HIV update - 29th March 2017

Tenofovir, bone health and kidney function

A three-year long study shows that the new version of tenofovir is better at maintaining an undetectable viral load and safer for the bones and kidneys than the older version of the drug.

Tenofovir disoproxil fumarate (DF) is one of the most widely used antiretroviral drugs. It is highly effective and generally safe and well-tolerated, but can cause kidney and bone problems in some people. Tenofovir DF is included in the tablets Truvada, Atripla, Eviplera and Stribild. 

The newer version, tenofovir alafenamide (AF), provides lower concentrations in the blood but reaches higher levels in cells, causing fewer kidney and bone problems. Tenofovir AF is included in the tablets Descovy, Genvoya and Odefsey.

The three-year data come from a study in which people beginning HIV treatment for the first time, with normal kidney and bone health, were randomly allocated to either take a combination containing tenofovir DF or AF.

At the end of the study, those on tenofovir AF had slightly higher rates of undetectable viral load (84%, compared to 80%). Nobody in the tenofovir AF arm stopped taking the drug because of kidney and bone problems. However in the tenofovir DF arm (which included 867 people), twelve people (1.4%) stopped due to kidney problems and six people (0.7%) stopped due to bone problems.

However the study findings are not directly relevant to treatment in England, as the newer version of tenofovir is not routinely available to people beginning HIV treatment who do not have kidney or bone problems.

The drug is available to people who have been taking the older version but have kidney or bone problems, or who have other medical reasons why they cannot take other HIV drugs. The higher cost of tenofovir AF is the reason for this policy.

The findings which are more relevant in England are from a separate study of people with low bone mineral density who switched from tenofovir DF to AF. There was no comparison group in the study, but after two years, bone mineral density in the spine and hip improved by 2.5% on average. A quarter of those who started the study with osteoporosis (weakened bones) no longer had this condition at the end of the study, although they still had osteopenia (lower bone mineral density than normal for their age).

The researchers say that – for people at risk of a fracture – switching from the older to newer version of tenofovir may be valuable.

For more information, read NAM’s factsheets on ‘Bone problems and HIV’ and ‘Chronic kidney disease and HIV’.

HIV diagnoses down in Scotland

After the encouraging news about falls in HIV diagnoses in London, we now have good news from Scotland. Nonetheless doctors are urging caution in how this is interpreted – these early figures will need to be confirmed.

During 2016 there were 285 people diagnosed with HIV in Scotland, the lowest figure since 2003 and a fall from 360 the previous year.

In gay men (half of diagnoses), there was a marked fall in infections in men who appeared to have acquired HIV within Scotland. This might be due to more people with HIV being on treatment with an undetectable viral load and also due to people importing PrEP drugs from overseas. (There is still no NHS provision of PrEP in Scotland or anywhere else in the UK.) It could also simply be due to fewer people getting tested.

Diagnoses in heterosexual men and women have been falling for several years, probably due to fewer people arriving from countries where HIV rates are high.

But with 36 infections in people who inject drugs, transmission in this group is higher than it was in previous years, due to an ongoing outbreak among people using drugs in Glasgow that began in 2015.

The HIV drug pipeline

A recent conference included studies on several new anti-HIV drugs in early stages of development. It’s unlikely that all will turn out to be safe and effective, but it is encouraging that there are more products in the ‘pipeline’ of potential new drugs than there have been in recent years.

Some of the drugs belong to new drug classes that work differently to existing antiretrovirals, including capsid inhibitors in early studies and monoclonal antibodies now in late-stage human trials.

Other studies were of new drugs in existing drug classes. Elsulfavirine (Elpida) is a non-nucleoside reverse transcriptase inhibitor (NNRTI) that was tested against efavirenz in a study of daily dosing. Now it will be tested for long-acting use – a once a week pill, or a less frequent injection. There’s been a lot of research on the integrase inhibitor cabotegravir (which may be provided as an injection) in the last few years. The conference heard about a new formulation that administers the drug in tiny particles designed to release it more slowly, so that the injections would be less frequent (every three months rather than every two months).

In the nucleoside/nucleotide reverse transcriptase inhibitor class (NRTIs or nukes), there is MK-8591 which could also be suitable for long-acting use. The conference also heard about GS-9131, an NRTI that works against HIV with resistance to other drugs in this class.

GS-PI1 is a protease inhibitor which may not need to be taken with a ‘booster’ such as ritonavir or cobicistat – which could make drug-drug interactions less likely.

Support for adherence

While everyone agrees that good adherence to HIV treatment is vital, it’s less clear what health professionals should do to help people adhere to their treatment. When researchers have evaluated projects to support adherence, the results have generally not been clear. This might be because the projects did not make enough of a difference to adherence. Or it could be because the studies were too small and so could not show a clear result.

Now an adherence support study conducted in the Netherlands has clearly shown that the intervention works. Specially trained adherence nurses had extra one-to-one discussions with people with HIV in their care, who were either having problems with adherence or were starting treatment for the first time.

These discussions included a visual presentation of the how different levels of adherence influence drug levels in the body and how this influences treatment outcomes. Patients set their own goals for the level of adherence they wanted to achieve and were given special pill bottles that record how often they are opened. The reports from the pill bottles show the levels of adherence that were achieved and were used by the nurses in follow-up discussions.

The nurses and patients discussed strategies for coping with adherence difficulties. People starting treatment for the first time also discussed both their reasons for starting treatment and any concerns they had.

Of 221 people taking part, half were randomly allocated to get the extra adherence support. In this group, 9% of people had problems keeping their viral load undetectable.

In the other group, those receiving usual care (including standard advice on adherence), 23% had problems keeping their viral load undetectable. In other words, treatment failure was three times higher in those receiving usual care.

The study gives a clear indication of practical ways in which nurses can help people adhere to their treatment. 

For more information on adherence, read NAM’s booklet ‘Taking your HIV treatment’.

Hepatitis A outbreak in gay men in Europe

An outbreak of hepatitis A in Europe has affected 287 people in at least 13 countries, mostly men who have sex with men.

One group of cases was first identified in the Netherlands, among men who had attended a sex-on-premises venue during the Europride festival in Amsterdam, and has been linked to cases in nine other countries.

In a group of cases first identified in the United Kingdom, many of the men involved report travel to Gran Canaria and other parts of Spain as well as use of dating apps, sex-on-premises venues and multiple partners. Genetic analysis shows that the strain of hepatitis A involved in this cluster has now spread to nine other countries.

Similarly, an outbreak first detected in Germany has been linked to cases in six other countries.

Hepatitis A can be prevented by vaccination. Public Health England is encouraging gay and bisexual men to seek vaccination at sexual health clinics. The European Centre for Disease Prevention and Control has called for vaccination campaigns to target men who have sex with men.

Hepatitis A is transmitted in faeces (shit) and can be transmitted through food or drink contaminated with faeces. It can be picked up through sexual contact, especially oral-anal sex (rimming). Fingers, hands or penises that come into contact with the anus and then the mouth can provide a route of transmission.

For more information, read ‘Hepatitis vaccinations’ and ‘Hepatitis A’ in NAM’s booklet ‘HIV and hepatitis’.