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Meta-Analysis Sees Good Results With Dolutegravir-Based Dual Maintenance
  16th European AIDS Conference, October 25-27, 2017. Milan
Mark Mascolini
A 14-study meta-analysis of maintenance therapy with dolutegravir monotherapy or dual therapy found better virologic and resistance results with dual-therapy maintenance [1]. In 7 dual-drug studies analyzed, no resistance to this potent integrase inhibitor emerged, but one nonnucleoside mutation developed in a dolutegravir/rilpivirine study.
Switching to dolutegravir/rilpivirine dual therapy proved noninferior to continued 3- or 4-drug therapy in a recently reported randomized trial [2]. Dual therapy incorporating the integrase inhibitor has also been tested for first-line treatment. Researchers at the University Hospital Geneva and the University Hospital Bern conducted a meta-analysis to produce precise estimates of virologic failure rates with dolutegravir-based maintenance monotherapy and dual therapy and to identify risk factors for failure.
The Geneva team searched electronic databases and meeting abstracts for randomized controlled trials, single-arm trials, or cohort studies with at least 5 participants. All study participants were adults with an undetectable viral load switching to dolutegravir-based maintenance. Studies had to report virologic outcomes with or without resistance data. The researchers used random-intercept logistic meta-regression to estimate pooled proportions of virologic failures and 95% confidence intervals (CI).
The investigators identified 941 potentially relevant references, assessed 31 full manuscripts, and selected 14 studies to analyze. Seven monotherapy studies included 220 participants, and 7 dual-therapy studies included 951 participants. One study in each set was a randomized controlled trial. Second drugs in dual-therapy trials were lamivudine, rilpivirine, and unboosted atazanavir. Age averaged 47 years across the 14 studies, 13 studies took place in Europe, 27% of participants were women, and nadir CD4 count averaged 300.
With dolutegravir monotherapy, pooled 24- and 48-week virologic failure rates were 3.18% and 8.91%. With dolutegravir dual therapy, pooled 24- and 48-week failure rates were much lower and changed less over time--0.32% and 0.41%. Univariate logistic regression identified only dual therapy versus monotherapy as a predictor of virologic failure at 24 weeks, with a 90% lower failure risk with dual therapy (odds ratio [OR] 0.10, 95% CI 0.03 to 0.38, P < 0.001). Neither age nor gender emerged as a failure risk factor in this analysis.
With dolutegravir monotherapy, integrase mutations emerged in 7 of 14 virologic failures. With dual therapy, nonnucleoside resistance (K101K/E) emerged in 1 of 3 dolutegravir/rilpivirine failures, and no resistance emerged with dolutegravir/lamivudine (1 virologic failure) or dolutegravir/atazanavir (no virologic failures).
The Geneva investigators noted that large randomized trials of dolutegravir maintenance are under way. They urged study of dolutegravir-based dual therapy in subgroups such as women, people with the M184V lamivudine/emtricitabine mutation, and people with multidrug-resistant virus.
1. Buzzi M, Wandeler G, Anderegg N, et al. Dolutegravir-based maintenance therapy in HIV-infected patients: systematic review and meta-analysis.16th European AIDS Conference. October 25-27, 2017. Milan. Abstract PS1/2.
2. Llibre JM, Hung CC, Brinson C, et al. Phase III SWORD 1&2: switch to DTG+RPV maintains virologic suppression through 48 wks. CROI 2017. February 13-16, 2017. Seattle. Abstract 44LB. http://www.natap.org/2017/CROI/croi_11.htm