Background
Long-acting injectable cabotegravir (CAB-LA) is highly effective as PrEP but may delay detection of HIV infection using conventional diagnostics. HIV RNA testing may assist with early detection of HIV infection and prevent the emergence of resistance. We evaluated the performance of HIV RNA screening in the HPTN 084 open-label extension (OLE).
Methods
HPTN 084 evaluated the effectiveness of long-acting injectable cabotegravir (CAB-LA) compared to daily oral TDF/FTC for PrEP in individuals born female aged 18-45 years in eastern and southern Africa. Sites performed one or two rapid tests, a laboratory-based antigen/antibody (Ag/Ab) test, and an HIV RNA test at each visit in the OLE. Final HIV status was adjudicated based on site-based test results and retrospective testing at a central laboratory. We calculated the sensitivity of RNA screening with other tests, and the positive predictive value (PPV) and false positive rate (FPR) of isolated positive HIV RNA results.
Results
Overall, 2,462 participants with 24,178 visits through November 30, 2023 were included in the analysis. HIV infection was confirmed in 8 (90.1%) of 88 participants with ≥1 reactive HIV test result (one at OLE entry, seven after OLE entry). Of these, 4/8 (50%) were detected by a positive isolated HIV RNA test (true positive cases). Fourteen additional participants had a positive isolated HIV RNA test but were adjudicated HIV negative (false positive cases). The overall sensitivity of RNA screening was 75% (34.9%-96.8%). The PPV and FPR for detection of HIV infection by isolated HIV RNA test were 22.2% (95% CI 6.4%-47.6%) and 77.8% (95% CI 52.4%-93.6%) respectively. When stratified by recent CAB use within the prior 6 months, the PPV was 20.0% (95% CI 4.3%-48.1%) with recent CAB compared to 33.3% (95% CI 0.8%-90.6%) without. False positive tests led to CAB injections delays of >70 days in 6 (42.9%) of 14 false positive cases.
Conclusions
HIV RNA testing performed poorly for detection of confirmed HIV infections. High CAB effectiveness and subsequent low prevalence of true infection in this population may explain the low PPV for HIV RNA screening. Although infrequent, most positive isolated HIV RNA tests were false positive with the potential for negative clinical consequences in some cases. Future HIV testing algorithm guidelines should consider the risks and benefits of HIV RNA screening in this setting.
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