Forty-one people out of 1603 participants (2.6%) became HIV
positive during the study. Thirteen of these were in the group that had elected
not to take PrEP (annual incidence rate, 2.6%) while 28 were in the majority
who had elected to receive PrEP (annual incidence rate 1.8%).
However, seven of these participants had actually stopped taking PrEP more than two months before they became HIV positive, in five
cases because of side-effects.
This meant that HIV infection rates in people on PrEP were 36%
lower than in people not on PrEP. However, people who chose not to take PrEP had,
as one might expect, lower rates of HIV risk behaviour at the start of the
study than those who elected to take PrEP. Adjusting for the higher risk of HIV acquisition
in people taking PrEP resulted in an effectiveness of 49%.
As noted above, there were no infections in participants
with drug levels consistent with taking PrEP at least four times a week. However,
only a third of participants actually achieved this level of adherence, underlining
the fact that the biggest challenge for the usefulness of PrEP will be
adherence. Adherence was higher in people with higher levels of education. It was 69% higher in participants
reporting receptive anal sex without a condom, 57% higher in participants
reporting more than five sexual partners
in the previous three months, and 40% higher in participants with a known HIV-positive partner, indicating that people were adjusting their PrEP use according to their perceived risk of acquiring HIV.
Principal researcher Professor Robert Grant, commenting on this, said: "If people were at higher risk they took more PrEP and adhered to it better. I think this contradicts previous assumptions that people together enough to use PrEP would already be managing risk in other ways: it shows that people who are at risk can take reasonable and appropriate decisions on their own behalf."
Age, however, was the strongest determent
of adherence: participants in their 30s were twice as likely to have detectable
drug levels in their blood as participants under 25, and over-40s three times as
likely. Rates of adherence were not associated with recreational drug use or alcohol.
Adherence tailed off gradually over time, and adherence that tailed off faster was associated with becoming infected with HIV.
The researchers noted a ‘PrEP cascade’ effect whereby 75% of
those whose risk behaviour indicated a need for PrEP actually chose to start taking it; 93% of
them returned three months later; 93% of them were still being dispensed PrEP but only 70% were actually
taking it in significant amounts. Adding in planned discontinuations for side-effects or by patient choice (during the study, 16% of participants were in a
planned discontinuation at one time or another), this meant that only 39% of
study participants who were at high risk of HIV at the start of the study were
taking clinically meaningful doses of PrEP three months later.
If people stopped, they tended to stop early, after what the
researchers called “a brief period of engagement with PrEP”. People were much
less likely to discontinue PrEP later on in the study.
Interestingly, although taking
PrEP was related to sexual risk, receiving
it was not, indicating that a lot of people were stockpiling it at home,
possibly for times they did feel at risk, though a pattern of intermittent use
was rarer than simply stopping taking it.
One other big influence on adherence was whether people believed
PrEP would work or not. News of the efficacy of PrEP from iPrEx and other RCTs
was released about halfway through the follow-up period in iPrEx OLE and after this
there was a substantial improvement in adherence seen in the men in Peru, who
also tended to be younger than the other groups.
Self-reported sexual risk behaviour declined during the
study: at the start 34% of those allocated PrEP reported receptive anal sex without
a condom and this dropped to 25% during the study: in those not allocated PrEP it started at 27% and ended at 20%, in other
words being allocated PrEP made no difference to risk behaviour. As an
independent measure of risk exposure, syphilis incidence was 7.2% a year in participants
allocated PrEP and 5.4% in those not allocated it, not a statistically