Point-of-care p24 antigen detection for early infant diagnosis of HIV infection: cross-sectional and longitudinal studies in Zambia

Abstract

Background Early infant diagnosis of HIV infection is challenging in sub-Saharan Africa, particularly in rural areas, leading to delays in diagnosis and treatment. Use of a point-of-care test would overcome many challenges. This study evaluated the validity of a novel point-of-care p24 antigen detection test (LYNX) in rural and urban settings in southern Zambia. Methods Two studies were conducted: a cross-sectional study from 2014 to 2015 at Macha Hospital (LYNX Hospital study) and a longitudinal study from 2016 to 2018 at 12 health facilities in Southern Province, Zambia (NSEBA study). In both studies, children attending the facilities for early infant diagnosis were enrolled and a blood sample was collected for routine testing at the central lab and immediate on-site testing with the LYNX test. The performance of the LYNX test was measured in comparison to nucleic acid-based testing at the central lab. Results In the LYNX Hospital study, 210 tests were performed at a median age of 23.5 weeks (IQR: 8.9, 29.0). The sensitivity and specificity of the test were 70.0 and 100.0%, respectively. In the NSEBA study, 2608 tests were performed, including 1305 at birth and 1222 on children ≥4 weeks of age. For samples tested at birth, sensitivity was 13.6% (95% CI: 2.9, 34.9) and specificity was 99.6% (95% CI: 99.1, 99.9). While specificity was high for all ages, sensitivity increased with age and was higher for participants tested at ≥4 weeks of age (80.6%; 95% CI: 67.4, 93.7). Children with positive nucleic acid tests were more likely to be negative by the LYNX test if their mother received antiretroviral therapy during pregnancy (60.7% vs. 24.2%; p = 004). Conclusions Considering the high specificity and moderate sensitivity that increased with age, the LYNX test could be of value for early infant diagnosis for infants ≥4 weeks of age, particularly in rural areas where centralized testing leads to long delays. Point-of-care tests with moderate sensitivity and high specificity that are affordable, easy-to-use, and easily implemented and maintained should be developed to expand access to testing and deliver same-day results to infants in areas where it is not feasible to implement nucleic acid-based point-of-care assays.

The Evolving Pediatric HIV Epidemic in Rural Southern Zambia: The Beneficial Impact of Advances in Prevention and Treatment at a District Hospital From 2007 to 2019

“…The third study, the Novel Screening for Exposed Babies (NSEBA) study, was a prospective cohort study conducted at several health facilities in the Macha Hospital catchment area from February 1, 2016, to March 31, 2020. 15,16 The objective was to evaluate strategies for implementing point-of-care technologies for infant diagnosis in Zambia. All HIV-exposed infants attending the study sites for infant diagnosis were eligible for enrollment.…”

Costs and cost-effectiveness of HIV early infant diagnosis in low- and middle-income countries: a scoping review

“…Unit costs per test are reported in Table 1. Seven studies reported unit costs for PoC assays [13,40,[50][51][52][53][54], 13 for laboratory testing [13,24,38,39,41,44,46,[50][51][52][53][54][55], two for rapid testing [41,56], and one for unspecified NAT [57] Variation in unit costs for PoC assays may be explained by inclusion of capital costs. Costs for m-PIMA that included equipment costs were > 20 USD higher than those that did not include equipment costs.…”

“…One study, conducted in Zambia, evaluated PoC p24 assays which may be more affordable than PoC-NAT tests (< 15 USD per test) and do not require specialized equipment [56]. Despite low sensitivity in very young infants, PoC p24 assays could play a role in diagnosing infants > 4 weeks of age at rural sites where the significant capital investment in PoC-NAT testing platforms is not feasible [56].…”

“…One study, conducted in Zambia, evaluated PoC p24 assays which may be more affordable than PoC-NAT tests (< 15 USD per test) and do not require specialized equipment [56]. Despite low sensitivity in very young infants, PoC p24 assays could play a role in diagnosing infants > 4 weeks of age at rural sites where the significant capital investment in PoC-NAT testing platforms is not feasible [56]. An assay that is 80% sensitive and links 99% of positive infants to care achieves the same level of ART coverage as an assay that is 95% sensitive and only links 85% of positive infants to care [58].…”

Factors associated with antiretroviral therapy use among pregnant women in rural and urban settings in Southern Province, Zambia: 2016–2019

“…The objective of the NSEBA Study was to evaluate strategies for implementing point-of-care technologies for early infant diagnosis of HIV in urban and rural Zambia. This included a cross-sectional validation study of a point-of-care platform for diagnosing HIV infection at birth in Livingstone City from February 2016 to August 2018 and a cohort study to validate a point-of-care testing platform for diagnosing HIV from birth through the post-weaning period in the Macha area from February 2016 to December 2019 [12]. Hospitals and UHCs/RHCs providing maternity services were selected based on the number of women living with HIV delivering at the facility and infants receiving HIV diagnostic testing in prior years.…”