Dataset Information

Comparative efficacy and safety and dolutegravir and lamivudine in treatment naive HIV patients.

ABSTRACT:

Objective

Compare the efficacy and safety of the 2-drug antiretroviral therapy regimen dolutegravir + lamivudine (DTG + 3TC) with traditional 3-drug regimens in treatment-naive patients with HIV-1.

Design

Data from double-blind, randomized controlled trials of at least 48 weeks' duration in treatment-naive patients with HIV-1 identified by systematic review were evaluated using a Bayesian network meta-analysis methodology.

Methods

The primary outcome was virologic suppression at Week 48 for 3-drug regimens versus DTG + 3TC (also analyzed in patient subgroup with baseline viral load >100 000 RNA copies/ml). Secondary outcomes included CD4 cell count change from baseline and safety (adverse events, serious adverse events, and drug-related adverse events) at Week 48.

Results

The network contains 14 unique regimens from 14 randomized controlled trials based on data from 10 043 patients. The proportional difference for viral suppression at 48 weeks for DTG + 3TC versus the other 13 regimens included in the network ranged from -2.7% (-11.0, 5.6%) versus DTG + tenofovir alafenamide/emtricitabine (FTC) to 7.3% (0.6, 13.8%) versus efavirenz + tenofovir disoproxil fumarate/FTC. DTG + 3TC was found to be significantly better than efavirenz + tenofovir disoproxil fumarate/FTC and similar to all other regimens analysed in terms of viral suppression at 48 weeks. With regard to other outcomes (CD4, adverse event, serious adverse event, drug-related adverse events) at 48 weeks, DTG+3TC was broadly similar to all regimens analysed.

Conclusion

This network meta-analysis demonstrates similar efficacy and safety outcomes over 48 weeks with DTG + 3TC compared with traditional 3-drug antiretroviral therapy regimens.

SUBMITTER: Radford M

PROVIDER: S-EPMC6686958 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BACKGROUND:Network meta-analyses (NMAs) provide comparative treatment effects estimates in the absence of head-to-head randomized controlled trials (RCTs). This NMA compared the efficacy and safety of dolutegravir (DTG) with other recommended or commonly used core antiretroviral agents. METHODS:A systematic review identified phase 3/4 RCTs in treatment-naïve patients with HIV-1 receiving core agents: ritonavir-boosted protease inhibitors (PIs), non-nucleoside reverse transcriptase inhibitors (NNRTIs), or integrase strand inhibitors (INSTIs). Efficacy (virologic suppression [VS], CD4+ cell count change from baseline) and safety (adverse events [AEs], discontinuations, discontinuation due to AEs, lipid changes) were analyzed at Week 48 using Bayesian NMA methodology, which allowed calculation of probabilistic results. Subgroup analyses were conducted for VS (baseline viral load [VL] ≤/> 100,000copies/mL, ≤/> 500,000copies/mL; baseline CD4+ ≤/>200cells/μL). Results were adjusted for the nucleoside/nucleotide reverse transcriptase inhibitors (NRTI) combined with the core agent (except subgroup analyses). RESULTS:The NMA included 36 studies; 2 additional studies were included in subgroup analyses only. Odds of achieving VS with DTG were statistically superior to PIs (odds ratios [ORs] 1.78-2.59) and NNRTIs (ORs 1.51-1.86), and similar but numerically higher than other INSTIs. CD4+ count increase was significantly greater with DTG than PIs (difference: 23.63-31.47 cells/μL) and efavirenz (difference: 34.54 cells/μL), and similar to other core agents. INSTIs were more likely to result in patients achieving VS versus PIs (probability: 76-100%) and NNRTIs (probability: 50-100%), and a greater CD4+ count increase versus PIs (probability: 72-100%) and NNRTIs (probability: 60-100%). DTG was more likely to result in patients achieving VS (probability: 94-100%), and a greater CD4+ count increase (probability: 53-100%) versus other core agents, including INSTIs (probability: 94-97% and 53-93%, respectively). Safety outcomes with DTG were generally similar to other core agents. In patients with baseline VL > 100,000copies/mL or ≤ 200 CD4+cells/μL (18 studies), odds of achieving VS with DTG were superior or similar to other core agents. CONCLUSION:INSTI core agents had superior efficacy and similar safety to PIs and NNRTIs at Week 48 in treatment-naïve patients with HIV-1, with DTG being among the most efficacious, including in patients with baseline VL > 100,000copies/mL or ≤ 200 CD4+cells/μL, who can be difficult to treat.

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