A Randomised Trial of Point-of-Care Early Infant HIV Diagnosis

Background:  Early infant diagnosis (EID) of HIV is critical to the care of the 1.3 million infants who are perinatally exposed to the virus each year. Point-of-care (POC) EID provides same-day results and the potential for improved survival through immediate initiation of antiretroviral therapy (ART). Methods:  We conducted a pragmatic randomised trial at 6 primary health centres in Lusaka, Zambia. HIV-exposed infants were equally allocated to either: (a) POC EID – on-site testing with the Alere q HIV-1/2 Detect instrument or (b) enhanced standard of care (SOC) EID – off-site testing at a public-sector laboratory. We provided a safety net if off-site EID results did not return within 4 weeks. Infants found to be HIV infected were immediately referred for care in the public sector and followed by the study for 12 months. Our primary outcome was programmatic success, defined as being alive, in care, and virally suppressed (<200 copies/mL) at 12 months. We also compared the time to receipt of result by the facility and by the participant’s parent/guardian. Findings:  Between March 2016 and November 2018, we randomised 4,000 HIV-exposed infants at a median age of 6.4 weeks to POC (n=1,989) or enhanced SOC (n=2,011). All but 2 infants in the POC group received same-day results, while the median time to result in the SOC group was 27 (IQR: 22-30) days. Most infants randomised to SOC relied on the trial’s diagnostic safety net. Eighty-one (2%, 95% CI: 1.6–2.5%) infants were diagnosed with HIV. Although ART initiation was high overall, there were 15 (19%) deaths, 15 (19%) follow-up losses, and 31 (38%) virologic failures during follow-up. By 12 months, only 20 of 81 (25%, 95% CI: 15–34%) HIV-infected infants were alive, in care, and virally suppressed: 13 (30%, 95% CI: 16–43%) infants in the POC group vs. 7 (19%, 95% CI: 6–32%) in the enhanced SOC group (RR: 1.56, 95% CI: 0.7–3.50). Interpretation:  Outcomes among HIV-infected infants were poor in both randomization groups. Although POC EID eliminated diagnostic delays and accelerated ART initiation, the POC EID strategy did not translate into a statistically significant improvement in programmatic success. Our findings are limited by a lower than anticipated number of HIV-infected infants in the trial, a welcome consequence of the success of Zambia’s perinatal HIV prevention program. Trial Registration: This trial is registered at https://clinicaltrials.gov (NCT02682810). Funding Statement:This research was funded by the U.S. National Institutes of Health (NIH) (U01AI100053). Biostatistical and laboratory support was provided by the UNC Center for AIDS Research, which is supported in part by the NIH (P30AI050410). Additional investigator and trainee support was provided by the NIH for BHC (K24AI120796) and CEF (T32HD075731, D43TW009340). Declaration of Interests: The authors declare no conflicts of interest. Ethics Approval Statement: Ethical approval for the trial (NCT02682810) was granted by the University of Zambia Biomedical Research Ethics Committee (BREC Ref: 010-02-13), the Zambian Ministry of Health, and the University of North Carolina at Chapel Hill Institutional Review Board (IRB Number: 12-1346).