Early Infant Diagnosis Program Research Articles

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OBJECTIVES/SPECIFIC AIMS: High-sensitivity diagnostics for early infant diagnosis (EID) of HIV at the point of care (POC) are not widely available. Lateral flow immunoassays (LFA) can detect HIV-p24, but are not sensitive enough in practice. With improvements, LFA are a compelling platform for POC in EID. We used functionalized magnetic beads and immunocomplex dissociation to improve sensitivity of HIV-p24 LFA. Here, we evaluate the utility for LFA to quantitatively report HIV-p24 concentration and estimate HIV viral load. Using purified p24 protein and virion constructs, we determined the limits of detection for HIV-p24 using LFA rapid tests. Using measurements from HIV-p24 ELISA, laboratory-developed RT-qPCR, droplet digital PCR, and gold standard clinical viral load, we further characterized the relationship between HIV-p24 concentration, HIV genomic RNA, and LFA test line signal. METHODS/STUDY POPULATION: We measured HIV-p24 concentration by ELISA (R&D Systems) and LFA (Alere Determine HIV-1/2 Ab/Ag Combo). An LFA reader instrument was used to image test lines and measure test line signal on the LFA. HIV viral loads were measured using RT-qPCR and droplet digital RT-PCR protocols adapted in our lab. We obtained gold standard viral load measurements using the Roche Cobas TaqMan system at Vanderbilt University Medical Center. Data analysis was performed using Prism 7 and Stata 14. RESULTS/ANTICIPATED RESULTS: LFA test line signal increases in a predictable, dose-dependent manner and correlates with concentration of purified HIV-p24 with a linear range between 50 and 1000 pg/mL (Spearman r=1; p=0.0004). We compared p24 concentration (ELISA). We evaluated the utility of LFA to quantify HIV-p24 from virions suspended in human plasma, which increased the limit of detection for HIV-p24 to 100 pg/mL and shifted the linear range 100–10,000 pg/mL (Spearman r=0.77; p<0.001). To evaluate the relationship between HIV-p24 concentration and concentration of HIV RNA, we employed 3 molecular techniques. The LFA is capable of detecting HIV-p24 concentrations that correspond to a range of viral loads between 653,000 and 1655 copies of viral RNA/mL. DISCUSSION/SIGNIFICANCE OF IMPACT: Our preliminary results are very promising, indicating that commercially available LFA can quantitatively measure HIV-p24 concentration to low levels. When coupled with our analysis of the relationship between HIV-p24 concentration and HIV RNA concentration, LFA may be a potential platform allowing us to estimate HIV viral burden at clinically relevant levels. Our next steps will be to evaluate this relationship in primary, clinical specimens in collaboration with the Tennessee Center for AIDS Research. We will incorporate technologies to improve the sensitivity of these LFA and evaluate their performance in field settings in Zambia. Our findings are broadly applicable for use in HIV care and treatment programs and early infant diagnosis programs around the world.

Evaluating turnaround times for early infant diagnosis samples in Kenya from 2011-2014: A retrospective analysis of HITSystem program data.

Long turnaround times (TAT) for the processing and posting of results of infant HIV DNA PCR samples can hinder the success of early infant diagnosis (EID) programs. The HITSystem is an eHealth intervention that alerts staff when services are overdue or results are delayed. We conducted a retrospective analysis of 3669 HIV-exposed infants enrolled in 15 Kenya hospital EID programs and three laboratories using the HITSystem from 2011–2014. We assessed mean and median TAT from when a sample was: 1) obtained to when it was shipped to the laboratory, 2) shipped to when it was received at the laboratory, 3) received to when a result was posted, and 4) the total time from obtaining the sample (step 1) to posting the result (step 3). TAT were compared by laboratory, clinic, year, and month of sample collection. 3625 infant samples had results posted by end of 2014. Mean TAT from sample collection to shipping was 5.2 days, from shipping to laboratory receipt was 2.0 days, and from laboratory receipt to result posting was 17.4 days. Altogether, it took an average of 24.7 days from sample collection until result posting. There was significant variation between laboratories, particularly in laboratory processing times (step 3). TAT showed a decreasing trend from 2011–2014, although TAT in December remained higher. Compared with other Kenyan studies, TAT in these HITSystem enrolled settings were shorter. Significant variation between laboratories, however, indicates the need to strengthen protocols and infrastructure to ensure that all laboratories can provide rapid, high-quality services.

Early infant diagnosis and outcomes in HIV-exposed infants at a central and a district hospital, Northern Malawi.

Setting: Mzuzu Central Hospital (MZCH), Mzuzu, and Chitipa District Hospital (CDH), Chitipa, Malawi. Objective: To compare management and outcomes of human immunodeficiency virus (HIV) exposed infants in early infant diagnosis (EID) programmes at MZCH, where DNA polymerase chain reaction (PCR) testing is performed on site, and CDH, where samples are sent to MZCH, between 2013 and 2014. Design: Retrospective cohort study. Results: Of infants enrolled at MZCH (n = 409) and CDH (n = 176), DNA PCR results were communicated to the children's guardians in respectively 56% and 51% of cases. The median time from sample collection to guardians receiving results was 34 days for MZCH and 56 days for CDH. In both hospitals, only half of the dried blood spot (DBS) samples were collected between 6 and 8 weeks. More guardians from MZCH than CDH received test results within 1 month of sample collection (25% vs. 10%). Among the HIV-positive infants, a higher proportion at MZCH (92%) started antiretroviral therapy than at CDH (46%). The relative risk (RR) of death was higher among infants with late DBS collection (RR 1.3, 95%CI 1.0-1.7) or no collection (RR 5.8, 95%CI 4.6-7.2), and when guardians did not receive test results (RR 8.3, 95%CI 5.7-11.9). Conclusion: EID programmes performed equally poorly at both hospitals, and might be helped by point-of-care DNA PCR testing. Better programme implementation and active follow-up might improve infant outcome and retention in care.

Missed diagnostic opportunities within South Africa's early infant diagnosis program, 2010-2015.

BackgroundSamples submitted for HIV PCR testing that fail to yield a positive or negative result represent missed diagnostic opportunities. We describe HIV PCR test rejections and indeterminate results, and the associated delay in diagnosis, within South Africa’s early infant diagnosis (EID) program from 2010 to 2015.MethodsHIV PCR test data from January 2010 to December 2015 were extracted from the National Health Laboratory Service Corporate Data Warehouse, a central data repository of all registered test-sets within the public health sector in South Africa, by laboratory number, result, date, facility, and testing laboratory. Samples that failed to yield either a positive or negative result were categorized according to the rejection code on the laboratory information system, and descriptive analysis performed using Microsoft Excel. Delay in diagnosis was calculated for patients who had a missed diagnostic opportunity registered between January 2013 and December 2015 by means of a patient linking-algorithm employing demographic details.ResultsBetween 2010 and 2015, 2 178 582 samples were registered for HIV PCR testing of which 6.2% (n = 134 339) failed to yield either a positive or negative result, decreasing proportionally from 7.0% (n = 20 556) in 2010 to 4.4% (n = 21 388) in 2015 (p<0.001). Amongst 76 972 coded missed diagnostic opportunities, 49 585 (64.4%) were a result of pre-analytical error and 27 387 (35.6%) analytical error. Amongst 49 694 patients searched for follow-up results, 16 895 (34.0%) had at least one subsequent HIV PCR test registered after a median of 29 days (IQR: 13–57), of which 8.4% tested positive compared with 3.6% of all samples submitted for the same period.ConclusionsRoutine laboratory data provides the opportunity for near real-time surveillance and quality improvement within the EID program. Delay in diagnosis and wastage of resources associated with missed diagnostic opportunities must be addressed and infants actively followed-up as South Africa works towards elimination of mother-to-child transmission.

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

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. 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. 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.

Risks associated with mother-to-child transmission of HIV infection.

Nguefack F, Koki-Ndombo P, Ngoh R, Soh Fru F, Kinkela MN, Chiabi A. Risks associated with mother-to-child transmission of HIV infection. Turk J Pediatr 2017; 59: 426-433. Early infant diagnosis (EID) permits the detection of Human Immunodeficiency Virus (HIV) infection in exposed children from 4-6 weeks by polymerase chain reaction (PCR). The aim of this study was to assess some maternal and infant characteristics associated with HIV infected children in an EID program. A retrospective study was performed using records of HIV exposed children enrolled in the EID program from 2009 to 2013. Patients recruited were from various health structures and at different clinical stages; some for the Prevention of Mother-to-Child Transmission (PMTCT) follow up, others with signs of HIV infection. Data was collected from completed hospital records of children aged 6 weeks to 18 months containing at least two PCR, one PCR and one serologic test, or one PCR test and viral load. HIV infection was considered if one of the of tests was positive. In all, 130 (5.3%) exposed children with only one positive PCR test, and 1,442 (59%) others with information lacking in their record were excluded. A total 107 out of 871 infants enrolled (12.2%) were infected. Only, 32.7% of the mothers were on antiretroviral therapy (ART). Of these, 53.3% had their first PCR performed between 6 weeks and 6 months. Children were less likely to be HIV infected when their mothers received antiretroviral (ARV) (OR=0.15, 95% CI 0.07-0.30, P=0.000). Factors associated with HIV infection in the children were the lack of ARV prophylaxis (OR=2.07, 95%CI 1.05-4.09, P=0.035) and having mixed feeding (OR=3.91, 95% CI 1.66-9.24, P=0.002) in multivariate analysis. The high rate of infection associated with the maternal and infant correlates of HIV infected children would result from the poor implementation of the PMTCT. Systematic screening of pregnant and breastfeeding women should be reinforced and the lifelong ARVs for PMTCT (Option B+) be promoted.

High Rates of Drug Resistance Among Newly Diagnosed HIV-infected Children in the National Prevention of Mother-to-child Transmission Program in Togo

Prevention of mother-to-child transmission (PMTCT) programs have been largely scaled-up, but data on infant HIV drug resistance from PMTCT programs implemented in resource-limited countries are lacking. Remnant dried blood spots from HIV-infected children (aged <18 months) tested through the Togo national early infant diagnosis program during 2012 and 2013 were collected and assessed for HIV drug resistance. Pol-RT (reverse transcriptase) region was amplified, sequenced and analyzed for the presence of drug resistance mutations (DRMs). Overall, 121 of 201 (60.2%) newly diagnosed children had detectable DRMs. Among the 131 of 201 (65.2%) children with reported exposure to maternal and/or infant antiretrovirals (ARVs), DRMs were detected in 99 children (75.6%). Importantly, in 41 of 201 children for whom no exposure to ARVs was reported, DRMs were detected in 11 children (26.8%). For 29 children, no data on ARV exposure were available. For the 121 of 201 children with DRMs, 99 of 121 (81.8%) had only nonnucleoside reverse transcriptase inhibitor DRMs detected but 21 of 121 (17.3%) had both nonnucleoside reverse transcriptase inhibitor and nucleoside reverse transcriptase inhibitor (NRTI) DRMs. Among breast-fed children, drug resistance was more frequent when mothers were on antiretroviral therapy (ART), 61 of 75 (81.3%) versus 14 of 39 (35.9%) when mothers were not on ART (P < 0.001). Nucleoside reverse transcriptase inhibitor resistance was more common when mothers were on ART. Scale-up and improvement of PMTCT strategies resulted in a global decrease of pediatric HIV infections, but our study shows high rates of drug resistance in infants for whom prevention failed.

Recommendations for the management of indeterminate HIV PCR results within South Africa’s early infant diagnosis programme

Indeterminate HIV PCR results represent missed diagnostic opportunities within South Africa’s early infant diagnosis programme. These results not only delay diagnosis and appropriate management but are also a source of confusion and apprehension amongst clinicians and caregivers. We describe the extent of indeterminate HIV PCR results within South Africa’s early infant diagnosis programme and provide recommendations for the management of these cases, both in terms of laboratory practice and the clinical care of the infants.

Recommendations for the management of indeterminate HIV PCR results within South Africa’s early infant diagnosis programme

Recommendations for the management of indeterminate HIV PCR results within South Africa’s early infant diagnosis programme

Hospital admissions from a pediatric HIV care and treatment program in Malawi.

BackgroundThe scale up of pediatric antiretroviral treatment programs across Sub-Saharan Africa over the last decade has brought increasing numbers of children into HIV care. This patient population requiring life-long care presents new challenges in the outpatient and inpatient settings. We sought to describe hospitalizations from a large pediatric HIV treatment facility to better understand the scope of the situation and identify areas for improved care delivery.MethodsWe conducted a retrospective case series of all HIV-infected and exposed patients <18 years enrolled at Baylor College of Medicine Children’s Foundation Malawi, from October 2004-October 2010. Patients admitted to the hospital on or after the day of enrollment were included. Data were extracted from electronic clinic records. Analysis was done at the patient and admission level, as some patients had multiple admissions.ResultsOf 5062 patients enrolled in care, 877 (17.3 %) had 1137 admissions at median age 24 months (IQR: 12–62). 191 (21.8 %) patients had multiple admissions. A high proportion of admissions occurred in patients under two years (49.4 %), those within one month of clinic enrollment (32.9 %), those with severe immune suppression (44.0 %), and those not on ART (48.5 %). The frequency of primary admission diagnoses varied across these same variables, with malnutrition, pneumonia, and malaria being the most common.ConclusionsIllness requiring hospitalization is common in HIV-infected and exposed children and these results reinforce the need for a comprehensive care package with special attention to nutrition. Strengthened programs for malaria prevention and expanded access to pneumococcal vaccine are also needed. The high burden of admissions in children under 24 months and those newly enrolled in care suggests a need for continued improvement of early infant diagnosis and provider-initiated testing programs to link patients to care before they are symptomatic. Similarly, the high proportion of admissions in those not yet started on ART emphasizes the importance of rapid initiation of ART for eligible pediatric patients.

Is integrating sickle cell disease and HIV screening logical?

Is integrating sickle cell disease and HIV screening logical?

Burden of sickle cell trait and disease in the Uganda Sickle Surveillance Study (US3): a cross-sectional study.

Sickle cell disease contributes substantially to mortality in children younger than 5 years in sub-Saharan Africa. In Uganda, 20,000 babies per year are thought to be born with sickle cell disease, but accurate data are not available. We did the cross-sectional Uganda Sickle Surveillance Study to assess the burden of disease. The primary objective of the study was to calculate prevalence of sickle cell trait and disease. We obtained punch samples from dried blood spots routinely collected from HIV-exposed infants in ten regions and 112 districts across Uganda for the national Early Infant Diagnosis programme. Haemoglobin electrophoresis by isoelectric focusing was done on all samples to identify those from babies with sickle trait or disease. Between February, 2014, and March, 2015, 99,243 dried blood spots were analysed and results were available for 97,631. The overall number of children with sickle cell trait was 12,979 (13·3%) and with disease was 716 (0·7%). Sickle cell numbers ranged from 631 (4·6%) for trait and 23 (0·2%) for disease of 13,649 in the South Western region to 1306 (19·8%) for trait and 96 (1·5%) for disease of 6581 in the East Central region. Sickle cell trait was seen in all districts. The lowest prevalence was less than 3·0% in two districts. Eight districts had prevalence greater than 20·0%, with the highest being 23·9%. Sickle cell disease was less common in children older than 12 months or who were HIV positive, which is consistent with comorbidity and early mortality. Prevalence of sickle cell trait and disease were high in Uganda, with notable variation between regions and districts. The data will help to inform national strategies for sickle cell disease, including neonatal screening. Cincinnati Children's Research Foundation.

Diagnóstico precoz de la infección por el virus de la inmunodeficiencia humana-1 en niños: programa de prevención de la transmisión maternoinfantil en Guinea Ecuatorial

BackgroundGreat efforts have been made in the last few years in order to implement the prevention of mother-to-child transmission (PMTCT) program in Equatorial Guinea (GQ). The aim of this study was to evaluate the rates of mother-to-child HIV transmission based on an HIV early infant diagnosis (EID) program. MethodsA prospective observational study was performed in the Regional Hospital of Bata and Primary Health Care Centre Maria Rafols, Bata, GQ. Epidemiological, clinical, and microbiological characteristics of HIV-1-infected mothers and their exposed infants were recorded. Dried blood spots (DBS) for HIV-1 EID were collected from November 2012 to December 2013. HIV-1 genome was detected using Siemens VERSANT HIV-1 RNA 1.0 kPCR assay. ResultsSixty nine pairs of women and infants were included. Sixty women (88.2%) had WHO clinical stage 1. Forty seven women (69.2%) were on antiretroviral treatment during pregnancy. Forty five infants (66.1%) received postnatal antiretroviral prophylaxis. Age at first DBS analysis was 2.4 months (IQR 1.2-4.9). One infant died before a HIV-1 diagnosis could be ruled out. Two infants were HIV-1 infected and started HAART before any symptoms were observed. The rate of HIV-1 transmission observed was 2.9% (95%CI 0.2-10.5). ConclusionsThe PMTCT rate was evaluated for the first time in GQ based on EID. EID is the key for early initiation of antiretroviral therapy and to reduce the mortality associated with HIV infection.

The Burden of HIV Associated Drug Resistance Mutations in an Early Infant Diagnosis Program: A Glance through the Paediatric Window of Zimbabwe

There is paucity of information on the prevalence of human immunodeficiency virus type 1 drug-resistance mutations in infants infected despite prevention of mother to child transmission in Zimbabwe. This study examined 32 dried blood spot specimens from HIV- 1 C infected infants born alive to women receiving antiretroviral therapy, who were part of the WHO/ResNet early infant diagnosis program between January 2010 and January 2011. The objective was to determine the patterns and levels of HIV drug resistance and inform on policy formulation. Overall HIV prevalence of the infants in the retrospect study period was 2.4% (32/1356). Half of the samples (16/32) analyzed had HIV associated drug resistance mutations, however excluding polymorphic mutations the HIV drug resistant mutations were 25% (8/32). Frequencies of the mutations were (E138A, n=6; G190A, n=1; M230ML, n=1; K103KN, n=1; Y181C, n=5; V90VI, n=1; E138G, n=1; E138EA, n=1). One patient had two mutations the K103KN and the Y181C. Of the sixteen patients with HIV drug resistance mutations, 5 had nevirapine only resistance, none had lamivudine resistance and 8 had both etravirine and rilpivirine resistance, 2 had both nevirapine, efavirenz and 1 had rilpivirine only. The study shows an apparent non-nucleoside reverse transcriptase inhibitor (NNRTI) drug resistance predominance and suggests a judicious use of NNRTI regimens and a prudent strategy to minimize the selection of drug resistance mutations.

Early infant diagnosis and post-exposure prophylaxis for HIV- exposed infants.

Recent scientific evidence suggests that early initiation of antiretroviral therapy (ART) among infants exposed perinatally to HIV has beneficial effects on their health and survival, and may even induce remission. This has led to the roll-out of early infant diagnosis (EID) of HIV and early treatment. Also, there is talk of using ART as post-exposure prophylaxis (PEP) to prevent mother-to-child transmission. EID involves carrying out diagnostic tests before initiating ART. In India, current programme design of centralised diagnosis has been resulting in poor access to diagnosis and treatment. To save the lives of HIV-infected infants, it is important to prevent delay. Another issue to be kept in mind is that the results of HIV tests may turn negative after the initiation of ART. This could be due to viral remission induced by ART or false positive initial results. Differentiating between the two is difficult. To deal with such cases, we need to develop a clinical algorithm and tools for capacity-building in counselling. The use of ART as PEP is expected to encounter further challenges. Between ART as PEP and EID, the later has advantages from an ethical perspective. There is a need to address the ethical issues within the EID programme by strengthening the current mechanisms for protecting the rights of HIV-exposed infants.

Implementation and Operational Research: Expedited Results Delivery Systems Using GPRS Technology Significantly Reduce Early Infant Diagnosis Test Turnaround Times.

The objective of this study was to quantify the impact of a new technology to communicate the results of an infant HIV diagnostic test on test turnaround time and to quantify the association between late delivery of test results and patient loss to follow-up. We used data collected during a pilot implementation of Global Package Radio Service (GPRS) printers for communicating results in the early infant diagnosis program in Mozambique from 2008 through 2010. Our dataset comprised 1757 patient records, of which 767 were from before implementation and 990 from after implementation of expedited results delivery system. We used multivariate logistic regression model to determine the association between late result delivery (more than 30 days between sample collection and result delivery to the health facility) and the probability of result collection by the infant's caregiver. We used a sample selection model to determine the association between late result delivery to the facility and further delay in collection of results by the caregiver. The mean test turnaround time reduced from 68.13 to 41.05 days post-expedited results delivery system. Caregivers collected only 665 (37.8%) of the 1757 results. After controlling for confounders, the late delivery of results was associated with a reduction of approximately 18% (0.44 vs. 0.36; P < 0.01) in the probability of results collected by the caregivers (odds ratio = 0.67, P < 0.05). Late delivery of results was also associated with a further average increase in 20.91 days of delay in collection of results (P < 0.01). Early infant diagnosis program managers should further evaluate the cost-effectiveness of operational interventions (eg, GPRS printers) that reduce delays.

Adherence to Early Infant Diagnosis Testing Algorithm, a Challenge to Early Infant Diagnosis Program in Resource Limited Settings of Uganda

Introduction: Early Infant Diagnosis (EID) targeting HIV exposed infants, happens over a period of time (6 weeks up to 18months), and employs different testing technologies at different testing time points. Being a process that is implemented over time and employing different testing technologies, a testing algorithm was designed to ensure reliable final diagnosis. This study was set out to estimate the level of adherence to the testing algorithm. Methods: Retrospective EID data was collected from 24 health facilities that covered the entire tier of the health system, from 4 geographic regions of Uganda. From each study site, all exposed infants that were tested in 2012 were tracked from the 1 st molecular test beginning at 6 weeks to the final rapid test at 18 months. st molecular test in 2012. Out of these, 3888 (92.1%) were HIV negative and 333 (7.9%) were HIV positive. Of the negative only 1543 (39.7%) did a 2 nd molecular test representing a loss of 60.3%. A total of 14 babies converted to HIV with the 2 nd molecular test, resulting in a total of 347 positive babies. Of the total positive babies, 212 (61.1%) initiated ART, representing a loss of 38.9%. Of the total who were screened with the 1 st molecular test, 1130 (26.8%) were tested with the final rapid test at 18 months, representing a loss of 73.2%. Discussion: The results indicate that, despite operational improvements, very poor adherence to EID testing algorithm was observed. This poor adherence may have an impact on the ultimate objectives of the whole program. Factors explaining high LTFU include; results long turnaround time (TAT), lack of patient follow-up mechanism, and poor patient counseling. There is therefore an urgent need to rethink the implementation of the EID program, not only in Uganda but also in other resourcelimited countries. Mechanisms of patient follow-up and linkage to care should be integrated into the testing process.

HIV-1 Early Infant Diagnosis is an Effective Indicator of the Prevention of Mother-to-Child Transmission Program Performance: Experience from Cameroon.

Despite improvement in HIV prevention of mother-to-child transmission (PMTCT), there are still over 1,500 African infants newly infected daily. PMTCT elimination requires antiretroviral therapy (ART) throughout pregnancy and breastfeeding periods, while early infant diagnosis (EID) of HIV implies early treatment for those infected. Our study aimed at assessing the utility of EID program data in evaluating the implementation of PMTCT program in Cameroon, and in identifying the efficacy of existing PMTCT interventions and breastfeeding options on the events of HIV vertical transmission. A study was conducted from 2010-2011 using PMTCT data from EID sites of six regions of Cameroon. PMTCT ARV regimens, breastfeeding options, and the child's HIV DNA-polymerase chain reaction (PCR) results were recorded. Statistical analyses were performed using Mann Whitney U and Fisher exact tests, with p<0.05 considered significant. A total of 2,505 mother-child pairs received ART, resulting is 4.3% (93) vertical transmission, against 31.3% (284/906) among mother-child pairs without exposure to any PMTCT intervention; p<0.00001. A statistically significant difference (p<0.00001) was also found between formula feeding (FF) (5.9%) versus exclusive breastfeeding (EBF) (12.5%), as well as between EBF versus mixed feeding (MF) (30%). With FF, when both mother-child pairs received PMTCT, only 2.9% (47/1603) vertical transmission was recorded versus 19.9% (48/241) for mother-child pairs without intervention; p<0.00001. Transmission rates were similar across infant age range [2.7% (10/376) for age ≤6 weeks, versus 2.5% (43/1807) for age >6 weeks-6 months]. Interestingly, babies aged 6 weeks receiving FF showed a significantly lower transmission rate (3.2%, 9/277) as compared to their counterparts with EBF (7.7%, 12/156); p<0.00001. Using EID dataset, it appears that considerable reduction in HIV MTCT may be achievable through access to ARV (option B+) and adequate infant feeding option (especially FF) in Cameroon. EID programme is therefore an effective routine approach for PMTCT programme evaluation in resource-limited settings.

Challenges in the Early Diagnosis of HIV Infection in Infants: Experience from Tamil Nadu, India.

To analyze critical steps in the testing algorithm of the National Early Infant Diagnosis (EID) program in India. A retrospective analysis of data on cases enrolled in the EID program during 2010-2012 from Tamil Nadu was undertaken. 2745 dried blood spots were tested; 9% of these tested positive. Median age of infants at the time of testing was 4 months. Second specimen for confirmation was received from 67% of cases with a turn-around time of 10-270 days. Even with high levels of uptake into the program, huge delays and loss-to-follow-up observed between the first and second sampling, suggests need for revision of the current testing algorithm.

Consolidating HIV testing in a public health laboratory for efficient and sustainable early infant diagnosis (EID) in Uganda.

Uganda introduced an HIV Early Infant Diagnosis (EID) program in 2006, and then worked to improve the laboratory, transportation, and clinical elements. Reported here are the activities involved in setting up a prospective analysis in which the Ministry of Health, with its NGO partners, determined it would be more effective and efficient to consolidate the initial eight-laboratory system for EID testing of HIV dried blood samples offered by two nongovernmental partners operating research facilities into a single well-equipped and staffed laboratory within the Ministry. A retrospective analysis confirmed that redesign reduced overhead cost per PCR test of HIV dried blood samples from US$22.20 to an average of $5. Along with the revamped system of sample collection, transportation, and result communication, Uganda has been able to vastly increase the HIV diagnosis of babies and engagement of them and their mothers in clinical care, including antiretroviral therapy. Uganda reduced turnaround times for results reporting to clinicians from more than a month in 2006 to just 2 weeks by 2014, even as samples tested increased dramatically. The next challenge is overcoming loss of babies and mothers to follow up.