HIV treatment side-effects – cardiovascular disease
US researchers have found that treatment with abacavir (Ziagen, also in the combination pills Kivexa and Trizivir) increases the risk of heart attack and stroke.
They also found that therapy with tenofovir (Viread, also in the combination pills Truvada and Atripla) causes a slight increase in the risk of heart failure – a gradual weakening of the heart.
It’s now well established that people with HIV have an increased risk of cardiovascular disease.
There a lot of debate about the causes, but the most important seem to be the damage caused by untreated HIV infection, and traditional risk factors such as smoking.
Nevertheless, several studies have shown that treatment with some anti-HIV drugs increases the risk of heart disease.
A lot of attention has focused on abacavir. One study has found that it increased the risk of heart attack by up to 90%.
However, this finding was contradicted by an analysis of clinical trials involving people randomised to take abacavir or a competitor drug. This found that abacavir did not increase the risk of heart attack in either the short- or long-term.
The latest research will add to the debate, and the findings are of especial relevance given recent HIV prescribing guidance issued in London. On grounds of cost, abacavir is preferred over tenofovir in most cases. However, people with risk factors for heart disease or a high viral load will be offered tenofovir instead.
When thinking about the risk of a heart attack, it is important to remember that heart attacks are very rare in people without major risk factors like smoking, high cholesterol and a family history of heart disease.
A doubling of risk, or a 50% increase in risk, is a cause for concern in anyone already at high risk of heart attack. But in otherwise healthy people, a doubling of risk would still leave heart attack as a very rare event.
In the latest research US doctors looked at rates of cardiovascular disease in over 10,000 HIV-positive people between 1997 and 2007.
They found that people who took abacavir were about 50% more likely to have a heart attack or other serious cardiovascular event than people taking tenofovir or other drugs. Abacavir was also associated with an increased risk of stroke.
But they also found that people who took tenofovir, especially if they had poor kidney function, had an increased risk of heart failure.
The results of all studies looking at the risk of cardiovascular disease in people with HIV need to be seen in a wider context.
The risk associated with any individual drug has consistently been shown to be less important than those associated with factors such as smoking and uncontrolled HIV.
Routine HIV care involves regular tests to monitor cardiovascular health, meaning that problems can be spotted early and appropriate action taken.
There’s also a lot you can do to look after your heart – for example not smoking, eating a healthy diet, and exercising regularly – help and advice about all these is available from your HIV clinic or GP.
HIV and bone health
These fractures are often called ‘fragility fractures’ and are usually seen in elderly patients who have thinning bones (osteoporosis).
It’s well established that patients with HIV have an increased risk of bone problems, and that possible causes include the effects of HIV itself, and possibly the side-effects of some anti-HIV drugs, especially tenofovir.
Now researchers have found that a CD4 cell count below 200 was associated with fragility fractures. Therapy with corticosteroids (used to treat serious infections that can occur in patients with a weak immune system) was also a risk factor, as was treatment with anti-epileptics.
However, unlike some other research, there was no evidence that HIV treatment increased the risk of fractures.
Outcomes and prognosis – non-HIV-related illnesses
Thanks to effective HIV treatment, many HIV-positive people can now look forward to living a long and healthy life.
As the HIV-positive population ages, illnesses associated with older age such as cardiovascular disease are becoming more common. Together with co-infections such as hepatitis C, these conditions are now an important cause of serious illness in people with HIV. Their prevention, prompt diagnosis and treatment are now a priority of HIV care.
Danish researchers monitored people who were diagnosed with HIV between 1997 and 2005 and compared each person with up to 99 age- and sex-matched controls from the general population.
They found that the mortality rate in people with HIV was a little over 2% – this was much higher than the 0.39% recorded in the HIV-negative population.
Another serious illness was present in 22% of people at the time of their HIV diagnosis.
Overall, the researchers calculated that 32% of deaths in HIV-positive people were caused by these pre-existing illnesses.
In addition, 45% of all deaths were caused by illnesses that were unrelated to HIV.
HIV and hepatitis C – hepatitis C treatment
People who had a gene called IL28b were more likely to clear hepatitis C infection when treated with pegylated interferon and ribavirin than those without the gene.
The association with the gene and better treatment responses was seen in people taking hepatitis C treatment for the first time, and also in people taking a second course of treatment.
But the gene was only associated with improved outcomes in people co-infected with hepatitis C genotypes 1 and 4, which are normally associated with a poorer response to therapy.
People who had the IL28b gene were more likely to have a very early response to treatment – an indicator of the long-term success of therapy.
Six months after the end of treatment, significantly more people with the gene had an undetectable hepatitis C viral load (sustained virologic response, or SVR), and were therefore considered cured of the infection.
The researchers conclude: “Our study demonstrates an important role for IL28b genotypes in predicting on-treatment virological responses to therapy in HIV/HCV-coinfected individuals…knowledge at baseline of the IL28b genotype may helpfully assist in treatment decisions.”