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

Matthew Radford, Daniel C Parks, Shannon Ferrante, Yogesh Punekar, Matthew Radford, Daniel C Parks, Shannon Ferrante, Yogesh Punekar

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.

Figures

Fig. 1
Fig. 1
(a) Preferred Reporting Items for Systematic Reviews and Meta-Analyses flow chart; (b) network of treatment comparisons contained within the randomized controlled trials.
Fig. 2
Fig. 2
Mean difference (%) in the proportion of (a) all patients, and (b) patients with baseline viral load more than 100 000 RNA copies/ml achieving virologic suppression at Week 48 with 3-drug regimens (comparator) versus dolutegravir + lamivudine (fixed-effects model).
Fig. 3
Fig. 3
CD4+ change from baseline at Week 48 with dolutegravir + lamivudine versus 3-drug regimens (fixed-effects model).
Fig. 4
Fig. 4
(a) Adverse events, (b) serious adverse events, and (c) drug-related adverse events by Week 48 with 3-drug regimens versus dolutegravir + lamivudine (fixed effects model).

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