Abstract
BackgroundA network meta-analysis can provide estimates of relative efficacy for treatments not directly studied in head-to-head randomized controlled trials. We estimated the relative efficacy and safety of dolutegravir (DTG) versus third agents currently recommended by guidelines, including ritonavir-boosted atazanavir (ATV/r), ritonavir-boosted darunavir (DRV/r), efavirenz (EFV), cobicistat-boosted elvitegravir (EVG/c), ritonavir-boosted lopinavir (LPV/r), raltegravir (RAL), and rilpivirine (RPV), in treatment-naive HIV-1–infected patients.MethodsA systematic review of published literature was conducted to identify phase 3/4 randomized controlled clinical trials (up to August 2013) including at least one third agent of interest in combination with a backbone nucleoside reverse transcriptase inhibitor (NRTI) regimen. Bayesian fixed-effect network meta-analysis models adjusting for the type of nucleoside reverse transcriptase inhibitor backbone (tenofovir disoproxil fumarate/emtricitabine [TDF/FTC] or abacavir/lamivudine [ABC/3TC]) were used to evaluate week 48 efficacy (HIV-RNA suppression to <50 copies/mL and change in CD4+ cells/µL) and safety (lipid changes, adverse events, and discontinuations due to adverse events) of DTG relative to all other treatments. Sensitivity analyses assessing the impact of NRTI treatment adjustment and random-effects models were performed.ResultsThirty-one studies including 17,000 patients were combined in the analysis. Adjusting for the effect of NRTI backbone, treatment with DTG resulted in significantly higher odds of virologic suppression (HIV RNA<50 copies/mL) and increase in CD4+ cells/µL versus ATV/r, DRV/r, EFV, LPV/r, and RPV. Dolutegravir had better or equivalent changes in total cholesterol, LDL, triglycerides, and lower odds of adverse events and discontinuation due to adverse events compared to all treatments. Random-effects and unadjusted models resulted in similar conclusions.ConclusionThree clinical trials of DTG have demonstrated comparable or superior efficacy and safety to DRV, RAL, and EFV in HIV-1–infected treatment-naive patients. This network meta-analysis suggests DTG is also favorable or comparable to other commonly used third agents (ATV/r, LPV/r, RPV, and EVG/c).
Highlights
Two of the primary goals of anti-HIV therapy are to suppress plasma HIV viral replication and preserve and restore the number of circulating CD4+ T cells, the immune cells attacked by HIV [1,2]
For treatment-naive patients, Highly active antiretroviral therapy (HAART) typically includes a combination of two nucleoside reverse transcriptase inhibitors (NRTIs, the ‘‘backbone’’) with one or more drugs from the more potent classes [1,2]
Pre-specified inclusion criteria included treatment-naive patients with HIV-1 infection; studies published in English; phase 3 or 4 randomized controlled trials (RCTs); patients aged $13 years; use of at least one of the third agents of interest; and reporting at least one of the efficacy outcomes of interest after 48 weeks of treatment
Summary
Two of the primary goals of anti-HIV therapy are to suppress plasma HIV viral replication and preserve and restore the number of circulating CD4+ T cells, the immune cells attacked by HIV [1,2]. The US Department of Health and Human Services (DHHS) and the European AIDS Clinical Society guidelines have recommended several third agents for the treatment of infection: ritonavir-boosted atazanavir (ATV/r), darunavir (DRV/r), lopinavir (LPV/r), efavirenz (EFV), cobicistat-boosted elvitegravir (EVG/c), raltegravir (RAL), and rilpivirine (RPV) [1,2]. RPV and LPV/r are recommended as alternative regimen options by DHHS [2] Many of these regimens have comparable efficacy but vary in dosing frequency, pill burden, drug interactions, and potential side effects. We estimated the relative efficacy and safety of dolutegravir (DTG) versus third agents currently recommended by guidelines, including ritonavir-boosted atazanavir (ATV/r), ritonavir-boosted darunavir (DRV/r), efavirenz (EFV), cobicistat-boosted elvitegravir (EVG/c), ritonavir-boosted lopinavir (LPV/r), raltegravir (RAL), and rilpivirine (RPV), in treatment-naive HIV-1–infected patients
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