HIV update - 5th August 2015

News from IAS 2015

This edition of HIV update covers news from the International AIDS Society conference (IAS 2015), which took place in Vancouver, Canada, in July.

Nineteen years ago, Vancouver was the venue for a historic International AIDS Conference. Research presented at that conference showed clearly that highly active antiretroviral therapy (HAART) prolonged life. The results presented at that conference, in 1996, transformed HIV infection from a terminal illness to a treatable condition and gave hope and health to millions of people living with HIV. Over the past two decades, further progress has made HIV treatment easier to tolerate and we now know that anyone diagnosed with HIV can expect a normal lifespan – if they receive HIV treatment.

The 2015 Vancouver conference represents another great transformation in the treatment – and prevention – of HIV. We learnt that it is never too early to start treatment, early treatment is not harmful, and that over a long period, effective treatment stops HIV transmission to sexual partners. Treatment soon after diagnosis will soon become the norm for people living with HIV.

Starting treatment

In May, we reported on the headline results of the START study, which showed that compared to starting treatment at a CD4 count below 350, early treatment for HIV protects against AIDS-defining illnesses and other serious illnesses.

Full results of the START study were presented at the International AIDS Society conference. The results showed that people who started treatment at CD4 cell counts above 500 were significantly less likely to die or to develop either an AIDS-defining illness or a serious non-AIDS illness during the study period. Early treatment reduced the risk of one of these outcomes by 57%. The study showed that early treatment was protective against AIDS-defining illnesses even though most people who delayed treatment spent most of their time in the study with a CD4 count well above the traditional 'danger zone' of below 200 or 350 cells/mm³.

One of the big questions the START study needed to answer was whether early treatment resulted in more treatment-related harm than the HIV-related harm it is intended to prevent. The answer was very clear: early treatment does not cause harm. There was no increase in serious drug toxicity in people who started treatment early.

The study also found that early treatment reduced the risk of developing cancer. This effect was most pronounced for the AIDS-defining cancers (Kaposi’s sarcoma and lymphoma). Early treatment did not reduce the risk of cardiovascular disease.

More than two-thirds of the AIDS and non-AIDS illnesses occurred at CD4 counts above 500, a level previously assumed to represent good health. This finding suggests two important changes to the accepted wisdom. Firstly, delaying treatment always carries a risk – we now know that it is potentially unsafe to delay treatment at any CD4 count, and that early diagnosis of HIV is essential. Secondly, the immune system begins to sustain damage very soon after HIV infection, and the CD4 count doesn’t always reflect that damage. Watching the CD4 count is no longer a reliable guide to when to start treatment.

The results of the START study will lead to a change in treatment guidelines all over the world. The World Health Organization has said that it will recommend treatment for all people living with HIV in guidelines due to be issued in September. In the United Kingdom, the British HIV Association has issued draft guidelines recommending treatment for all people living with HIV. The British guidelines stress the importance of readiness for treatment. In particular, people starting treatment should have an understanding of why treatment is needed, how it works and why it is important to take all doses as prescribed (adherence).

Same-day start to treatment is acceptable

A study in San Francisco found that starting HIV treatment on the day of HIV diagnosis was highly acceptable to people diagnosed with HIV at testing clinics in the city, with 95% of people accepting an offer to start treatment on the day of diagnosis, or on the following day.

The study was originally designed to encourage rapid uptake of treatment by people very recently infected with HIV, in the hope that a quick start to treatment would limit the size of the HIV reservoir in the body. Restricting the number of cells infected with HIV – the reservoir – might offer a better chance of curing HIV in the future, scientists have suggested. 70% of participants in this study had been infected very recently (acute infection).

San Francisco had already implemented a policy of offering HIV treatment to everyone at the time of diagnosis. This pilot found that offering treatment on the day of diagnosis more than halved the average time from HIV diagnosis to achieving undetectable viral load, by eliminating delays in visiting the clinic and picking up medication.

The programme also found that once people started treatment, they reached an undetectable viral load more quickly than people who started treatment at similar clinics in San Francisco after a delay between diagnosis and the offer of treatment. The researchers say that part of the reason for the more rapid response may have been the routine use of integrase inhibitors such as raltegravir (Isentress) and dolutegravir (Tivicay) in first-line treatment.

Treatment as prevention

Another important study presented at IAS 2015 showed that after more than four years of extra follow up, the study which proved that HIV treatment prevents HIV transmission continues to show no new infections in the partners of people taking HIV treatment. The HPTN 052 study compared the effects of early and delayed HIV treatment on transmission of HIV to regular partners. In 2011, the study reported that early treatment reduced HIV transmission to regular partners by 96%.

Follow up of couples in the study since 2011 continues to show no transmission to partners when people on HIV treatment have undetectable viral load. As in the first phase of the study, the follow up phase showed that transmission to partners had only taken place in the weeks immediately after starting treatment, before viral load was fully controlled (undetectable), or after treatment failure (viral rebound).

PrEP

Pre-exposure prophylaxis (PrEP) is a way of avoiding HIV infection by taking two antiretroviral drugs (tenofovir and emtricitabine) in one pill (Truvada). PrEP is a highly effective means of preventing HIV when taken according to dosing instructions. Studies have shown that daily dosing and dosing only around the time of sex provide the same level of protection.

Taking PrEP only around the time of sex might be preferred by some people who do not wish to take pills every day and who know roughly when they are likely to be having sex.

Large studies reported at IAS 2015 looked in more detail at how people coped with taking PrEP around the time of sex, and whether this is likely to be a feasible strategy for most people. In one study conducted in Bangkok, Cape Town and New York, the researchers wanted to see how many times people had sex after missing doses of PrEP – what they called 'coverage'. The studies found that in some places, taking daily PrEP resulted in better coverage than taking it either twice a week or only taking PrEP doses before and after sex. But in Bangkok there was no difference. Taking the dose two hours after sex was often reported to be a problem by people taking PrEP only before and after sex. Another before-and-after dosing schedule, used in a French PrEP study called Ipergay, advised taking a first post-sex dose within 24 hours after sex.

Studies of drug levels in people taking non-daily PrEP suggest that intermittent dosing will be suitable for anal sex, but it’s less clear that the same is true for vaginal sex.

Another study looking at how PrEP is being used in practice in the United States found that one-quarter of participants in the study had a primary partner living with HIV. Adherence to PrEP dosing was good, especially in those who reported condomless sex with at least two partners in the past three months. People without stable housing had greater difficulty in taking PrEP regularly.

These findings strongly suggest that there is no one-size-fits-all way of taking PrEP, and that people at higher risk of HIV infection will take PrEP – if they have access to it and if medical services are geared to their needs.

UK community organisations working on HIV prevention have issued a statement calling for access to PrEP now for all who need it – you can endorse it here.

Hepatitis C treatment

There was further good news regarding hepatitis C treatment at IAS 2015. Studies show that interferon-free antiviral treatment for hepatitis C is just as effective in people with hepatitis C and HIV co-infection as in people with hepatitis C alone. Until recently, hepatitis C treatment consisted of a combination of one direct-acting antiviral with pegylated interferon and ribavirin, which cured between 40% and 60% of people. This treatment is hard to tolerate and a lot of people don’t finish the treatment course. Interferon-free treatment cures over 90% of previously untreated people with most hepatitis C genotypes.

Studies presented at IAS 2015 now show that all the interferon-free combinations on the market – and a new combination being developed by Merck – achieve very high hepatitis C cure rates in people living with HIV. However, some studies showed a slightly lower response rate in people with cirrhosis, which is concerning, because in many countries access to these new interferon-free combinations is being restricted to people with cirrhosis on the grounds of cost.