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
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).
Authors
- Kerri J. Penrose (ORCID: https://orcid.org/0000-0002-0370-5140)
- Jessica M. Fogel (ORCID: https://orcid.org/0000-0003-3143-9000)
- Amber Moser
- Beatriz Gilda Jegerhorn Grinsztejn (ORCID: https://orcid.org/0000-0003-3692-5155)
- John W. Mellors (ORCID: https://orcid.org/0000-0002-3737-9742)
- Michael Seisa
- Christos J. Petropoulos (ORCID: https://orcid.org/0000-0001-5496-8090)
- Raphael J. Landovitz (ORCID: https://orcid.org/0000-0002-1442-714X)
- Marybeth McCauley
- James F. Rooney (ORCID: https://orcid.org/0000-0003-3261-0711)
- Hannah P. Moore (ORCID: https://orcid.org/0000-0001-7566-4213)
- Elias K. Halvas (ORCID: https://orcid.org/0000-0002-4890-1209)
- Javier Valencia-Huamaní
- Susan H. Eshleman (ORCID: https://orcid.org/0000-0002-4587-791X)
- Mark A. Marzinke (ORCID: https://orcid.org/0000-0003-1670-8786)
- Urvi M. Parikh (ORCID: https://orcid.org/0000-0002-4016-0629)
- Alex R. Rinehart
- Lydia Soto-Torres
- Amelia L Price
- Zhe Wang (ORCID: https://orcid.org/0000-0003-0786-9887)
Institutions
- Family Health International 360 (US)
- National Institutes of Health (US)
- APLA Health (US)
- Johns Hopkins University (US)
- University of Pittsburgh (US)
- Asociación Civil Impacta Salud y Educación (PE)
- Johns Hopkins Medicine (US)
- Fred Hutch Cancer Center (US)
- Triangle (US)
- Ideaya Biosciences (United States) (US)
- National Institute of Allergy and Infectious Diseases (US)
- Gilead Sciences (United States) (US)
- Instituto Evandro Chagas (BR)
Publication Details
- Journal
- Open Forum Infectious Diseases
- Published
- 2025-10-13
- DOI
- https://doi.org/10.1093/ofid/ofaf645
- Primary Topic
- HIV/AIDS drug development and treatment
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- Gilead Sciences
- ViiV Healthcare
- National Institutes of Health
- National Institute of Mental Health
- National Institute of Allergy and Infectious Diseases