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New Study Suggests Four Days of ARV Treatment Equal to Seven

Even though HIV-positive people are recommended to take antiretroviral drugs daily, as prescribed, a new trial study has shown that a “four days on, three days off” regimen can still result in a fully suppressed viral load among patients.

By adhering to a proper HIV regimen of antiretroviral medications, HIV-positive people are able to have healthy immune systems, fight off infections, and prevent various cancers. Poor antiretroviral adherence can lead to death and sickness, and can increase the risk of drug resistance.

Despite the importance of a regular HIV regimen, many studies of different groups of HIV-positive individuals in the United States show suboptimal rates of adherence. The optimal level for durable virologic and clinical success is adhering to medication at a rate of at least 95 percent.

A four-day-on, three-day-off routine could help relieve the burden of having to remember to take a pill daily as well as relieve HIV treatment costs. A French pilot study presented at the International Congress on Drug Therapy in HIV infection a few weeks ago set out to determine whether such a weekly treatment routine would compromise viral suppression.

The `four days on, three days off’ antiretroviral regimen kept viral load fully suppressed in 96 percent of people for 48 weeks. The study recruited people whose viral load had been fully suppressed on treatment for a median of four years and did not include people who had begun treatment recently.

Participants were predominantly male (82%) and white (81%). Approximately two-thirds were men who have sex with men. After 48 weeks of follow-up, 96 of 100 participants had maintained viral suppression below 50 copies/ml. Three participants experienced virologic rebound and another discontinued the treatment strategy after four weeks.

The study showed evidence from therapeutic drug monitoring that sufficient blood levels of many antiretroviral drugs persist for several days after dosing, keeping HIV under control even when a patient misses taking a single dose.

While Scientists thought that short interruptions have been able to maintain viral suppression because drug levels persist, the study found that even where drug levels declined to barely-detectable levels by the end of the off-treatment period, viral suppression is maintained.

The study is one of several clinical trials that have investigated whether it is possible to miss two consecutive doses and take a weekend off treatment. The FOTO study found that taking two days off treatment each week maintained viral suppression in people taking efavirenz-based treatment, and a larger study conducted in Uganda found that a four-day treatment was just as effective as continuous treatment.

The BREATHER study in adolescents and young people found that taking two days off efavirenz-based treatment each week was just as likely to keep viral load suppressed as daily treatment, and was beneficial to this demographic as young people have harder time following a daily treatment regimen.

A four-day regimen may suit those with a standard working week who do not wish to think about taking medication over the weekend. In the study, participants were offered two patterns of pill-taking: take medication each day from Monday to Thursday, or take medication each day from Tuesday to Friday. In addition to convenience, the regimen also reduces the cost of treatment.

“In our aging, long-HIV enduring, multi-treated patient cohort, on treatment four days a week and less over 421 intermittent treatment years reduced prescription medicines by 60 percent, sparing 3 million euros on just 94 patients, at the cost of 2.2 intrinsic viral failure per 100 hyper intermittent treatment-years,” the French study concluded. “At no risk of viral escape, maintenance therapy 4 days a week would quasi universally offer 40 percent cuts off current over-prescriptions.”

While it still may be too early to give the go ahead on a four-day-on, three-day-off regimen, this new type of treatment plan could benefit people who have trouble adhering to everyday treatment.

An adherence sub-study, previously presented at the 21st International AIDS Conference (AIDS 2016) in Durban in July 2016, examined adherence by electronic pill bottle caps and self-report in 26 participants. The study found that MEMS caps were opened on exactly four days a week in a median of 44 weeks during the study, but were opened less frequently than four days a week in a median of four weeks during the study. Self-report of adherence during the previous week showed that 21 percent reported taking fewer than 80 percent of their medication on at least one visit and only 6 percent reported 100 percent adherence at one visit.

A larger follow-up study is being planned, which will involve 640 people undergoing the four-day-on, three-day-off routine for two years. Researchers are interested in seeing the long-term effects of such a regimen, including how it could affect a patient emotionally and financially.

The new trial will also include people taking integrase inhibitors in order to reflect newer treatment recommendations, and will follow patients for up to two years to check virological outcomes and impact on side effects and quality of life.