The United States Ending the HIV Epidemic (EHE) initiative was always challenged by structural and implementation barriers to HIV care. On top of that, since 2025, there are additional political and policy barriers that make this goal seem increasingly difficult to achieve. This review identified evidence-based structural, implementation and biomedical interventions available to support each of the EHE pillars and estimated their potential population-level impact, accounting for potential barriers.
We conducted a targeted literature review of US studies presenting data on efficacy or effectiveness of interventions pertaining to the EHE pillars—prevention, diagnosis, treatment and response—published as of September 2025. We searched interventions included in the US Centers for Disease Control and Prevention HIV Compendium and Response Evidence Brief, all publicly available EHE jurisdictional plans, and the peer-reviewed literature. Potential population impact of an intervention was determined as the product of its effectiveness and scale of delivery. Scale was the product of population reach, provider adoption and structural barriers.
Of 570 studies identified, 57 met the inclusion criteria. We estimated that pre-exposure prophylaxis (PrEP) uptake could increase as much as nearly two-fold (risk ratio [RR]: 1.93, 95% CI: 1.30, 1.96) through pharmacies integrated in primary care clinics. Online HIV self-testing kits were among the most promising interventions to increase testing uptake by two-fold (RR: 1.99, 95% CI: 1.56, 2.57) Finally, a clinic-based education app offering tailored health education could result in a 45% absolute increase (RR: 1.45, 95% CI: 1.29, 1.70) in viral suppression among people living with HIV.
Interventions that address barriers to PrEP, HIV testing and adherence to treatment have substantial population-level impact on HIV care outcomes across EHE pillars through changing the context of how care is offered, understood and delivered.
Histoplasmosis remains a significant cause of morbidity and mortality in people with HIV . We examined disseminated histoplasmosis incidence, risk factors, and outcomes from North and South American HIV clinical sites.
Cohorts from Brazil, Chile, Honduras, Mexico, Peru and the United States (Tennessee) contributed data on PLWH ≥18 years old from 2000 to 2021. Stratifying by US and Latin American cohorts, we examined diagnosed disseminated histoplasmosis incidence and risk factors with modified Poisson regression models. Cox proportional hazard models examined factors associated with mortality after histoplasmosis.
Of 26,672 people with HIV (Latin America n = 19,836; United States n = 6836), 214 had incident histoplasmosis(Latin America n = 140; United States n = 74). From 2000 to 2021, histoplasmosis incidence decreased from 16.08 to 0.93 in Latin America and 13.4 to 0.67 per 1000 person-years in the United States. In Latin America, histoplasmosis risk was higher for males (aRR = 2.50 [95% CI: 1.62−3.86]), pre-antiretroviral therapy initiation (aRR = 7.76 [95% CI: 5.05−11.90]) and those who had migrated from a histoplasma-endemic country (aRR = 6.12 [95% CI: 1.81−20.69]). Risk was also higher for older people with HIV, those with low CD4, earlier calendar year and differed by site. In the United States, risk was higher in people with HIV with low CD4, higher HIV viral load, earlier calendar year and pre-antiretroviral therapy initiation (aRR = 2.65 [95% CI: 1.11−6.36]). Mortality after histoplasmosis was higher in people with HIV with an earlier year of histoplasmosis 2000 versus 2010 (aHR = 2.00 [95% CI: 1.26−3.17]) and among those who developed histoplasmosis after antiretroviral therapy initiation compared to before antiretroviral therapy (aHR = 2.66 [95% CI: 1.43−4.95]).
Despite concern for underdiagnosis of disseminated histoplasmosis in Latin America, its incidence in people with HIV decreased, as it did in the United States. Low CD4 cell count and time before antiretroviral therapy initiation remain strongly associated with histoplasmosis risk. Further attention to early HIV diagnosis and treatment is needed.
Despite substantial gains in the global HIV response, infants and young children continue to experience poorer outcomes across the HIV testing and care cascade. Rates of early infant diagnosis, timely antiretroviral therapy (ART) initiation, retention in care and viral suppression remain unacceptably low in paediatric populations. These disparities are compounded by systemic challenges, including fragmented service delivery, limited availability of child-friendly ART and other drug formulations, and health systems that fail to integrate HIV services within broader maternal and child health platforms. As a result, many children living with HIV are diagnosed and start treatment late and face high risks of mortality and morbidity, particularly in the first 2 years of life.
In this commentary, we advocate for the urgent reimagining of paediatric HIV service delivery, emphasizing the need to centre infants and young children within models of care. We highlight four promising approaches: (1) Integrated mother−infant follow-up models that ensure continuity of care from pregnancy through the postpartum period and infancy until the infant's final HIV status is determined; (2) Family-centred models that treat the household as the unit of care; (3) Advanced HIV care strategies tailored to the needs of children with late presentation or treatment failure, including paediatric tailored ART regimens and diagnostics; and (4) Community-based interventions that leverage peer support, lay health workers, and provide stigma-free entry points to expand access and retention to care and treatment. These approaches have demonstrated that when services are designed to reflect the developmental, clinical and social needs of children and their caregivers, outcomes significantly improve. However, many of these models remain underutilized, fragmented or inadequately resourced.
To close the paediatric HIV treatment gap, we must move beyond pilot projects towards national, integrated and adequately funded child-centred systems. This requires political will, strategic investment and prioritization of children in HIV policy, innovation and implementation research. A sustained and equitable HIV response must include infants and young children not as an afterthought, but as a core priority. Epidemic control cannot be achieved if the youngest children are left behind.
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