- Drug trial stopped: Studies into the investigational NRTI drug, DFC, are stopped due to safety concerns.
- Discrimination: A study has found that many HIV-positive people think that they have experienced discrimination because of their HIV infection when using medical services.
- Disease progression: A low CD4 cell count and high amounts of HIV’s genetic material in cells shortly after infection with HIV are associated with faster disease progression.
- Side-effects: HIV-positive men with lipodystrophy have lower levels of growth hormone.
- Resistance to anti-HIV drugs: A study finds that the amount of time resistance to NNRTIs persist in people can vary considerably between people and a second study finds that the length of time it takes for the body to clear efavirenz (Sustiva) is influenced by a genetic mutation.
Drug trial stopped
Before any medicine is approved for use it has to go through clinical trials to ensure that it is safe and effective.
Many potential anti-HIV drugs which looked promising in early laboratory studies failed to make it through the clinical trials process. It was announced last week that the development of the drug DFC (Reverset) has been discontinued because of concerns about its safety.
DFC belongs to the nucleoside reverse transcriptase inhibitor (NRTI) class of anti-HIV drugs and is similar in the way it works against HIV to the approved drugs 3TC (lamivudine, Epivir) and FTC (emtricitabine, Emtirva).
Earlier studies suggested that DFC could be dosed once daily and was effective against HIV that was resistant to other NRTIs. However, the company developing DFC, Incyte, stopped trials of the drug after up to 40% of patients taking the 200mg daily dose of the drug experienced a side-effect called hyperlipasaemia, which can increase the risk of the very serious illness, pancreatitis. People taking DFC in combination with ddI (didanosine, Videx) were most likely to experience this side-effect.
Trials into the drug were being conducted in the US, Germany and France and everybody taking DFC should have been contacted by their HIV clinic so they can meet with their doctor and discuss their treatment options.
Discrimination
The UK Disability Discrimination Act means that it is illegal to discriminate against people with HIV from the moment of diagnosis in areas such as employment, housing and the provision of goods and services. In addition, the Department of Health and National Health Service have produced an action plan to tackle discrimination against people with HIV.
However, a small study presented to the recent conference of the British HIV Association found that over a quarter of patients using an HIV clinic in east London thought they had experienced discrimination from medical professionals because they had HIV.
The study involved just under 1700 people and of these 475 (28%) said that they thought that they had been treated differently by medical staff because they had HIV. A quarter of these people said they had experienced discrimination from a dentist, 18% from a GP, and 10% from hospital staff.
NAM has a series of factsheets on HIV and NHS services which provide information on what you should expect from your healthcare providers, and what action to take if you are not happy about the level of service you are receiving.
Risk of disease progression
Potent anti-HIV treatment can mean a longer and healthier life and since it became available in the late 1990s the amount of serious illness and death caused by HIV has dropped dramatically in the UK. Many HIV doctors are now very optimistic about the prognosis of people who do well on anti-HIV drugs and believe that HIV is an illness that they will die with, not from.
Nevertheless, research is still being conducted to try and identify why some people experience a faster rate of HIV disease progression. Knowing this could help guide decisions about the best time to start anti-HIV treatment. It is also currently unknown if there is any long-term benefit from treating HIV immediately after infection occurs.
French doctors looked at the rate of HIV disease progression in 163 people who were diagnosed with HIV soon after they were infected with the virus. They found that two years after diagnosis with HIV, 34% of people had experienced a fall in their CD4 cell count to below 350, and that this had increased to 42% after three years.
The doctors found that having a low CD4 cell count during the period of initial infection with HIV (often called primary infection) and high amounts of HIV DNA in blood cells were associated with faster disease progression.
In the UK, it is only recommended to take treatment during primary infection as part of a clinical trial.
Side-effects
Lipodystrophy – a disturbance in the way the body process and stores fat – can be one of the most significant and distressing side-effects of anti-HIV treatment.
Doctors are learning more about the causes of lipodystrophy, and it is now recommended that the NRTI drug d4T (stavudine, Zerit) should not be used for people who have other options because it is associated with fat loss. AZT (zidovudine, Retrovir) has also been associated with fat loss but at a slower rate than d4T, and it is recommended that use of AZT and AZT-containing drugs (such as Combivir and Trizivir) should also be avoided.
Lower levels of growth hormone were not associated with the use of any particular anti-HIV drug, but low levels of growth hormone were related to fat gain around the organs.
The researchers also found that Caucasian men had lower levels of growth hormone production than non-Caucasian men.
Growth hormone has been examined as a possible treatment for lipodystrophy with mixed results. The doctors who conducted this study hope that their findings suggesting that Caucasian men with fat gain around the middle have lower growth hormone production might lead to the treatment being targeted at those who will get the most benefit from it. However, before that can happen, more trials into its safety and effectiveness are needed.
Resistance to anti-HIV drugs
HIV can develop resistance to antiretroviral drugs and it is particularly easy to develop resistance to the two currently available drugs in the non-nucleoside reverse transcriptase inhibitor (NNRTI) class (nevirapine, Viramune , and efavirenz, Sustiva ).
A common change – or mutation – in HIV which makes the virus resistant to NNRTIs is called K103N and researchers using a very sensitive test have found that the amount of time it takes for HIV with this mutation to ‘decay’ or be overtaken by HIV that is sensitive to NNRTI drugs can vary considerably between people. Their research involved six people and they found that after stopping treatment with NNRTIs, one person still had 100% of HIV that was resistant to NNRTI drugs six years later, whereas in another patient the amount of NNRTI-resistant HIV fell from 100% to just 3% within a little over six months. The test is very expensive so it is unlikely to be used in routine HIV care, but will be useful for future research into drug resistance.
Efavirenz is cleared from the body very slowly and this can mean that people who stop taking all their anti-HIV drugs, including efavirenz, are at the same time at risk of developing resistance to the drug. Because of this risk, efavirenz is often replaced by a protease inhibitor for a few days before treatment is stopped. It is not necessary to do this, however, if treatment with a new drug combination is started immediately after efavirenz is stopped.
American researchers found that people with a genetic mutation associated with slower clearance of efavirenz from the body would have sufficient quantities of the drug in their body for resistance to develop eleven days after stopping treatment. This compared to six days in people who had the ‘normal’ genetic variation.
The particular genetic mutation is seen more often in people of African origin compared to those of European origin.
Although a genetic test is now being routinely used to see who will develop an allergic reaction to the anti-HIV drug abacavir (Ziagen), it’s unlikely that the findings of this study will lead to the wider use of genetic testing. The way to reduce the risks of efavirenz resistance developing in people stopping treatment is already known, and the study researchers also pointed out that knowledge of the mutation cannot accurately predict how long efavirenz will linger in the body because of ‘overlap’ between genes in people.
Nevertheless, the study does highlight how genes are being increasingly investigated within the field of HIV medicine.