Comparative efficacy and safety of dolutegravir relative to common core agents in treatment-naïve patients infected with HIV-1: a systematic review and network meta-analysis

Snedecor, Sonya J.; Radford, Matthew; Kratochvil, D.; Grove, Richard; Punekar, Yogesh Suresh

doi:10.1186/s12879-019-3975-6

Cited by 49 publications

(57 citation statements)

References 83 publications

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“…Network meta-analysis (NMAs) allows comparison of individual core agents, based on a network of randomized clinical trial evidence, where head to head data are unavailable. A recent meta-analysis compared these core agents on efficacy outcomes such as VS and CD4+ cell count change from baseline, and safety outcomes including adverse events [AEs], discontinuations, discontinuation due to AEs and lipid changes [6]. Authors concluded INSTIs to have superior efficacy and comparable safety to PIs and NNRTIs with DTG being among the most efficacious INSTI in treatment-naïve HIV-infected patients.…”

Section: Introductionmentioning

confidence: 99%

Comparative efficacy, safety and durability of dolutegravir relative to common core agents in treatment-naïve patients infected with HIV-1: an update on a systematic review and network meta-analysis

Nickel¹,

Halfpenny

Snedecor

et al. 2021

BMC Infect Dis

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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-naïve 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/μL 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/μL 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-naïve 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/μL, who can be difficult to treat.

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Section: Introductionmentioning

confidence: 99%

Comparative efficacy, safety and durability of dolutegravir relative to common core agents in treatment-naïve patients infected with HIV-1: an update on a systematic review and network meta-analysis

Nickel¹,

Halfpenny

Snedecor

et al. 2021

BMC Infect Dis

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“…Amongst third agents, INSTIs are the most preferred as evident in studies that showed it be superior or equivalent to other third agents in safety and efficiency. In addition, it is reported that INSTIs are more tolerable to patients, in turn reducing discontinuation rates [20][21][22][23]. However, for patients that are at higher risk of non-adherence, PIs as the third agent would be most appropriate because of their genetic barrier to resistance [24].…”

Section: Introductionmentioning

confidence: 99%

Real-world adherence and persistence for newly-prescribed HIV treatment: single versus multiple tablet regimen comparison among US medicaid beneficiaries

et al. 2020

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Background: Once-daily, single-tablet regimens (STRs) have been associated with improved patient outcomes compared to multi-tablet regimens (MTRs). This study evaluated real world adherence and persistence of HIV antiretroviral therapy (ART), comparing STRs and MTRs.Methods: Adult Medicaid beneficiaries (aged ≥ 18 years) initiating ART with ≥ 2 ART claims during the identification period (January 1, 2015-December 31, 2016) and continuous health plan enrollment for a 12-month baseline period were included. For STRs, the first ART claim date was defined as the index date; for MTRs, the prescription fill claim date for the last drug in the regimen was defined as the index date, and prescription fills were required to occur within a 5-day window. Adherence was assessed in 30-day intervals over a 6-month period, with adherence defined as having less than a 5-day gap between fills. Persistence was evaluated as median number of days on therapy and percent persistence at 12 months. Cox Proportional Hazard models were used to evaluate risk of discontinuation, controlling for baseline and clinical characteristics. Results:A total of 1,744 (STR = 1290; MTR = 454) and 2409 (STR = 1782; MTR = 627) patients newly prescribed ART had available data concerning adherence and persistence, respectively. Average age ranged 40-42 years. The patient population was predominantly male. Adherence assessments showed 22.7% of STR initiators were adherent to their index regimens over a 6-month period compared to 11.7% of MTR initiators. Unadjusted persistence analysis showed 36.3% of STR initiators discontinued first-line therapy compared to 48.8% for MTR initiators over the 2-year study period. Controlling for baseline demographic and clinical characteristics, MTR initiators had a higher risk of treatment discontinuation (hazard ratio [HR] =

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“…Since 2007, antiretroviral therapy (ART) regimens based on an integrase strand transfer inhibitor (INSTI) have been introduced and largely used both in treatment-naïve and treatment-experienced people because of their safety and efficacy, as demonstrated in many clinical trials and observational studies [ 1 , 2 ]. The widespread use of INSTI-based regimens, particularly first-generation agents, has led to the emergence of INSTI resistance in a limited proportion of people with HIV-1 infection (PWH) [ 3 ].…”

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confidence: 99%

Burden of Disease in PWH Harboring a Multidrug-Resistant Virus: Data From the PRESTIGIO Registry

Antoni

Santoro

Corbelli

et al. 2020

Open Forum Infectious Diseases

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Background Currently, no data are available on the burden of morbidity and mortality in people living with HIV-1 (PLWH) harboring a 4-class drug resistant (4DR) virus (NRTI, NNRTI, PI, INSTI). The study aimed to assess the incidence of clinical events or death in this population. Methods Cohort study on PLWH, from the PRESTIGIO Registry, with a documented 4DR virus.The burden of disease was defined as the occurrence of any new event including AIDS-defining event (ADE) or non-AIDS-defining event (NADE) or death for any cause, after 4DR evidence (baseline).Cox regression models evaluated factors associated with the risk of new clinical events/death. Results Among 148 PLWH followed for a median of 47 months (IQR=32-84) since 4DR evidence, 38 PLWH had 62 new events or died for any cause [incidence rate, 9.12/100-PYFU (95%CI=6.85-11.39)]: 12 deaths (6 AIDS-related and 6 non-AIDS-related), 18 ADE, 32 NADE; 20 of the 38 NADE (45%) of the incident clinical events were malignancies. The 4-year cumulative incidence of death was 6% (95%CI=3%-13%) and that of ≥1 event or death was 22% (95%CI=16%-31%). A higher risk of new clinical events/death was more likely in PLWH with previous clinical events (aHR=2.67, 95%CI=1.07-6.67) and marginally associated with lower baseline CD4+/CD8+ ratio (aHR=0.82, 95%CI=0.65-1.02). Conclusions PLWH harbouring 4DR have a high burden of disease with a worrying incidence of malignancies, strongly advising for close prevention and monitoring interventions as well as access to innovative therapeutic strategies, especially in people with a history of clinical events and low CD4+/CD8+ ratio.

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Comparative efficacy and safety of dolutegravir relative to common core agents in treatment-naïve patients infected with HIV-1: a systematic review and network meta-analysis

Cited by 49 publications

References 83 publications

Comparative efficacy, safety and durability of dolutegravir relative to common core agents in treatment-naïve patients infected with HIV-1: an update on a systematic review and network meta-analysis

Comparative efficacy, safety and durability of dolutegravir relative to common core agents in treatment-naïve patients infected with HIV-1: an update on a systematic review and network meta-analysis

Real-world adherence and persistence for newly-prescribed HIV treatment: single versus multiple tablet regimen comparison among US medicaid beneficiaries

Burden of Disease in PWH Harboring a Multidrug-Resistant Virus: Data From the PRESTIGIO Registry

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