Short Cycle ART Noninferior to Continuous Therapy in Youth With HIV

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Standard-dose efavirenz-based short cycle therapy is a viable option for virologically suppressed HIV-1-infected young people receiving first-line antiretroviral therapy with 3-monthly viral load monitoring.

Short cycle therapy (SCT) comprising an antiretroviral therapy (ART) regime of 5 days on and 2 off achieved sustainable noninferiority of virological suppression in young people with HIV compared with continuous therapy (CT) over a median of 3.6 years, according to research published in PLos One.

Participants aged 8 to 24 years with virological suppression receiving an efavirenz (EFV)-based first-line ART were included in open-label, noninferiority trial (BREATHER; identifier: NCT01641016). They were randomly assigned 1:1, stratified by age and non-African/African sites, to continue receiving CT or to switch to SCT. The results indicated SCT was noninferior to CT after 48 weeks, and results of the extended follow-up, a median of 185.3 weeks, were reported here.

Participants consenting to the extended follow-up totalled 99 for SCT and 100 on CT. Of the 199 total participants, 53% were boys with a baseline median age of 14 years (interquartile range [IQR], 12-18 years) and median CD4 count 735 cells/μL (IQR, 576-968 cells/μL). At the end of extended follow-up, 16 participants in each group had confirmed viral load ≥50 copies/mL (hazard ratio [HR], 1.00; 95% CI, 0.50-2.00). The estimated difference in percentage with viral rebound (SCT minus CT) by week 144 was 1.9% (90% CI, −6.6% to 10.4%; P =.72) and was similar in a per protocol analysis.

No significant differences in proportions of participants with grade 3/4 adverse events (18 SCT vs 16 CT participants; P =.71) or ART-related adverse events (10 vs 12; P =.82) were observed between groups. Fewer ART-related adverse events were observed in the SCT group in the first 48 weeks, but this was not maintained during the extended follow-up.

The study, however, was not powered to show subtle differences in toxicity profiles. More participants in the SCT group experienced at least 1 serious adverse event, which did not resemble results in trials with adults in which serious adverse events were similar between SCT and CT groups. This may be attributable to the lack of blinding, which may have led to increased tendencies for SCT participants to be admitted to hospital. Evidence for this was seen when the blinded Endpoint Review Committee deemed that more than half of the serious adverse events were a result of non-HIV-related causes.

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Investigators concluded that standard dose EFV-based treatment with 2 days off a week is suitable for adherent HIV-1-infected young people who are virologically suppressed. This option may alleviate treatment fatigue, improve lifestyle, and reduce cumulative toxicity of antiretrovirals during the patient’s lifetime, as well as save costs. It was further recommended that this option be used when patients undergo 3-monthly viral load monitoring.

Future work should focus on the generalizability of SCT to other ART regimes and less frequent monitoring schedules.            


Turkova A, Moore CL, Butler K, et al; BREATHER (PENTA 16) trial group. Weekends-off efavirenz-based antiretroviral therapy in HIV-infected children, adolescents and young adults (BREATHER): extended follow-up results of a randomised, open-label, non-inferiority trial. PLoS One. 2018;13(4):e0196239.