Some people living with HIV can maintain viral suppression with just four consecutive days of antiretroviral therapy, leading to considerable cost savings, according to a study presented at the 10th International AIDS Society Conference on HIV Science, which took place this week in Mexico City.

The evolution of antiretroviral therapy from three-times-daily dosing with complex food requirements to a single daily pill has been a remarkable medical achievement, but many people still find it hard to adhere to daily therapy or don’t want to be reminded about HIV every day.

Prior studies have clearly shown that “drug holidays” that involve interrupting treatment for weeks or months are dangerous. This allows the virus to come surging back, damaging the immune system and triggering inflammation that can contribute to a host of non-AIDS conditions—even if therapy is resumed before the CD4 count drops. It can also lead to drug resistance. But less is known about treatment breaks lasting a few days in the era of more potent drugs with a higher barrier to resistance.

Roland Landman, MD, of Université Paris Diderot, and fellow investigators with the QUATUOR study asked whether intermittent maintenance therapy could improve the convenience and tolerability and lower the cost of antiretroviral treatment for people who have achieved viral suppression on a standard regimen.

This open-label randomized Phase III trial included 636 participants from multiple centers in France who enrolled between September 2017 and January 2018. More than 80% were men, and the median age was 49. About 80% were from Europe and 15% from sub-Saharan Africa. At baseline, they a median CD4 count of nearly 700, but about half had fallen below 300 in the past.

At the start of the study they had undetectable viral load (below 50 copies) on a three-drug regimen containing an integrase inhibitor (48%), non-nucleoside reverse transcriptase inhibitor (NNRTI; 47%) or protease inhibitor (6%). More than 70% paired this with tenofovir disoproxil fumarate/emtricitabine (the drugs in Truvada) or tenofovir alafenamide/emtricitabine (the drugs in Descovy). They had been on antiretroviral therapy for a median of seven years, with viral suppression for six years, and they had no evidence of drug resistance.

Participants were randomly assigned to either stay on their daily regimen or take the same medications for four consecutive days followed by three days off.

At 48 weeks, both groups had a high rate of continued viral suppression: 95.6% in the four-day group and 97.2% in the daily group. This difference was not statistically significant, meaning it could have been driven by chance. There was also no significant difference in the occurrence of viral “blips,” or single detectable viral load measurements, in the two groups. These findings demonstrate that the four-days-on/three-days-off schedule was noninferior to, or as good as, the seven-day schedule.

Just six people (1.9%) in the four-day group and four of those (1.3%) in the daily group experienced virological treatment failure. Of these, three and one, respectively, developed resistance mutations. No one taking a protease inhibitor had virological failure, while three people taking NNRTIs in both treatment groups did so. Among those taking integrase inhibitors, there were three virological failures in the four-day group and one in the daily group. Treatment failure was not associated with lowest-ever CD4 count, CD4/CD8 ratio, duration of viral suppression or a history of past virological failure.

Treatment was well tolerated in both groups. The frequency of all adverse events (72.3% and 73/9%) and severe adverse events (7.9% and 9.4%) was similar in both groups. Only one person in the four-day group discontinued treatment because of an adverse event (depression). There were two deaths in the four-day group and none in the daily group, but neither was considered treatment related (sudden cardiac death and lung cancer).

The researchers also plan to evaluate other measures including adherence, drug concentrations, inflammation and immune activation biomarkers, viral load in the semen—which has implications for transmission risk—and quality of life.

As far as cost, taking meds four days a week instead of seven leads to a direct cost reduction of 43% in high-income countries, and could allow more people to access treatment in low-income countries, Landman said.

 

Click here to read the study abstract.