The genetic barrier to resistance of dolutegravir: a systematic review and meta-analysis for 11,798 patients.
PHE ePoster Library. Liew Z. 09/10/18; 221406; 118
Ms. Zara Liew
Ms. Zara Liew
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Abstract Background:The integrase inhibitor dolutegravir (DTG) is being introduced into low- and middle income countries (LMICs). It's co-formulation with tenofovir (TDF) and lamivudine (3TC) will cost a median of $75 per person-year. To inform about implications of the scale-up of DTG use in such treatment-diverse populations, we analyse the drug resistance of DTG when used in triple, dual and monotherapy in naïve, switch and treatment-experienced patients. Methods:We searched for randomised controlled trials and prospective and retrospective cohort studies that reported the virological failures or treatment-emergent resistance mutations. We searched Embase and MEDLINE for reports published from Jan 1, 2010 to Mar 23, 2018. A meta-analysis of absolute risks with Mantel-Haenszel methods and random effects model was used to compare the occurrence of treatment-emergent resistance mutations in patients on DTG versus other treatments. Results:The study included 27 clinical trials and 22 cohort studies with a total of 11,798 patients. Treatment-emergent resistance mutations were greater in the monotherapy group compared to those on triple or dual therapy. There was no significant difference in mutations between patients recieving DTG versus other treatments, except in one subgroup. Treatment-experienced patients who received DTG as a triple therapy had significantly less mutations than those who received the comparator (p= < 0.0001). Conclusion:DTG dual and triple therapy has little resistance across all patient populations assessed. This is finding is particularly significant in LMICs where within 5 years up to 15 million people could be on DTG and where viral genotypic testing is rarely performed.
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