# Evaluation of HIV-1 DNA resistance evolution in highly treatment-experienced and multi-resistant individuals under suppressive antiretroviral therapy: a longitudinal study from the PRESTIGIO Registry

## TL;DR

This study found that HIV drug resistance in DNA remains stable in patients with suppressed virus, except for specific mutations that decline when certain drugs are not used.

## Contribution

Demonstrates that HIV-1 DNA resistance mutations are largely stable under suppressive therapy, with notable exceptions like M184V and NNRTI resistance.

## Key findings

- HIV-1 DNA levels remained stable over time in virologically suppressed individuals.
- NNRTI resistance mutations significantly decreased in individuals not receiving NNRTI drugs.
- M184V mutations declined over time, especially in those on 3TC-/FTC-sparing regimens.

## Abstract

This study aimed to clarify whether resistance detected in HIV-1 DNA might evolve in virologically suppressed highly treatment-experienced (HTE) individuals with multidrug resistance (MDR).

Twenty-three virologically suppressed HTE MDR individuals from the PRESTIGIO Registry with two longitudinal samples available under virological suppression at two different time points (T0−T1) were analysed. HIV-1 DNA levels were quantified using droplet digital PCR, and resistance was assessed through next-generation sequencing (NGS) set at 5%. Mutational load was also evaluated.

At T0, individuals had been virologically suppressed for a median time of 3 years (IQR 3–5) under a salvage regimen, mostly containing dolutegravir (95.7%) and/or darunavir (69.6%). The median HIV-1 DNA level was 2588 copies/106 CD4+ cells at T0 and remained stable at T1 (2322 copies/106 CD4+ cells; P = 0.831). Individuals with at least ≥3-class resistance in HIV-1 DNA were 20 (87.0%) at T0 and 18 (78.2%) at T1 (P = 0.607). In those receiving NNRTI-sparing treatment (52.2%), the number of NNRTI major resistance mutation (MRM) significantly decreased over time (T0, 2 [1–3]; T1, 0 [0–1]; P = 0.027). No significant temporal differences in the number of PI, NRTI and integrase strand transfer inhibitor (INSTI) MRM were found. Specific MRM, such as M184V, decreased over time, particularly in individuals who were receiving a 3TC-/FTC-sparing salvage regimen or with a T0 mutational load of <1000 copies/106 CD4+ cells.

Over a year, HIV-1 DNA MRM generally remained unchanged in suppressed HTE MDR people with HIV (PWH) except for a significant decline in M184V and a reduction of NNRTI resistance in the absence of NNRTI pressure.