Infant HIV Diagnosis Research Articles

Optimizing infant HIV diagnosis with additional screening at immunization clinics in three sub-Saharan African settings: a cost-effectiveness analysis.

IntroductionUptake of early infant HIV diagnosis (EID) varies widely across sub‐Saharan African settings. We evaluated the potential clinical impact and cost‐effectiveness of universal maternal HIV screening at infant immunization visits, with referral to EID and maternal antiretroviral therapy (ART) initiation.MethodsUsing the CEPAC‐Pediatric model, we compared two strategies for infants born in 2017 in Côte d’Ivoire (CI), South Africa (SA), and Zimbabwe: (1) existing EID programmes offering six‐week nucleic acid testing (NAT) for infants with known HIV exposure (EID), and (2) EID plus universal maternal HIV screening at six‐week infant immunization visits, leading to referral for infant NAT and maternal ART initiation (screen‐and‐test). Model inputs included published Ivoirian/South African/Zimbabwean data: maternal HIV prevalence (4.8/30.8/16.1%), current uptake of EID (40/95/65%) and six‐week immunization attendance (99/74/94%). Referral rates for infant NAT and maternal ART initiation after screen‐and‐test were 80%. Costs included NAT ($24/infant), maternal screening ($10/mother–infant pair), ART ($5 to 31/month) and HIV care ($15 to 190/month). Model outcomes included mother‐to‐child transmission of HIV (MTCT) among HIV‐exposed infants, and life expectancy (LE) and mean lifetime per‐person costs for children with HIV (CWH) and all children born in 2017. We calculated incremental cost‐effectiveness ratios (ICERs) using discounted (3%/year) lifetime costs and LE for all children. We considered two cost‐effectiveness thresholds in each country: (1) the per‐capita GDP ($1720/6380/2150) per year‐of‐life saved (YLS), and (2) the CEPAC‐generated ICER of offering 2 versus 1 lifetime ART regimens (e.g. offering second‐line ART; $520/500/580/YLS).ResultsWith EID, projected six‐week MTCT was 9.3% (CI), 4.2% (SA) and 5.2% (Zimbabwe). Screen‐and‐test decreased total MTCT by 0.2% to 0.5%, improved LE by 2.0 to 3.5 years for CWH and 0.03 to 0.07 years for all children, and increased discounted costs by $17 to 22/child (all children). The ICER of screen‐and‐test compared to EID was $1340/YLS (CI), $650/YLS (SA) and $670/YLS (Zimbabwe), below the per‐capita GDP but above the ICER of 2 versus 1 lifetime ART regimens in all countries.ConclusionsUniversal maternal HIV screening at immunization visits with referral to EID and maternal ART initiation may reduce MTCT, improve paediatric LE, and be of comparable value to current HIV‐related interventions in high maternal HIV prevalence settings like SA and Zimbabwe.

Associations of Sociodemographic and Clinical Factors with Late Presentation for Early Infant HIV Diagnosis (EID) Services in Kenya.

Background:Understanding the missed opportunities in early infant HIV testing within the PMTCT program is essential to address any gaps. The study set out to describe the clinical and sociodemographic characteristics of the infants presenting late for early infant diagnosis in Kenya.Methods:We abstracted routinely collected clinical and sociodemographic characteristics, in a cross-sectional study, on all HIV-infected infants with a positive polymerase chain reaction (PCR) test from 1,346 President’s Emergency Plan for AIDS Relief (PEPFAR) supported health facilities for the period October 2016 to September 2018. We used multivariate logistic regression to examine the association of sociodemographic and clinical characteristics with late (>2 months after birth) presentation for infant HIV testing.Results:Of the 4,011 HIV-infected infants identified, the median infant age at HIV diagnosis was 3 months [interquartile range (IQR), 1-16 months], and two-thirds [2,669 (66.5%)] presented late for infant HIV testing. Factors that were associated with late presentation for infant testing were: maternal ANC non-attendance, adjusted odds ratio (aOR) 1.41 (95% confidence interval (CI) 1.18 -1.69); new maternal HIV diagnosis, aOR 1.45, (95%CI 1.24 -1.7); and lack of maternal antiretroviral therapy(ART), aOR 1.94, (95% CI 1.64 - 2.30). There was a high likelihood of identifying HIV-infected infants among infants who presented for medical services in the outpatient setting (aOR 18.9; 95% CI 10.2 - 34.9) and inpatient setting (aOR 12.2; 95% CI 6.23-23.9) compared to the infants who presented late in maternity.Conclusion and Global Health Implications:Gaps in early infant HIV testing suggest the need to increase maternal pre-pregnancy HIV diagnosis, timely antenatal care, early infant diagnosis services, early identification of mothers who seroconvert during pregnancy or breastfeeding and improved HIV screening in outpatient and inpatient settings. Early referral from the community and access to health facilities should be strengthened by the implementation of national PMTCT guidelines.

Infant HIV diagnosis and turn-around time for testing in Malawi, 2015.

BackgroundFor HIV-exposed infants in Malawi, there are missed opportunities at each step of the testing and treatment cascade.ObjectiveThis study assessed factors associated with HIV positivity among infants in Malawi and turn-around times for infant HIV testing.MethodsHIV testing data for infants aged 0–18 months from 2012 to 2015 were extracted from the Malawi HIV laboratory information management system and analysed using logistic regression. Turn-around time was defined as time between collection of samples to results dispatch from the laboratory.ResultsA total of 106 997 tests were included in the analyses. A subset of 76 006 observations with complete dates were included in the turn-around time analysis. Overall positivity was 4.2%. Factors associated with positivity were increasing age (infants aged 3–6 months: adjusted odds ratio [aOR] = 2.24; infants aged 6–9 months: aOR = 3.42; infants aged > 9 months: aOR = 4.24), female sex (aOR = 1.08) and whether the mother was alive and not on antiretroviral therapy at time of the infant’s test (aOR = 1.57). Provision of HIV prophylaxis to the infant after birth (aOR = 0.38) was found to be protective against HIV positivity. The median turn-around time was 24 days (increased from 19 to 34 days between 2012 and 2015).ConclusionInfant HIV positivity has decreased in Malawi, whereas turn-around time has increased. Factors associated with positivity include increasing age, female sex, and whether the mother was alive and not on antiretroviral therapy at the time of the infant’s test.

Feasibility and acceptability of implementing early infant diagnosis of HIV in Papua New Guinea at the point of care: a qualitative exploration of health worker and key informant perspectives

IntroductionEarly infant diagnosis (EID) of HIV and timely initiation of antiretroviral therapy can significantly reduce morbidity and mortality among HIV-positive infants. Access to EID is limited in many low-income and...

Programmatic evaluation of feasibility and efficiency of at birth and 6-week, point of care HIV testing in Kenyan infant.

BackgroundTesting infants at birth and with more efficient point of care (POC) HIV diagnostic can streamline EID and expedite infant ART initiation. We evaluated the implementation of at birth and 6-week POC testing to assess the effectiveness and feasibility when implemented by existing hospital staff in Kenya.MethodsFour government hospitals were randomly assigned to receive a GeneXpert HIV-1 Qual (n = 2) or Alere m-PIMA (n = 2) machine for POC testing. All HIV-exposed infants enrolled were eligible to receive POC testing at birth and 6-weeks of age. The primary outcome was repeat POC testing, defined as testing both at birth and 6-weeks of age. Secondary outcomes included predictors of repeat POC testing, POC efficiency (turnaround times of key services), and operations (failed POC results, missed opportunities).ResultsOf 626 enrolled infants, 309 (49.4%) received repeat POC testing, 115 (18.4%) were lost to follow up after an at-birth test, 120 (19.2%) received POC testing at 6-weeks only, 80 (12.8%) received no POC testing, and 2 (0.3%) received delayed POC testing (>12 weeks of age). Three (0.4%) were identified as HIV-positive. Of the total 853 POC tests run at birth (n = 424) or 6-weeks (n = 429), 806 (94.5%) had a valid result documented and 792 (98.3%) results had documented maternal notification. Mean time from sample collection to notification was 1.08 days, with 751 (94.8%) notifications on the same day as sample collection. Machine error rates at birth and 6-weeks were 8.5% and 2.5%, respectively. A total of 198 infants presented for care (48 at birth; 150 at 6-weeks) without receiving a POC test, representing missed opportunities for testing.DiscussionAt birth POC testing can streamline infant HIV diagnosis, expedite ART initiation and can be implemented by existing hospital staff. However, maternal disengagement and missed opportunities for testing must be addressed to realize the full benefits of at birth POC testing.

The potential for quality assurance systems to save costs and lives: the case of early infant diagnosis of HIV.

Scaling up of point-of-care testing (POCT) for early infant diagnosis of HIV (EID) could reduce the large gap in infant testing. However, suboptimal POCT EID could have limited impact and potentially high avoidable costs. This study models the cost-effectiveness of a quality assurance system to address testing performance and screening interruptions, due to, for example, supply stockouts, in Kenya, Senegal, South Africa, Uganda and Zimbabwe, with varying HIV epidemics and different health systems. We modelled a quality assurance system-raised EID quality from suboptimal levels: that is, from misdiagnosis rates of 5%, 10% and 20% and EID testing interruptions in months, to uninterrupted optimal performance (98.5% sensitivity, 99.9% specificity). For each country, we estimated the 1-year impact and cost-effectiveness (US$/DALY averted) of improved scenarios in averting missed HIV infections and unneeded HIV treatment costs for false-positive diagnoses. The modelled 1-year costs of a national POCT quality assurance system range from US$ 69359 in South Africa to US$ 334341 in Zimbabwe. At the country level, quality assurance systems could potentially avert between 36 and 711 missed infections (i.e. false negatives) per year and unneeded treatment costs between US$ 5808 and US$ 739030. The model estimates adding effective quality assurance systems are cost-saving in four of the five countries within the first year. Starting EQA requires an initial investment but will provide a positive return on investment within five years by averting the costs of misdiagnoses and would be even more efficient if implemented across multiple applications of POCT.

Pooled testing: A tool to increase efficiency of infant HIV diagnosis and virological monitoring.

BackgroundPooled testing, or pooling, has been used for decades to efficiently diagnose relatively rare conditions, such as infection in blood donors. Programmes for the prevention of mother-to-child transmission of HIV and for antiretroviral therapy (ART) are being rolled out in much of Africa and are largely successful. This increases the need for early infant diagnosis (EID) of HIV using qualitative nucleic acid testing and for virological monitoring of patients on ART using viral load testing. While numbers of patients needing testing are increasing, infant HIV infections and ART failures are becoming rarer, opening an opportunity for pooled testing approaches.AimThis review highlights the need for universal EID and viral load coverage as well as the challenges faced. We introduce the concept of pooled testing and highlight some important considerations before giving an overview of studies exploring pooled testing for EID and virological monitoring.ResultsFor ART monitoring, pooling has been shown to be accurate and efficient; for EID it has not been tried although modelling shows it to be promising. The final part attempts to place pooling into the context of current mother-to-child transmission of HIV and ART programmes and their expected trajectories over the next years.ConclusionSeveral points warrant consideration: pre-selection to exclude samples with an elevated pre-test probability of positivity from pooled testing, the use of dried blood or plasma spots, and choosing a pooling strategy that is both practically feasible and economical. Finally, novel ideas are suggested to make pooling even more attractive.

Trend and predictors for early infant diagnosis by PCR among HIV-exposed infants in Dar es Salaam region, Tanzania, 2014-2016

BACKGROUND
 Early infant diagnosis (EID) of HIV and timely initiation of antiretroviral therapy reduces morbidity and mortality in HIV-infected infants and children. Although the WHO had a global target for 2018 that 90% of HIV-exposed infants (HEI) should be tested by the age of 8 weeks, by 2015 only half were being tested. This study describes trends and predictors for HIV first testing in HEI in Dar es Salaam, Tanzania, from 2014 to 2016.
 METHODS
 We conducted a cross-sectional study of HEI attending HIV services using secondary data collected at health facilities and collated at the national level. We estimated odds ratios and 95% confidence intervals for factors affecting uptake of HIV testing.
 RESULTS
 Of 12,117 HEI, the proportion tested for HIV by age 8 weeks increased from 53.2% in 2014 to 69.2% in 2016; 2.3% were HIV-positive. Replacement feeding (aOR=2.94, 95% CI 2.31 – 3.74) and receiving nevirapine prophylaxis (aOR=1.55, 95% CI 1.28-1.88) were predictors for EID testing uptake. HEI born to mothers with WHO stage II (aOR=0.53, 95% CI 0.41 – 0.67), stage III (aOR=0.64, 95% CI; 0.52 – 0.79) and stage IV (aOR=0.58, 95% CI 0.34 – 0.99) were less likely to be tested than those born to mothers with WHO stage I disease progression.
 CONCLUSION
 There was an increasing trend in the uptake of HIV testing of infants at age 8 weeks during the study period. However, it is still below the global target. Efforts to promote EID testing are still needed.

Human Resource Time Use for Early Infant HIV Diagnosis: A Comparative Time‐Motion Study at Centralized and Point‐of‐Care Health Facilities in Zimbabwe

Research ObjectivePoint‐of‐care (POC) assays for early infant diagnosis of HIV (EID) increase access to testing, shorten time to results, and expedite initiation of antiretroviral therapy when compared with laboratory‐based (centralized) assays. However, there is a significant gap in our understanding of its human resource impact at the facility‐level. This study evaluated the human resource labor time associated with the use of EID platforms by facility‐based health workers (HWs).Study DesignUsing time‐motion methodology, we collected direct observation and self‐reported time‐use data on EID tasks performed by HWs at health facilities in Zimbabwe. Data collection occurred at three EID facility types in Zimbabwe—five POC hubs (test samples from the hub and lower‐volume, nearby facilities), nine POC spokes (lower‐volume), and eleven facilities that use centralized laboratories.EID activities were grouped into pre‐result (counseling, administrative, blood sampling, and preparation) and total EID time (counseling to result communication). Total EID time was observed in POC hub facilities. Since EID tests were not performed on‐site at facilities using centralized laboratories and POC spoke facilities, tasks related to logging and communicating results were not observed. Instead, direct observation data were complemented with HW surveys at those facilities.Mean difference comparisons between centralized and POC EID services were performed with a two‐sample t test with allowance for unequal variances. Bootstrapping with 10 000 replicates was used to estimate the bias‐corrected and accelerated 95% confidence intervals for each measure and difference in means test. To assess whether results were robust, group comparison was performed with two‐sided permutation tests with 10 000 replicates, with same inference to those from the bootstrapped two‐sample t tests. A P‐value of <0.05 was considered statistically significant.Population StudiedFacility‐based health workers in Zimbabwe.Principal FindingsData collectors observed 30 EID processes and 30 HWs provided self‐reported time. Observed average total labor time per EID test at POC hubs was 28 minutes, 22 seconds (95% CI, 22:51‐35:48). HWs performed other tasks while the POC EID machine processed assays.Observed average pre‐result time (counseling to sample preparation) was 18 minutes, 6 seconds (95% CI, 13:00‐23:42) for POC compared with 27 minutes, 48 seconds (95% CI, 23:48‐32:50) for facilities using centralized laboratories. The mean difference of 9 minutes, 42 seconds (95% CI, 03:04‐16:18) was statistically significant. The major driver of this difference was the longer time to prepare dried blood spots (DBS) compared with POC assays.Self‐reported average labor time per negative EID was 49 minutes, 30 seconds (95% CI, 0:42:56‐0:57:08) for facilities using centralized laboratories compared with 53 minutes, 4 seconds (95% CI, 0:40:24‐1:04:44) for POC assays. The differences for self‐reported time were not statistically significant, and results were similar for positive EIDs.ConclusionsPOC EID did not incur significant additional facility‐based human resource time compared to centralized EID.Implications for Policy or PracticeThis study, combined with previously published data demonstrating that POC EID significantly improves timely ART initiation and is cost‐effective, furthers the evidence that POC EID is a feasible intervention for low‐resource contexts, where health facilities are short‐staffed.Primary Funding SourceUNITAID.

‘If the results are negative, they motivate us’. Experiences of early infant diagnosis of HIV and engagement in Option B+

ABSTRACT Few studies have explored the relationship between early infant diagnosis (EID) of HIV and mothers’ engagement in care under Option B+. We conducted in-depth interviews with 20 women who initiated antiretroviral therapy (ART) under Option B+ in rural South Africa to explore the interactions between EID and maternal care engagement. Drawing on practice theory, we identified themes relating to Option B+ care engagement and EID. Women’s practice of engagement with HIV care shaped their decision-making around EID. Mothers who disengaged from care during pregnancy were less inclined to utilise EID as they lacked information about its availability and benefits. For some mothers, tensions between wanting to breastfeed and perceptions that it could facilitate transmission led to repeated utilisation of EID as reassurance that the child remained negative. Some mothers used their child’s negative result as a proxy for their status, subsequently disengaging from care. For some participants, an HIV diagnosis of their infant and the subsequent double burden of treatment visits for themselves and their infant, contributed to their disengagement. Women’s care-seeking practices for themselves and their infants work in a symbiotic ecosystem and should be viewed interdependently to tailor interventions to improve EID uptake and Option B+ care engagement.

Acceptability of Routine Point-of-Care Early Infant Diagnosis in Eight African Countries: Findings From a Qualitative Assessment of Clinical and Laboratory Personnel.

The Elizabeth Glaser Pediatric AIDS Foundation introduced point-of-care (POC) testing for early infant diagnosis (EID) of HIV in 8 African countries. Understanding experiences and opinions of users can help facilitate introduction and sustainability. Cameroon, Côte d'Ivoire, Eswatini, Kenya, Lesotho, Mozambique, Rwanda, and Zimbabwe. Structured interviews with health care workers (HCWs) providing EID services and semistructured interviews with national and regional laboratory managers or EID program managers were conducted before and after the implementation of POC EID. Survey responses were analyzed and compared; open-ended responses were analyzed by theme. In total, 234 and 175 interviews with HCWs and 28 and 14 interviews with laboratory or program managers were conducted before and after the introduction of POC EID, respectively. In preintervention interviews, challenges identified with laboratory-based EID testing included distance from patients' residence to the health facility, time-consuming sample transportation to central laboratories, stockout of testing kits, and long wait times for results. Postintervention data revealed that HCWs found POC EID easy to use and were very satisfied with the fast turnaround time and ability to initiate treatment for HIV-infected infants sooner. Laboratory managers were also supportive of scaling-up POC testing although cautious of the need for reliable infrastructure to operate platforms. The recommendation was that POC EID be integrated within the national diagnostic testing network. Support for POC EID from key stakeholders is essential for sustainability. Overall, participants supported the rollout of POC testing for EID, noting challenges and opportunities for scaling-up POC EID and recommending integration into the overall EID system.

Use of Point-of-Care Nucleic Acid Tests Beyond Early Infant Diagnosis of HIV: A Retrospective Case Review in Lesotho.

Rapid diagnostic tests (RDTs) for HIV antibodies remain the primary method of diagnosis of HIV in individuals over age 18 months in Lesotho. Although antibody tests have high sensitivity and specificity, up to 2.3% of serial two-test algorithms can have discrepant results between RDTs. In the case of inconclusive RDT results, Lesotho guidelines at the time of this study recommended either repeat testing with the same RDT algorithm after 14 days or immediately collect a blood sample to be sent for laboratory-based polymerase chain reaction testing. Point-of-care qualitative nucleic acid tests (POC qual NAT) may have benefits in rapidly resolving these inconclusive results, particularly when compared with repeating RDTs later or conventional polymerase chain reaction testing at the National Reference Laboratory. Hospitals and clinics at 29 locations throughout Lesotho that had access to point-of-care nucleic acid testing. Retrospective case review. We identified 100 testing records where POC qual NAT was used to resolve inconclusive RDTs per Lesotho guidelines. Eighty-nine percent of patients received their results in a median of one day from their inconclusive RDT result (interquartile range 0-7 days). Sixty-eight patients (68%) were determined to be HIV positive based on POC nucleic acid tests (NATs), of which 54 (79%) were started on antiretroviral therapy (ART). Median time from inconclusive RDT result to initiation of ART therapy was 2 days (interquartile range 0-14 days). Three patients in this review were pregnant at the time of testing; one was HIV positive by POC qual NAT and was started on ART therapy the same day. As the availability of POC qual NAT platforms increases, they may serve as feasible options for rapid resolution of inconclusive results and initiation of ART, particularly in populations with high risk of imminent transmission.

Challenges in the Early Infant HIV Diagnosis and Treatment Cascade.

The first step in improving morbidity and mortality among children living with HIV is the timely and early identification of HIV infection, which must be followed by rapid engagement in care and provision of antiretroviral therapy. However, in 2018, only 59% of HIV-exposed infants received an infant nucleic acid diagnostic test by age 2 months and only 54% of children living with HIV received treatment. Because infant diagnosis requires molecular techniques to detect viral nucleic acid, programs for early diagnosis of infection in infants are more complex than those in adults and often require coordination and management of multiple health facilities as well as logistic, financial, and human resource challenges. This article will discuss challenges at each step in the early infant diagnosis cascade and innovations that may help overcome these challenges.

A mobile health-facilitated behavioural intervention for community health workers improves exclusive breastfeeding and early infant HIV diagnosis in India: a cluster randomized trial.

IntroductionIndia’s national AIDS Control Organization implemented World Health Organization’s option B+ HIV prevention of mother‐to‐child transmission (PMTCT) guidelines in 2013. However, scalable strategies to improve uptake of new PMTCT guidelines to reduce new infection rates are needed. This study assessed impact of Mobile Health‐Facilitated Behavioral Intervention on the uptake of PMTCT services.MethodsA cluster‐randomized trial of a mobile health (mHealth)‐supported behavioural training intervention targeting outreach workers (ORWs) was conducted in four districts of Maharashtra, India. Clusters (one Integrated Counselling and Testing Center (ICTC, n = 119), all affiliated ORWs (n = 116) and their assigned HIV‐positive pregnant/postpartum clients (n = 1191)) were randomized to standard‐of‐care (SOC) ORW training vs. the COMmunity home Based INDia (COMBIND) intervention – specialized behavioural training plus a tablet‐based mHealth application to support ORW‐patient communication and patient engagement in HIV care. Impact on uptake of maternal antiretroviral therapy at delivery, exclusive breastfeeding at six months, infant nevirapine prophylaxis, and early infant diagnosis at six months was assessed using multi‐level random‐effects logistic regression models.ResultsOf 1191 HIV‐positive pregnant/postpartum women, 884 were eligible for primary outcome assessment; 487 were randomized to COMBIND. Multivariable analyses identified no statistically significant differences in any primary outcome by study arm. COMBIND was associated with higher uptake of exclusive breastfeeding at two months (adjusted Odds Ratio (aOR), 2.10; 95% CI 1.06 to 4.15) and early infant diagnosis at six weeks (aOR, 2.19; 95% CI 1.05 to 3.98) than SOC.ConclusionsThe COMBIND intervention was easily integrated into India’s existing PMTCT programme and improved early uptake of two PMTCT components that require self‐motivated health‐seeking behaviour, thus providing preliminary evidence to support COMBIND as a potentially scalable PMTCT strategy. Further study would identify modifications needed to optimize other PMTCT outcomes.

Barriers to early infant diagnosis of HIV in the Wa Municipality and Lawra District of Upper West Region, Ghana

We identified socio-demographic, health system and psycho-social barriers to Early Infant Diagnosis (EID) of HIV in the Upper West Region of Ghana. An unmatched case control study of 96 cases and 96 controls was conducted in the ART centers in Lawra district and Wa Municipality between December 2014 and April 2015. A public health facility. We defined a case as an HIV positive mother with an exposed infant who received EID service between January 2011 and December 2014. A control was defined as HIV Positive Mother with an exposed infant who did not receive EID services between January 2011 and December 2014. EID by dry blood spot Deoxyribonucleic acid Polymerase chain reaction. A total of 192 mother-infant pairs were assessed. The mean age of infants at testing for cases was 17.3±14.9 weeks. Mother-to-child-transmission-rate was 2.3%. Factors associated with EID testing included: mother being formally employed (cOR=2.0: 95%CI:1.1-3.8), maternal formal education (cOR=2.0, 95%CI: 1.1-3.6) and maternal independent source of income (cOR 2.2, 95%CI 1.2-4.1). After adjusting for confounders, maternal independent income source was associated with EID testing (aOR 2.2, 95%CI 1.2-4.1). Median turn-around time of EID result was 11 weeks (IQR 4-27 weeks). Women need to be empowered to gain an independent source of income. This can help maximize the benefits of e-MTCT and increase EID in the Upper West Region of Ghana. This work was funded by the authors.

Point-of-care assays good value for infant HIV diagnosis in Zimbabwe

Point-of-care assays good value for infant HIV diagnosis in Zimbabwe

Birth Testing for Infant HIV Diagnosis in Eswatini: Implementation Experience and Uptake Among Women Living With HIV in Manzini Region.

HIV testing at birth of HIV-exposed infants (HEIs) may improve the identification of infants infected with HIV in utero and accelerate antiretroviral treatment (ART) initiation. ICAP at Columbia University supported implementation of a national pilot of HIV testing at birth (0-7 days) in Eswatini at 2 maternity facilities. Dried blood spot (DBS) samples from neonates of women living with HIV (WLHIV) were collected and processed at the National Molecular Reference Laboratory using polymerase chain reaction (PCR). Mothers received birth test results at community health clinics. We report data on HIV birth testing uptake and outcomes for HIV-positive infants from the initial intensive phase (October 2017-March 2018) and routine support phase (April-December 2018). During the initial intensive pilot phase, 1669 WLHIV delivered 1697 live-born HEI at 2 health facilities and 1480 (90.3%) HEI received birth testing. During the routine support phase, 2546 WLHIV delivered and 2277 (93.5%) HEI received birth testing. Overall October 2017-December 2018, 22 (0.6%) infants of 3757 receiving birth testing had a positive PCR test, 15 (68.2%) of whom were successfully traced and linked for confirmatory testing (2 infants were reported by caregivers to have negative follow-up HIV tests). Median time from birth test to receipt of results by the caregiver was 13 days (range: 8-23). Twelve (60.0%) of 20 infants confirmed to be HIV-positive started ART at median age of 17.5 days (12-43). One mother of an HIV-positive infant who was successfully traced refused ART following linkage to care and another child died after ART initiation. Three infants (15.0%) had died by the time their mothers were reached and 4 (15.0%) infants were never located. This pilot of universal birth testing in Eswatini demonstrates the feasibility of using a standard of care approach in a low resource and high burden setting. We document high uptake of testing for newborns among HIV-positive mothers and very few infants were found to be infected through birth testing.

Dried Blood Spot Tests for the Diagnosis and Therapeutic Monitoring of HIV and Viral Hepatitis B and C.

Blood collected and dried on a paper card – dried blood spot (DBS) – knows a growing interest as a sampling method that can be performed outside care facilities by capillary puncture, and transported in a simple and safe manner by mail. The benefits of this method for blood collection and transport has recently led the World Health Organization to recommend DBS for HIV and hepatitis B and C diagnosis. The clinical utility of DBS sampling to improve diagnostics and care of HIV and hepatitis B and C infection in hard to reach populations, key populations and people living in low-income settings was highlighted. Literature about usefulness of DBS specimens in the therapeutic cascade of care – screening, confirmation, quantification of nucleic acids, and resistance genotyping -, was reviewed. DBS samples are suitable for testing antibodies, antigens, or nucleic acids using most laboratory methods. Good sensibility and specificity have been reported for infant HIV diagnosis and diagnosis of hepatitis B and C. The performance of HIV RNA testing on DBS to identified virological failure on antiretroviral therapy is also high but not optimal because of the dilution of dried blood in the elution buffer, reducing the analytical sensitivity, and because of the contamination by intracellular HIV DNA. Standardized protocols are needed for inter-laboratory comparisons, and manufacturers should pursue regulatory approval for in vitro diagnostics using DBS specimens. Despite these limitations, DBS sampling is a clinically relevant tool to improve access to infectious disease diagnosis worldwide.

Performance evaluation of the Aptima HIV-1 Quant Dx assay for detection of HIV in infants in Kenya

BackgroundEarly infant diagnosis (EID) of HIV-1 exposed infants enables timely initiation of antiretroviral therapy (ART), thereby allowing early diagnosis and treatment to slow disease progression and reduce mortality. Turn-around time to results, partially caused by low to medium throughput technology, remains a hindrance to early treatment. A major solution to this challenge is to incorporate high throughput and accurate technologies in the testing process. The Hologic Aptima Quant Dx Assay (Aptima) is a CE marked Real-Time TMA assay running on the high throughput Panther system. ObjectivesThe objective of this study was to evaluate the performance of Aptima for EID using dried blood spots. Study designThis was a cross-sectional prospective study of 2,048 infants seeking HIV services from health facilities in Western Kenya, Africa. Capillary Dried Blood Spot samples DBS were collected from infants with the consent of their mothers. The qualitative performance of Aptima was compared with the Roche COBAS Ampliprep/ COBAS Taqman HIV-1 Qualitative Test v2.0 (CAP/CTM), using these DBS. Demographic information of the participants was also collected. ResultsA total of 1,975 successful comparisons between the two platforms were included in the analysis. The overall agreement between the assays was 99.65 %. The sensitivity and specificity of Aptima was 95.24 % (95 % CI 88.40–98.19 %) and 99.84 % (95 % CI 99.49–99.92 %) respectively. ConclusionsAptima assay has performance characteristics that are comparable to those of the Roche CAP/CTM for qualitative testing on DBS taken from infants. The two assays can therefore be used interchangeably for Early Infant Diagnosis of HIV.

Earlier Antiretroviral Therapy Initiation and Decreasing Mortality Among HIV-infected Infants Initiating Antiretroviral Therapy Within 3 Months of Age in South Africa, 2006-2017.

Early infant diagnosis of HIV and antiretroviral therapy (ART) has been rapidly scaled-up. We aimed to examine the effect of expanded access to early ART on the characteristics and outcomes of infants initiating ART. From 9 cohorts within the International epidemiologic Databases to Evaluate AIDS-Southern Africa collaboration, we included infants with HIV initiating ART ≤3 months of age between 2006 and 2017. We described ART initiation characteristics and the probability of mortality, loss to follow-up (LTFU) and transfer out after 6 months on ART and assessed factors associated with mortality and LTFU. A total of 1847 infants started ART at a median age of 60 days [interquartile range: 29-77] and CD4 percentage (%) of 27% (18%-38%). Across ART initiation calendar periods 2006-2009 to 2013-2017, ART initiation age decreased from 68 (53-81) to 45 days (7-71) (P < 0.001), median CD4% improved from 22% (15%-34%) to 32% (22-43) (P < 0.001) and the proportion with World Health Organization clinical disease stage 3 or 4 declined from 81.6% to 32.7% (P < 0.001). Overall, the 6-month mortality probability was 5.0% and LTFU was 20.4%. Mortality was 10.6% (95% confidence interval: 7.8%-14.4%) in 2006-2009 and 4.6% (3.1%-6.7%) in 2013-2017 (P < 0.001), with similar LTFU across calendar periods (P = 0.274). Pretreatment weight-for-age Z score <-2 was associated with higher mortality. Infants with HIV are starting ART younger and healthier with associated declines in mortality. However, the risk of mortality remained undesirably high in recent years. Focused interventions are needed to optimize the benefits of earlier diagnosis and treatment.