PMID- 33637050
OWN - NLM
STAT- MEDLINE
DCOM- 20210322
LR  - 20210413
IS  - 1471-2334 (Electronic)
IS  - 1471-2334 (Linking)
VI  - 21
IP  - 1
DP  - 2021 Feb 26
TI  - Comparative efficacy, safety and durability of dolutegravir relative to common 
      core agents in treatment-naive patients infected with HIV-1: an update on a 
      systematic review and network meta-analysis.
PG  - 222
LID - 10.1186/s12879-021-05850-0 [doi]
LID - 222
AB  - BACKGROUND: The objective of this study was to assess the durability of response 
      of dolutegravir (DTG) as an antiretroviral core agent by comparing its efficacy 
      and safety with other recommended or commonly used core agents up to 96-weeks 
      (W96). METHODS: A previously published systematic review was updated to identify 
      phase 3/4 randomised controlled trials (RCTs) of core agents in treatment-naive 
      HIV-1 patients. Efficacy [virologic suppression (VS), CD4(+) cell change from 
      baseline] and safety [adverse events [AEs], discontinuations, drug-related AEs 
      [DRAEs]] were analysed at W96 using Bayesian network meta-analysis (NMA) 
      adjusting for nucleoside/nucleotide reverse transcriptase inhibitors' (NRTIs') 
      backbone. Subgroups of patients with VL > 100,000 copies/mL or CD4(+) </= 200 
      cells/muL at baseline were analysed separately. RESULTS: The NMA included 20 
      studies reporting data at W96. A higher proportion of patients receiving DTG 
      achieved VS compared to those on protease inhibitors 
      [PI:Range:8.7%(CrI:3.1,16.0)-19.9%(10.8,30.5)], efavirenz [EFV:6.9%(1.3,10.8)] 
      and cobicistat-boosted elvitegravir [EVG/c:8.2%(0.2,17.4)], and similar but 
      numerically higher compared to rilpivirine [RPV:5.0%(- 2.8,12.5)], raltegravir 
      [RAL:2.9%(- 1.6,7.7)] and bictegravir [BIC:2.7%(- 2.7,10.6)]. The probability 
      that more patients on DTG would achieve VS at W96 compared to any other core 
      agent was greater than 80%. A higher proportion of patients on DTG achieved VS 
      compared to PI/rs [Range:33.1%(13.6,50.4)-45.3%(24.1,61.6)] and RAL 
      [16.7%(3.3,31.2)] in patients with VL > 100,000 copies/mL at baseline, and 
      similar VS was achieved in patients with CD4(+) </= 200 cells/muL at baseline. DTG 
      also achieved greater increase in CD4(+) cells from baseline compared to EFV 
      [32.6(10.7,54.7)], ritonavir-boosted darunavir [DRV/r:25.7(3.6,48.1)] and BIC 
      [24.7(1.5,47.7)]. Patients receiving DTG had lower odds of discontinuing therapy 
      by W96 compared to PI/rs, EFV, RAL and EVG/c. Patients on DTG had lower odds of 
      experiencing an adverse event (AE) compared to patients on EFV [odds 
      ratio:0.6(0.3,0.9)], ATV/r [0.4(0.3,0.6)] and LPV/r [0.3(0.2,0.5)]. For patients 
      on DTG, the odds of experiencing a drug-related AE were lower than the odds for 
      patients on EFV [0.3(0.2,0.4)], comparable to patients on RAL [1.1(0.8,1.4)] and 
      higher than those on BIC [1.5(1.1,2.0)]. CONCLUSION: Un-boosted integrase 
      inhibitors had better efficacy and similar safety compared to PI/rs at W96 in 
      treatment-naive patients with HIV-1, with DTG being among the most efficacious 
      core agent, particularly in patients with baseline VL > 100,000 copies/mL 
      or </= 200 CD4(+) cells/muL, who can be difficult to treat.
FAU - Nickel, Katharina
AU  - Nickel K
AD  - Pharmerit International, Berlin, Germany.
FAU - Halfpenny, Nicholas J A
AU  - Halfpenny NJA
AD  - Pharmerit International, Rotterdam, Netherlands.
FAU - Snedecor, Sonya J
AU  - Snedecor SJ
AD  - Pharmerit International, Bethesda, MD, USA.
FAU - Punekar, Yogesh Suresh
AU  - Punekar YS
AUID- ORCID: 0000-0002-7531-1319
AD  - ViiV Healthcare, GSK House, 980 Great West Rd, Brentford, Middlesex, TW8 9GS, UK. 
      yogesh.q.punekar@gsk.com.
LA  - eng
PT  - Journal Article
PT  - Systematic Review
DEP - 20210226
PL  - England
TA  - BMC Infect Dis
JT  - BMC infectious diseases
JID - 100968551
RN  - 0 (Anti-HIV Agents)
RN  - 0 (HIV Integrase Inhibitors)
RN  - 0 (Heterocyclic Compounds, 3-Ring)
RN  - 0 (Oxazines)
RN  - 0 (Piperazines)
RN  - 0 (Pyridones)
RN  - DKO1W9H7M1 (dolutegravir)
SB  - IM
EIN - BMC Infect Dis. 2021 Apr 12;21(1):340. PMID: 33845777
MH  - Adult
MH  - Anti-HIV Agents/therapeutic use
MH  - Female
MH  - HIV Infections/*drug therapy
MH  - HIV Integrase Inhibitors/*therapeutic use
MH  - HIV-1/drug effects
MH  - Heterocyclic Compounds, 3-Ring/*therapeutic use
MH  - Humans
MH  - Male
MH  - Network Meta-Analysis
MH  - Oxazines/*therapeutic use
MH  - Piperazines/*therapeutic use
MH  - Pyridones/*therapeutic use
MH  - Treatment Outcome
PMC - PMC7908737
OTO - NOTNLM
OT  - Antiretroviral therapy
OT  - Dolutegravir
OT  - HIV-1
OT  - Integrase strand inhibitors
OT  - Network meta-analysis
OT  - Non-nucleoside reverse transcriptase inhibitor
OT  - Protease inhibitor
OT  - Systematic review
OT  - Treatment-naive
COIS- KN, NJAH and SJS are employees of Pharmerit International and were contracted to 
      conduct this study on behalf of ViiV Healthcare. YSP is an employee of ViiV 
      Healthcare and holds stock in GlaxoSmithKline.
EDAT- 2021/02/28 06:00
MHDA- 2021/03/23 06:00
PMCR- 2021/02/26
CRDT- 2021/02/27 05:26
PHST- 2020/10/30 00:00 [received]
PHST- 2021/01/28 00:00 [accepted]
PHST- 2021/02/27 05:26 [entrez]
PHST- 2021/02/28 06:00 [pubmed]
PHST- 2021/03/23 06:00 [medline]
PHST- 2021/02/26 00:00 [pmc-release]
AID - 10.1186/s12879-021-05850-0 [pii]
AID - 5850 [pii]
AID - 10.1186/s12879-021-05850-0 [doi]
PST - epublish
SO  - BMC Infect Dis. 2021 Feb 26;21(1):222. doi: 10.1186/s12879-021-05850-0.