The study is aimed at the feasibility of changing antiretroviral drugs from daily to four days a week. The results showed that viral suppression rates were similar for both regimens, but higher rates of virological failure and resistance were observed in the group administered four days a week.
Previous studies have had promising results with three pills** for five and four consecutive days per week. Researchers believe that this "intermittent administration" can reduce *** and cost, making it more convenient for people living with HIV. However, some experts are critical of the long-term persistence of intermittent dosing and the risk of leading to drug resistance. Although intermittent and daily dosing were studied to have similar rates of viral suppression, intermittent dosing appears to slightly increase the risk of failure** in the long term, and risk and benefit assessments remain questionable.
Intermittent dosing has never been attempted in a double** before. Although dual ** (the use of two antiretroviral drugs instead of three) has been shown to be equally effective, some experts remain pessimistic. Combining these two concepts is a rather bold idea.
Research
The research process involved several HIV** centres in France, where a total of 433 people living with HIV were recruited and lasted from June 2021 to January 2022. Participants need to be serially undetectable for more than a year and have no resistance to the drugs in the dual** regimen. They were then randomly assigned to two groups: 219 people in the intermittent dosing group (four consecutive days a week) and 214 people in the daily dosing group. Intermittent** regimens must maintain a similar virologic failure rate to daily dosing for one year to be considered equally effective.
Of the participants, 66% took dovato, 34% took juluca, and only 3 took darunavir plus lamivudine. Other characteristics (e.g., age, time after diagnosis, and time undetectable by the virus) were similar between the two groups.
Viral inhibition rates are similar
After one year, there was little difference in viral suppression between the two dosing regimens. Of the participants administered intermittently, 945% of people still couldn't detect the virus, compared to 96 percent of participants who took the drug daily3%。
Intermittent dosing** has a high failure rate
Eight cases of failure occurred in the intermittent dosing group, compared to none in the daily dosing group. Studies have not yet reached "non-inferiority", i.e. they have failed to demonstrate that intermittent dosing is as effective as daily dosing. Of the 8 ** failures of intermittent dosing, 6 occurred in patients taking Dovato. This is not surprising because lamivudine has a short half-life and a relatively low resistance barrier.
Most losers still have a sufficient amount of the drug in their blood at the time of measurement, but this does not rule out that they experienced a brief period of drug concentration deficiency before the failure.
*The time span of failure ranges from 4 weeks to 36 weeks. Most of the time, although the virus can be detected, the viral load is still less than 200 copies (unable to spread). But two of the participants had viral loads of about 1,000 copies.
Resistance to intermittent administration
Of the 8 participants who failed intermittent dosing**, 4 developed resistance to the current**. Two of them had developed resistance to the drug before the study. One of the four drug-resistant cases had low levels of the drug in their blood, which may have contributed to drug resistance.
In the end, 7** participants who failed were switched to daily dosing, and another was treated with long-acting cabotegravir plus lilpivirine (vocabria and rekambys) and reached an undetectable state.
Summary
Studies exploring intermittent dosing have demonstrated the efficacy of contemporary three-drug HIV**. However, intermittent dosing of dual ** seems to be beyond what is possible and reasonable. Double** is already a way to reduce the burden of drugs, and in this case, it is unreasonable to further reduce drug exposure and increase the risk of failure. The study also suggests that double** may be less tolerant of skipping and missing doses.