HIV update - 4th November 2015

More research on the impact of starting treatment early

As HIV Update has previously reported, the results of a groundbreaking study which demonstrated the benefits of starting HIV treatment early were released in the summer.

The headline findings are clear and have already led to changes in treatment guidelines. All international guidelines now recommend that treatment is started as soon as people are diagnosed with HIV.

However, researchers continue to examine the data from the study and to better understand what they can tell us about how HIV causes disease.

Professor Jens Lundgren, who led the study, recently said that the results showed that we can't rely solely on the CD4 count to tell us about damage to the immune system. Although people who delayed HIV treatment often had a CD4 count above 500, they were still more likely to have serious illnesses than people who started HIV treatment immediately. It seems that damage to the immune system happens early in HIV infection and is not fully reversible, even with effective HIV treatment.

In particular, people who delayed treatment were more likely to have cancer. “This points to the fact that there's something we haven't understood about immune deficiency that lets cancers develop which antiretroviral therapy can repair partially but not fully,” Professor Lundgren said.

People who delayed treatment were also more likely to have tuberculosis.

On the other hand, rates of some other health problems – including heart disease and kidney disease – were no different. This may be partly because people who took part in the study were relatively young (many were in their thirties) and these diseases typically occur when people are older.

The researchers have been looking more closely at some issues thought to be associated with HIV infection or its treatment.

They have found that starting HIV treatment early or later makes no difference to the brain, as measured by various tests of memory, mental processing and motor skills. This is reassuring, especially as many participants were taking efavirenz (Sustiva, also in the combination pill Atripla).

Similarly, there were no differences in lung function between the two groups. This issue was investigated because doctors are not sure why many people living with HIV have chronic obstructive pulmonary disease (COPD).

On the other hand, those starting treatment early did have more loss of bone mineral density at the hip and spine than those who delayed treatment. This was identified by X-rays (DEXA scans) – it wasn’t serious enough for people to have more broken bones.

Loss of bone mineral density can be a side-effect of the anti-HIV drug tenofovir (Viread, also in the combination pills Truvada, Atripla, Eviplera and Stribild) which many people in the study were using. A newer version of tenofovir, called tenofovir alafenamide (TAF), has less effect on the bones (and kidneys).

Heart attack risks

A new study shows that the risk of heart attack increases the longer someone has been living with HIV. This is an ‘extra’ effect, on top of what can be expected as people get older and in addition to the impact that some anti-HIV drugs may have on the risk of heart attack.

This is likely to be because the presence of HIV in the body causes inflammation, in other words the active response of the immune system against the infection. This happens even when HIV is well controlled with treatment. Inflammatory chemicals seem to contribute to the process of atherosclerosis – the hardening and narrowing of arteries – that leads up to a heart attack.

This was a large European study, based on over 18,000 people who were followed for an average of seven years each. During this time, 116 had a heart attack.

After making statistical adjustments for people’s age and for the anti-HIV drugs they were taking, the researchers found that the risk of heart attack increased with the number of years that a person had been living with HIV.

During the first five years of having HIV, four people in every 10,000 had a heart attack each year.

Among those who’ve had HIV for five to ten years, eight people in every 10,000 had a heart attack each year.

And in people who’ve had HIV for more than fifteen years, this rose to 26 people in every 10,000 having a heart attack.

Surprisingly, having a high or an undetectable viral load did not make any difference to the risk of heart attack. But having a low CD4 count (below 100) did substantially raise the risk.

We know from the general population that the risk of a heart attack increases as people get older. But this study showed that each ten years of HIV infection had a similar impact to ten years of ageing on the risk. In other words, a person living with HIV aged 40, infected with HIV for ten years, might have a similar risk of heart attack as a person without HIV aged 50.

This underlines the importance of people with HIV improving their diet, getting more exercise and giving up smoking to reduce their risk. This is especially the case for people who have had HIV for a long time.

For more information on these topics, see NAM’s factsheets on The heart, Stroke and Cholesterol.

Treatment simplification with dolutegravir

A recent conference heard from several small studies which are trying to reduce the number of pills in HIV treatment. This should mean fewer side-effects and a lower cost to the NHS.

Rather than needing to take three or four drugs, the idea is to see if just one or two drugs can be effective. This has been tried before – using protease inhibitors – but had mixed results.

However, the newer studies all involve the drug dolutegravir (Tivicay – an integrase inhibitor). This may be more powerful and more effective in lowering viral load than other drugs. It also has very few side-effects and few problems with drug resistance. This may make it more suitable for being used without other drugs.

The early results are promising.

One strategy is for people taking HIV treatment for the first time. In this case, doctors paired dolutegravir with lamivudine (Epivir or 3TC), another drug with very few side-effects.

In a study, all 20 participants quickly achieved an undetectable viral load and kept it that way for the first six months of the study (which is continuing). They had very few side-effects.

Another possible strategy is for people who have had HIV for many years and have tried many previous treatments. They may have resistance to several anti-HIV drugs and find that other treatments cause unpleasant side-effects. It’s often hard for people in this situation to find a new treatment which works well for them.

In one study, 33 people who already had an undetectable viral load from previous treatment switched to dolutegravir on its own. After six months, all but one still had an undetectable viral load. People had fewer side-effects.

Both of these approaches will now be tested in larger studies. This is essential as the studies so far are small pilot studies without comparison groups. The short-term results are good but problems may only emerge after a year or two.

Doctors have different views about the benefits and risks of these strategies. Some think that it is essential to find HIV treatment regimens that have fewer side-effects, are simpler and are easier to take. Others say that HIV treatment is already much better than it used to be and that these aren’t such big issues any more.

Many doctors see these as risky strategies, especially for people with higher viral loads and drug resistance. Others say that if a one-drug approach doesn’t perform well, quickly adding in extra drugs may fix the problem.