– Dr Adeodata R. Kekitiinwa
Short-cycle therapy (SCT) has previously shown promise in maintaining viral suppression among young people living with HIV. In this Q&A, conducted at the IAS Conference on HIV Science 2025, Dr Adeodata R. Kekitiinwa, Chief Investigator of the BREATHER Plus trial, highlights the rationale for evaluating SCT using dolutegravir-based regimens, key findings from the 96-week data, and the implications for adolescent HIV care in resource-limited settings.1 Dr Kekitiinwa also shares insights into adherence patterns and emerging alternatives such as long-acting injectables.
Adolescents living with HIV often have poorer treatment outcomes than other age groups and can face additional adherence challenges and lifelong antiretroviral therapy (ART) exposure. We conducted a previous trial (BREATHER) in children and young people living with HIV aged 8-24 which included Uganda. BREATHER used a different regimen that was efavirenz-based. This was previously considered the ‘gold standard’. BREATHER showed that SCT (five days on, two days off) controlled viral load just as well as daily ART and, importantly, was preferred by young participants who liked having weekends off medication.
The efavirenz-based combination therapy has now been universally replaced by tenofovir/lamivudine/dolutegravir (TLD) because dolutegravir is more robust than efavirenz and has fewer side-effects. This is why we wanted to test whether SCT with TLD would have similar results in BREATHER Plus to the prior BREATHER trial, because there are some pharmacological differences between efavirenz and dolutegravir. There is minimal evidence to date investigating SCT with dolutegravir-based triple drug ART.
The BREATHER Plus trial tested SCT, where participants took HIV medicines for five consecutive days, and then had two days off treatment. This was compared to CT, where people took their HIV medicines every day. The aim of the trial was to test whether SCT was as safe and as effective at keeping the HIV viral undetectable as CT.
Participants were young adolescents aged 12-19 years enrolled in five sites in four African countries (Uganda, Kenya, Zimbabwe and South Africa). To enrol, they had to be virologically suppressed and already on dolutegravir-based triple ART and have an HIV viral load <50 copies/ml for more than a year, and no history of treatment failure.
At 96 weeks, BREATHER Plus found that SCT with TLD was less effective at maintaining viral suppression than CT (keeping the HIV viral load <50 copies/ml). The proportion of young people with two consecutive tests with viral loads ≥50 copies/mL was 10% in the SCT group, compared to 5% of those in the CT group. This difference was significant, showing that SCT was inferior to CT at maintaining viral suppression to <50 copies/ml or “undetectable”.
In BREATHER Plus, viral load monitoring was every 6-12 months to align with standard of care in the countries included in the trial. The results differ from previous trials of SCT, which have found it is as good as CT when used in adults, or young people predominately on different ART combinations, all of whom had relatively frequent (at least every 12 weeks) real-time viral load monitoring which were shared with the clinicians to support patient management. In these previous studies, the risk of failure may have been reduced through identifying viral ‘blips’ earlier in parallel with enhanced clinical contact and adherence counselling to help participants resuppress quickly without returning to CT. Ultimately BREATHER Plus findings are applicable to settings with 6-12 monthly viral load testing.
The Medication Event Monitoring System (MEMS) Cap sub-study was in 210 adolescents – so just under 50% of all participants in the trial. Half the sub-study participants used MEMS Caps for 6 months in year 1, and half for 6 months in year 2. Over Monday to Thursday (when all adolescents in the SCT group and the daily TLD CT group should have taken their ART) we saw 92% bottle openings in both groups. Adherence was higher than in the previous BREATHER trial MEMS Cap sub-study (mentioned above), where bottle openings were 84% in the SCT group and 89% in the daily BREATHER group. In BREATHER Plus the adherence demonstrated in the MEMS Cap sub-study was slightly lower than self-reported adherence. In the MEMS Cap sub-study there was >90% adherence on days tablets were prescribed as per strategy in both trial groups. It should be emphasized that adherence by both self-report and MEMS Cap were relatively good in BREATHER Plus and likely to be higher than in the real-life setting.
It is important to remember that the frequency of study visits and adherence counselling at each visit in BREATHER Plus was much more than could ever be offered outside of a trial (8 weekly visits in year 1 and 12 weekly visits in year 2 onwards). Additionally, all the participants in the trial had to meet stringent inclusion criteria to participate, including having a viral load <50 copies/ml for over a year. Despite this we still saw that SCT did not work as well as daily treatment.
In a general setting, these results reinforce that the current treatment, which involves taking oral ART every day, is the best way to keep HIV below 50 copies/mL (undetectable). This will have individual health benefits in terms of overall health and the potential for development of drug resistance but also at the population level in terms of onward transmission (vertical and horizontal). Therefore, our results indicate that young people living with HIV should continue to take their tablets every day without breaks.
Although disappointing, BREATHER Plus findings were very clear. We are continuing to work on new trials to help young people living with HIV manage their treatment more easily. For example, our LATA trial (NCT05154747) is investigating if long-acting injectable HIV medicines work as well as HIV medicines, to keep the virus under control. We expect to find out the results from LATA in 2026.2
The World Health Organization formally recommended Gilead’s lenacapavir as a twice-yearly long-acting injectable pre-exposure prophylaxis (PrEP) at IAS 2025. With nearly 100% efficacy in trials, it offers a game‑changing alternative for individuals who struggle with daily pill routines, especially key populations facing adherence, stigma, or access barriers. This marks a major policy shift emphasizing expanded PrEP choices for those that need the service.
Presented at IAS 2025: OAS0104LB: 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
About Dr Adeodata R. Kekitiinwa
Dr Adeodata R. Kekitiinwa is a Ugandan paediatrician, Emeritus Associate Professor of Paediatrics at Baylor College of Medicine, Texas, USA, and Clinical Research Site Leader at Baylor Foundation Uganda. She is the Chief Investigator for the BREATHER Plus trial and an Investigator on the LATA trial. Dr Kekitiinwa also serves as the Investigator of Record on the MPAACT P1115 and 2028 trials. With a career spanning over 30 years, she has led pioneering work in paediatric HIV care and research, including establishing Uganda’s Ministry of Health Paediatric and Adolescent HIV unit. She has authored more than 90 peer-reviewed articles and received multiple international awards for her contributions to maternal and child health and HIV research.
Editor: Katey Gabrysch, Editorial Director.
Disclosures: Adeodata R. Kekitiinwa has nothing to disclose in relation to this interview. No funding was received in the publication of this article.
This content has been developed independently by Touch Medical Media for touchINFECTIOUS DISEASES. Views expressed are the speaker’s own and do not necessarily reflect the views of Touch Medical Media.
Cite: Anti-CGRP therapies improve migraine control and adherence: Simona Sacco, EAN 2025. touchINFECTIOUS DISEASES. 17 July 2025.
References:
- Celum C, Bekker LG, Mullick S, et al. PURPOSE 1: Twice-yearly lenacapavir for HIV prevention in adolescent girls and young women in South Africa and Uganda. Presented at: 25th International AIDS Conference (AIDS 2025). 22–26 July 2025. Abstract #6712. Kigala, Rwanda.
- ClinicalTrials.gov. Long-Acting Treatment in Adolescents (LATA) (LATA) NCT05154747. Available at: https://clinicaltrials.gov/study/NCT05154747 (accessed 17 July 2025).
