First-line dolutegravir/lamivudine in HIV-1 infection: lymph node penetration and reservoir decline in a randomized open-label clinical trial
Abstract
Dual antiretroviral therapy with dolutegravir and lamivudine (DTG/3TC) is a recommended first-line regimen for people with HIV, but whether reduced-drug therapy maintains adequate antiviral pressure within lymph node (LN) reservoirs remains uncertain. In the DUALITY clinical trial (EudraCT number 2019-002733-10), the prespecified primary endpoint-change in proviral HIV-1 DNA in peripheral blood CD4 + T cells from baseline to week 48-was similar between participants initiating DTG/3TC or dolutegravir-based triple therapy. Here, we investigated prespecified secondary endpoints comprising viral persistence and antiretroviral drug penetration and distribution in LN using multimodal imaging. In 39 participants undergoing inguinal LN excision at baseline or during the first year of treatment, HIV-1 DNA and RNA were detected by DNAscope/RNAscope and antiretroviral spatial distribution was mapped by mass spectrometry imaging. HIV-1-infected cells declined rapidly after treatment initiation across both treatment groups. Antiretrovirals were widely detected within LN tissue regions containing or adjacent to HIV-positive cells. These findings provide spatial evidence that DTG/3TC reaches LN tissue and HIV-positive cells, extending peripheral blood observations to a key anatomical HIV reservoir.
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BibTeX
@article{rosen2026firstline,
title = {{First-line dolutegravir/lamivudine in HIV-1 infection: lymph node penetration and reservoir decline in a randomized open-label clinical trial}},
author = {Elias P. Rosen and Stephen Bondoc and Lucía Bailón and Lidia Blay and Albert Caballero and Maria C. García-Guerrero and Maria C. Puertas and Igor Moraes-Cardoso and Andrea Vazquez-Escobales and Julià Blanco and Beatriz Mothe and Angela DM Kashuba and Jacob D. Estes and Javier Martinez-Picado and Jose Molto and On behalf of the DUALITY study group and Elias P. Rosen and Stephen Bondoc and Lucía Bailón and Lidia Blay and Albert Caballero and Maria C. García-Guerrero and Maria C. Puertas and Igor Moraes-Cardoso and Andrea Vazquez-Escobales and Julià Blanco and Beatriz Mothe and Angela DM Kashuba and Jacob D. Estes and Javier Martinez-Picado and Jose Molto and Joan Francesc Julian and Yovaninna Alarcón-Soto and Susana Benet and Cristina Miranda and Aroa Nieto and Roger Paredes and Angel Rivero and Sofia Sabato and Ester Aparicio and Christian Brander and Silvia Marfil and Alex Olvera and Edwards Pradenas and Victor Urrea and Yury Desyaterik and Nicole White},
journal = {Nature Communications},
year = {2026},
month = oct,
doi = {10.1038/s41467-026-78190-9},
url = {https://www.nature.com/articles/s41467-026-78190-9},
note = {CC BY-NC-ND 4.0},
}
RIS
TY - JOUR
TI - First-line dolutegravir/lamivudine in HIV-1 infection: lymph node penetration and reservoir decline in a randomized open-label clinical trial
AU - Elias P. Rosen
AU - Stephen Bondoc
AU - Lucía Bailón
AU - Lidia Blay
AU - Albert Caballero
AU - Maria C. García-Guerrero
AU - Maria C. Puertas
AU - Igor Moraes-Cardoso
AU - Andrea Vazquez-Escobales
AU - Julià Blanco
AU - Beatriz Mothe
AU - Angela DM Kashuba
AU - Jacob D. Estes
AU - Javier Martinez-Picado
AU - Jose Molto
AU - On behalf of the DUALITY study group
AU - Elias P. Rosen
AU - Stephen Bondoc
AU - Lucía Bailón
AU - Lidia Blay
AU - Albert Caballero
AU - Maria C. García-Guerrero
AU - Maria C. Puertas
AU - Igor Moraes-Cardoso
AU - Andrea Vazquez-Escobales
AU - Julià Blanco
AU - Beatriz Mothe
AU - Angela DM Kashuba
AU - Jacob D. Estes
AU - Javier Martinez-Picado
AU - Jose Molto
AU - Joan Francesc Julian
AU - Yovaninna Alarcón-Soto
AU - Susana Benet
AU - Cristina Miranda
AU - Aroa Nieto
AU - Roger Paredes
AU - Angel Rivero
AU - Sofia Sabato
AU - Ester Aparicio
AU - Christian Brander
AU - Silvia Marfil
AU - Alex Olvera
AU - Edwards Pradenas
AU - Victor Urrea
AU - Yury Desyaterik
AU - Nicole White
PY - 2026
DA - 2026/10/02
JO - Nature Communications
DO - 10.1038/s41467-026-78190-9
UR - https://www.nature.com/articles/s41467-026-78190-9
AB - Dual antiretroviral therapy with dolutegravir and lamivudine (DTG/3TC) is a recommended first-line regimen for people with HIV, but whether reduced-drug therapy maintains adequate antiviral pressure within lymph node (LN) reservoirs remains uncertain. In the DUALITY clinical trial (EudraCT number 2019-002733-10), the prespecified primary endpoint-change in proviral HIV-1 DNA in peripheral blood CD4 + T cells from baseline to week 48-was similar between participants initiating DTG/3TC or dolutegravir-based triple therapy. Here, we investigated prespecified secondary endpoints comprising viral persistence and antiretroviral drug penetration and distribution in LN using multimodal imaging. In 39 participants undergoing inguinal LN excision at baseline or during the first year of treatment, HIV-1 DNA and RNA were detected by DNAscope/RNAscope and antiretroviral spatial distribution was mapped by mass spectrometry imaging. HIV-1-infected cells declined rapidly after treatment initiation across both treatment groups. Antiretrovirals were widely detected within LN tissue regions containing or adjacent to HIV-positive cells. These findings provide spatial evidence that DTG/3TC reaches LN tissue and HIV-positive cells, extending peripheral blood observations to a key anatomical HIV reservoir.
SN - 2041-1723
ER -