False-positive rapid diagnostic tests in paediatric and obstetric patients in South Africa.

INTRODUCTION: Providing easily accessible, quick and accurate human immunodeficiency virus (HIV) testing services (HTS) is central to achieving the Joint United Nations Programme on HIV/AIDS (UNAIDS) 90-90-90 targets. Rapid diagnostic tests (RDTs) for HIV are affordable and technically easy to perform. Two positive RDTs from different manufacturers are required to make a diagnosis of HIV in South Africa. Difficulty arises when there are discordant results from the two kits. In this case report, we will discuss four instances of false-positive RDTs. PATIENT PRESENTATION: Case 1 is a 10-year-old female, referred for initiation of antiretroviral treatment (ART). She was diagnosed using two of the same brand RDT at her local clinic. Case 2 is a 21-year-old female who presented to obstetric admissions in labour. Case 3 is a 39-year-old female who was screened for HIV during a routine antenatal appointment. Case 4 is a 22-year-old female who was admitted 21 days postpartum with puerperal sepsis. All four cases had discordant RDTs when screened for HIV at our facility. MANAGEMENT AND OUTCOME: The results of all the investigations conducted on all four patients confirmed HIV negative status. The reference laboratory verified the results and reran the RDTs, which remained discordant. This confirmed a false-positive result in all four cases with the screening RDT. CONCLUSION: With high numbers tested and a low yield of new cases, each individual case of discordancy may cause unnecessary distress, confusion and treatment, particularly in high-risk scenarios like pregnancy. Trends of false-positive and discordant RDT results should be monitored and inform HTS guidelines.

Point-of-care HIV maternal viral load and early infant diagnosis testing around time of delivery at tertiary obstetric units in South Africa: a prospective study of coverage, results return and turn-around times.

INTRODUCTION: Maternal viral load monitoring (mVL) and early infant diagnosis (EID) are necessary to achieve elimination of mother-to-child transmission of HIV. Point-of-care testing can achieve better outcomes compared to centralized laboratory testing (CLT). We describe the first implementation of point-of-care (POC) mVL and EID testing around delivery at four high volume tertiary obstetric units (TOUs) in Gauteng, South Africa. METHODS: Prospective study of pregnant women living with HIV (WLHIV) and their infants. During the period 1 June 2018 to 31 March 2019, routine staff collected blood specimens from women and their infants around delivery. Specimen collection occurred throughout the week while dedicated POC operators, conducted testing during working hours on weekdays. Descriptive statistics and multivariable Poisson regression with robust error variance were used to describe outcomes and associated factors. Outcomes determined were (i) coverage of mVL and EID testing defined as a proportion of live births to WLHIV admitted at each facility (ii) results returned prior to discharge (iii) turn-around time (TAT) and iv) performance of POC testing compared to CLT. RESULTS: In total, 8147 live births to pregnant WLHIV were recorded in the implementation period. Of these, 2912 mVL and 5074 EID specimens were included in the analysis, with 131 (4.5%) mVL and 715 (14.1%) EID specimens having initial invalid/error results. Overall coverage of POC mVL and EID testing was 35.6% (range 20.9% to 60.1%) and 61.9% (range 47.0% to 88.0%) respectively. Proportions of POC tested mothers and infants with results returned prior to discharge were 74.3% (range 39.0% to 95.7%) and 73.0% (range 50.0 to 97.9%). Return of results was independently associated with TOU, after-hours specimen collection, having an initial invalid or error result and period of implementation. Overall TAT for specimens collected from mother-infant pairs where both had POC testing, during weekdays was longer for EID compared to mVL testing (median 3.3 hours vs. 2.9 hours, p-value sign test <0.001). POC results were comparable to those from laboratory testing. CONCLUSION: Accurate and timely POC mVL and EID testing around delivery was implemented with variable success across TOUs. Further scale up would need to address health system factors at facility level and high analytical error rates.

HIV diagnostic challenges in breast-fed infants of mothers on antiretroviral therapy.

BACKGROUND: Prompt initiation of antiretroviral therapy (ART) for HIV-infected infants is strongly recommended but diagnostic confirmation is important as committing children to life-long ART carries serious health and social implications. METHODS: Two HIV-exposed infants in Johannesburg, South Africa were identified presenting with unusual trajectories of diagnostic nucleic acid amplification tests (NAAT) and viral load results. RESULTS: Case 1 had repeat indeterminate NAAT results during the first 3 weeks of life; repeat testing thereafter was negative with undetectable viral load including after daily nevirapine prophylaxis ended. ART was not initiated at this time. Case 2 had a single positive NAAT result at 1 month of age that prompted initiation of ART. Subsequent results were negative and ART was discontinued. Repeat negative NAAT with viral load below the limit of quantification or undetectable continued to be obtained. Shortly after and around weaning, positive NAAT results with high viral load (7.1 and 6.03 log10 copies/ml for Cases 1 and 2, respectively) were observed in both children. Both mothers were treated with tenofovir, emtricitabine and efavirenz during breastfeeding. Testing with ultrasensitive assays on early samples conclusively revealed HIV-1 proviral DNA in Case 1. Testing with ultrasensitive assays after the early period but prior to weaning did not detect HIV in either infant. CONCLUSION: We hypothesize that breast milk from the mothers of these two rare cases had HIV-specific or nonspecific factors that led to the undetectable results in already infected infants until breastfeeding ended. Our results raise the importance of repeat testing of HIV-exposed breast-fed infants after complete cessation of all breastfeeding.

Early infant diagnosis of HIV: review of current and innovative practices.

PURPOSE OF REVIEW: Only 51% of HIV-exposed infants receive an HIV test between 4 and 6 weeks of age, with even lower repeat testing rates at older ages, and only 49% of infants tested are initiated on antiretroviral therapy. The purpose of this article is to discuss potential solutions for increasing coverage of early infant diagnosis (EID), decreasing turnaround time for result return, improving linkages to care and treatment and fulfilling the objective of improving outcomes for HIV-infected children. RECENT FINDINGS: Differences in HIV testing guidelines have emerged in different countries, with some recommending HIV testing at birth. Although EID programs are not yet optimal, some solutions have proven successful including the use of short message service printers, community-based interventions and support and education of mothers. Birth and EID point-of-care testing have emerged as potential game changers for improving EID programs. SUMMARY: For EID programs to impact on child health outcomes, by preventing HIV-associated morbidity and mortality, and provide more value than a mere surveillance tool, efforts need to be aligned toward the implementation of a comprehensive set of interventions that take cognizance of different contexts, epidemiology and health systems, and that are backed by political and community support.

Cytomegalovirus viral load kinetics in patients with HIV/AIDS admitted to a medical intensive care unit: a case for pre-emptive therapy.

BACKGROUND: Cytomegalovirus (CMV) infection is associated with severe diseases in immunosuppressed patients; however, there is a lack of data for pre-emptive therapy in patients with HIV/AIDS. METHOD: This was a retrospective study, which enrolled patients diagnosed with HIV/AIDS (CD4<200 cells/µl), who had detectable CMV viral load (VL) during their stay in an adult medical intensive care unit between 2009-2012. RESULTS: After screening 82 patients' records, 41 patients met the enrolment criteria. Their median age was 37 (interquartile range [IQR]: 31-46), and median CD4 count was 29 cells/µl (IQR: 5-55). Sixteen patients (39%) had serial measurements of CMV VL before treatment with ganciclovir. Patients whose baseline CMV VL values were between 1,000-3,000 copies/ml had significantly higher values (median of 14,650 copies/ml) on follow-up testing done 4-12 days later. Those with undetectable VLs at baseline testing had detectable VLs (median of 1,590 copies/ml) mostly within 20 days of follow-up testing. Patients who had VLs >1,000 copies/ml at baseline testing had significantly higher mortality compared to those who had <1,000 copies/ml {hazard ratio of 3.46, p = 0.003 [95% confidence interval (CI): 1.55-7.71]}. Analysis of the highest CMV VL per patient showed that patients who had VLs of >5,100 copies/ml and did not receive ganciclovir had 100% mortality compared to 58% mortality in those who received ganciclovir at VLs of >5,100 copies/ml, 50% mortality in those who were not treated and had low VLs of <5,100 copies/ml, and 44% mortality in those who had ganciclovir treatment at VLs of <5,100 copies/ml (p = 0.084, 0.046, 0.037, respectively). CONCLUSION: This study showed a significantly increased mortality in patients with HIV/AIDS who had high CMV VLs, and suggests that a threshold value of 1,000 copies/ml may be appropriate for pre-emptive treatment in this group.