Brief Report: High Sensitivity and Specificity of the Cepheid Xpert HIV-1 Qualitative Point-of-Care Test Among Newborns in Botswana

Abstract

Background HIV point-of-care (POC) testing allows for early infant HIV diagnosis and treatment, but POC accuracy at birth and in the setting of antiretroviral prophylaxis for the prevention of mother-to-child HIV transmission (MTCT) is unknown. Methods We evaluated the Cepheid Xpert® HIV-1 Qual POC test against the Roche Taqman HIV-1 PCR platform using dried blood spots from 15 HIV-infected and 75 HIV-exposed uninfected newborns. These infants were screened for HIV at <96 hours of life at 5 hospital maternity wards in Botswana; all infants received post-exposure antiretroviral prophylaxis (PEP) and most mothers received 3-drug antiretroviral therapy in pregnancy and at delivery. Results Fourteen of 15 PCR positive samples tested positive by Cepheid POC, yielding a sensitivity of 93.3% (95%CI: 68.1–99.8%). Baseline viral load among positive infants ranged from <40 to >10,000,000 copies/ml, with a median of 2,403 copies/mL. The HIV RNA for the infant with false negative POC testing was 1,661 copies/mL. Of note, two infants with low HIV RNA (< 40 copies/mL and 272 copies/ml) were correctly identified as HIV positive by Cepheid POC. All of the 75 PCR-negative samples tested negative by Cepheid POC, yielding a specificity of 100% (95% CI: 96.1 –100%). Discussion Our study demonstrates high sensitivity and specificity for the Cepheid POC assay in the first week of life despite early infection and antiretroviral prophylaxis. This platform may be a useful approach for adding early infant HIV diagnosis to current testing programs.

Field Evaluation of Performance of Alere and Cepheid Qualitative HIV Assays for Pediatric Point-of-Care Testing in an Academic Hospital in Soweto, South Africa

“…The two technologies were tested in parallel and had perfect concordance across 102 HIV PCR-positive and 220 HIV PCR-negative specimens from children younger than 18 months. These POC technologies showed high sensitivity and specificity compared to the SOC HIV PCR test in South Africa, supporting previous studies on the Alere q HIV-1/2 Detect (18,21) and Cepheid Xpert HIV-1 Qual (19,20,23,24) assays. Over 100 PCR-positive specimens were tested, which enabled a precise estimate of POCT sensitivity.…”

“…Reported C T values of Ͻ32 and RFI values of Ն4 are indicative of HIV-infected infants (25). All 4 indeterminate results occurred in the neonatal age group, a time when prevention of mother-to-child transmission (PMTCT) infant prophylaxis may reduce the sensitivity of PCR tests (14), which may account for the reduced sensitivity in the neonatal period noted in previous evaluations (18,19,22).…”

“…Higher error rates have been reported in the field evaluations, ranging from 4.8% to 12% (22)(23)(24). Two laboratory evaluations, each on approximately 90 neonates Ͻ7 days old, reported lower POCT sensitivity (93%) than those reported in older infants for Alere (18) and Cepheid (19). Similarly, a field evaluation of Alere on 291 neonates, Ͻ1 day old, reported a sensitivity of 92% (22).…”

“…Evidence from laboratory and field evaluations is limited, and those including prototype devices are not comparable. Laboratorybased evaluations conducted on the Alere technology in South Africa (18) and the Cepheid technology in Botswana (19) and Malawi (20) indicated high sensitivity (93.3% to 100%) and specificity (99.8% to 100%) in specimens from children aged Ͻ18 months. Error rates ranged from 2% to 6% (18)(19)(20).…”

“…Laboratorybased evaluations conducted on the Alere technology in South Africa (18) and the Cepheid technology in Botswana (19) and Malawi (20) indicated high sensitivity (93.3% to 100%) and specificity (99.8% to 100%) in specimens from children aged Ͻ18 months. Error rates ranged from 2% to 6% (18)(19)(20). Field evaluation studies conducted in Mozambique (21) and South Africa (22) on the Alere technology and in Tanzania (23) and South Africa (24) on the Cepheid technology reported sensitivities and specificities ranging from 92% to 100% and 95% to 100%, respectively.…”