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Meta-analysis and systematic review of the efficacy and resistance for human immunodeficiency virus type 1 integrase strand transfer inhibitors.

Abstract：

:Integrase strand transfer inhibitors (INSTIs) are the most recent class of antiretroviral drugs with potent and durable antiviral activity used to treat human immunodeficiency virus type 1 (HIV-1) infection. However, development of drug resistance increases the risk of treatment failure, disease progression and mortality. A better understanding of drug efficacy and resistance against INSTIs is crucial for their efficient use and the development of new antiretrovirals. A meta-analysis of studies reporting efficacy and resistance data on INSTI use in HIV-infected patients was performed. Odds ratios (ORs) of efficacy outcome data favouring INSTI use in different clinical settings demonstrated that INSTIs have higher efficacy compared with drugs of other classes. For combination antiretroviral therapy-naïve patients and virologically-suppressed patients who switched to INSTI-based therapy, the OR was 1.484 (95% CI 1.229-1.790) and 1.341 (95% CI 0.913-1.971), respectively. ORs of resistance data indicated decreased treatment-emergent resistance development to dolutegravir (DTG) upon virological failure than to non-INSTIs (OR = 0.081, 95% CI 0.004-1.849), whereas the opposite was observed for raltegravir (RAL) (OR = 3.137, 95% CI 1.827-5.385) and elvitegravir (EVG) (OR = 1.886, 95% CI 0.569-6.252). Pooled analysis of resistance data indicated that development of resistance to DTG and bictegravir was rare, whereas EVG and RAL had low genetic barriers to resistance and the intensive cross-resistance between them limits INSTI efficiency. Efficient means of monitoring the emergence of resistance to INSTIs and the development of drugs with high genetic barriers are clear paths for future research.

journal_name

Int J Antimicrob Agents

journal_title

International journal of antimicrobial agents

authors

Yang LL,Li Q,Zhou LB,Chen SQ

doi

10.1016/j.ijantimicag.2019.08.008

subject

Has Abstract

pub_date

2019-11-01 00:00:00

pages

547-555

issue

eissn

0924-8579

issn

1872-7913

pii

S0924-8579(19)30219-5

journal_volume

pub_type

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Meta-analysis and systematic review of the efficacy and resistance for human immunodeficiency virus type 1 integrase strand transfer inhibitors.