HIV update - 3rd August 2016

News from AIDS 2016

This edition of HIV update focuses on research from the recent International AIDS Conference (AIDS 2016) that is particularly relevant to people living with HIV in the UK.

Treatment as prevention: more confidence in zero transmission risk

New data from the PARTNER study looking at the infectiousness of people taking HIV treatment has added to confidence that individuals with an undetectable viral load are extremely unlikely to transmit HIV to their sexual partners – the risk may even be zero.

The research involves couples in which one person is living with HIV and one person is not. The researchers are interested in the effectiveness of HIV treatment as prevention.

Early results released in 2014 showed no transmissions after sex without a condom when the HIV-positive partner had an undetectable viral load. Now the researchers have more data on more couples, so can state their conclusions with more confidence.

The latest data were collected from 888 couples, 38% of them gay men. Each couple was followed for an average of 1.6 years.

They had sex without a condom a total of 58,213 times, but on no occasion was HIV passed on.

Nonetheless, there were eleven new HIV infections. Genetic analysis showed that in every case the virus acquired by the HIV-negative partner was quite different from their partner’s virus, suggesting it had been acquired from sex outside the relationship.

The vagaries of statistical analysis mean that researchers are not yet prepared to say that an undetectable viral load means a zero risk of transmission – although that may well be the case. The researchers are continuing to collect more data from gay men so that they can give firmer conclusions on the risk of transmission during anal sex.

Nonetheless, the lack of any transmissions in couples – gay or heterosexual – in the context of an undetectable viral load is remarkable.

For more information on this topic, read NAM’s factsheet, ‘Viral load and transmission – a factsheet for people with HIV’.

Progress towards a cure

A cure for HIV is a research priority and the conference heard about several different approaches.

A particularly interesting study involved 24 young South African women who started HIV treatment within 15 days of acquiring HIV. Aged between 18 and 23, the participants were recruited to the study when they were HIV-negative but identified as being at high-risk of acquiring HIV. As the women tested for HIV twice a week, the researchers could identify participants with very recent HIV infection and give them antiretroviral treatment immediately.

This very early treatment has had a powerful effect: whereas viral loads are usually exceptionally high soon after infection, they were far lower in this group of women. Moreover, their CD4 counts remained good and key immune system functions were preserved.

The women will remain on HIV treatment for at least another two or three years. The women and their doctors will then have to decide whether or not to interrupt HIV treatment to see if the women can maintain control of HIV without the need for treatment.

Another study, using a different approach, had disappointing results, producing no significant change in the viral load or number of infected cells in people taking part. The approach attempts to ‘flush’ HIV out of the long-lived reservoir cells that make HIV infection lifelong. Three drugs were used – the cell-stimulating drug vorinostat, the anti-malaria drug hydroxychloroquine, which dampens inflammation, and the HIV entry inhibitor maraviroc. This study disproves the idea that the immune system itself will kill off HIV-infected reservoir cells if they are activated. It appears cytotoxic (cell-killing) drugs will need to be used to target reactivated reservoir cells.

Another approach is known as gene editing. This is a very hi-tech therapy in which the immune system is deliberately infected with an artificially-generated virus which, once inside immune cells, then targets, cuts and destroys DNA in the cells’ nucleus at specific points. Gene therapy is at a very early stage of development and in the case of HIV has not even been tried in animals yet. Results from laboratory experiments so far are mixed, but the conference heard some encouraging results.

Finally, there is work to use so-called broadly neutralising antibodies (bNAbs) as long-acting HIV drugs. However, HIV either acquires resistance to single bNAbs quickly or, in many cases has pre-existing resistance. Preliminary results from studies using combinations of two, three or four of these antibodies have better results. Combining these antibodies with certain other drugs could lead to a therapy that might be used as a once- or twice-yearly injection.

Because of the problem of HIV developing resistance to single agents, a senior scientist told the conference that curing people of HIV will have to involve combinations of drugs and approaches, just as HIV treatment does. Dr Anthony Fauci said that HIV cure research was roughly at the stage HIV treatment was at in 1990. Early experience with the first HIV drug AZT suggested that single agents might only have a limited effect, and dual combinations were starting to show more promise.

Injectable HIV therapies

A study in which two anti-HIV drugs were taken as injections every four or every eight weeks had good results. People taking part in the study had not taken HIV treatment before but needed to take HIV treatment as daily tablets for a few months before they could switch to the injections.

The injectable antiretrovirals were cabotegravir (a new integrase inhibitor) and rilpivirine (a non-nucleoside reverse transcriptase inhibitor).

In the study, one third of participants took these two injections every four weeks, one third took them every eight weeks (at a higher dose) and one third took daily tablets instead.

After almost a year, around nine in ten people had an undetectable viral load. Results were similar in all groups.

Nobody taking the injections had serious side-effects, although almost all had injection-site reactions (for example pain or swelling at the injection site, usually lasting a day or two). In interviews, most participants said that the injection side-effects were worthwhile when compared to taking daily pills.

Participants said that long-acting injectables were more simple, convenient and discreet than daily pills. Some said they helped reduce stigma and gave them relief from the daily reminder of living with HIV.

Other treatment news

Among the other studies on treatments:

• The integrase inhibitor raltegravir can be taken once a day, rather than twice a day (as is current practice). But a different dose needs to be given.

• A small study (with only 20 participants, all new to HIV treatment) suggested that a two-drug regimen of the integrase inhibitor dolutegravir and the nucleoside reverse transcriptase inhibitor (NRTI) lamivudine can suppress viral load to undetectable levels. We reported earlier results from this study last year.

• A new hepatitis C treatment, a tablet containing sofosbuvir and velpatasvir (Epclusa) is effective for people living with HIV who have hepatitis C. The treatments works for all hepatitis C genotypes.

Stigma and resilience

In an era of widespread HIV treatment and undetectable viral load, stigma remains a persistent feature in the lives of almost half of people living with diagnosed HIV in the UK, according to a study presented at the conference. Anticipated stigma (the person with HIV expecting someone else to have a poor opinion or bad reaction to them) was frequently reported, especially in the context of disclosing to potential sexual partners.

Nonetheless, the majority of people living with HIV scored highly on measures of psychological resilience, enabling them to cope better with stigma. For example, in response to the statement “I tend to bounce back after hardships”, two-thirds said this was often or nearly always true. In relation to “I am able to handle unpleasant or painful feelings”, half said this was often or nearly always true.

Overall, 27% of respondents had low resilience, 39% had medium resilience and 34% had high resilience. People with low resilience were more likely to experience stigma and to report negative experiences of living with HIV.

As an example of a person with high resilience, the researchers included this quote from an interview:

“I do not feel I require others’ acceptance or approval. I do not feel this status fundamentally changes the person I am but my willingness to believe in myself as undiminished has required of me to dig deep within and be courageous.”

For more information on stigma and how to deal with it, read NAM’s booklet ‘HIV, stigma & discrimination’.

PrEP judicial review ruling

A judicial review in the High Court has ruled that NHS England is responsible for funding pre-exposure prophylaxis (PrEP) and decisively rebutted all the arguments used by NHS England to avoid paying for the use of PrEP.

On 31 May, NHS England confirmed that it would not commission PrEP. NHS England said it does not have the legal power to commission PrEP as local authorities are the responsible commissioner for HIV prevention services.

In response National AIDS Trust sought a judicial review of the decision. This week Mr Justice Green said that NHS England was mistaken in its interpretation of its responsibilities. Furthermore, since the NHS pays for post-exposure prophylaxis (PEP), it should pay for PrEP too. The NHS is wrong to argue that the two interventions are different: they work in exactly the same way, by preventing infection from becoming established after transmission has taken place, the judge concluded.

NHS England said in response that the High Court ruling does not mean the medication will end up being funded by the NHS, and that in any case it will appeal against the ruling. NHS England says that a group of medications for various conditions, including PrEP, will now be assessed for prioritisation on the grounds of cost and impact. As part of this process manufacturers will have to submit new price offers to determine which of the interventions offer best value for money. This process is unlikely to be completed before the end of October. Only then will the NHS decide whether or not it will provide PrEP.

The health policy editor of The Guardian commented this week that the NHS’s handling of PrEP is symptomatic of a drive “to cut costs, at all costs.”

National AIDS Trust is seeking support to cover the legal costs of the judicial review. You can contribute to their crowdfunding campaign here.