Five doses a week could be a safe option for adults: crisis response to ART stock-outs
16 July 2025. Related: Early access, Conference reports, Treatment strategies, IAS 13th Kigali 2025.
Simon Collins, HIV i-Base
The potential to use reduced dosing was one of the controversial issues at IAS 2025 with conflicting conclusions from two late-breaker studies (covered below and in a second report).
A systematic review and meta-analysis of eight studies using 5, 4 or 3 compared to 7 daily doses each week found this to be both safe and effective. This study was to look at a potential crisis response to sudden cuts in PEPFAR and USAID funding. Results were presented by Cassie Fairhead from the Royal Free Hospital in London. [1]
The combined studies included 1356 participants (22% women), generally followed for 24 to 28 weeks. Exclusion criteria generally included pregnancy, active HBV and high baseline CD4 (in four studies).
Study size ranged from 19 to 636 participants, with the largest being the French QUATUOR study (that supports French guidelines recommending 4- or 5-dose ART in selected cases). Four studies used 5 doses a week, one used 4, and two went down to as few as 3 doses a week, but these were the smallest studies and participants had no previous drug resistance or treatment failure.
The study found that across eight trials, there was no difference in efficacy between taking ART 5 days a week and continuous ART. This included viral load suppression (including ultra-sensitive), dosing strategy, risk of drug resistance and markers of inflammation. The few cases of viral failure resuppressed when returning to daily dosing.
Both self-reported adherence and acceptability were also high.
These studies selected participants with a long history of viral suppression and good adherence. They also included frequent access to viral load and resistance tests, which enabled early switching back to daily dosing before the chance for resistance to develop.
The study concluded that for countries with urgent drug shortages, extending ART supplies could have clinical benefits for people with HIV and population benefits of minimising HIV transmission. Also, that the results support the need for rapid studies in other settings.
The study was recently published in the journal AIDS. [2]
comment
Although this study showed that less than daily dosing can be safe and effective in some settings, the BREATHER-Plus study, presented later at IAS 2025, reported that only taking 5 compared to 7 daily doses was inferior at 96 weeks in adolescents using tenofovir/lamivudine/dolutegravir (TLD). [3, 4]
There is now an urgent need for whether similar results can be achieved in other settings.
This is a crisis option as many people have already been forced to interrupt ART since 20 January.
These studies provide data on whether maintaining lower dosing is a better strategy than interrupting ART.
Results are also keenly awaited from the BREATHER-Plus study being presented as a late-breaking oral presentation later in the conference. This large randomised study in more than 400 adolescents will add to the data on using 5-on 2-off dosing. [3]
Simon Collins was a community representative on this study.
References
- Fairhead C et al. Systematic review and meta-analysis of the efficacy of intermittent antiretroviral therapy dosing: a crisis response to the sudden cuts in USAID and PEPFAR funding. IAS 2025. Oral late-breaker abstract OAB0106LB.
https://programme.ias2025.org/Abstract/Abstract/?abstractid=6516 - HTB. Reduced dosing: a possible crisis response to ART stockouts and closed clinics. (5 May 2025).
https://i-base.info/htb/51001 - 5-on 2-off dosing is inferior to continuous ART in adolescents in BREATHER Plus study. HTB (16 July 2025).
https://i-base.info/htb/51842 - Kekitiinwa A et al for the BREATHER-Plus study group. Short cycle antiretroviral therapy (ART) with weekends off is inferior to continuous ART in adolescents living with HIV receiving tenofovir disoproxil fumarate/lamivudine/dolutegravir (TLD) in sub-Saharan Africa: BREATHER Plus 96-week results. IAS 2025. Oral late-breaker abstract OAS0104LB.
https://programme.ias2025.org/Abstract/Abstract/?abstractid=6712