Poor adherence may be an obstacle to intermittent PrEP

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Adherence to intermittent pre-exposure prophylaxis (PrEP) is significantly poorer than adherence to daily PrEP, according to a study published in PLoS One.

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 study participants.



A pill or liquid which looks and tastes exactly like a real drug, but contains no active substance.


How well something works (in a research study). See also ‘effectiveness’.

concentration (of a drug)

The level of a drug in the blood or other body fluid or tissue.

prospective study

A type of longitudinal study in which people join the study and information is then collected on them for several weeks, months or years. 


Studies aim to give information that will be applicable to a large group of people (e.g. adults with diagnosed HIV in the UK). Because it is impractical to conduct a study with such a large group, only a sub-group (a sample) takes part in a study. This isn’t a problem as long as the characteristics of the sample are similar to those of the wider group (e.g. in terms of age, gender, CD4 count and years since diagnosis).

“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 acceptability.

The treatment used in the study was Truvada.  Participants were randomised into four arms.

  • Daily Truvada.

  • Daily placebo.

  • Intermittent Truvada (Monday, Friday and within two hours after sex).

  • Intermittent placebo.

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.

“Daily 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.”


Mutua G et al. Safety and adherence to intermittent pre-exposure prophylaxis (PrEP) for HIV-1 in African men who have sex with men and female sex workers. PLoS One, 7 (4): e33103, 2012 (click here for the open-access article).