Quality of life viral and Immunological dynamics in patients with effectively suppressed HIV who switch second or furtherline cART to a Once daily High genetic barrier Antiretroviral regimen of boosted darunavir and dolutegravir

In the last two decades combination antiretroviral therapy (cART) has brought a
substantial decrease in the death rate due to HIV-1 infection, changing it from
a rapidly lethal disease into a chronic manageable condition. Unfortunately
challenges remain. Due to a combination of adherence issues, whether or not
related to toxicity, and the use of regimens with a low genetic barrier to
development of antiviral resistance, viral rebound induced by drug resistant
viruses is regularly observed. After each therapy failure, follow-up regimens
tend to become more complex characterised by a higher pill burden, multiple
dosing and increased toxicity which are all at odds with long-term adherence
and augment the burden of disease. The main focus of HIV treatment was to
improve life expectancy, treat comorbidities and improve quality of life (QOL)
through immune recovery by suppression of HIV, but in recent years the scope
has broadened and other factors, such as long-term toxicity and intake schemes
are becoming more prominent. Treatment simplification has been shown to be a
major determinant for QOL and is expected to have positive effects on cART
adherence and as such reduces the risk for drug resistance development and
subsequent treatment failure. Combination of the newly licensed dolutegravir
with the most active boosted protease inhibitor darunavir will make once daily
therapy once again accessible for patients on second or further line therapy.
This high genetic barrier combination is becoming common practice in the
Netherlands. We aim to study quality of life and viral and immunological
dynamics in these patients who change or have changed from suppressive second
or further line therapy to dolutegravir and boosted darunavir.

The primary objective is to investigate quality of life after switch to a
combination therapy including boosted DRV and DTG. Secondary objectives are to
investigate 1) the residual viral replication, 2) level of virus production
from infected cells (reservoir), 3) number of HIV virological failures and 4)
immunological markers. 5) Evaluating dolutegravir and darunavir drug levels
(adherence). 6) Development of resistance mutations against dolutegravir or
darunavir.

An observational cohort-study of 24 weeks in subjects on second or further line
therapy with suppressed viremia that undergo or have undergone a treatment
change (based on clinical reasons) towards a dual regimen with two high genetic
barrier drugs. For the study, extra blood samples will be taken and digital
quality of life questionnaires will be performed. After explicit consent also
retrospective inclusion of patients meeting the inclusion criteria AND with
blood stored at baseline, wk2 and/or wk4 and wk12 is also allowed (depending on
timing of inclusion).

The study will follow the normal visits to the outpatient clinic after a
therapy switch and therefore no extra visits are involved. An additional
volume of blood will be taken at 5 time points during regular blood draws
Normal clinical practice regarding clinical history taking, physical
examination, viral load assessment, CD4 count measurements and safety controls
in blood to monitor potential side-effects is followed. The additional burden
lies in answering the quality of life questionnaires and the additional volume
of blood that is taken during routine visits for the virological and
immunological analyses.