Clinical use of HIV integrase inhibitors: a systematic review and meta-analysis.
BACKGROUND
Optimal regimen choice of antiretroviral therapy is essential to achieve long-term clinical success. Integrase inhibitors have swiftly been adopted as part of current antiretroviral regimens. The purpose of this study was to review the evidence for integrase inhibitor use in clinical settings.


METHODS
MEDLINE and Web-of-Science were screened from April 2006 until November 2012, as were hand-searched scientific meeting proceedings. Multiple reviewers independently screened 1323 citations in duplicate to identify randomized controlled trials, nonrandomized controlled trials and cohort studies on integrase inhibitor use in clinical practice. Independent, duplicate data extraction and quality assessment were conducted.


RESULTS
48 unique studies were included on the use of integrase inhibitors in antiretroviral therapy-naive patients and treatment-experienced patients with either virological failure or switching to integrase inhibitors while virologically suppressed. On the selected studies with comparable outcome measures and indication (n = 16), a meta-analysis was performed based on modified intention-to-treat (mITT), on-treatment (OT) and as-treated (AT) virological outcome data. In therapy-naive patients, favorable odds ratios (OR) for integrase inhibitor-based regimens were observed, (mITT OR 0.71, 95% CI 0.59-0.86). However, integrase inhibitors combined with protease inhibitors only did not result in a significant better virological outcome. Evidence further supported integrase inhibitor use following virological failure (mITT OR 0.27; 95% CI 0.11-0.66), but switching to integrase inhibitors from a high genetic barrier drug during successful treatment was not supported (mITT OR 1.43; 95% CI 0.89-2.31). Integrase inhibitor-based regimens result in similar immunological responses compared to other regimens. A low genetic barrier to drug-resistance development was observed for raltegravir and elvitegravir, but not for dolutegravir.


CONCLUSIONS
In first-line therapy, integrase inhibitors are superior to other regimens. Integrase inhibitor use after virological failure is supported as well by the meta-analysis. Careful use is however warranted when replacing a high genetic barrier drug in treatment-experienced patients switching successful treatment.
General Internal Medicine and Infectious Diseases, Ghent University Hospital, Ghent, Belgium.
Peter
P
Messiaen
Annemarie M J
AM
Wensing
Axel
A
Fun
Monique
M
Nijhuis
Nele
N
Brusselaers
Linos
L
Vandekerckhove
D002986:Clinical Trials as Topic; D024882:Drug Resistance, Viral / Q000187:drug effects; D004359:Drug Therapy, Combination; D015658:HIV Infections / Q000188:drug therapy / Q000821:virology; D019428:HIV Integrase Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D015497:HIV-1 / Q000187:drug effects; D006801:Humans; D011480:Protease Inhibitors / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use; D018894:Reverse Transcriptase Inhibitors / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use; D016896:Treatment Outcome; D019562:Viral Load / Q000187:drug effects
D019428:HIV Integrase Inhibitors; D011480:Protease Inhibitors; D018894:Reverse Transcriptase Inhibitors