People with HIV are changing their regimens twice as often as a decade ago which may reflect the availability of safer options and the possibility of tailoring regimens to people’s individual needs. At the 19th European AIDS Conference (EACS 2023) in Warsaw, Dr Nicklas Brown of the Chelsea & Westminster Hospital in London highlighted that the most encountered reason for treatment change was drug intolerance, while the least frequent reason was treatment failure. The researchers also calculated toxicity switch rates for each drug, showing vast differences between drugs.
Similarly to ten years ago, in this large cohort of people with HIV the main reason for treatment change was drug intolerance accounting for 37% of all switches. Second to intolerance were drug interactions causing 33% to change their therapy, showing an eight-fold increase compared to ten years ago; less common reasons were treatment simplification at 17% and 3% switched treatment due to inefficacy.
The rise in treatment switches may be explained by the rapid increase in options on the HIV drug market in the last decade. The more frequent switches are not necessarily a cause for concern; on the contrary, they may reflect the availability of better options and the willingness of both clinicians and people with HIV to try different regimens in order to minimise side effects and drug interactions.
The investigators collected medical data on 10,905 people with HIV from four London clinics who changed treatment between August 2021 and January 2022. In this period, 984 regimens were changed adding up to a yearly switch rate of 18%.
Switches due to intolerance
Thirty-seven per cent of all switches were due to intolerance to the drug (toxicity). However, intolerance rates were not equally distributed between the different drugs. Efavirenz, present in Atripla, accounted for a quarter of all intolerance-related switches. Unsurprisingly, three-quarters of all efavirenz-related intolerances were due to central nervous system disturbances and neuropsychiatric side effects. Thirteen per cent of efavirenz-related intolerances were linked to cardiovascular concerns.
The second most frequent intolerance-related switch was from tenofovir disoproxil (TDF), which is present in multiple single-tablet regimens, accounting for 23%. Of those, 39% were due to negative effects on bone health and 57% on kidney function – two well-known TDF-related adverse effects. The high rate of people switching away from TDF may also be due to the availability of a possibly safer alternative – tenofovir alafenamide (TAF).
Dolutegravir, a component of Triumeq, Juluca and Dovato, made its way to the top three of most switched drugs due to intolerance, leading to 13% of all intolerance-related treatment changes. Of those, 60% discontinued dolutegravir due to neuropsychiatric side effects and 17% due to weight gain – again, well-characterised side effects of the drug.
The other more frequently discontinued drugs due to intolerance were abacavir (12% switched mainly due to negative effects on heart health), doravirine (5% switched mostly due to neuropsychiatric side effects), and tenofovir alafenamide (5%).
Based on these switch rates due to drug intolerance, the researchers calculated the rate of switching each drug due to toxicity. For every 1000 people taking efavirenz per year, 87 people stopped taking the drug. Similarly, 57 in every 1000 people per year switched away from abacavir, 33 in 1000 people switched away from dolutegravir and 23 in 1000 people switched from doravirine. For all other drugs, the switch rate did not exceed 20 per 1000 people per year.
Other reasons for treatment switch
The second most common reason accounting for 33% of all switches in this cohort were drug interactions which may reflect the ageing of many people with HIV. With the advancement of age, treatment for other chronic health conditions may increase the likelihood of unwanted drug-drug interactions. One example is the ability of boosters, such as ritonavir and cobicistat, to increase the concentrations of many other medications. Fortunately, most of the newer HIV drugs come with fewer interactions.
Treatment simplification was the third most common reason accounting for 17% of all switches. The most frequently observed simplification was switching from Triumeq to Dovato. This is a switch from a three-drug pill containing dolutegravir, lamivudine and abacavir to a two-drug pill with the first two molecules but without abacavir.
Encouragingly, the least frequent reason for treatment switch was inefficacy representing only 3% of all switches.
Corteville S et al (presenter Brown N). Rates and reasons for antiretroviral switches with implicated drug associations: a post-COVID 10-year comparison. 19th European AIDS Conference, Warsaw, abstract RA2.O8, 2023.