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18th Conference on Retroviruses and Opportunistic Infections, Boston, 27 February-2 March 2011


HIV treatment: experimental attachment inhibitor does well in study

A new type of anti-HIV drug that targets the first step in HIV’s entry into cells has done well in a Phase IIa study.

Currently known as BMS-663068, the drug was shown to be safe and to work against the virus.

HIV cell entry is a three-step process. The virus must first attach to the CD4 receptor on the surface of a cell, then bind to a co-receptor (either CCR5 or CXCR4) and, finally, fuse with the cell membrane, releasing viral components into the cell. Of other drugs that target cell entry, the CCR5 antagonist maraviroc (Celsentri in Europe and Selzentry in the US) targets the second step and the fusion inhibitor T-20 (enfuvirtide, Fuzeon) acts at the third step.

BMS-663068 would be the first drug to target the initial step. The active form of the drug has the laboratory name BMS-626529.

The study involved 50 HIV-positive patients. All had a CD4 cell count above 200 cells/mm3 and a viral load of at least 5000 copies/ml.

They were divided into five arms, and treated with various doses of the drug, once or twice daily, with or without a ritonavir (Norvir) booster. The study lasted eight days.

Viral load fell substantially, and there were good increases in CD4 cell count.

Both once- and twice-daily dosing were effective, but boosting with ritonavir only marginally increased the potency of the drug.

None of the patients experienced serious side-effects. However, mild side-effects were common, especially headache and rash.

The drug will be examined in further studies starting later this year.

HIV treatment and cardiovascular disease: no link with abacavir

The US FDA (Food and Drug Administration) has concluded that there’s insufficient evidence to show that heart attack is associated with taking abacavir (Ziagen, also in the combination pills Kivexa and Trizivir).

It conducted an analysis of 26 previous clinical trials involving abacavir and found no evidence to show that treatment with the drug increased the risk of heart attack.

A large study looking at HIV treatment and the risk of side-effects has previously shown that treatment with abacavir increases the risk of heart attack by 70%. Some other large studies have also shown that treatment with abacavir is associated with an increase in heart attack risk.

However, GlaxoSmithKline (GSK), the manufacturer of the drug, always insisted that its own studies showed there was no link between abacavir and heart attack.

The 26 studies in the FDA analysis were all randomised trials. They involved, in total, 5028 abacavir recipients and 4804 patients who did not take the drug. These people were followed for an average of one-and-a-half years.

In total, 47 heart attacks were recorded; these occurred in participants in 18 of the studies.

Treatment with abacavir was associated with an insignificant 2% increase in the risk of heart attack.

This led the FDA to announce there was insufficient evidence to conclude that the drug increased the risk of heart attack.

HIV care in resource-limited settings: viral load not essential

Viral load is not essential for making decisions about switching HIV treatment in poorer countries, two studies show.

Monitoring CD4 cell count and clinical symptoms was shown to be a reliable guide of when to change antiretroviral therapy.

The first study was conducted in Thailand.

It compared outcomes in patients who changed treatment after their viral load increased, to those seen in individuals whose therapy was switched if their CD4 cell count fell by 30%.

No long-term advantage was associated with viral load-guided treatment changes. Rates of death and new AIDS-defining illnesses were comparable to those seen in patients who changed treatment after substantial falls in their CD4 cell count.

A separate study in Cameroon had broadly similar findings. It found no significant difference in the risk of death, disease progression, viral suppression or drug resistance according to whether patients were monitored and switched on the basis of clinical signs or laboratory markers (CD4 and viral load) during two years of follow-up.

Prognosis: decreased limb muscle and abdominal fat linked to mortality risk

Loss of muscle from the limbs and abdominal fat gain are associated with an increased mortality risk for people with HIV.

Investigators from the FRAM (Fat Redistribution and Metabolic Change in HIV Infection) study used MRI scans to monitor muscle and fat levels in 1200 patients.

Two-thirds were men, their average age was about 40, and their mean BMI (body mass index) was 25 – just on the threshold for overweight.

Mortality was monitored over a five-year period.

Decreased muscle mass in the limbs, and fat gain around the belly, were both associated with an increased risk of death.

The researchers took into account other factors associated with mortality in people with HIV.

Their analysis showed that people with the lowest amounts of muscle in their limbs, and the highest amounts of abdominal fat, were twice as likely to die. The researchers calculated that 15% of the excess mortality seen in people with HIV could be attributed to these factors.

However, lipoatrophy – loss of fat caused by some anti-HIV drugs, especially d4T (stauvidine, Zerit) and, to a lesser extent, AZT (zidovudine, Retrovir) – was not linked to an increased mortality risk.

What implications does this research have?

Loss of muscle and fat gain are both part of the natural ageing process.

The researchers expressed concern that BMI wasn’t always an accurate measure of an individual’s body composition. Instead, they recommended that abdominal fat should be assessed by measuring waist circumference.

Studies in HIV-negative people have shown that muscle strength is an important marker of prognosis. The researchers found this hopeful as it suggested that exercise could help improve prognosis in people with HIV.

Preventing HIV: PrEP

Updated results from the iPrEx pre-exposure prophylaxis (PrEP) study have been presented to CROI.

Results from the study were first published last year, and showed that taking PrEP reduced the risk of infection with HIV for gay men and other men who have sex with men. But there were concerns that overall levels of adherence were poor.

However, updated trial results show that adherence levels differed between study sites. Near-perfect adherence was seen in the US. In addition, men who had risky sex had high levels of adherence.

There was also more information on the safety of PrEP. Modest declines in bone mineral density, a possible side-effect of tenofovir (Viread), were seen in individuals taking PrEP.

Other resources from NAM: publications

As well as news and conference coverage, we produce information resources for people with HIV and for professionals. Most of our publications are available free of charge on our website.

You can download patient information booklets and our innovative illustrated series, the basics.

You can also access information from our directories – evidence-based information on HIV treatment, transmission and testing, HIV and the criminal law, as well as an archive of HIV Treatment Update (aimed at a UK audience) and HIV & AIDS Treatment in Practice (aimed at professionals in resource-limited settings).

Not sure where what type of resource you need? Visit our huge topics area, where you can find our resources, feature articles and news arranged by over 100 subjects, including: