Observational, Retrospective Analysis in HIV-1 Infected Patients. (ORASWIRAL)

Observational, Retrospective Analysis to Evaluate Switching to Raltegravir Plus Abacavir/Lamivudine in HIV-1-Infected Patients. ORASWIRAL Study

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

Study Overview

• Status: Completed
• Conditions: HIV

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.

• Study Type: Observational
• Enrollment (Actual): 100

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

patient HIV-1 positive treated with raltegravir plus abacavir and lamivudine

Description

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.

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Durability of an antiretroviral regimen of raltegravir plus abacavir and lamivudine	time to treatment failure through 96 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cumulative probability of virological failure	Kaplan-Meier curves	through 96 weeks
Proportion of patients with virological failure		through 96 weeks
Proportion of patients with treatment failure		through 96 weeks
Proportion of patients with more or equal to grade 2 abnormal laboratory tests		through 96 weeks
Change in Lymphocytes CD4+	cells/uL	through 96 weeks
Change in Lymphocytes CD8+	cells/uL	through 96 weeks
Change in Lymphocytes CD4+/CD8+ ratio		through 96 weeks
Changes in total cholesterol	mg/dL	through 96 weeks
Changes in HDL cholesterol	mg/dL	through 96 weeks
Changes in LDL cholesterol	mg/dL	through 96 weeks
Changes in triglycerides	mg/dL	through 96 weeks
Changes in glucose	mg/dL	through 96 weeks
Changes in creatinine	mg/dL	through 96 weeks
Changes in phosphate	mmol/L	through 96 weeks
Changes in AST	U/L	through 96 weeks
Changes in ALT	U/L	through 96 weeks
Changes in ALP	U/L	through 96 weeks
Changes in FIB-4 (liver index)		through 96 weeks
Changes in eGFR	ml/min/1.73m^2	through 96 weeks
Changes in proteinuria	mg/dL	through 96 weeks
Occurrence of HIV genotypic mutations in plasma samples from patients with virological failure		through 96 weeks
Proportion of patients with Adverse events and/or Serious Adverse Events, also according to their severity		through 96 weeks

Collaborators and Investigators

• Sponsor: IRCCS San Raffaele
• Collaborators: Merck Sharp & Dohme LLC

Publications and helpful links

General Publications

• Raffi F, Jaeger H, Quiros-Roldan E, Albrecht H, Belonosova E, Gatell JM, Baril JG, Domingo P, Brennan C, Almond S, Min S; extended SPRING-2 Study Group. Once-daily dolutegravir versus twice-daily raltegravir in antiretroviral-naive adults with HIV-1 infection (SPRING-2 study): 96 week results from a randomised, double-blind, non-inferiority trial. Lancet Infect Dis. 2013 Nov;13(11):927-35. doi: 10.1016/S1473-3099(13)70257-3. Epub 2013 Sep 25.
• Suzuki A, Uehara Y, Saita M, Inui A, Isonuma H, Naito T. Raltegravir and Abacavir/Lamivudine in Japanese Treatment-Naive and Treatment-Experienced Patients with HIV Infection: a 48-Week Retrospective Pilot Analysis. Jpn J Infect Dis. 2016;69(1):33-8. doi: 10.7883/yoken.JJID.2014.236. Epub 2015 May 12.
• Fabbiani M, Mondi A, Colafigli M, D'Ettorre G, Paoletti F, D'Avino A, Ciccarelli N, Sidella L, Murri R, Fortuna S, Vullo V, Cauda R, De Luca A, Di Giambenedetto S. Safety and efficacy of treatment switch to raltegravir plus tenofovir/emtricitabine or abacavir/lamivudine in patients with optimal virological control: 48-week results from a randomized pilot study (Raltegravir Switch for Toxicity or Adverse Events, RASTA Study). Scand J Infect Dis. 2014 Jan;46(1):34-45. doi: 10.3109/00365548.2013.840920. Epub 2013 Oct 28.
• 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.
• 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.

Helpful Links

• Italian Guidelines for the management of antiretroviral therapy of the subjects with HIV-1 infection.

Study record dates

Study Major Dates

• Study Start: April 1, 2016
• Primary Completion (Actual): November 1, 2016
• Study Completion (Actual): December 1, 2016

Study Registration Dates

• First Submitted: March 2, 2016
• First Submitted That Met QC Criteria: March 14, 2016
• First Posted (Estimated): March 15, 2016

Study Record Updates

• Last Update Posted (Actual): February 9, 2024
• Last Update Submitted That Met QC Criteria: February 7, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Other Study ID Numbers: ORASWIRAL

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Abstract to Scientific Congress