HIV update - 13th November 2019

Weight gain and HIV treatment

One of the most important topics discussed at the 17th European AIDS Conference (EACS 2019), held in Switzerland last week, was people putting on weight after starting HIV treatment.

We’ve become more aware of this issue over the last two years. While at first attention was focused on a drug called dolutegravir, the problem actually appears to be associated with a wider range of antiretrovirals. Weight gain on modern antiretroviral treatment involves an increase in body fat and waist circumference. It is not the same as the fat loss and gain (lipodystrophy) that happened with older medications two decades ago.

Part of the explanation is that people who start treatment with low CD4 cell counts or high viral load have a general improvement in health. But that isn’t the whole story – some drugs and some drug combinations seem to cause more problems than others. These drugs include the integrase inhibitors dolutegravir and bictegravir, the newer formulation of tenofovir called TAF, and the NNRTI rilpivirine.

For example, in a recent study in South Africa, after taking a drug combination that included both dolutegravir and TAF for almost two years, 51% of women and 42% of men were at least 10% heavier than they were before starting the treatment. This compares with 23% of women and 18% of men taking a combination that didn’t include either of those medications.

In all studies, women and black people have had the greatest gains in weight. This might be due to the impact of genetics on the metabolism of drugs, but researchers do not yet have a clear understanding of the reason why.

One problem is that most research studies don’t include enough women and black people – the South African study is one exception. This makes it harder to properly research the issue.

Studies involving people switching from one drug combination to another can give useful information. As most people changing drug regimens will already have an undetectable viral load, it’s less likely that weight gain will be due to a ‘return to health’.

A Dutch study looked at people with HIV switching to a new combination that included an integrase inhibitor (such as dolutegravir). They were compared both with HIV-positive people who did not change treatment and with HIV-negative people. In general, people only put on a little weight (an average of 0.2kg a year).

But averages don’t tell the whole story. The researchers also found that 24% of those switching to an integrase inhibitor gained at least 5% in body weight, compared with 13% of the HIV-positive control group and 12% of the HIV-negative control group.

And this kind of substantial weight gain was more likely to occur in black women than in other people. Similarly, Swiss researchers found that women, black people and current smokers had a 50% greater likelihood of substantial weight gain after switching to dolutegravir.

Researchers are now turning their attention to whether these increases in fat and weight are also associated with other health problems, such as heart disease, diabetes and cancer.

For more information, read NAM's page 'Weight gain, weight loss and HIV'.

HIV treatment for older people and bone health

As mentioned above, most research studies – especially the studies done to show that new drugs are safe and effective – recruit people living with HIV who do not fully represent the range of people who use those medications. More often than not, study participants tend to be male, white, relatively healthy and relatively affluent. 

They also tend to be middle aged. So a new study which only recruited people over 60 years of age living with HIV is interesting. It’s the first phase 3, randomised clinical trial of HIV treatment just for this age group to be done.

The researchers wanted to know whether a newer version of a medication has a better side effect profile than an older one. They were specifically interested in bone mineral density as this can be a problem as we get older, and because the older version of the medication occasionally harms people’s bones.

The scientists recruited 167 people who were already taking an HIV treatment combination that included tenofovir disoproxil fumarate (TDF) – the older medication. One third continued to take this combination while two-thirds were asked to switch to a new combination that included tenofovir alafenamide (TAF) – the newer formulation of the same drug.

TDF and TAF are very widely used anti-HIV drugs. Many of the tablets which combine several drugs in one pill include one of them.

After almost a year, bone mineral density increased in those taking the newer medication TAF, while it decreased very slightly in those on TDF. This suggests that bone loss is reversible in older people living with HIV.

TAF was also better for people’s kidneys.

While weight gain has been a problem in other studies in TAF, it was not in this study.

But the findings were not all in favour of the newer version of the drug. Blood fats – total cholesterol, LDL cholesterol and triglycerides – all increased in those taking TAF.

This implies that people need to think about which health problems they are most concerned about when choosing anti-HIV drugs. For someone who already has bone problems, switching from TDF to TAF might be a good option. For someone who has raised cholesterol, it may be better to stick with TDF.

For more information, read NAM's page 'Bone problems and HIV'.

Anal cancer

Doctors sometimes do tests which find abnormal cell changes that are called ‘precancerous’. But they don’t always lead to cancer. And quite often they go away on their own.

That’s shown by a new study which recruited 617 gay and bisexual men in Australia. For three years, they were all regularly checked for these abnormal cell changes in the anal area as well as for anal cancer.

A lot of the men had abnormal cell changes – 32% of HIV-negative men and 47% of HIV-positive men at the beginning of the study. But during the study only one man out of 617 progressed to anal cancer. This seems like a much lower rate than has been reported by other researchers.

The development of new abnormal cell changes was no higher in smokers and not much higher in men with HIV than in other men, although both groups are usually thought to be at higher risk.

Another encouraging finding was that clearance of these abnormal cells was more common than their appearance. Twenty-two per cent of men cleared their abnormal cells per year compared with 11% who developed them.

For more information, read NAM's page 'Anal cancer and HIV'.