copies/mL before switch
* BMI
* Hematology (Hb, PLT)
* Creatinine
* eGFR epidermal growth factor receptor (Chronic kidney disease -EPI formula)
* Phosphorus
* Calcium
* Aspartate aminotransferase (AST)
* ALT
* FIB-4 (liver index)
* alkaline phosphatase
* total, direct, indirect bilirubin
* proteinuria
* hemoglobinuria
* total, HDL-, LDL-cholesterol
* triglycerides
* glycemia
* HIV-RNA
* lymphocytes (CD4+, CD8+, CD4/CD8 ratio) since the start of raltegravir
* previous antiretroviral regimen and number of previous antiretroviral agents.

Data Sources

The data source is the Infectious Diseases Database of San Raffaele Hospital (IDD-OSR), collecting all the data of patients followed in the outpatient clinic.

Data are collected during routine clinical activity. Adverse Events that occurred after the initiation of the study treatment will be recorded and classified as drug-related or not and according to severity.

Power/Sample Size:

100 patients fulfilling the specified inclusion criteria will be available for this analysis.

When the estimated treatment efficacy proportion is 80%, a sample size of 100 subjects produces a two-sided 95% confidence interval with a precision equal to 8%.

Data Analysis Baseline characteristics of enrolled patients will be described by median and interquartile range or frequency (%), according to the variable type.

Follow-up will count from the date of starting with Raltegravir plus Abacavir and lamivudine to Treatment Failure or last available visit, whichever will first occur.

Primary analysis Kaplan-Meier curves and proportional hazards regression models will be used in reference to the primary endpoint.

Secondary analyses Trend over time of continuous variables (height, weight, BMI, Hb, PLT, creatinine, eGFR, phosphorus, calcium, AST, ALT, FIB-4, alkaline phosphatase, total, direct, indirect bilirubin, total, HDL-, LDL-cholesterol, triglycerides, glycaemia, HIV-RNA, CD4+ cell count) will be assessed by the ANOVA for repeated measures or univariate mixed linear models (depending on the data structure); chi-square test for trend will be applied on categorical variables (proteinuria, hemoglobinuria).

The non-parametric Wilcoxon signed rank test will be applied to assess significant changes of continuous variables since baseline and the last available visit; to test for changes in proportions between baseline and the last available visit, the McNemar test will be calculated.

Relationships among continuous variables (height ,weight, BMI, Hb, PLT, creatinine, eGFR, phosphorus, calcium, AST, ALT, FIB-4, alkaline phosphatase, total, direct, indirect bilirubin, total, HDL-, LDL-cholesterol, triglycerides, glycaemia, HIV-RNA, CD4+ cell count) will be tested calculating the correlation coefficients (Spearman rho, as appropriate).

Safety data analysis will be descriptive only. Adverse Events, Serious Adverse Events will be tabulated, also according to their severity, for a descriptive purpose only.

A two-sided alpha level of 0.05 will be taken as reference to detect statistical significance.

All analyses will be performed with Statistical Analysis Software, release 9.2.

Eligibility criteria: Subject Selection: Inclusion Criteria

All consecutive patients fulfilling the following inclusion criteria will be considered:

* HIV-1 infected patients,
* age \> 18 years,
* Human leukocyte antigen (HLA) B5701-negative
* treatment-experienced patients with viral suppression (HIV-RNA \<50 copies/mL), who switched from any antiretroviral drug to raltegravir plus abacavir and lamivudine because of toxicity, convenience or other reasons
* switch from Protease Inhibitor to Raltegravir in patients on Abacavir and lamivudine, switch from any Nucleoside analog reverse-transcriptase inhibitors (NRTI) combination to abacavir and lamivudine in patients on raltegravir, switch to raltegravir plus abacavir and lamivudine from any other combination will all allow the inclusion in the study
* At least one viral load assessed before and at least once after starting the study regimen.

Subject Selection: Exclusion Criteria

* Documented drug-resistance or virological failure to integrase inhibitors, abacavir or lamivudine before starting the study regimen.
* Pregnancy at the start of the study regimen.
* HBsAg positive.

Primary outcomes:
measure: Durability of an antiretroviral regimen of raltegravir plus abacavir and lamivudine
timeFrame: time to treatment failure through 96 weeks
Secondary outcomes:
measure: Cumulative probability of virological failure
timeFrame: through 96 weeks
measure: Proportion of patients with virological failure
timeFrame: through 96 weeks
measure: Proportion of patients with treatment failure
timeFrame: through 96 weeks
measure: Proportion of patients with more or equal to grade 2 abnormal laboratory tests
timeFrame: through 96 weeks
measure: Change in Lymphocytes CD4+
timeFrame: through 96 weeks
measure: Change in Lymphocytes CD8+
timeFrame: through 96 weeks
measure: Change in Lymphocytes CD4+/CD8+ ratio
timeFrame: through 96 weeks
measure: Changes in total cholesterol
timeFrame: through 96 weeks
measure: Changes in HDL cholesterol
timeFrame: through 96 weeks
measure: Changes in LDL cholesterol
timeFrame: through 96 weeks
measure: Changes in triglycerides
timeFrame: through 96 weeks
measure: Changes in glucose
timeFrame: through 96 weeks
measure: Changes in creatinine
timeFrame: through 96 weeks
measure: Changes in phosphate
timeFrame: through 96 weeks
measure: Changes in AST
timeFrame: through 96 weeks
measure: Changes in ALT
timeFrame: through 96 weeks
measure: Changes in ALP
timeFrame: through 96 weeks
measure: Changes in FIB-4 (liver index)
timeFrame: through 96 weeks
measure: Changes in eGFR
timeFrame: through 96 weeks
measure: Changes in proteinuria
timeFrame: through 96 weeks
measure: Occurrence of HIV genotypic mutations in plasma samples from patients with virological failure
timeFrame: through 96 weeks
measure: Proportion of patients with Adverse events and/or Serious Adverse Events, also according to their severity
timeFrame: through 96 weeks
Other outcomes:
Locations:
Study officials:
References:
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citation: Martinez E, d'Albuquerque PM, Perez I, Pich J, Gatell JM. Abacavir/lamivudine versus tenofovir/emtricitabine in virologically suppressed patients switching from ritonavir-boosted protease inhibitors to raltegravir. AIDS Res Hum Retroviruses. 2013 Feb;29(2):235-41. doi: 10.1089/AID.2012.0150. Epub 2012 Sep 24.
citation: Young B, Vanig T, Dejesus E, Hawkins T, St Clair M, Yau L, Ha B, Shield Study Team. A pilot study of abacavir/lamivudine and raltegravir in antiretroviral-naive HIV-1-infected patients: 48-week results of the SHIELD trial. HIV Clin Trials. 2010 Sep-Oct;11(5):260-9. doi: 10.1310/hct1105-260.