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Proposal 1058

Title of the Proposed Research

Ritonavir-boosted protease inhibitor-based versus non-nucleoside reverse transcriptase inhibitor-based highly active antiretroviral therapy regimens: a systematic review and individual patient data meta-analysis

Lead Researcher

Alvaro H Borges, MD, MSc

Affiliation

Centre for Health & Infectious Diseases Research
Rigshospitalet, University of Copenhagen
Copenhagen, Denmark

Funding Source

Independent funding is not required to support the project at this time. This study represents a secondary analysis that will use existing data previously collected as part of the trials that met the entry criteria.

Potential Conflicts of Interest

None

Data Sharing Agreement Date

19 August 2014

Lay Summary

Background and importance of the research:
There are several options for initial treatment of people living with HIV. Two of the most commonly used treatment regimens contain either drugs from the protease inhibitors (PI) class or the non-nucleoside reverse-transcriptase inhibitors (NNRTI) class. Some previous studies suggest that patients receiving PIs have a better immunological recovery while patients receiving NNRTI control the virus more quickly. It remains unknown, however, whether this leads to differences in terms of mortality or progression of the disease. Most of the randomised studies comparing the drugs have used surrogate endpoints; i.e., immunological or virological parameters that do not necessarily correspond to measurable differences in terms of death or development of opportunistic infections. In this project, we intend to perform an individual patient data meta-analysis of all studies that compared the two treatments. Datasets from individual studies will be recoded using a standardised codebook, merged centrally and re-analysed. This will be a very powerful tool to compare the two treatments, because it increases the power to detect differences as data from a much larger number of patients are taken into account. The results of our analyses will be very clinically relevant because they will help patients living with HIV and their doctors to choose which treatment is the best to start with.

Aim: to identify which is the best initial treatment for people living with HIV
Objectives: to compare, among treatment-naïve people living with HIV, PI-based versus NNRTI-based regimens in terms of immunological recovery, control of the virus, death, progression of the disease and side effects

How the research will be conducted:
All the studies comparing PI- versus NNRTI-regimens for the initial treatment of HIV infection were identified by a systematic review. We contacted the corresponding authors of all such studied. They agreed to share the datasets and contribute with intellectual input to the development of this project. The datasets are now in the process of being recoded into a standardised format. They will be subsequently merged and analysed using powerful statistical methods to perform pre-defined comparative analyses.

Dissemination activities:
Preliminary results will be presented at the Infectious Diseases Week, a big conference that will take in Philadelphia on Oct 8-12th. A paper describing the main findings will be written and send for publication in peer-reviewed, high impact, scientific journal.

Study Data Provided

Study ESS40001: A Phase II, Open-Label, Randomized Study to Compare the Efficacy and Safety of EPIVIR/ZIAGEN/Zerit (3TC/ABC/d4T) Versus EPIVIR/ZIAGEN/Sustiva (3TC/ABC/EFV) Versus EPIVIR/ZIAGEN/GW433908/Norvir (3TC/ABC/908/RTV) for 96 Weeks in the Treatment of HIV-1 Infected Subjects Who are Antiretroviral Therapy Naïve

Statistical Analysis Plan

Publication Citation

“Nonnucleoside Reverse-transcriptase Inhibitor- vs Ritonavir-boosted Protease Inhibitor–based Regimens for Initial Treatment of HIV Infection: A Systematic Review and Metaanalysis of Randomized Trials” Clin Infect Dis. (2016) 63 (2): 268-280 first published online April 18, 2016 doi:10.1093/cid/ciw236