Non-daily PrEP regimens provide extra options, but adherence is often better with daily dosing

Tim Holtz and Sharon Mannheimer at IAS 2015. Photo by Liz Highleyman,
This article is more than 9 years old. Click here for more recent articles on this topic

For some people in some settings, less frequent pre-exposure prophylaxis (PrEP) regimens with doses linked to sexual activity are feasible, with high numbers of sexual acts protected by PrEP, studies that were presented on Monday to the Eighth International AIDS Society Conference (IAS 2015) in Vancouver, Canada, show.

This may give people, who want to use PrEP, and their doctors additional options, allowing people to find a pattern of taking PrEP that best suits them. But the studies also found that more people are able to adhere to daily PrEP than non-daily regimens. Further, the actual effectiveness of non-daily regimens remains uncertain.

The studies presented today were in part inspired by the French IPERGAY study, so far the only study to demonstrate that a schedule of non-daily PrEP, with doses before and after sex, could be effective. (There were 86% fewer infections). However IPERGAY was conducted in a population of gay men who tended to have sex quite frequently. To prevent transmission during anal sex, four doses a week appear to be almost equivalent to seven doses. But it’s possible that people who have sex less frequently – and therefore take pills less frequently – will have lower levels of the drug in the body that are not protective.


event driven

In relation to pre-exposure prophylaxis (PrEP), this dosing schedule involves taking PrEP just before and after having sex. It is an alternative to daily dosing that is only recommended for people having anal sex, not vaginal sex. A double dose of PrEP should be taken 2-24 hours before anticipated sex, and then, if sex happens, additional pills 24 hours and 48 hours after the double dose. In the event of sex on several days in a row, one pill should be taken each day until 48 hours after the last sexual intercourse.

detectable viral load

When viral load is detectable, this indicates that HIV is replicating in the body. If the person is taking HIV treatment but their viral load is detectable, the treatment is not working properly. There may still be a risk of HIV transmission to sexual partners.


An umbrella term for people whose gender identity and/or gender expression differs from the sex they were assigned at birth.


Abnormal bowel movements, characterised by loose, watery or frequent stools, three or more times a day.


The feeling that one is about to vomit.

Presented in Vancouver in a late breaker session on Monday afternoon, HPTN 067/ADAPT is a trio of three randomised trials, investigating the feasibility and acceptability of different PrEP regimens with three distinct populations, in Bangkok, Harlem (New York) and Cape Town. The studies give insights into patterns of use and adherence but were not designed to answer questions about effectiveness. Larger, phase III trials would be needed to do that.

The researchers found that in a group of well-educated, motivated Thai gay men, each of the three PrEP regimens tested were feasible, acceptable and likely to protect against most exposures to HIV. The non-daily regimens required far fewer pills to be taken.

Challenging social circumstances were more commonly experienced by participants in Harlem and Cape Town. Adherence was generally not as good in these two locations. Moreover the daily regimen resulted in better adherence and likely protection against HIV than the non-daily options.

For qualitative data from ADAPT exploring barriers to and facilitators of taking PrEP, see this report.

The studies

In each city, around 180 participants were recruited and randomised to receive one of three Truvada PrEP regimens:

  • daily dosing,
  • twice-weekly dosing + an extra dose after sex, or
  • event-driven dosing (one dose up to 48 hours before sex, another 2 hours after sex).

Follow up was for six months. Adherence was measured by providing PrEP in pill-bottles which send an electronic signal when they are opened. Weekly phone calls to the participants collected information about recent sexual activity, which was correlated with the data on when pills were taken.

The populations in the three cities had different social, cultural and demographic characteristics. The researchers expected these to influence the acceptability of different regimens – they did not expect to find one regimen that would be appropriate everywhere.

  • Bangkok, Thailand: 176 men who have sex with men and two transgender women. Most were university educated, few were unemployed and average age was 31. 
  • Harlem, New York City, United States: 176 men who have sex with men and three transgender women. Over two-thirds were unemployed and over two-thirds were black. Average age was 30. 
  • Cape Town, South Africa: 179 women. Four-fifths were unemployed, a similar proportion was unmarried and average age was 26.

In each of the study sites, the participants had sex an average of once a week.


Across all sites, adherence was somewhat higher for the daily rather than the non-daily doses. For example, in Bangkok, 85% of daily doses, 79% of twice-weekly doses, and 65% of event-driven doses were taken as prescribed. In Harlem, the respective figures were 65%, 46% and 41%.

The primary analysis was of the percentage of reported sexual acts which were protected by PrEP, with doses both before and after sex.

  • In Bangkok, the daily regimen protected 85% of sexual acts, the twice-weekly regimen protected 84% and the event-driven regimen protected 74%.
  • In Harlem, the daily regimen protected 66% of sexual acts, the twice-weekly regimen protected 47% and the event-driven regimen protected 52%.
  • In Cape Town, the daily regimen protected 75% of sexual acts, the twice-weekly regimen protected 56% and the event-driven regimen protected 52%.

The doses that were missed were most often those which were meant to be taken after sex (both in the twice-weekly and event-driven regimens). Participants often found it difficult to take this dose when they were still with a sexual partner or were away from home.

The researchers also tested blood samples twice during the study to see if tenofovir could be detected, restricting the analysis to those participants who reported having sex in the previous week. In Bangkok, over 90% of participants in each arm had detectable drug, with no significant differences between arms.

In contrast, Harlem and Cape Town participants were more likely to have detectable drug if they had been asked to take PrEP daily.

Six people prescribed PrEP became HIV-positive (five in Cape Town, one in Harlem) but each had low or negligible levels of drug in their body.

One hoped-for advantage with non-daily regimens is that by reducing the number of pills, side-effects may be less frequent. However the data so far doesn't show statistically significant differences in the experience of side-effects between arms. This may be partly due to the limited number of people in each arm and the short period of follow-up. The side-effects that were reported (dizziness, headaches, nausea, diarrhoea etc.) were mild and mostly experienced during the first two months of taking PrEP.

But the non-daily regimens did require considerably fewer Truvada tablets, which could make providing PrEP more affordable. Sexual behaviour didn’t differ between PrEP regimens.


Presenting the Bangkok data, Timothy Holtz summed up several advantages of daily regimens: clearly proven to be effective, likely to offer more protection, more forgiving of missed doses, and helping people develop habits of daily pill-taking.

But he said that non-daily PrEP could be an option for those men who have sex somewhat infrequently and know in advance when they are likely to do so. The findings suggest some flexibility in the way in which PrEP can be prescribed.

Robert Grant, who led the HPTN 067/ADAPT studies, told a press conference that PrEP needs to be adaptable to the different circumstances of people’s lives. And non-daily use is happening anyway: “People do choose how to use PrEP, when to take it and when not to take it,” he said.


Holtz TH et al. HPTN 067/ADAPT study: a comparison of daily and non-daily pre-exposure prophylaxis dosing in Thai men who have sex with men, Bangkok, Thailand.  8th International AIDS Society Conference on HIV Pathogenesis, Treatment and Prevention, Vancouver, abstract MOAC0306LB, 2015.

You can download the slides from this presentation from the conference website here.

Mannheimer S et al. HPTN 067/ADAPT study: a comparison of daily and intermittent pre-exposure prophylaxis (PrEP) dosing for HIV prevention in men who have sex with men and transgender women in New York city. 8th International AIDS Society Conference on HIV Pathogenesis, Treatment and Prevention, Vancouver, abstract MOAC0305LB, 2015.

You can download the slides from this presentation from the conference website here.

Grant R et al. HPTN 067/ADAPT methods and results from women in Cape Town. 8th International AIDS Society Conference on HIV Pathogenesis, Treatment and Prevention, Vancouver, abstract MOSY0103, 2015.

A webcast of this presentation is available on the conference YouTube channel.

You can download the slides from this presentation from the conference website here.

The Cape Town results had been previously presented at CROI 2015 and reported on

Where available, you can view details of sessions, view abstracts, download presentation slides and find webcasts using the conference 'Programme at a Glance' tool.

You can also download a PDF of the abstract book from the conference website.