HIV Weekly - March 28th 2006

  • HIV treatment: People are staying on their first anti-HIV drug combination for longer.

  • Side-effects and interactions: Graves’ disease, a disorder of the thyroid gland seems to be a rare immune restoration inflammatory illness; debate continues about whether atazanavir/ritonavir and antacids interact; and anti-HIV drugs that get into the brain don’t impair brain function.

  • Treatment for wasting: A steroid can boost lean muscle in men with HIV-related wasting, but has side-effects.

     

    Very last call for testimonies for inclusion in the next edition of Living with HIV. If you would like your experiences of life with HIV included then your contribution needs to be submitted by Wednesday March 29th.

HIV treatment

The aim of anti-HIV treatment for people who have never taken it before, is to get viral load

The aim of anti-HIV treatment for people who have never taken it before, is to get viral load suppressed to undetectable levels in the blood and to keep it there. This substantially reduces the risk of HIV developing resistance to antiretroviral drugs. Suppressing your viral load will allow your immune system, measured by counting the key CD4 cells in your blood, to recover, therefore reducing the risk of illness and death.

To have the best chance of this happening, the combination of anti-HIV drugs that you take needs to be powerful, tolerable, and easy to take. When combination HIV therapy first became available it often included weaker drugs which HIV could become resistant to relatively easily. Some drugs also caused unpleasant side-effects and were difficult to adhere to – often involving as many as three separate doses with food restrictions a day. This has gradually changed, and the HIV drugs that are recommended for first-line treatment today are much more powerful, have fewer side-effects and often only need to be taken once a day.

A large international study involving almost 4,000 individuals has confirmed that this is the case and has found that the risk of the first anti-HIV combination failing fell by half between 1996 and 2002.

Researchers found that the risk of viral load rebounding fell from 28% in 1996 to 12% in 2002. They further established that people who had a lower risk of treatment failure had a lower viral load below they started treatment, were older and had had a prior AIDS-defining illness.

The type of HIV drug used also reduced the risk of treatment failure. People who took a single protease inhibitor such as indivinavir, nelfinavir (Viracept) or hard-gel saquinavir had a higher risk of treatment failure than those who took a ritonavir-boosted protease inhibitor or the non-nucleoside reverse transcriptase inhibitor, efavirenz (Sustiva).

Side-effects and drug interactions

Graves’ disease

A very small number of people who start anti-HIV treatment develop forms of AIDS-defining infections usually seen in people with very weak immune systems. This usually occurs during the first few months of treatment with anti-HIV drugs and is thought to be because the improving immune system is mounting an overly aggressive response to infections. Doctors often call this immune recovery disease or immune restoration inflammatory syndrome. It is seen most frequently in people who’d had treatment in the past for active tuberculosis and needs specialist management.

Now doctors from the US have reported seeing a series of cases of Graves’ disease in people who recently started anti-HIV treatment. Graves’ disease is an autoimmune disease, meaning that the immune system is attacking itself, and causes over-activity in the thyroid gland.

A total of five cases were seen by the American doctors, and four of the people who developed Graves’ disease started anti-HIV treatment with a very low CD4 cell count, which then increased significantly in the following months. Unlike most immune inflammatory illness, Graves’ disease did not develop until a year to 25 months after HIV treatment was started.

Symptoms included anxiety, tremor, a fast heart rate and weight loss.

The doctors conducted a literature search and found a total of 23 other cases of immune restoration-related Graves’ disease. HIV-positive women were disproportionately affected and the illness developed an average of 21 months after HIV treatment was started.

Graves disease can be treated, but this can involve removal of the thyroid gland.

Remember though, there are millions of people taking anti-HIV treatment around the world and only 28 cases of Graves’ disease have been reported. The chances of you experiencing it are slim. Nevertheless, you should always report any unusual symptoms, no matter how trivial they may seem to you, to your doctor.

 

Atazanavir/ritonavir and antacids

Last year, two studies found that people taking the protease inhibitor atazanavir (Reyataz), boosted by low-dose ritonavir (Norvir), who were also taking types of anatacid medicine called proton pump inhibitors (for example omprazole – Losec) or histamine-2 blockers (like ranitidine, Zantac) risked having low blood levels of atazanavir/ritonavir in their blood. One of these studies involved HIV-negative people, the other a small number of HIV-positive individuals.

Atazanavir is absorbed in the stomach and a high level of stomach acidity is needed if this is to happen properly. If the drug isn’t properly absorbed, then not enough of the drug will reach the blood stream to fight HIV and resistance may develop.

However, doctors aren’t universally convinced that there may be an interaction between atazanavir/ritonavir and antacids, with conflicting evidence recently published.

Researchers in Maryland, USA, found that people taking atazanavir/ritonavir and a proton pump inhibitor were just as likely to get a viral load below 500 copies/ml as those who were taking the boosted protease inhibitor without the antacid. The interpretation of the original study results finding an interaction is also called into question by the doctors who conducted this study.

However, this is countered by the researchers who originally found the interaction, who assert that their study was rigorously conducted and reliable.

Both set of researchers, however, agree that there should be large studies to look at this question in more detail.

Until the results of such a study are available, people taking atazanavir are recommended to avoid the use of proton pump inhibitors or if they have to taken them, to have the blood levels of their atazanavir regularly checked.

Anti-HIV drugs and brain function

The use of anti-HIV drugs that get into the brain is not linked with the degree of brain impairment a person has, a study has found.

People with very low CD4 cell counts have a risk of developing a number of conditions that can affect the brain. Thanks to effective anti-HIV treatment, the number of new cases of conditions such as dementia has fallen.

The anti-HIV drugs AZT (zidovudine, Retrovir), d4T (stavudine, Zerit), 3TC (lamivudine, Epivir), abacavir (Ziagen), nevirapine (Viramune), efavirenz (Sustiva) and indinavir (Crixivan) are known to get into the brain.

Italian researchers looked at brain function in people taking anti-HIV drugs with activity in the brain. All the people in their study had been taking anti-HIV drugs for at least six months and who either had either symptoms or brain impairment or a CD4 cell count below 200 – the level at which there is increased risk of serious illness – were included in the study.

50% of people in the study had reduced neurocognitive functioning.

Factors associated with reduced brain function were older age and a high viral load.

The researchers believe that their findings could have implications for a person’s choice of anti-HIV drugs. In particular, the use of brain-penetrating anti-HIV drugs may not be necessary to prevent neurocognitive impairment in patients with only mild damage to the immune system.

Treatment for wasting

The use of potent antiretroviral treatment has lead to a substantial decline in the amount of HIV-related illness experienced by HIV-positive people. Nevertheless, unintended weight loss, often called wasting syndrome, still remains relatively common amongst HIV-positive people, and the unintentional loss of just 3% of body weight is associated with an increased risk of illness and even death.

Paying attention to nutrition can help preserve weight or promote weight gain, but often weight gained through increased eating is in the form of fat – and increased levels of body fat are not associated with increased survival.

Anabolic steroids have been used to promote the development of lean muscle in people with HIV, but the studies that found this only involved a small number of patients.

American researchers therefore looked at the use of the steroid oxandrolone by 262 HIV-positive men. All the men had HIV-related wasting. The study was conducted between 1996 and 1998, and the men had an average CD4 cell count of 250 and an average viral load of 120,000. No details of the use of anti-HIV treatment by the men in the study were provided.

The researchers found that men who took 40mg of oxandrolone a day for twelve weeks gained more lean muscle than men who took a dummy placebo pill. Gains in muscle were sustained after twelve weeks when the dose of oxandrolone was lowered to 20mg a day.

However, treatment with the steroid did have side-effects including increased levels of bad LDL cholesterol and problems with liver function.

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