# 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

**Authors:** Hannah P Moore, Jessica M Fogel, Mark A Marzinke, Elias K Halvas, Urvi M Parikh, John W Mellors, Kerri J Penrose, Michael Seisa, Christos Petropoulos, Amelia L Price, Amber Moser, Zhe Wang, Marybeth McCauley, Javier Valencia-Huamaní, Alex R Rinehart, James F Rooney, Lydia Soto-Torres, Beatriz Grinsztejn, Raphael J Landovitz, Susan H Eshleman

PMC · DOI: 10.1093/ofid/ofaf645 · 2025-10-15

## TL;DR

A person with HIV who had resistance to some drugs still achieved long-term virus suppression using a treatment including dolutegravir.

## Contribution

Demonstrates sustained HIV suppression despite pretreatment resistance to dolutegravir and lamivudine.

## Key findings

- Viral suppression was achieved within a year and maintained for over three years.
- Pharmacologic testing showed DTG concentrations were sufficient to overcome resistance mutations.
- The transmitted virus retained susceptibility to DTG at higher drug concentrations.

## Abstract

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).

## Linked entities

- **Chemicals:** tenofovir disoproxil fumarate (PubChem CID 5486830), lamivudine (PubChem CID 60825), dolutegravir (PubChem CID 54726191)

## Full-text entities

- **Chemicals:** Tenofovir Disoproxil Fumarate (MESH:D000068698), 3TC (MESH:D019259), DTG (MESH:C562325)
- **Species:** Homo sapiens (human, species) [taxon 9606], Human immunodeficiency virus 1 (no rank) [taxon 11676]
- **Mutations:** G140S, Q148H

## Figures

2 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12575077/full.md

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Source: https://tomesphere.com/paper/PMC12575077