Optimizing Treatment
Providers may hesitate to change a patient’s regimen, but there may be compelling reasons to do so, including1:
Reducing pill burden
Tolerability and toxicity considerations
Potential drug-drug interactions
Food requirements
Patient access
Barrier to resistance
According to the DHHS guidelines, the fundamental principle of regimen optimization is to maintain viral suppression without jeopardizing future treatment options.1
A regimen’s barrier to resistance is important to consider when choosing a treatment, even if a patient is virally suppressed1
As discussed in the DHHS guidelines, the SWITCHMRK 1 and 2 studies illustrated the importance of considering the possibility of underlying drug resistance before switching therapy in those with virologic suppression. This is particularly important when the new regimen may not include three fully active agents and when the new regimen may have a lower overall barrier to resistance.1
Resistance Is Permanent and Irreversible1
Preexisting resistance is a critical consideration when switching ART in virologically suppressed PLWH
Longer duration of ART is a factor associated with developing resistance.2 In a 2023 survey that included PLWH over the age of 50 or living with HIV for more than 15 years (N=673), the reported average number of years on ART was 23.3
M184V/I is one of the most common resistance mutations associated with treatment failure4:
The M184V/I resistance mutation was present in 31% of samples with any drug resistance mutation in a 2017 analysis from a large US database.4,*
M184V/I reduces susceptibility to some NRTIs >200-fold and increases susceptibility to other NRTIs.5,6
Commercial resistance assays may fail to detect a mutation if it constitutes less than 20% of circulating virus.1 Genotypic identification of resistance mutations, including M184V/I, may be complicated by the reemergence of wild-type virus in the absence of selective pressure from HIV treatment.1,7
*The analysis for 2017 included about 10,000 samples. The number of samples with any drug resistance mutation was not provided.
Before switching therapy in the setting of virologic suppression, it's important to consider underlying resistance and review full ART history, including virologic response.1
How do you approach real-world discussions for switching treatments?
Having conversations around optimizing regimens can help providers and patients who are assessing their options.
Wide Diversity in Clinical Trial Data May Help Inform Treatment Discussions
Increasing the amount of clinical trial data available for specific populations may enhance patient trust8
Increasing diversity and inclusion in clinical trials can provide more generalizable evidence—potentially improving patient trust and advancing health equity. Enhanced patient trust can lead to better retention in care, especially when patients are included as partners.8
While every patient is different, people living with HIV may be inclined towards taking a collaborative approach to shared clinical decision-making.
In a 2010 study, 7 out of 10
patients preferred to engage in shared decision-making when it came to their HIV treatment (n=434)9
DHHS, US Department of Health and Human Services
Reference:
1. Panel on Antiretroviral Guidelines for Adults and Adolescents. Guidelines for the use of antiretroviral agents in adults and adolescents with HIV. Department of Health and Human Services. Updated December 06, 2023. Accessed December 07, 2023. https://
