Q&A on the PROUD study and PrEP results from CROI

24 March 2015. Related: Conference reports, CROI 22 (Retrovirus) 2015.

This Q&A page relates to presentations on Tuesday 24 February in Seattle at an important HIV conference called CROI.

What is new from the PROUD Study?

Important news in Seattle included the details of how many people became HIV positive in the PROUD Study. As the study is still running, the results were up until October 2014, when the study was changed.

We already knew that PrEP worked and that much more people had become HIV positive in the group that were not taking PrEP.  But we didn’t know how  big the difference was.

The presentation at CROI included these figures. It included information about the people who became HIV positive. So the new results tell us how effective PrEP was.

Out of 545 people in the study, about half were in the immediate PrEP group and half had to wait for a year.

How many people in the study became HIV positive?

Overall, 22 people in the study have since tested HIV positive. Only 3 of these people were in the group taking PrEP compared to 19 in the group waiting for PrEP. This difference was very significant.

Adjusting for different time people contributed to the study allows the researchers to compare the results more evenly. This reports results as the number of people who became positive out of 100 people over one year.

These rates were 1.3 vs 8.9 per 100 patient years of follow, for the PrEP vs deferred groups, respectively.

How does this compare to HIV rate that were expected?

The rate of new infections was much higher than expected. The researchers only expected to see 3 new infections for every 100 people follow for a year.

The higher rate was because the study was able to enrol people at very high risk.

Is this aspect of the PROUD results shocking?

No. We already know that each year in the UK about 6000 people are diagnosed HIV positive and about half of these are gay men.

The HIV rate in the study is important for showing that the researchers were able to connect to people who were at very high risk of becoming HIV positive.

This means that PrEP can be put into practice. It means that offering PrEP to people who are at high risk should also be easy to do.

The higher rates of HIV in the study do not mean that HIV rates themselves are any higher – just that the study was able to enrol the people who were most likely to benefit.

How effective was PrEP?

Overall, PrEP reduced the chance of HIV transmission by 86%.

This is worked out by comparing the different HIV rates in each study group.

There was very little chance that this just happened by chance. Researchers define how significant something is by using something called a p-value. A p-value that is smaller than 0.05 is called significant. The p-value for the PROUD result was 0.0002 which means it is highly significant.

However, because researchers have to allow for other factors, they estimate range around the 86% rate which might also be the true rate. This minimum and maximum effectiveness range was 56% to 98%. This is called the 95% confidence interval.

Does this mean that someone taking PrEP only gets 86% protection?

No. The 86% figure is an average level of protection calculated from the people in both two groups. Some people didn’t stay in the study. Some people might not have been taking the meds. These people are still included in the 86% protection.

Why did some people in the PrEP group became positive?

This is a very important aspect of the study.

It also makes the results even more compelling and could be interpreted as PrEP being higher than 86% effective.

Brief details were available for the three people in the PrEP group who became HIV positive.

One of these participants was negative when they enrolled but HIV positive at week four in the study. This means they could have been infected before the study started, or before they started taking PrEP.

The other two people had taken long breaks from visiting the study clinic – one for 14 months and another four nine months.These breaks make it unlikely that they were taking daily PrEP, because they had not returned to the clinic to get their prescription renewed.

These three cases might mean that no one in the study actually become HIV positive while taking PrEP.

Were there any safety concerns from taking PrEP?

Everyone taking PrEP was monitored for side effects.

There were few reports of side effects. Only ten people stopped treatment because of side effects (4%) and nine of these people restarted PrEP later.

There were no serious kidney-related side effects.

Did anyone in the study develop drug resistance? 

Three people developed resistance to one of the drugs used in PrEP.

This was to the drug in PrEP called FTC.

Although this is important it has less impact on future use of treatment than drug resistance to tenofovir. No-one in the study develop resistance to tenofovir.

Drug resistance can only occur if someone becomes HIV positive and continues taking PrEP.

When did the people become positive who were not getting PrEP?

Of the 19 people who became positive in the deferred PrEP group, six tested HIV positive after the first month. These people may therefore have been infected before or as they entered the study.

The other 13 people became HIV positive at different times during the study.

Did people on PrEP change their level of risk?

Getting PrEP didn’t make people started having more risky sex. This was even though people already knew that PrEP worked before the study started.

PrEP studies usually report the opposite effect. Sometimes risky sex is because there is no out let for people to be able to talk about HIV, sex and risk.

Many people say PrEP makes them more aware of HIV. As a result, people are often more in control of the type of sex that they have.

This was mainly shown in PROUD by not seeing any difference in other STIs between the two groups. If the PrEP group had been changing their behaviour to have more risky sex, then it would be expected they would have more STIs.

Although the study include questionnaires on risk behaviour, not enough people engaged with this side of the research.

Did anyone use Post Exposure Prophylaxis (PEP) in the study?

The is a good question. In the year before entering the study about one third of participants had used PEP and 17 people had used PEP more than once.

In the UK, PEP involves taking HIV meds for a month and this includes the same meds used in PrEP.

During the study, 83 out of 269 people in the deferred group (31%) also used PEP. This group used PEP 174 times with some people using PEP more than once.

Even with this protection, HIV rates were still much higher than in the group using PrEP.

What about other PrEP studies at the same conference?

Several other PrEP studies at CROI were also important, including the IPERGAY study.

What were the results from IPERGAY?

IPERGAY is a French and Canadian study that has been running at the same time as PROUD. When PROUD found and early result that PrEP was effective, the IPERGAY team looked at their results and went on the change their study too.

IPERGAY studied an experimental way of dosing PrEP. This study also included a placebo pill so that people in the study did not know whether they were getting the active drug or an inactive dummy pill.

Instead of taking a daily pill, IPERGAY looked at people taking PrEP only when they expected to be having sex.

The dosing in IPERGAY involved:

• Taking a double-dose of PrEP (two pills) on the day before having sex. This could be up to 24 hour before but not less than two hours before.
• Taking PrEP on the day of sex, and on each subsequent day they had sex.
• Taking a final PrEP the day after sex.
• Other than the first dose, not to take PrEP more than once in any 24 hour period.

Out of 414 people in the study, 16 became HIV positive: 2 who were getting the active pill and 14 who were getting the dummy pill.

This resulted in the IPERGAY study also showing that PrEP was 86% effective.

Can people in PROUD switch to the IPERGAY dosing?

No, this is not recommended. Currently there is more evidence to support taking daily PrEP.

Although the IPERGAY results are very interesting they will be the focus of more detailed analysis.

It is important that people in the PROUD study continue to take daily PrEP. Please talk to your doctor about the IPERGAY results though,

Can I get PrEP in the UK on the NHS?

Currently, PrEP is only available on the NHS to people who are already enrolled in the PROUD Study.

Will PrEP become available soon?

Several groups that are responsible for making deciding about PrEP are already reviewing these and other study results.

The speed that it takes the NHS to decide on PrEP might depend on the level of demand that doctors get from their patients. This is something to ask your doctor about.

You can also show your support by signing this online community statement asking for early access. It already has more than 1300 signatures.
http://www.prepaccess.org.uk

Where can I get more information about PrEP results?

This link includes information about PrEP that was produced for earlier in the study.

Q&A on PrEP in the UK and changes to the HIV PROUD study

The PROUD website includes more information about these results.
http://www.proud.mrc.ac.uk