Adherence to intermittent pre-exposure
prophylaxis (PrEP) is significantly poorer than adherence to daily PrEP,
according to a study published in PLoS
The research involved men who have sex with
men (MSM) and female sex workers in Kenya. Average adherence among the
individuals taking daily treatment was 83%, but fell to just 55% for those
taking intermittent therapy.
However, daily and intermittent PrEP
appeared to be equally safe and both regimens were highly acceptable to the
“Our findings suggest that adherence to
intermittent dosing regimens…may be more difficult than adherence to daily
dosing,” write the authors.
Nevertheless, they believe that
intermittent dosing may still be appropriate “if intracellular drug levels,
which correlate with prevention of HIV acquisition, can be attained with less
than daily dosing and if barriers to adherence can be addressed”.
PrEP is a promising HIV prevention
technology. It involves HIV-negative people taking daily antiretroviral therapy to reduce their risk of
infection with HIV. Its safety and efficacy is currently being investigated in
clinical trials. The most widely used regimen is Truvada (FTC/tenofovir). Results
of the iPrEX study involving MSM showed that the therapy reduced the overall
risk of acquisition of HIV by 44%. Adherence was key to the success of the
treatment. If participants took 90% of more of their doses, then the treatment had
73% efficacy, which increased to 92% among people who had detectable
levels of antiretrovirals.
Critics of PrEP cite cost and long-term toxicities
as barriers to its use. Intermittent dosing may help overcome these obstacles. But
little is known about adherence to intermittent PrEP, its safety and its
acceptability to at-risk populations.
Therefore, investigators from the
International AIDS Vaccine Initiative (IAVI) designed a prospective, randomised,
placebo-controlled trial involving MSM and female sex workers comparing rates
of adherence between the two treatment strategies, as well as their safety and
The treatment used in the study was Truvada.
Participants were randomised into four arms.
Adherence was recorded electronically each
time the cap containing the assigned therapy was opened. Data on post-coital
adherence was collected via text messaging.
A total of 67 MSM and five female sex
workers were recruited to the study, which lasted four months.
Median overall adherence to the daily
regimen (both Truvada and the
placebo) was 83%. This compared to an adherence rate of 55% for the
intermittent regimen (Monday and Friday doses). The difference in the rate of
adherence to daily and intermittent dosing was significant (p = 0.003). Preliminary
analysis suggested that only 26% of post-coital doses were taken.
pill-taking behaviour is more routine and may be easier to remember than fixed,
intermittent, twice weekly doses,” suggest the investigators. Alternatively,
the poor rate of adherence to intermittent treatment could be due to perceived
risk of HIV. The investigators explain: “If perceived HIV risk is low on
assigned days, adherence may be lower, whereas daily pill adherence may involve
less frequent consideration of perceived HIV risk.”
When the investigators adjusted their
results to take account of extra opening of pill containers and the removal of
doses to carry in pillboxes, the rate of adherence to daily therapy increased
to 92% and the rate of adherence to post-coital dosing increased to 88%.
Safety data were comparable for daily and
intermittent dosing and between the treatment and placebo arms. Both daily and
intermittent dosing were highly acceptable (80 vs 86%).
There was little evidence that
participation in the study was associated with sexual disinhibition. The median
number of monthly sex partners was three at baseline. This had increased to a
median of four by month four of the study. However, the investigators believe
that sexual activity at the start of the study was under-reported.
Aware that their findings are limited by
the small sample size, the investigators call for further research comparing
daily and intermittent PrEP. “Larger studies…with longer follow-up in
additional at-risk populations can examine whether fixed intermittent PrEP
regimens can achieve drug levels comparable to the minimum effective
concentration which may be determined by ongoing efficacy trials.”