Four-days-on, three-days-off HIV treatment - HIV update, 1 November 2023

Four-days-on, three-days-off HIV treatment

All HIV treatments which are taken as tablets are normally taken seven days a week – usually once a day, although a few need to be taken twice a day. But for several years now, doctors in France have been trying different dosing regimens, such as only taking the tablets four days a week, although not all experts agree this is a safe strategy.

A possible advantage of taking medication this way is that it may reduce any harmful effects of the medication, such as side effects and long-term impacts on the kidneys, bones and so on. The disadvantage may be that it slightly increases the risk of treatment failure.

Doctors at one of Paris’s largest HIV clinics say that now one in seven of their patients are taking their HIV medication this way. And a larger group are taking a combination of two antiretroviral drugs (rather than three) – which is another way to reduce the burden of medications.

So far, it seems that as many people on the intermittent drug regimen are as undetectable as people taking their medication seven days a week. And they haven’t needed to use hospital facilities more often, while the cost of medication was reduced by more than half.

A separate French study looked specifically at this four-days-a-week strategy for people taking a combination of two antiretroviral drugs. In this study, the majority of people were taking dolutegravir plus lamivudine (Dovato) and most of the other people were on dolutegravir plus rilpivirine (Juluca). Previous studies tested a four-days-a-week strategy in people taking a standard combination of three drugs.

They were randomly assigned either to take their medication four days a week or seven days a week. After one year, the difference in the rates of viral suppression between the dosing schedules was negligible. Of those assigned to intermittent dosing, 94.5% maintained an undetectable viral load compared to 96.3% of the participants who took their medication daily.

But there were eight cases of treatment failure in the intermittent group and none in the daily group. Four of those with treatment failure had resistance to their current treatment.

So while a four-days-a-week strategy might be possible with a combination of three antiretroviral drugs, it does not seem safe with a combination of two drugs. The study also suggests that two-drug combinations – especially Dovato – might be less forgiving of skipped and missed doses.  

Post-traumatic stress disorder

Post-traumatic stress disorder (PTSD) occurs when a person has experienced a traumatic event and is unable to process the shock properly. Such events could include a serious injury, illness, or accident; being abused or sexually assaulted; multiple bereavements; being rejected because of stigma or prejudice; war, political violence or forced migration.

PTSD can cause flashbacks, nightmares, a powerful sense of dread, nervousness and an avoidance of reminders of the event. Memories of the event can also be affected and people often say they have difficulty concentrating as they are easily distracted by worries.

As very little research on this topic has been done among people with HIV in European countries, HIV clinicians in Amsterdam included questions about possible symptoms of PTSD in questionnaires that they asked their patients to complete.

They found that 13% had symptoms of PTSD. This is higher than in the general population (in global surveys, 4% of people who have experienced a traumatic event), and is comparable to figures for people with cancer (15%), people with chronic pain (10%) and military veterans (14%).

Younger people living with HIV were more likely to have symptoms than older people.

The researchers say that healthcare providers should consider including screening for post-traumatic stress disorder as a routine part of clinical care for all people with HIV. Even if clinicians are not trained in mental health, they can work with the person living with HIV to identify preferred follow-up actions, such as referral to peer support or professional mental health services.

Changing treatment

There are a number of reasons why you may need to – or want to – change your HIV treatment. All drug regimens come with different pros and cons and there may be more options now than when the drugs you are currently on were chosen.

Doctors at the Chelsea & Westminster Hospital in London say that each year, 18% of their patients change their HIV treatment. This is roughly double the rate seen a decade ago. This is probably because there are now more alternatives than before, including drugs which are safer and easier to take.

• 37% of drug switches were because of side effects and intolerance to the medication. The three medications which people most commonly switched from were efavirenz (most often because of problems with concentration, mood swings or sleep disturbance), abacavir (usually because of its impact on heart health) and dolutegravir (for the same reasons as efavirenz, or because of weight gain).
• 33% of switches were because of drug interactions – when taking drugs together risks altering the effectiveness or side effects of the medication. While today’s HIV medications generally have fewer problems with drug interactions than older HIV medications, an increasing number of people living with HIV need to take treatment for other health conditions, so drug interactions are often a concern.
• 17% of switches were in order to simplify an HIV treatment regimen, for example by changing from three drugs to two drugs.
• Only 3% of switches were because the treatment was not working – because it failed to suppress the virus to undetectable levels.

COVID-19 and cardiovascular health

People with HIV who were diagnosed with COVID-19 are at higher risk of having a major cardiovascular event in the following year compared to other people with HIV, a Spanish study has found.

Among 1000 people with HIV who didn’t have COVID-19, there were 57 major cardiovascular events (heart attack, stroke, angina, heart failure etc) in a year. Among 1000 people with HIV who had had COVID-19, there were 70 major cardiovascular events in the year following COVID-19.

The increased risk was particularly seen in relation to thrombosis (disorders caused by blood clots), heart failure (failure of the heart to pump sufficient blood) and other heart disorders including aneurysms (where a blood vessel balloons and may suddenly rupture).  

The researchers say that cardiovascular health should be a focus of care in people with HIV recovering from COVID-19. They say it’s also important that people with HIV are vaccinated against COVID-19 and keep up to date with booster doses as people with HIV already have an increased risk of heart disease.

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