HIV Weekly - September 26th 2007

Anti-HIV treatment – new drugs

Maraviroc

The CCR5 inhibitor maraviroc (Celsentri) looks like it works in the long-term. The drug belongs to a completely new type of anti-HIV drug that prevents HIV from infecting human cells.

It is an important new treatment option for people who have taken a lot of anti-HIV drugs in the past and have drug resistant HIV. Formal approval was granted in the US this summer and European approval has just been granted.

A one year study showed that the majority of heavily treatment-experienced people who took maraviroc along with the best possible combination of anti-HIV drugs selected by resistance testing (called the optimised background therapy) had a long-lasting fall in their viral load and a good increase in their CD4 cell counts. By contrast, only a fifth of people who took the dummy placebo pill had a fall in their viral load to below 400 copies.

Particularly good results were seen in people who took maraviroc who also started T-20 (enfuvirtide, Fuzeon) for the first time.

Vicriviroc

Vicriviroc is another new CCR5 inhibitor currently being examined in clinical trials.

It hasn’t progressed as far as maraviroc in trials and studies to find the best, safe dose of the drug have only just finished.

Two year results showed that 60% of 39 heavily treatment-experienced patients who took vicriviroc with optimised background therapy had a viral load below 50 (undetectable) after two years on the drug, with the average CD4 cell count increasing by 84.

Earlier results were presented in July and they showed that people receiving vicriviroc were much more likely to have an undetectable viral load than those patients who were given the dummy (placebo) pill.

But cancers occurred more frequently in the vicriviroc-treated patients. However, detailed analysis showed that these often developed in people with a previous history of cancer and were the types of cancers that occur in people with very advanced HIV disease (a category which people in the study fell into). None of the cancers could be linked with vicriviroc treatment.

Vicriviroc will now be examined in bigger, phase III trials.

Raltegravir

Integrase inhibitors are another new class of anti-HIV drugs currently in development. They work by stopping HIV integrating in human cells.

Results of a one year trial for the experimental drug raltegravir (Isentress) are highly encouraging.

The study was placebo controlled, meaning that some patients in the study were chosen at random to receive a dummy medicine instead of raltegravir. Patients took raltegravir or the placebo with an optimised background of HIV drugs chosen by resistance testing.

Researchers found that after one year, over 50% of raltegravir-treated patients had an undetectable viral load compared to only 13% of those who took the placebo.

Similar numbers of patients who took raltegravir and the placebo had side-effects.

Elvitegravir

Another integrase inhibitor being studied in clinical trials is elvitegravir. It produces the best results in treatment-experienced people when combined with at least one other drug that is active against HIV.

Researchers wanted to make sure that the elvitegravir didn’t interact with a new NNRTI currently in development called TMC125. This is encouraging because TMC125 is active against most virus already resistant to the NNRTIs nevirapine and efavirenz, providing a potentially active drug to use alongside elvitegravir.

Both drugs are processed by the liver, so an interaction is theoretically possible.

But studies found that there were no important interactions between the two drugs and that they could be safely taken together.

Anti-HIV drugs – resistance

HIV can become resistant to the drug used to treat it. You can minimise the risk of this happening by making sure that you take your anti-HIV drugs properly.

But resistance to some drugs can also develop when anti-HIV treatment is stopped, even under medical supervision.

This is because some drugs linger in the body. There’s not enough of the drug present to suppress HIV and this allows resistance to develop. The risk of this happening is particularly high with NNRTI drugs (nevirapine/Viramune  and efavirenz/Sustiva ).

Researchers have found that the risk of resistance is reduced if treatment with NNRTIs is stopped a week to ten days before therapy with two nucleoside analogues.

Anti-HIV drugs – nelfinavir

In June the protease inhibitor nelfinavir (Viracept) was withdrawn from the market after it was found that some batches had been contaminated with excess amounts of a potentially cancer-causing substance used in the drug’s manufacture.

Nelfinavir’s European license was temporarily suspended because of this contamination. But European drug regulatory authorities are now satisfied that nelfinavir’s makers, Roche, have taken steps to make sure the contamination never happens again and are recommending that the drug’s license is returned.

Very few people were taking nelfinavir in the UK when the drug was recalled. But the drug does have important “niche” uses, including use for post-exposure prophylaxis and during pregnancy. But US drug regulatory authorities recently recommended that pregnant women should not take nelfinavir because a substance linked to cancer is used in its manufacture. The advice was issued even though the excess contamination did not affect the US. It is therefore doubtful that nelfinavir will again be used during pregnancy in Europe.

Side-effects

Atazanavir – urinary stones

Doctors have found that urinary stones may be a rare side-effect of atazanavir (Reyataz). French doctors found that about 1% of patients who received atazanavir boosted by ritonavir developed this painful side-effect.

The side-effect developed after approximately two years of treatment with the drug. A prior history of urinary stones and not drinking enough fluids appeared to be risk factors.

Lipodystrophy – fat gain after switching from d4T to tenofovir

It is now well known that treatment with some anti-HIV drugs can cause disturbances in the way the body stores and processes fat. Doctors call this collection of side-effects lipodystrophy.

The drug d4T (stavudine, Zerit) has been particularly associated with fat loss from the limbs, buttocks and face. Fat loss, at a slower rate, is also a side-effect of AZT (zidovudine).

It is recommended that people taking d4T or AZT should switch to abacavir (Ziagen) or tenofovir (Viread). Neither of these drugs has been associated with fat loss although they do have other side-effects.

Fat returns slowly in the limbs in people who switch to abacavir and tenofovir, and the latest research shows that people who switch to tenofovir continue to have these gains three years after changing drugs.

Illness

The amount of HIV-related illness and death has fallen dramatically in the UK and similar countries since effective anti-HIV treatment became available.

But people with HIV can still become unwell, and doctors have seen some important changes in the causes of illness and death in people with HIV in recent years.

For example, the AIDS-defining cancers Kaposi’s sarcoma and non-Hodgkin’s lymphoma are now very rarely seen. But researchers have noticed that people with HIV are more likely than the general population to develop some non-AIDS-defining cancers. The latest research from America shows that people with HIV are more likely to develop anal cancer, Hodgkin’s lymphoma, liver cancer and lung cancer. It is thought that this is because some of these cancers – for example anal cancer, liver cancer and lymphoma – are linked to other infections, and also because the long-term effects of immune suppression caused by HIV leave the body more vulnerable to cancer.

However, even if the rates of some cancers were elevated, its important to remember that they were still rare.

Researchers have also found that some bacterial infections, heart and lung disease, depression and nerve problems occur more often in people with HIV. They found that older people, and those with a low CD4 cell count and high viral load were most at risk.

Some doctors think that the risk of non-AIDS related illness at lower CD4 cell counts is a powerful argument for starting HIV treatment when a person’s CD4 cell count is 350. At the moment, treatment guidelines say that treatment should be started when a person has a CD4 cell count between 200 – 250.

Hepatitis C

Doctors in England and several northern European countries have found evidence of the sexual transmission of hepatitis C virus in HIV-positive gay men.

There’s now good evidence of sexual transmission of hepatitis C amongst HIV-positive gay men in Australia.

There are a number of reasons why sexual transmission of hepatitis C may be more likely in HIV-positive gay men. It has been shown that hepatitis C viral load is higher in the semen of HIV-positive men. There’s also good evidence that sexual practices, like fisting and group sex, combined with drug use also have a high risk of hepatitis C transmission because they might involve damage to the rectum and exposure to blood.  

Human papilloma virus

Vaccines have been developed that provide protection against strains 16/18 of human papilloma virus (HPV). These strains of HPV are high risk for cervical and anal cancer.

Research now shows that one of the vaccines, Gardasil, also protects against ten strains of HPV that have a cancer risk.

The HPV vaccines work best in people who have never been exposed to HPV. They do not help “cure” HPV in people who already have the virus. Because of this, the NHS is recommending that the vaccine is only given to girls aged twelve and 13 who are not yet sexually active and haven’t been exposed to HPV.

There are currently no trial results to show if the vaccines are safe and effective in boys and men, or in people with HIV, although such studies are now underway.

Some people are paying for HPV vaccination from private doctors. If you are considering doing this, make sure that the doctor tests you to see if you are already infected with HPV.

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