HIV update - 3rd February 2016

Resistance to tenofovir

A significant proportion of people who experienced failure of HIV treatment have resistance to tenofovir, one of the key drugs used in HIV treatment. Tenofovir is a component of the tablets Viread, Truvada, Atripla, Eviplera and Stribild.

This story has been widely reported in the mainstream media, but not always accurately. Media reports may have given the impression that, in some regions, half of all people with HIV have resistance. In fact, the study only looked at people who had taken tenofovir and whose treatment did not work (they did not maintain an undetectable viral load).

It’s unsurprising that some drug resistance is found when treatment fails. But resistance to tenofovir develops more slowly than resistance to some other antiretrovirals – the high rates of tenofovir resistance seen in people in Africa in this study may reflect groups of patients not receiving frequent viral load testing. When viral load testing is available, it helps quickly identify treatment failure and people can be switched to another treatment before tenofovir resistance develops.

The study found that after treatment failure, the proportion of people with tenofovir resistance ranged from 20% in Western Europe to 60% in sub-Saharan Africa.

Given that between 15% and 35% of people who begin tenofovir-based treatment in African countries have treatment failure, between 8% and 18% of people starting tenofovir-based treatment there may have tenofovir resistance within a year.

People with HIV subtype C – common in people from sub-Saharan Africa, India and Brazil – were more likely to have resistance than other people. This also applied to migrants and other people with this subtype in Europe.

People beginning treatment with a very low CD4 cell count (below 100) and people also taking nevirapine (Viramune) or lamivudine (3TC, Epivir) were more likely to have resistance. This may reflect people receiving sub-optimal treatment – treatment should be begun at much higher CD4 cell counts. Further, more powerful drug combinations are currently recommended.

When higher quality healthcare is provided, rates of resistance are lower.

For more on drug resistance, you may find some of our information resources helpful. For example, the booklet ‘Taking your HIV treatment’ explains drug resistance and why taking your HIV treatment is so important. In our illustrated series, ‘The basics’, there is a title on ‘Drug resistance’. And our online tool ‘Talking points’ is designed to help you prepare any questions about HIV treatment you might have for your next clinic appointment.

Cognitive impairment

Many people living with HIV are concerned by reports that mild cognitive impairment is more common, and occurs at a younger age, in people living with HIV than in other people. A new study from Holland gives us a clearer picture of this problem.

Mild cognitive impairment can become evident in the form of changes such as reduced attention span, slower information processing, reduced fluency in the use of language, and a reduced ability to plan and organise everyday life or to solve problems. These changes are greater than the declines in memory and mental sharpness that are typical as people get older.

Regardless of HIV, there are a wide range of causes of cognitive impairment, including cardiovascular disease, drug use, medication side-effects, vitamin and thyroid deficiency, and depression or anxiety. Many of these are treatable.

The researchers recruited 103 HIV-positive men over the age of 45 (their average age was 54). They were all doing well on HIV treatment and had had an undetectable viral load for an average of eight years. But in the past many had spent some time unwell due to HIV and had had a low CD4 cell count. Most were gay men.

Their results were compared with those of a very similar group of HIV-negative men.

Some previous studies have probably over-estimated the number of people with cognitive impairment. The researchers refined their techniques to estimate this and used a battery of tests to assess neurocognitive function.

They did find a clear difference in the rates of cognitive impairment. Their results showed that 17% of the HIV-positive men and 5% of the HIV-negative men had mild impairment.

They looked further to identify the factors associated with cognitive impairment in the HIV-positive group. They were:

• Cannabis use
• Cardiovascular disease: build-up of plaque in the arteries, chest pain due to heart problems, heart attack etc.
• Kidney problems
• Type 2 diabetes
• Having excess fat around the belly (a high waist-to-hip ratio)
• Symptoms of depression
• Having previously had a very low CD4 count.

The most important of these factors are at the top of the list. The researchers emphasise that it is a combination of factors which appears to raise the risk of cognitive impairment.

They say that it is biologically plausible that heart and kidney problems contribute to cognitive impairment – and that these issues are increasingly common as people with HIV get older. Having experienced severe immune deficiency in the past (a low CD4 count) also contributes.

Treatment to prevent anal cancer only partially effective

A widely used treatment for pre-cancerous anal lesions is only partially effective and new treatments are urgently required, Spanish researchers have reported.

The main cause of anal cancer is infection with some types of human papillomavirus (HPV). This can result in cell changes which may then lead to pre-cancerous anal lesions. These lesions may be classified as ‘low-grade’ or ‘high-grade’.

Although the high-grade lesions are associated with an increased risk of anal cancer, only a minority of people who have them actually go on to have anal cancer.

Doctors can use a variety of techniques to destroy or remove these lesions under a local anaesthetic – one of the most commonly used is known as electrocautery ablation. Doctors in Barcelona looked back at their results in 83 HIV-positive men who have received the treatment since 2009. While two-thirds initially had some response to treatment, in a quarter of this group the anal lesions came back. This happened on average two to three years after the initial treatment.

The researchers say better treatments – or combinations of treatments – need to be developed.

The lack of effective treatments also puts into question the benefits of screening for anal cancer.

Polypharmacy

One issue as people get older and for people with other health conditions as well as HIV is known as ‘polypharmacy’ – taking a large number of different medicines. Canadian doctors have reported that in a group of over 1000 people with HIV, one third of patients were taking at least five medications on top of their HIV treatment.

They also found that people in this situation were more likely than others to change their HIV treatment or to stop taking it.

Polypharmacy can make adherence more difficult and increase the number of side-effects experienced. Another issue is that there is a greater risk of drug interactions. The researchers say that doctors, pharmacists and people with HIV need to work together to manage situations where multiple medications are needed.

Hepatitis C and cardiovascular disease

People who have hepatitis C have an increased risk of heart disease according to an analysis which pooled the results of 22 separate studies.

The researchers looked first at the build-up of plaque in the arteries – this raises the risk of heart problems. People with hepatitis C were almost two-and-a-half times more likely to have plaque than other people. The effect was most pronounced in people who smoke, showing that smoking exacerbates the effect of hepatitis C on cardiovascular disease.

People with hepatitis C were 30% more likely to have a stroke, heart attack or other cardiovascular event. They were 65% more likely to die due to cardiovascular disease.

The viral infection may raise the risk of metabolic problems and may also cause inflammation of the immune system, raising the risk of heart problems.