Nearly one in five children with HIV under the age of one year who experienced an interruption in treatment in 2024 subsequently died, a review of over half a million children receiving HIV treatment through US-funded PEPFAR programmes shows. The findings were presented at the Conference on Retroviruses and Opportunistic Infections (CROI 2025) in San Francisco on Monday.
The findings highlight the importance of maintaining continuity of care for children with HIV, who are especially vulnerable to rapid progression of HIV disease in the early years of life. Although the study was designed to establish rates of loss from care and resumption of care in PEPFAR programmes over time, the findings also starkly illustrate the risks associated with interruptions to funding of treatment programmes.
Since the new US administration took office on 20 January, the closure of USAID and a devastating freeze on overseas assistance have thrown many US-supported HIV treatment programmes into crisis.
On 26 February, the Elizabeth Glaser Pediatric AIDS Foundation was notified of an immediate halt to USAID funding of its HIV programmes in Lesotho, Eswatini, and Tanzania, which provide HIV treatment to 350,000 people, including nearly 10,000 children and more than 10,000 pregnant women living with HIV.
A larger question hangs over the future of PEPFAR funding for HIV treatment. PEPFAR funding must be reauthorised by the US Congress by 25 March, but it's unclear if funding will be reauthorised at the same level as previous years or who will be able to deliver services.
Interruptions to HIV treatment are known to be harmful to the health of people with HIV. Two decades ago, it was thought that periods off treatment – so-called structured treatment interruptions – might reduce any harm associated with the side effects of older HIV drugs. However, a study to test this theory was halted in 2006 after it became clear that people with HIV who were randomly assigned to stop treatment until their CD4 counts fell to a certain level were more likely to experience HIV-related illnesses and serious complications including heart attack, stroke and advanced kidney and liver disease.
Although trials of structured treatment interruptions in children (PENTA 11 and CHER) did not show increases in illness in those who interrupt treatment, declines in CD4 count were rapid and children who interrupted treatment soon resumed medication.
Unplanned treatment interruptions in adults are known to be associated with an increased risk of death, and a cohort study in southern Africa found that a treatment interruption during the first six months of antiretroviral therapy increased the risk of death in children with HIV by 52% in the period between 2004 and 2016.
Treatment interruptions in PEPFAR
To investigate the relationship between interruptions to HIV treatment and mortality in children, researchers looked for interrupted treatment in children under the age of 15 receiving HIV care in 53 PEPFAR-supported countries. They defined interrupted treatment as gaps in clinical contact or delays in antiretroviral medication pick-up lasting more than 28 days.
They also looked at the reason recorded for treatment interruption: had the child died, did the child’s carer refuse treatment, was the child’s care transferred to another facility, or was the reason for treatment interruption unknown? They investigated whether outcomes differed according to the time on antiretroviral treatment in those with an unknown reason for treatment interruption, and looked at causes of death. They also assessed what proportion of those who interrupted treatment subsequently resumed treatment.
The analysis identified 523,285 children with HIV receiving antiretroviral treatment in PEPFAR-supported programmes in the 53 countries in 2024 (Nigeria and Cambodia were excluded due to data collection issues.) During that period, 21,325 experienced a treatment interruption.
Mortality after treatment interruption was highest in those under one year of age. The proportion of those who subsequently died after interrupting treatment was reported for each quarter (three-month period) and ranged from 13.6% to 19.6% per quarter in those under one year of age, and from 7.5% to 10.2% per quarter in those under five years of age.
Treatment interruption occurred earlier in the youngest children, most commonly within three months of starting treatment in those under one year of age. In older children, treatment interruption was most likely to occur after at least six months on treatment.
Information on the cause of death was only reported in 22% of cases in 2024. In just over half the cases (54%), the cause was HIV-related.
In every quarter since the beginning of 2022, the number of unexplained treatment interruptions – children assumed still to be alive – has exceeded the number of children who returned to care after a treatment interruption. This highlights the challenge of bringing children back to care once they have interrupted treatment, said Michelle Yang of the US Department of State, who presented the study.
Community-based services and family-centred models for the delivery of care are needed to improve retention in care, she said. Point-of-care testing and testing of all family members after one HIV diagnosis in a family are also needed, to improve rates of early infant diagnosis.
Yang M et al. Assessing IIT and mortality among CLHIV <15 yo in PEPFAR-supported countries, FY21 - FY24. Conference on Retroviruses and Opportunistic Infections, San Francisco, abstract 121, 2025.