Sustained HIV Suppression With Co-formulated Tenofovir Disoproxil Fumarate/Lamivudine/Dolutegravir in a Person With Transmitted Dolutegravir Resistance and Pretreatment Resistance to Lamivudine: a Case Report From HPTN 083.

Publisher: Published by Oxford University Press on behalf of the Infectious Diseases Society of America Country of Publication: United States NLM ID: 101637045 Publication Model: eCollection Cited Medium: Print ISSN: 2328-8957 (Print) Linking ISSN: 23288957 NLM ISO Abbreviation: Open Forum Infect Dis Subsets: PubMed not MEDLINE

Original Publication: Cary, NC : Published by Oxford University Press on behalf of the Infectious Diseases Society of America, [2014]-

Integrase strand transfer inhibitors (INSTIs) are recommended in most first-line HIV treatment regimens. We describe a participant in a clinical trial with transmitted INSTI resistance. The participant had no history of INSTI use and had no evidence of INSTI exposure prior to HIV acquisition. Treatment with tenofovir disoproxil fumarate, lamivudine (3TC), and dolutegravir (DTG) was started 3 weeks after HIV diagnosis. Viral suppression was achieved within a year and was sustained for >3 years on treatment. Retrospective HIV genotyping of a pretreatment sample detected major resistance mutations in 3 drug classes, with predicted high-level resistance to DTG and 3TC. HIV phenotyping confirmed that the transmitted virus had DTG and 3TC resistance but retained susceptibility to DTG at higher drug concentrations. Pharmacologic testing indicated that the DTG concentrations observed in this case were sufficient to overcome the effects of 2 major baseline INSTI resistance mutations (G140S and Q148H).
(© The Author(s) 2025. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Potential conflicts of interest. None of the authors has a commercial or other association that might pose a conflict of interest, with the following exceptions: MS and CP are employees of Monogram Biosciences. RJL has served on a scientific advisory board for Merck and has received honoraria from ViiV (financial interest) and Redqueen Therapeutics. ARR is an employee of ViiV Healthcare. JFR is an employee and stockholder of Gilead Sciences.

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P30 AI094189 United States AI NIAID NIH HHS

Keywords: HIV; INSTI; TLD; drug resistance; transmitted

Date Created: 20251103 Date Completed: 20251103 Latest Revision: 20260307

20260307

PMC12575077

10.1093/ofid/ofaf645

41180007