News in brief

Risk factors for heart attacks in people with HIV

There’s now significant evidence showing that people with HIV have an increased risk of cardiovascular disease (CVD). The reasons for this are debated, but are likely to be a mix of traditional risk factors (such as smoking and male gender), the effects of some anti-HIV drugs and infection with HIV itself.

US researchers have found more evidence that having a low CD4 cell count increases the risk of heart attack.¹ Their study of over 6000 patients between 1998 and 2008 found about 4% had a heart attack.

After traditional risk factors were taken into account, investigators found that a CD4 cell count below 200 substantially increased the risk of heart attack. There was some evidence that having a viral load above 100,000 copies/ml also increased risk.

The anti-HIV drug abacavir (Ziagen, also in Kivexa and Trizivir) has been associated with an increased risk of CVD and heart attack, as shown in the 2008 results of the D:A:D study.²

At first sight, the statistics were alarming, with those taking the drug apparently 90% more likely to have a heart attack than people in the general population. As a result, treatment with abacavir is not recommended for people with other risk factors for CVD.

Now, researchers have reassessed the heart attack risk associated with abacavir treatment, taking into account individual risk factors.³

They estimated that a 40-year-old man on abacavir, with no other risk factors for CVD, had a 1-in-1000 risk of a heart attack in the next five years. The risk increased with each traditional risk factor a patient had. These include lipid levels (such as cholesterol), blood pressure, age, smoking and previous history of CVD.

The researchers have developed an online tool for doctors and patients to calculate the impact of abacavir use on CVD risk, taking into account individual risk factors (see www.cphiv.dk/TOOLS/NNHforabacavir/tabid/436/Default.aspx).

Are people with HIV developing cancer at a younger age?

Two studies came to different conclusions about the risks of people with advanced HIV disease developing so-called ‘non-AIDS defining’ cancers.

Since the 1980s it’s been known that some types of cancer occur more frequently in people with HIV than in the general population. Some cancers, including Kaposi’s sarcoma (KS) and non-Hodgkin’s lymphoma, are considered to be AIDS-defining illnesses.

Thanks to effective HIV treatment, far fewer people have these AIDS-defining cancers than before.

But some research has shown that, even in the era of effective HIV therapy, people with HIV also have an increased risk of having other cancers.

Italian researchers reported that patients with AIDS are seven times more likely to die of a non-HIV-related cancer than people of the same age and sex in the general Italian population.⁴

Their study involved approximately 10,000 patients who developed an AIDS-defining illness between 1999 and 2006. A total of 3209 of these people died, with a non-AIDS-related cancer as the cause of death in 7% of patients. The most common cancers were those of the lung (58 cases), liver (28), Hodgkin’s lymphoma (28) and of the head and neck (18).

The researchers noted that death rates associated with cancers caused by viral infections were especially high. The mortality rate from anal cancer – caused by certain strains of human papillomavirus (HPV) – was 240 times higher in people with HIV than in the general population, and 174 times higher for Hodgkin’s lymphoma, caused by the Epstein-Barr virus. Deaths from liver cancer were eleven times higher in people with HIV, possibly due to HIV and hepatitis C co-infection.

The researchers feel the results “highlight the importance of monitoring the cancer burden on mortality of people with AIDS”.

In contrast, a US study reported that people with AIDS are generally not developing non-HIV-related cancers at a younger age than people in the general population.⁵

Although people with AIDS who have cancers do tend to be younger than other people with cancers, the researchers say that this is simply because a smaller proportion of people with AIDS (with or without cancer) are over the age of 65, compared to the general population.

The study took into account differences in the age profiles of people with AIDS and the general population. After adjustment, there was no real difference in age of diagnosis for most cancers.

Nonetheless, they did find that people with AIDS developed anal cancer and lung cancer earlier than in the general population. These might be explained by differences in sexual behaviour and in rates of smoking.

The researchers do not believe that cancer is associated with premature ageing in people with HIV or that more intensive cancer screening is warranted for people with HIV.

No benefit from adding drugs to already successful therapy

New research has shown that there’s no benefit from adding an extra anti-HIV drug – one that crosses the blood-brain barrier – to a combination that is already suppressing viral load to undetectable levels.⁶

An undetectable viral load in the blood is now, with advances in HIV treatment, a realistic goal for many people with HIV. But ultra-sensitive viral load tests have shown that most people still have low levels of HIV in their blood. Moreover the virus may continue reproducing in other parts of the body, including cerebrospinal fluids. Even very low levels of HIV replication may be damaging, causing harmful inflammation and immune activation.

The researchers investigated whether adding an additional drug to successful regimens lowered residual viral load in cerebrospinal fluids and blood, and reduced immune activation and inflammation in the brain.

This small study involved ten patients and lasted eight weeks. All participants were taking HIV treatment, with an undetectable viral load for an average of 6.5 years. Most of the patients had evidence of inflammation in the brain.

Treatment was intensified by the addition of either maraviroc (Celsentri) or lopinavir/ritonavir (Kaletra), both of which have good penetration into the central nervous system, and then with T-20 (enfuvirtide, Fuzeon), which does not.

This intensified therapy did not reduce residual viral load any further, in either cerebrospinal fluids or blood. Also, it did not reduce inflammation or immune activation.

Saquinavir side-effect warning

Some protease inhibitors have been associated with an irregular heartbeat. It’s already known that this is the case with saquinavir/ritonavir.⁷

Now drug regulatory bodies in both the US and Europe have strengthened their warnings about heart rhythm disturbances caused by ritonavir-boosted saquinavir (Invirase).⁸

Although this side-effect is rare, it’s now recommended that all patients should have an electrocardiogram (ECG) before they start treatment with saquinavir.

The US Food and Drug Administration recommends that anyone taking the drug should: “Seek immediate care if you experience an abnormal heart rate or rhythm or other symptoms including dizziness, light-headedness, fainting or heart palpitations.”

European regulators have made specific recommendations about saquinavir doses for those starting HIV treatment for the first time. These state that the dose of saquinavir for the first week of treatment will be reduced from 1000mg twice daily to 500mg twice daily. This dosage adjustment is not necessary in patients who are switching from other antiretroviral drugs; the European Medicines Agency says the risk of an irregular heart beat is greatest in people who have never taken antiretroviral drugs before.