Systematic review shows rapid diagnostic tests offer faster, cheaper HIV detection for LAI-PrEP users with low certainty evidence.

BACKGROUND: Long-acting injectable pre-exposure prophylaxis (LAI-PrEP) is a highly effective biomedical intervention for the prevention of HIV acquisition. There is a strong interest among communities and policymakers for LAI-PrEP scale-up, accelerating the demand for clear guidance on testing approaches that balance accuracy with scalability. Unlike oral pre-exposure prophylaxis, LAI-PrEP may overcome adherence challenges, such as difficulty with frequent clinic visits. However, LAI-PrEP results in prolonged subtherapeutic drug levels after discontinuation, which can increase the risk of drug resistance among those who have an undetected HIV infection. This systematic review evaluates how different HIV testing strategies, including rapid diagnostic tests (RDTs), laboratory-based immunoassays and nucleic acid testing (NAT), affect clinical utility and programme delivery of LAI-PrEP. METHODS AND FINDINGS: We searched databases and retrieved studies up to April 8, 2025, and supplemented findings with data collected through a World Health Organization (WHO) survey among ongoing and completed LAI-PrEP implementation studies. We included publications reporting original or primary data on clinical, diagnostic and resource-use outcomes of HIV testing for LAI-PrEP. Meta-analyses were conducted using random-effects models. Chi-square tests were used to examine differences between related outcomes. Certainty of evidence was determined using the GRADE methodology (Prospero: CRD42024605562). Risk Of Bias In Non-randomised Studies of Interventions, Version 2 (ROBINS-I V2) assessment tool was used to assess bias for non-randomised comparative studies. Of 7,698 records identified, 38 reports representing 22 studies (cabotegravir: 20, lenacapavir: 2) across 15 countries were included. The overall certainty of evidence was low. Most were observational cohorts (n = 13) or non-randomised comparator studies (n = 7). Among 8,171 LAI-PrEP users in four randomised controlled trials, HIV detection rates were similar across strategies (9/8171 (RDT) versus 14/8171 (NAT) (Odds ratio (OR) 0.66 (95% confidence interval: 0.29-1.50; P = 0.87)), with no difference in adverse events. Compared with laboratory-based tests, RDTs enabled faster turnaround (same-day versus up to 7 days), more rapid treatment initiation (1 day versus 6-9 days), and lower test costs (US$4 versus US$22). All tests had similar negative predictive value (~100%) at LAI-PrEP initiation and comparable positive predictive value (~55%) at continuation. There was little difference in delayed HIV detection (11/8171 (RDT) versus 0/8171 (NAT)). In the HPTN 083 trial, NAT use was occasionally associated with false-positive results, leading to unnecessary PrEP holds or discontinuation (7/2483). NAT might have detected HIV before resistance emerged, though no prospective or modelling evidence showed clinical benefit at a population level. There was limited evidence of HIV self-testing for LAI-PrEP delivery. We noted that our assessment of performance accuracy in different testing strategies may introduce selection bias. CONCLUSIONS: RDT-based testing strategies have comparable accuracy to laboratory-based strategies and are more accessible and scalable, which can ensure that testing does not become a barrier to accessing or continuing LAI-PrEP. As countries expand access to LAI-PrEP amid increasingly constrained resources, adoption of new WHO guidance supporting the use of RDTs can enable simpler, more affordable, and user-centred HIV testing approaches.