High performance of CD4 rapid testing by lay providers in Malawi: Results from a prospective diagnostic accuracy study supporting decentralized advanced HIV disease screening

CD4 testing is essential for identifying people with Advanced HIV Disease to enable provision of a diagnostic package (serum cryptococcal antigen testing and urine lipoarabinomannan testing) and prophylaxis. Lay providers (HIV diagnostic assistants) might be able to perform CD4 testing and advanced HIV diagnostics using lateral flow assays (LFAs). We conducted a prospective diagnostic accuracy study comparing LFA(Visitect) CD4 results performed by HIV diagnostic assistants and by laboratory technicians, using paired quantitative CD4 results from the PIMA device (performed by a nurse) as the reference standard. We also compared results of serum cryptococcal antigen (CrAg) and urine lipoarabinomannan (LAM) tests performed by HDAs to those performed by nurses. Implementation costs were estimated. We recruited 308 participants. Median CD4 was 248 cells/mm3; 115 (37.3%) patients had values below 200 cells/mm3. Sensitivity and specificity for determining CD4 below 200 cells/mm3 using the LFA operated by HIV diagnostic assistants was 94.8% (95%CI 89.1 - 97.6%) and 92.2% (95%CI 87.6 - 95.2%), respectively. Test performance of the LFA performed by laboratory technicians on batch after storage for up to eight hours was substantially worse. Subsequent serum-CrAg and urine-LAM test performed by HIV diagnostic assistants and nurses showed an agreement of 98.1% (kappa=0.74) and 98.1% (k=0.85), respectively. Incremental cost for CD4 test performed by on near patient device based quantitative test was $8.69 and for semi-quantitative LFA by HIV diagnostic assistants was $5.24 (in 2024 US dollars). Trained lay providers can accurately perform CD4, TB-LAM, and CrAg testing. Delaying CD4 testing by batching LFAs at the end of the day led to highly inaccurate results. Our findings support task sharing for decentralized advanced HIV disease testing.