The Hidden Gap in Infant HIV Diagnosis: A Call for Complementary Diagnostics in the Point-of-Care and Prophylaxis Era

Abstract The remarkable success of Prevention of Mother-to-Child Transmission (PMTCT) programs has significantly lowered infant HIV prevalence. However, this success, along with widespread maternal and infant prophylaxis and the increasing reliance on Point-of-Care (POC) diagnostics, has inadvertently created a new diagnostic challenge. Our research quantifies a critical, previously overlooked gap in HIV detection among infants born to HIV-positive mothers. We observed that a substantial proportion (over 18%) of HIV-infected infants now present with extremely low viral loads (Ct values above 31), which is likely due to the suppressive effects of prophylaxis. Importantly, external quality assessment studies reveal that most current POC platforms in use cannot be single-handedly relied on to detect HIV at these low concentrations. This means that sole reliance on POC testing risks leaving a significant cohort of approximately 18% of HIV-infected infants undiagnosed for prolonged periods, leading to severe clinical outcomes and undermining PMTCT gains. We emphasize the essential role of highly sensitive conventional PCR platforms, capable of accurately interpreting very low positive results, and advocate for a complementary diagnostic strategy where conventional PCR serves as a confirmatory test for all HIV-exposed infants. This article highlights the urgent need for a revised diagnostic approach to optimize PMTCT strategies and ensure timely care for every HIV-exposed infant. Competing Interest Statement The authors have declared no competing interest. Funding Statement I didnt not recieve any funding Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: Uganda National Health Laboatory Research and Ethics Committe gace ethical approval for this work I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes Data Availability HIV Test dataa