Background
Since the beginning of HIV treatment, changes in the use of antiretroviral (ARV) drugs have often led to changes in HIV resistance mutation patterns. The integrase inhibitor (INI) class has benefited from many developments: first raltegravir (RAL) and elvitegravir (EVG), followed by dolutegravir (DTG), cabotegravir (CAB) and bictegravir (BIC). The aim of this study was to evaluate changes in resistance levels and profiles to INIs in relation to changes in the use of different INIs over 17 years in people living with HIV (PLWHIV) treated with ARVs and in virological failure.
Methods
We analyzed in parallel the use of the different INIs in ARV-treated PLWHIV in an academic center (Pitié Salpêtrière Hospital, Paris, France, 2007-2023) and the HIV INI resistance profiles in RNA (2008-2023; analyzed using the latest ANRS-MIE algorithm v33).
Results
The total number of PLWHIV on ARV treatment was 3 100 people in 2007 and has increased to 4 364 people in 2023. During this period (2007-2023), the proportion of INI users among the total number of ARV-treated PLWHIV increased from 3.3% (n=102/3 100) to 72.2% (n=3 152/4 364).
For the whole cohort, there was an increase (3.2% in 2007 to 21.5% in 2013) followed by a decrease (to 4.4% in 2023) in the use of RAL (Figure 1A). The same usage profile was observed for EVG (0.03% in 2007 to 15.7% in 2019 and 2.4% in 2023). Over the period of their use, DTG and BIC continued to increase (0.03% in 2007 to 39.3% for DTG and 2.0% in 2019 to 28.1% in 2023 for BIC). The use of CAB is reported in 2017 (0.07%) and represents 3.8% in 2023.
The number of HIV RNA integrase genotypic resistance tests increased from 97 at the start of testing in 2008 up to 365 in 2023. During the first 3 years of INI use, a dramatic level of resistance was observed. The resistance rate decreased significantly over time from 45-50% in 2008 for all INIs, with similar resistance rates in 2023 for DTG, CAB and BIC (5.1%), but remained high for RAL (10.3%) and EVG (11.0%), respectively (Figure 1B).
Conclusions
The INI class of ARVs is now widely used and, finally, large increase in use within this class do not increase the resistance over time in ARV-treated PLWHIV with virological failure. The very high level of INI resistance at the beginning of INI use was probably due to the use of RAL in combination with other ARVs that were not fully sensitive during the first 3 years. The INIs used today have a higher genetic barrier that limits the emergence of resistance mutations.