So how infectious are we really?

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Post by David Menadue02 Sep 2011

It’s not surprising that the recent news about the reduced infectiousness of people with HIV on effective treatment has raised a lot of interest.

I spoke with Andrew Grulich from the Kirby Institute in Sydney and he believes that it’s all starting to look very much like another 1996 moment.

"What we saw in 1996 was a revolution in the treatment of HIV through the introduction of highly active antiretroviral therapy (HAART)," he said. "Now with the results of several recent studies, there is hope that we can go one step further and that treatment to prevent HIV may become a reality."

Professor Grulich is referring to HPTN 052, a study that was investigating whether the positive partners in serodiscordant couples could still transmit HIV on HAART .The trial was discontinued recently after they found that there was a 96% reduction in HIV transmission within the group who had commenced treatment versus those who hadn’t.

He is also referring to the moderate effectiveness of the 2010 pre-exposure prophylaxis study, iPREX. Results showed that the group who took tenofovir as a prophylaxis against HIV experienced 42% fewer infections than those in the non-treatment arm. What’s more, this reduction rose to more than 72% for those who took their treatments on 90% or more of the days required.1

A GAME-CHANGER FOR HIV PREVENTION?

HPTN 052 was run by the National Institute of Allergy and Infectious Diseases (NIAID) in the United States. It recruited 1,763 serodiscordant couples from nine countries, 97% of whom were heterosexual.2

Approximately half the couples were put on HAART immediately and the other half were counselled on safe sex, provided with free condoms and treated for sexually transmitted infections (STIs).

The trial started in 2005 and was due to run until 2015 but was halted by the Data and Safety Monitoring Board when it discovered that out of 28 new infections that had occurred, 27 were in the delayed treatment arm .Clearly, this group had higher rates and so was put on ART immediately.

This news comes after the Swiss Statement concluded in 2008 that the risk of transmitting HIV was greatly reduced if people were on effective antiretrovirals with an undetectable viral load .

It brings hope to organisations like UNAIDS that, providing funds can be found, antiretrovirals may play a major role in ending the epidemic in developing countries.

REASSURANCE FOR HETEROSEXUALS

This news will be of greatest reassurance to heterosexual serodiscordant couples, although scientific experts have cautioned people against abandoning safe sex.

Further studies will test the validity of this trial and, for some, even a 96% reduction in HIV risk is not enough to contemplate doing away with condoms altogether.

The difficulty now is how gay male serodiscordant couples can interpret these findings.

Professor Grulich claims that receptive anal sex is about 15 times more risky for HIV transmission than vaginal sex. It’s time gay couples were studied to compare the relative rates of transmission.

AUSTRALIAN STUDY IN GAY COUPLES

Such a trial has already been funded and approved in Australia by the National Health and Medical Research Council, to be led by Professor Grulich and his team at the Kirby Institute.

In what is possibly a world first, the study will begin recruiting gay male serodiscordant couples in Sydney and Melbourne. Later recruitment may also be extended to Brisbane, Adelaide and to Bangkok in Thailand. Recruitment will be through doctors’ clinics.3

Both partners will be required to enrol in the trial. It will involve a greater commitment on the part of the negative partner as he will be required to get regular check-ups for HIV and STIs and complete behavioural questionnaires at interview. The positive partner will just need to provide normal blood results as a part of their regular care, and complete occasional attitudinal questionnaires. There is also an option for the positive partner to provide regular semen samples for HIV viral load testing, although this is not a requirement for participation in the study.

"The difficulty now is how gay male serodiscordant couples can interpret these findings."

Grulich is already seeing a great interest in the study.

"There is understandable concern amongst gay serodiscordant couples about risk-taking and many people want to be able to quantify that risk," he says. "Many are not interested in throwing away condoms altogether but want to decrease their anxiety if occasional unprotected sex happens."

The results of the study and other studies in gay men around the world will be very important. There are unanswered questions about HIV transmission between gay men. We have not seen a sustained decrease in the level of HIV infections amongst gay men since the '90s, even though we have had relatively effective treatments since then.

Grulich wants to know the reason for this.

"We know approximately one-third of new infections are transmitted by people who don’t know they have the virus and many of these are at their most infectious stage if they have just contracted it," he continues. "Certainly the increases in sexually transmitted infections (STIs) in gay men have played a role as we know that people’s viral load  and infectiousness also increases in the presence of an STI."

LOWER RATE OF INFECTIONS?

Professor Kit Fairley, Director of the Melbourne Sexual Health Centre, thinks there is evidence of a decrease in the infectiousness of HIV-positive people. He says there has been a decline in the numbers of HIV notifications for every 100 people living with HIV infection.

In other words: as the numbers of positive people are increasing, the numbers of new diagnoses has not gone up proportionately.

This, he believes, is probably due to HIV-positive people being less infectious.

An alternative explanation may be that as many HIV-positive people enter their 50s and 60s, they may be having less at-risk sex than previously.

"The critical time for HIV infection is when it is in the early stages in someone’s body," says Fairley.

He explained how science has shown that, out of the hundreds of thousands of virions present in a positive person’s body, usually only one gets through to make the infection happen. The virus is naturally more infectious than the others and so when it multiplies rapidly during early infection, all the HIV viruses present are naturally more infectious. Five years down the track, the viruses have changed so most are less infectious than these early ones. Therefore, people with early HIV infection are more infectious than those with established HIV infection even if their viral load is exactly the same.

Fairley believes this is an argument for getting people tested as early and frequently as possible to try to limit potential new infections. Dr Tim Read, also from the Centre, is running a trial on rapid testing in men who have sex with men (MSM) to see if this increases their frequency of testing. Rapid testing provides results in 20 minutes compared with the current one-week wait for laboratory results.

These rapid tests are currently not licensed in Australia and if they are to be in the future, it would seem likely that they will only be for clinical use.

There are too many concerns about people receiving a positive result on their own for authorities to be likely to approve the idea of home testing for HIV.

PRESSURE TO TREAT EARLIER

By showing that treatment in people with more than 350 T-cells reduces infections, HPTN 052 will undoubtedly give rise to arguments that positive people should be treating sooner.

At the moment, the Australian Guidelines state that it is recommended that a person with HIV go on treatment when their CD4 counts get between 350 and 500. The commentary on the US Guidelines is currently suggesting that a start at 500 CD4s will soon be recommended and soon there may be pressure for Australian authorities to move in this direction, too.

A monograph from AFAO called Trick or Treat looked at the ethical and clinical implications of getting positive people onto treatments sooner rather than later.

In his chapter in the monograph, Dr Sean Slavin from NAPWHA says that his organisation has always maintained that there must be a demonstrated clinical benefit for people to treat earlier and it should not just be about protecting others.4 The START Study has been enrolling people with HIV in Australia (and many other countries) for some months now. It is designed to determine the best time to start treatments by comparing people who start when their CD4s get to 350 with people who begin at 500.

In the absence of some of the unpleasant side effects many of us experienced in the early days of HAART and with new evidence about the long-term effects of HIV on the body, the theory is that starting earlier will have significant clinical benefits to PLHIVin the long term.

There is also no doubt that those of us with negative partners will be keen to reduce our infectiousness and the probability of transmitting the virus to our partner. This could mean that positive people may ask their doctors if they can go on treatments earlier. For this to happen, the Antiretroviral Guidelines will need to be updated. And this will require more evidence such as the results of START when it reports.

Similarly, positive people who have a lot of casual sex will want to know how to reduce infectiousness – but for these people, there will always likely be complications. Having an increased number of partners greatly increases the chances of getting an STI ,and a higher viral load  certainly makes people more infectious.

Not every positive person will be ready or willing to take HIV treatments earlier, either. It takes a psychological adjustment to start taking pills for the rest of your life and it is important to get your mental approach to treatments right so you take them properly and they will be effective.

For the moment, condoms and lube will have to remain an essential part of our sex lives. There is still some risk for heterosexual serodiscordant couples on treatment and considerable uncertainty about the risks for gay couples. Taking treatments and getting an undetectable viral load have still not been proven to be an effective prevention strategy on their own.

  1. Results of the iPrEx Pre-Exposure Prophylaxis trial AfAo briefing Paper, November 2010. See www.afao.org.au
  2. See www.niaid.nih.gov/news/Qa/pages/hptn052qa.aspx
  3. For more information contact Ben Bavington at the Kirby Institute:bbavington@kirby.unsw.edu.au
  4. Dean Murphy (ed) Trick or Treat, AFAO monograph, 2009: Sean Slavin ‘Treatment as Prevention: A Paradox We can live With’