Highlights of the Trial
The study provides several critical insights into the integration of rapid diagnostic feedback within the HIV care continuum:
1. Primary Outcome: Providing next-day laboratory-based HIV viral load (VL) results did not significantly increase the overall rate of linkage to care (LTC) within 12 weeks compared to standard antigen/antibody testing (Hazard Ratio [HR], 1.28; 95% CI, 0.80-2.05).
2. Targeted Benefit: In a modified intention-to-treat analysis, the time to linkage to care was significantly shorter for persons living with HIV (PWH) who received the next-day results (log-rank P = .03).
3. Prevention Gap: The intervention did not appear to significantly influence the speed or rate of linkage for those seeking HIV preexposure prophylaxis (PrEP).
4. Retention Challenges: Only 47.7% of the participants completed the full 12-week follow-up, highlighting the systemic difficulties in maintaining engagement within high-risk urban populations.
Background: The Critical Window for Linkage to Care
The management of HIV has transitioned from a focus on terminal care to a focus on chronic disease management and prevention. Central to this transition are two pillars: early initiation of antiretroviral therapy (ART) for those living with HIV and the uptake of preexposure prophylaxis (PrEP) for those at risk. However, the ‘leaky bucket’ of the HIV care continuum remains a persistent challenge. Linkage to care (LTC)—the process of transitioning from a positive test or risk assessment to a clinical encounter—is often where the system fails.
In the United States, traditional laboratory-based HIV viral load testing typically involves a turnaround time of several days. This delay can lead to missed opportunities, particularly in emergency departments (EDs) or community settings where patients may not return for follow-up. The theoretical advantage of next-day results is the ability to provide actionable data while the patient’s motivation is high and their contact information is current. This trial, conducted by Hamill and colleagues, sought to determine if closing the feedback loop by just a few days could catalyze systemic improvements in LTC.
Study Design: Testing the Speed of Laboratory Feedback
This randomized clinical trial was conducted between August 2021 and February 2023. The researchers utilized a convenience sample of 195 adults recruited from an academic emergency department in Baltimore, Maryland, and through social media advertisements. The study population was diverse and reflective of the urban HIV epidemic: 57.4% identified as Black or African American, and 17.4% were already known to be persons living with HIV (PWH) who were not currently on daily ART.
Participants were randomized in a 1:1 ratio into two groups:
1. Intervention Group: Received a laboratory-based plasma HIV viral load test with results delivered the next day, in addition to the standard-of-care HIV antigen/antibody (Ag/Ab) test.
2. Control Group: Received only the standard-of-care HIV Ag/Ab assay results.
The primary endpoint was the proportion of participants linked to care for either ART or PrEP within a 12-week window. Linkage was rigorously defined as a confirmed clinical visit with a prescribing provider. Secondary endpoints included the time to linkage and differences in outcomes stratified by HIV status.
Results: Analyzing the Primary and Secondary Endpoints
The trial screened 1105 potential participants, eventually enrolling 195. The results underscore the complexity of healthcare navigation in vulnerable populations. By the end of the 12-week follow-up period, 69 participants (35.4%) across both groups were successfully linked to care.
Overall Linkage to Care
In the intention-to-treat analysis, 38 participants (38.8%) in the intervention group were linked to care, compared to 31 (32.0%) in the control group. While the intervention group showed a numerically higher rate, the difference was not statistically significant (P = .31). The hazard ratio of 1.28 suggests a trend toward benefit, but the wide confidence interval (0.80-2.05) indicates that the study may have been underpowered to detect a small effect size or that the intervention alone was insufficient to overcome other barriers to care.
Subgroup Analysis: Persons Living with HIV (PWH)
One of the most compelling findings emerged when the researchers looked specifically at PWH. For individuals already diagnosed with HIV but not on ART, receiving a next-day viral load result significantly reduced the time to linkage. The log-rank test for this subgroup yielded a P-value of .03, suggesting that for those with a known diagnosis, the physiological data of a viral load count may serve as a more powerful motivator for treatment re-engagement than a simple positive antibody test.
PrEP Linkage
Conversely, for those at risk of HIV but not yet infected, the next-day viral load (which would be undetectable) did not significantly change the trajectory of PrEP initiation. This suggests that for HIV prevention, the barriers to care are likely more related to perceived risk, cost, and logistics rather than the speed of laboratory confirmation that they are currently HIV-negative.
Expert Commentary: Barriers Beyond Laboratory Speed
The findings of this trial reflect a reality often seen in urban public health: diagnostic speed is only one piece of a much larger puzzle. While next-day results are an improvement over weekly results, they still require a ‘next-day’ interaction. In a population where housing instability, substance use disorders, and economic precarity are prevalent, even a 24-hour delay can result in a loss of contact.
The significant finding in the PWH subgroup is clinically relevant. It suggests that ‘viral load literacy’—understanding that a high viral load correlates with health risk and transmissibility—might be a lever for behavioral change. When a patient sees a numerical value representing the virus in their blood, the abstract concept of ‘HIV’ becomes a concrete medical priority.
However, the study’s high attrition rate (over 50% lost to follow-up) is a stark reminder of the limitations of clinical trials in real-world ED settings. It also raises the question: if next-day results aren’t enough, is point-of-care (POC) testing the answer? POC testing provides results in less than two hours, potentially allowing for ‘test and treat’ models where the first dose of ART or PrEP is administered before the patient even leaves the clinic.
Conclusion: Moving Toward Point-of-Care Solutions
The study by Hamill et al. concludes that while next-day laboratory-based HIV VL testing does not provide a universal solution for improving linkage to care, it offers measurable benefits for specific populations, particularly those needing to re-engage with ART. The lack of impact on PrEP linkage suggests that prevention efforts require different structural interventions beyond rapid diagnostics.
For clinicians and policy experts, the takeaway is clear: reducing diagnostic turnaround time is beneficial but must be paired with robust navigation services. The trend toward faster results should ideally culminate in true point-of-care viral load testing, which could bypass the need for a ‘next-day’ follow-up entirely, thereby closing the gap in the HIV care continuum.
Funding and Trial Registration
This research was supported by grants from the National Institutes of Health (NIH) and the Centers for Disease Control and Prevention (CDC). The trial is registered at ClinicalTrials.gov with the identifier NCT04793750.
References
1. Hamill MM, Bayan MH, Boudreau A, et al. Next-Day HIV Viral Load Test Result and Linkage to Care Among Persons Living With or at Risk of HIV: A Randomized Clinical Trial. JAMA Netw Open. 2025;8(12):e2548380. doi:10.1001/jamanetworkopen.2025.48380.
2. Thompson MA, Horberg MA, Agwu AL, et al. Antiretroviral Treatment and Prevention of HIV Infection in Adults: 2022 Recommendations of the International Antiviral Society-USA Panel. JAMA. 2022;328(24):2433-2445.
3. Centers for Disease Control and Prevention. HIV Testing in Clinical Settings. Published 2023. Accessed June 2024.