Dolutegravir based antiretroviral therapy compared to other combined antiretroviral regimens for the treatment of HIV-infected naive patients: A systematic review and meta-analysis


Autoři: Mario Cruciani aff001;  Saverio G. Parisi aff002
Působiště autorů: Infectious Diseases Unit, AULSS 9 scaligera-Verona, Verona, Italy aff001;  Department of Biotechnology, University of Padua, Padua, Italy aff002
Vyšlo v časopise: PLoS ONE 14(9)
Kategorie: Research Article
doi: https://doi.org/10.1371/journal.pone.0222229

Souhrn

Background

Numerous randomized clinical trials (RCTs) were conducted to evaluate dolutegravir based triple antiretroviral therapy (ART) compared to other triple antiretroviral regimens in naïve patients, and a summary of the available evidence is required to shed more light on safety and effectiveness issues.

Methods

Systematic review and meta-analysis of RCTs comparing dolutegravir-containing ART to non-dolutegravir containing ART in HIV-infected naive patients. Primary outcomes: % of patients with viral load<50 copies/mL at 48 weeks, stratified according to baseline viral load levels (< or >100.000 copies/mL); overall rate of discontinuation and/or switching for any cause (virologic failure, clinical failure, adverse events). Measure of treatment effect: Risk Difference (RD) with 95% confidence intervals (CIs). The GRADE system was used to assess the certainty of the body of evidence,

Results

We included 7 RCTs (13 reports, 6407patients) comparing dolutegravir containing to non-dolutegravir containing ART, both in combination with 2 NRTIs. Controls were raltegravir or bictegravir (3 RCTs), boosted atazanavir or darunavir (2 RCTs) or efavirenz (2 RCTs). Rates of patients with VL <50 copies/ml were higher in dolutegravir recipients compared to controls at 48 weeks (RD, 0.05; 95% CIs, 0.03/0.08, p = 0.0002) and 96 weeks (RD, 0.06; 95% CIs, 0.03/0.10, p<0.0001); the average benefit of using dolutegravir was particularly evident at 48 weeks in the subgroup of patients with high baseline viral load (RD, 0.10; 95% CIs, 0.05/0.15; p< 0.0001; GRADE assessment: "high certainty of evidence"). Overall rate of discontinuation were lower in dolutegravir compared to controls (RD,-0.03, 95% CIs -0.05/-0.01; p = 0.007). No significant differences were observed in rates of discontinuation due to adverse events (RD, -0.02; 95% CIs, -0.05/0.00), virologic failure (RD, -0.01; 95% CIs, -0.02/0.01), and most common adverse events (GRADE assessment: from “very-low” to “moderate certainty of evidence”)

Conclusion

Starting treatment in naive patients with dolutegravir containing ART has an increased likelihood of achieving viral suppression in the comparison with non-dolutegravir containing ART. The average benefit is particularly evident in those with high baseline viral load.

Klíčová slova:

Research and analysis methods – Research design – Clinical research design – Adverse events – Research assessment – Systematic reviews – Biology and life sciences – Vaccination and immunization – Microbiology – Medical microbiology – Microbial pathogens – Viral pathogens – Immunodeficiency viruses – HIV – HIV-1 – Retroviruses – Lentivirus – Virology – Viral transmission and infection – Viral load – Antivirals – Antiretrovirals – Microbial control – Antimicrobials – Organisms – Viruses – RNA viruses – Medicine and health sciences – Immunology – Public and occupational health – Preventive medicine – Antiviral therapy – Pathology and laboratory medicine – Pathogens – Pharmacology – Drugs – Infectious diseases – Viral diseases – HIV infections – Engineering and technology – Electronics – Comparators


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2019 Číslo 9
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