First-line dolutegravir/lamivudine in HIV-1 infection: lymph node penetration and reservoir decline in a randomized open-label clinical trial

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. In this study, Jose Molto and colleagues report data from a randomised open-label clinical trial showing of first-line dolutegravir/lamivudine treatment for HIV-1. They report that the treatment reaches lymph nodes and regions containing HIV-positive cells, which strengthens evidence for antiviral exposure within a key anatomical HIV reservoir.