HIV update - 11th April 2018

When is TAF better than TDF?

Tenofovir disoproxil fumarate (TDF) is one of the most widely used drugs in HIV treatment. It is included in the pills Truvada, Eviplera, Stribild and Atripla.

TDF is highly effective and doesn’t usually cause many side-effects, but can make kidney and bone problems worse for a few people.

Because of this, a new form of the drug, called tenofovir alafenamide (TAF) has been developed. It delivers tenofovir more efficiently and can be taken at lower doses. This means less drug exposure for the kidneys, bones and other organs and tissues with potentially fewer side-effects. TAF is included in the pills Descovy, Odefsey, and Genvoya.

The catch is that the new pills containing TAF are much more expensive than those containing TDF. A cheaper, generic version of TDF is available, and a drug combination containing it could potentially cost as little as £100 a year. On the other hand, TAF is a new product exclusive to the pharmaceutical company Gilead and protected by patent. The cheapest drug combination containing TAF costs almost £6000 a year in the UK.

NHS decision makers and doctors need to work out when it is worth paying the premium price.

At the moment in the UK, drug combinations containing TDF (rather than TAF) are generally used, except for people who already have kidney disease, bone disease or risk factors for them. In these cases, a combination containing TAF is often a suitable alternative.

A new analysis suggests that TAF only has an advantage over TDF when it is taken alongside ritonavir or cobicistat. These are boosting agents which need to be taken with protease inhibitors and the integrase inhibitor elvitegravir to boost levels of those drugs.

For example, people often take one of these combinations containing ritonavir or cobicistat:

• atazanavir, ritonavir, tenofovir disoproxil fumarate (TDF) and emtricitabine
• darunavir, ritonavir, tenofovir disoproxil fumarate (TDF) and emtricitabine
• elvitegravir, cobicistat, tenofovir disoproxil fumarate (TDF) and emtricitabine.

Many other people take TDF as part of an unboosted regimen, in other words without ritonavir or cobicistat. For example, they may be taking dolutegravir, raltegravir or rilpivirine along with tenofovir disoproxil fumarate (TDF) and emtricitabine.

Researchers identified all the previous studies done on TDF and TAF. They pooled the results of eleven studies with a total of just over 8000 people. A little over half the study participants took a drug combination containing a ritonavir or cobicistat booster.

These were the results:

• The treatment’s effectiveness in keeping viral load undetectable – no difference between TDF and TAF as part of an unboosted regimen. When a boosting agent was taken, TAF was associated with 2% higher rates of effectiveness.
• Changing treatment because of kidney problems – no difference between TDF and TAF as part of an unboosted regimen. When a boosting agent was taken, TAF was associated with 1% fewer changes of treatment.
• Changing treatment because of bone problems – no difference between TDF and TAF as part of an unboosted regimen. When a boosting agent was taken, TAF was associated with 1% fewer changes of treatment.
• Bone fractures – no difference between TDF and TAF as part of an unboosted regimen. When a boosting agent was taken, TAF was associated with 1% fewer fractures.
• Serious side-effects overall – no difference between TDF and TAF, whether or not the regimens were boosted.

The researchers conclude that the safety benefits of TAF over TDF may have been overstated. In particular, they found no advantage to TAF when the HIV drug combination was unboosted, in other words did not contain ritonavir or cobicistat.

NAM publishes antiretroviral drug factsheets on each of the combination pills which contain TDF or TAF: Truvada and Descovy; Eviplera and Odefsey; Stribild and Genvoya; and Atripla. We also have factsheets on Chronic kidney disease and HIV and Bone problems and HIV.

Depression and health outcomes

Six weeks ago, we reported on a study which showed that people with HIV who spend more time living with depression have poorer engagement with care and have worse long-term outcomes. They were more likely to miss appointments, have a viral load above the limit of detection and to die.

Another study has confirmed some of these findings, but specifically in women living with HIV in the United States. Each year, 3 in 100 of the women in this study died, from a variety of causes. The more time women spent depressed, the greater their risk of dying.

Depression may increase the risk of death through several pathways including being less engaged with healthcare, not looking after oneself, not taking medication as prescribed, drug or alcohol abuse, or suicide. Depression is very common in people with HIV, especially women.

The study suggests that doctors should pay more attention to depression in their patients and offer treatment when women have it. 

For more information, read NAM’s booklet HIV, mental health & emotional wellbeing.

Chemsex

Mental health was also an important theme at a recent European conference of activists and health professionals working on chemsex, in particular when this behaviour has become problematic for gay men. Chemsex is the use of crystal meth, mephedrone or GHB/GBL to enhance or facilitate sex.

The forum opened with a minute of silence for those men who have died of drug overdoses and drug-related suicides. “In the eighties and nineties I saw too many gay men dying of AIDS and I don’t want to see this happen again,” said one of the delegates.

Leon Knoops, who works with men involved in chemsex in Amsterdam, asked what the underlying issues were for different men involved in chemsex. “Do they use because everyone seems to do it? Call it peer pressure. Is it the role of a lack of confidence, because they’re out of shape, or think they are too old? Call it body shaming. Or is it the struggle with their HIV status? What if they miss profound connections or steady partners?” he asked.

Jan Großer, a counsellor working in Berlin, said that many men use drugs to overcome their inhibitions, but many of these inhibitions relate to very ‘normal’ concerns such as having a less than perfect body. “At the moment it feels like a lot of gay men feel obliged to censor and suppress some of their emotions in order to have sex,” he said. We need a cultural shift, so that men are able to accept and express their emotions, he suggested.

The conference also highlighted the issue of non-consensual sex in chemsex parties. “We have heard many stories of men who, during sexual marathons that last for days, pass out on GHB or GBL, while the sex continues to take place,” said Leon Knoops. “When they come around, they often have no recollection of what happened.

“Men have spoken from two sides of the coin, and many wonder if this could be considered rape or if it’s just a part of the game. This often triggers immense shame and guilt.”

In UK law, a person who is incapacitated through drink or drugs, or is unconscious, cannot give their consent to a sexual act. In UK law, having penetrative sex with that person is rape.

A doctor from Manchester said that one third of the men attending a specialist chemsex clinic had experienced non-consensual sex.

Eight-week cure for acute hepatitis C

An eight-week course of grazoprevir/elbasvir (Zepatier) led to a sustained virological response (SVR) in most people with HIV and acute (recently acquired) hepatitis C in a small study.

Modern hepatitis C drugs have made its treatment shorter, easier to tolerate and much more effective, including for people with HIV co-infection. Researchers are investigating how short the treatment for acute hepatitis C can be. A study last year showed that sofosbuvir/ledipasvir (Harvoni) taken for eight weeks was effective for people with HIV and acute hepatitis C, genotype 1 or 4.

For the new study of grazoprevir/elbasvir (Zepatier), interim data were presented on 63 gay men with acute hepatitis C. Most of the participants were also living with HIV and around two-thirds had genotype 1a and one-third genotype 4.

Participants took grazoprevir/elbasvir daily for eight weeks. Twelve weeks after completing treatment, 59 participants were undetectable for hepatitis C (SVR12), one participant did not become undetectable and three had acquired a new hepatitis C infection.

The treatment was generally safe and well tolerated.

Some experts now believe that hepatitis C treatment should be started as soon as possible in acute infection, without waiting to see if the body clears the infection on its own (which happens in a fifth of cases). This is because treatments are now so safe and effective, with treatment able to lessen unpleasant symptoms, prevent liver damage and stop onward transmission of the virus.

For more information, read NAM’s booklet HIV & hepatitis.