HIV update - 6th August 2014

The search for a cure

This edition of HIV update focuses on some key research from the recent International AIDS Conference (AIDS 2014) in Melbourne, Australia.

Finding a cure for HIV was one of the major themes of the conference – various treatment strategies and avenues for future research were discussed. But it’s becoming clear that very early antiretroviral therapy doesn’t achieve a cure.

Delegates were given an update about the so-called ‘Mississippi baby’. Sadly the child was recently found still to have replicating HIV after having an undetectable viral load for two years without therapy. However, researchers stressed that they have learnt a lot from the case, especially that better tests are needed to detect HIV in the body and that new strategies are needed to eliminate long-lived reservoirs of HIV-infected cells.

Information was also provided about the use of an anti-cancer drug as part of a “kick and kill” treatment strategy – stimulating latently infected cells which are then eliminated with antiretroviral therapy. Doctors in Denmark described how they had treated six people – taking long-term antiretroviral therapy – with the chemotherapy drug romidepsin. The drug kicks dormant cells, including those infected with HIV, out of their resting stage.

The strategy appears to have been partially successful, but researchers don’t think that the treatment had a significant impact on the size of the viral reservoir. However, Professor Steven Deeks said that the study proved it was possible to locate the hidden reservoir and shock it into activity. This was “the single most important advance of this meeting and it will have a major impact in the future,” he told a press conference.

So it doesn’t seem that either very early HIV treatment or the stimulation of resting cells can achieve a ‘functional cure’ – control of HIV without the need for antiretroviral therapy.

Two other approaches were also reported. One Australian research group introduced artificial genes into human cells that caused them to generate antiviral entry inhibitors. The cells were less likely to become infected with HIV. Another Australian research group introduced artificial gene fragments to maintain latently infected cells in a locked-down state that resisted strong immune stimulation. This approach might keep the HIV reservoir under control without the need for antiretroviral drugs.

Where now? One expert predicted that cure research will focus on the development of therapeutic vaccines or immune-based therapies.

Anal cancer

It may not be necessary to treat all gay men living with HIV who have anal lesions that might progress to cancer, Australian researchers have found. In the majority of cases, lesions disappear without treatment, and close monitoring may do less harm in most cases than surgical and pharmaceutical treatment.

Anal cancer and its precursors, abnormal cell growths, tissue changes and lesions, are more common among people living with HIV – especially men who have sex with men – than in the general population.

Some types of anal human papillomavirus (HPV) infections are associated with anal cancer. HPV can cause changes to the appearance and function of cells in the anal canal, which may progress to anal lesions, which may then progress to anal cancer. But things do not always progress in this way and the situation often clears up without treatment.

Some doctors favour routine treatment of high-grade anal lesions – which may involve chemotherapy, radiation, cauterisation (burning) or surgery – but this view is controversial. The treatment is difficult, does not always work and can involve side-effects. What’s more, up to half of gay men living with HIV have these lesions so would potentially need to be treated.

A study is following gay men with and without HIV in Australia to find out what proportion of men with anal lesions develop anal cancer. The interim results show early abnormalities disappeared in almost half of men, with no differences according to age or HIV status.

These findings "provide a very strong justification that not all high grade anal disease requires treatment, and suggests that treatment can be targeted to people with persistent high-grade disease," said Dr Andrew Grulich of the Kirby Institute at the University of New South Wales. Most high-grade disease noticed on a single test "will simply go away", he said.

Treatment for hepatitis C

The International AIDS Conference in Melbourne heard more news of effective treatments for hepatitis C, in trials which only enrolled people living with both HIV and hepatitis C.

It was previously thought that people with HIV co-infection usually have a poorer response to hepatitis C treatment. In fact, it now appears that when a potent combination of two or more hepatitis C drugs is taken, people with HIV co-infection can have results that are comparable to people who only have hepatitis C.

Moreover, some of these drug combinations do not include pegylated interferon, the injectable drug that gives some people side-effects.

A small study evaluated the safety and effectiveness of a combination of drugs – the ‘3D’ combination produced by the AbbVie company, taken with ribavirin. Most of the study participants had the harder-to-treat genotype 1a and two thirds were taking hepatitis therapy for the first time. When people took the drugs for twelve weeks, 94% of participants were cured of hepatitis C (a sustained virological response) twelve weeks after the completion of therapy.

None of the participants experienced serious side-effects or stopped treatment early because of adverse events. Mild/moderate fatigue, nausea and headache were the most common side-effects.

A second study evaluated the two-drug combination of sofosbuvir (Sovaldi) and ribavirin, taken for 24 weeks. Participants had a range of genotypes, most had never taken hepatitis therapy before and 20% had liver cirrhosis. The proportion of people cured of hepatitis C was between 84 and 89%, depending on their hepatitis C genotype.

The numbers cured are impressive when compared with treatment with pegylated interferon and ribavirin. However, some other all oral-combinations have achieved 90-100% cure rates in people with HIV co-infection.

Memory, thought processes and concentration

Two studies have reported reassuring news about neurocognitive impairment – in other words, problems with memory, concentration, thinking ability, fine motor skills or visual-spatial abilities.

In the 1980s, dementia was common in people with very advanced HIV disease, but became unusual after the introduction of effective HIV treatment. Nonetheless, some studies since then have shown that a number of people living with HIV have had mild impairments in mental function, with some doctors believing that these might be caused by HIV itself or by specific anti-HIV drugs. However, few studies have rigorously compared neurocognitive abilities in comparable groups of HIV-negative and HIV-positive people.

The first study examined rates of neurocognitive impairment in UK gay men, comparing 248 HIV-positive and 45 HIV-negative men. Overall, 14% of those living with HIV had a ‘problem’ that was picked up by tests but which the person had not themselves noticed, 6% had mild impairment and under 1% had dementia.

But the HIV-negative gay men taking part in the study had very similar results. The kinds of problems and disorders that are picked up by the tests used appear to be commonly experienced by people who do not have HIV and are, in any case, often so mild that they do not affect the person’s day to day life.

The second study looked at people taking the drug efavirenz (Sustiva, also in the Atripla tablet). This drug, which is widely recommended for first-line HIV treatment, has a well-known association with side-effects such as insomnia, vivid dreams, hallucinations and dizziness. The possibility of a link between efavirenz and neurocognitive impairment is more controversial – previous studies have had conflicting results.

The study of 859 people taking antiretroviral therapy in Italy showed that, compared to people taking other anti-HIV drugs, those taking efavirenz did not have poorer memory, concentration, thinking ability, fine motor skills or visual-spatial abilities.

But individuals with neurocognitive impairment were more likely to be older, have more severe HIV disease, have hepatitis C co-infection or have a history of injection drug use.