Infant HIV Research Articles

Performance and usability of Cepheid GeneXpert HIV-1 qualitative and quantitative assay in Kenya.

BackgroundIn Kenya, access to early infant diagnosis and viral load monitoring services for HIV patients on ART is significantly hampered by sample transportation challenges and long turnaround times. Near patient care testing technologies have the potential to obviate such constraints. The Cepheid GeneXpert was launched in 2010 as a TB assay and in 2014 as a potential point of care HIV viral load assay. Whereas it is widely is used for TB in Kenya, its utility for HIV testing has not been evaluated.ObjectiveTo investigate the performance and usability characteristics of the GeneXpert HIV-1 qualitative and quantitative assay.MethodsThis was a cross sectional study among 911 HIV Exposed infants and 310 HIV positive adults. Existing machines used for routine TB diagnosis were used in this study. The diagnostic accuracy of the qualitative assay was assessed using Roche CAP/CTM while the quantitative assay was assessed using with Abbott m2000 as the reference assays respectively. Statistical analysis was done using Stata/MP Version 14 for Mac. Concordance values and misclassification were calculated at the clinical cutoff of 1000 cp/ml.ResultsThe sensitivity, specificity and accuracy of the GeneXpert HIV-1 qualitative assay were 99.23% (95% CI 97.24–99.90%), 98.91% (95% CI 97.76–99.55%) and 99.00% respectively. For the quantitative assay, they were 92.50% (95% CI 79.61–98.43%), 100.00% and 97.00% respectively. All 30 (100%) users reported that the GeneXpert machine was easy to use, workflow was simple and TB diagnosis was not negatively affected. In our hands, the median turn-around time for an individual qualitative and quantitative test was 90 minutes. A total of 58 (4.34%) errors and 28 (2.10%) invalid outcomes were experienced; 44 (3.29%) tests did not run to completion due to power outages.ConclusionGeneXpert HIV-1 qualitative and quantitative assay is an accurate test for the diagnosis of HIV in infants and for viral load monitoring. At the point of care, the GeneXpert machine’s simple work flow, ease of use and short test turnaround time present the potential to improve access to HIV testing and viral load monitoring. To integrate HIV diagnosis into the existing GeneXpert platforms for TB Diagnosis, there is need to scale up the infrastructure and to change the way work is done.

Rare Detection of Antiviral Functions of Polyclonal IgA Isolated from Plasma and Breast Milk Compartments in Women Chronically Infected with HIV-1.

The humoral response to invading mucosal pathogens comprises multiple antibody isotypes derived from systemic and mucosal compartments. To understand the contribution of each antibody isotype/source to the mucosal humoral response, parallel investigation of the specificities and functions of antibodies within and across isotypes and compartments is required. The role of IgA against HIV-1 is complex, with studies supporting a protective role as well as a role for serum IgA in blocking effector functions. Thus, we explored the fine specificity and function of IgA in both plasma and mucosal secretions important to infant HIV-1 infection, i.e., breast milk. IgA and IgG were isolated from milk and plasma from 20 HIV-1-infected lactating Malawian women. HIV-1 binding specificities, neutralization potency, inhibition of virus-epithelial cell binding, and antibody-mediated phagocytosis were measured. Fine-specificity mapping showed IgA and IgG responses to multiple HIV-1 Env epitopes, including conformational V1/V2 and linear V2, V3, and constant region 5 (C5). Env IgA was heterogeneous between the milk and systemic compartments (Env IgA, τ = 0.00 to 0.63, P = 0.0046 to 1.00). Furthermore, IgA and IgG appeared compartmentalized as there was a lack of correlation between the specificities of Env-specific IgA and IgG (in milk, τ = -0.07 to 0.26, P = 0.35 to 0.83). IgA and IgG also differed in functions: while neutralization and phagocytosis were consistently mediated by milk and plasma IgG, they were rarely detected in IgA from both milk and plasma. Understanding the ontogeny of the divergent IgG and IgA antigen specificity repertoires and their effects on antibody function will inform vaccination approaches targeted toward mucosal pathogens.IMPORTANCE Antibodies within the mucosa are part of the first line of defense against mucosal pathogens. Evaluating mucosal antibody isotypes, specificities, and antiviral functions in relationship to the systemic antibody profile can provide insights into whether the antibody response is coordinated in response to mucosal pathogens. In a natural immunity cohort of HIV-infected lactating women, we mapped the fine specificity and function of IgA in breast milk and plasma and compared these with the autologous IgG responses. Antigen specificities and functions differed between IgG and IgA, with antiviral functions (neutralization and phagocytosis) predominantly mediated by the IgG fraction in both milk and plasma. Furthermore, the specificity of milk IgA differed from that of systemic IgA. Our data suggest that milk IgA and systemic IgA should be separately examined as potential correlates of risk. Preventive vaccines may need to employ different strategies to elicit functional antiviral immunity by both antibody isotypes in the mucosa.

Early infant diagnosis HIV-1 PCR cycle-threshold predicts infant viral load at birth

BackgroundHIV-1 viral load (VL) has been found to be an independent predictor for disease progression among untreated HIV-infected children. However, qualitative polymerase chain reaction (PCR) assays are routinely used for early infant diagnosis (EID). ObjectivesTo predict HIV-1 VL at birth using qualitative EID real-time PCR cycle-threshold (Ct) values. Study designThis study was a secondary analysis of results from a cohort of intrauterine HIV-1 infected neonates. Neonates were enrolled at Rahima Moosa Mother & Child Hospital in Johannesburg, South Africa between June 2014 and November 2017. Laboratory EID HIV-1 PCR testing was performed at birth using COBAS AmpliPrep/COBAS TaqMan HIV-1 Qualitative Test v2.0 (EID CAP/CTM). Some infants had simultaneous EID point-of-care (POC) testing using Xpert HIV-1 Qualitative assay (EID Xpert). Neonates with a confirmed HIV-1 detected EID result and plasma HIV-1 RNA VL test were included in this analysis. Bland-Altman analysis was used to determine extent of agreement between Ct values of both EID assays. Multivariable linear regression models adjusting for time between EID and VL testing were used to describe the association between EID Ct values and VL and to predict VL at given EID Ct values. ResultsAmong 107 HIV-1 infected neonates included in the study, 59 had POC EID testing. Median VL was 28 400 copies per millilitre (cps/ml) (IQR: 1 918-218 358) - two neonates had VL < 100 cps/ml prior to antiretroviral therapy initiation. There was good correlation between Ct values of both EID assays (Spearman correlation coefficient 0.9, 95% CI: 0.8–1.0). The limits of agreement between EID CAP/CTM and Xpert Ct values were 4–11 cycles. For every one cycle increase in Ct value there was 0.3 log10 RNA decrease (95% CI: −0.3 to −0.2) for both EID assays. An EID CAP/CTM Ct value ≤ 23 and an EID Xpert Ct value ≤ 31 predicted a VL of > 5.0 log10 cps/ml in 82.2% (95% CI: 73.9–88.3) and 84.7% (95% CI: 73.7–91.8) of cases, respectively. ConclusionEID Ct values at birth predict VL and accurately identify infants with VL > 5.0 log10 cps/ml.

PrEP Implementation for Mothers in Antenatal Care (PrIMA): study protocol of a cluster randomised trial

IntroductionWomen in regions with high HIV prevalence are at high risk of HIV acquisition during pregnancy and postpartum, and acute maternal HIV contributes a substantial proportion of infant HIV infections....

Pooled PCR testing of dried blood spots for infant HIV diagnosis is cost efficient and accurate

BackgroundAccess to qualitative HIV PCRs for early infant diagnosis (EID) is restricted in resource-limited settings due to cost. We hypothesised that pooling of dried blood spots (DBS), defined as combining multiple patient samples in a single test with subsequent individual testing of positive pools, would be cost saving while retaining clinical accuracy compared to individual patient testing.MethodsCost savings: A model was developed to simulate reagent and consumable cost saving of pooled compared to individual sample testing. Daily sample/result data of a public health laboratory in South Africa were used to illustrate outputs from the model. Samples were randomly allocated to pools and the process was repeated 1000 times to measure variation in estimates due to this stochasticity.Clinical accuracy: 1170 patient samples were tested using the Roche CAP/CTM Qual assay in pools of five 50 μl DBS. Negative pools comprised DBS previously tested in single reactions; positive pools included 1 positive sample.ResultsPooling would have saved 64% of laboratory costs in 2015. The model is published as an R-based web tool, into which the user enters sample/positivity estimates and workflow management parameters to obtain cost saving estimates at an optimal pool size.Sensitivity of pooled testing was 98.8% overall; 100% for strongly reactive pools. One pool tested false positive which would not impact clinical specificity as individual patient testing is performed prior to reporting.ConclusionsPooled PCR testing for EID remains accurate and dramatically reduces costs in settings with moderate to low prevalence rates and sufficient sample numbers.

Clinical effect and cost-effectiveness of incorporation of point-of-care assays into early infant HIV diagnosis programmes in Zimbabwe: a modelling study

New point-of-care (POC) assays for early infant HIV diagnosis are costlier than conventional total nucleic acid assays, but could increase access to testing, shorten time to results, and expedite initiation of antiretroviral therapy. We aimed to assess the clinical benefits and cost-effectiveness of incorporating these POC assays into early infant diagnosis programmes in Zimbabwe. We used the Cost Effectiveness of Preventing AIDS Complications (CEPAC)-Pediatric model to examine the clinical benefits, costs, and cost-effectiveness of replacing conventional assays for early infant HIV diagnosis with POC assays at age 6 weeks in Zimbabwe. We simulated two strategies for early infant HIV diagnosis: conventional and POC. Modelled assays differed in sensitivity; specificity; time to, and probability of, return of results; and cost. Model outcomes included survival, life expectancy, and mean lifetime per-person treatment cost, which were reported separately for all HIV-exposed infants and all infants with HIV. We calculated incremental cost-effectiveness ratios with discounted (3% per year) costs and life expectancy from a health-care system perspective for all HIV-exposed infants. We judged incremental cost-effectiveness ratios of $1010 (Zimbabwe's annual gross domestic product per person) or less per year of life saved to be cost-effective. When conventional assays were used for early infant diagnosis, projected undiscounted life expectancy was 22·7 years for infants with HIV and 62·5 years for all HIV-exposed infants, at a cost of $610 per HIV-exposed infant. Use of POC assays for early infant HIV diagnosis improved projected undiscounted life expectancy to 25·5 years among infants with HIV and 62·6 years among HIV-exposed infants at a cost of $690 per HIV-exposed infant. At age 12 weeks, survival among all infants with HIV was 76·1% with the conventional testing strategy and 83·5% with the POC testing strategy. The incremental cost-effectiveness ratio of POC assays versus conventional assays for early infant diagnosis was $680 per year of life saved. When conventional assay characteristics remained constant, this ratio remained under the cost-effectiveness threshold as long as the specificity and sensitivity of the POC assay were greater than 92% and 65%, respectively. Our results were robust to plausible variations in POC assay cost, the probability of ART initiation, and probability of return of the results of POC testing. Compared with conventional assays, POC assays for early infant HIV diagnosis in Zimbabwe will improve survival, extend life expectancy, and be cost-effective for HIV-exposed infants. Elizabeth Glaser Pediatric AIDS Foundation, US National Institute of Allergy and Infectious Diseases, Eunice Kennedy Shriver National Institute of Child Health and Human Development, and Unitaid.

Infant HIV testing at birth using point-of-care and conventional HIV DNA PCR: an implementation feasibility pilot study in Kenya

BackgroundInfant HIV diagnosis by HIV DNA polymerase chain reaction (PCR) testing at the standard 6 weeks of age is often late to mitigate the mortality peak that occurs in HIV positive infants’ first 2–3 months of life. Kenya recently revised their early infant diagnosis (EID) guidelines to include HIV DNA PCR testing at birth (pilot only), 6 weeks, 6 months, and 12 months postnatal and a final 18-month antibody test. The World Health Organization (WHO) approved point-of-care (POC) diagnostic platforms for infant HIV testing in resource-limited countries that could simplify logistics and expedite infant diagnosis. Sustainable scale-up and optimal utility in Kenya and other high-prevalence countries depend on robust implementation studies in diverse clinical settings.MethodsWe will pilot the implementation of birth testing by HIV DNA PCR, as well as two POC testing systems (Xpert HIV-1 Qual [Xpert] and Alere q HIV-1/2 Detect [Alere q]), on specimens collected from Kenyan infants at birth (0 to 2 weeks) and 6 weeks (4 to < 24 weeks) postnatal. The formative phase will inform optimal implementation of birth testing and two POC testing technologies. Qualitative interviews with stakeholders (providers, parents of HIV-exposed infants, and community members) will assess attitudes, barriers, and recommendations to optimize implementation at their respective sites. A non-blinded pilot study at four Kenyan hospitals (n = 2 Xpert, n = 2 Alere q platforms) will evaluate infant HIV POC testing compared with standard of care HIV DNA PCR testing in both the birth and 6-week windows. Objectives of the pilot are to assess uptake, efficiency, quality, implementation variables, user experiences of birth testing with both POC testing systems or with HIV DNA PCR, and costs.DiscussionThis study will generate data on the clinical impact and feasibility of adding HIV testing at birth utilizing POC and traditional PCR HIV testing strategies in resource-limited settings. Data from this pilot will inform the optimal implementation of Kenya’s birth testing guidelines and of POC testing systems for the improvement of EID outcomes.Trial registrationClinicalTrials.gov, NCT03435887. Registered 26 February 2018.

Protocol for the evaluation of the population-level impact of Zimbabwe\u2019s prevention of mother-to-child HIV transmission program option B+: a community based serial cross-sectional study

BackgroundWHO recommends that HIV infected women receive antiretroviral therapy (ART) minimally during pregnancy and breastfeeding (“Option B”), or ideally throughout their lives regardless of clinical stage (“Option B+”) (Coovadia et al., Lancet 379:221–228, 2012). Although these recommendations were based on clinical trials demonstrating the efficacy of ART during pregnancy and breastfeeding, the population-level effectiveness of Option B+ is unknown, as are retention on ART beyond the immediate post-partum period, and the relative impact and cost-effectiveness of Option B+ compared to Option A (Centers for Disease Control and Prevention, Morb Mortal Wkly Rep 62:148–151, 2013; Ahmed et al., Curr Opin HIV AIDS 8:473–488, 2013). To address these issues, we conducted an impact evaluation of Zimbabwe’s prevention of mother to child transmission programme conducted between 2011 and 2018 using serial, community-based cross-sectional serosurveys, which spanned changes in WHO recommendations. Here we describe the rationale for the design and analysis.Methods/designOur method is to survey mother-infant pairs residing in the catchment areas of 157 health facilities randomly selected from 5 of 10 provinces in Zimbabwe. We collect questionnaires, blood samples from mothers and babies for HIV antibody and viral load testing, and verbal autopsies for deceased mothers/babies. Using this approach, we collected data from two previous time points: 2012 (pre-Option A standard of care), 2014 (post-Option A / pre-Option B+) and will collect a third round of data in 2017–18 (post Option B+ implementation) to monitor population-level trends in mother-to-child transmission of HIV (MTCT) and HIV-free infant survival. In addition, we will collect detailed information on facility level factors that may influence service delivery and costs.DiscussionAlthough the efficacy of antiretroviral therapy (ART) during pregnancy and breastfeeding for prevention of mother-to-child transmission of HIV (PMTCT) has been well-documented in randomized trials, little evidence exists on the population-level impact and cost-effectiveness of Option B+ or the influence of the facility on implementation (Siegfried et al., Cochrane Libr 7:CD003510, 2017). This study will provide essential data on these gaps and will provide estimates on retention in care among Option B+ clients after the breastfeeding period.Trial registrationNCT03388398 Retrospectively registered January 3, 2018.

The Effect of Human Immunodeficiency Virus-1 Infection on Low Birth Weight, Mother to Child HIV Transmission and Infants’ Death in African Area

Background: It is yet a controversy subject whether low birth weight and infant death are associated to human immunodeficiency virus-1 infection. Objective: To appreciate association between low birth weights, mother to child HIV transmission and infant mortality in HIV-1 infected pregnant women delivering between 2011 and 2016. Materials: We conducted 6 years cohort study in urban Mali. Outcome included preterm delivery, small for gestational age, infant survival status and HIV transmission. Comparison concerned women clinical WHO stage, mother viro-immunological status, and newborn anthropometric parameters. Results: HIV-1 infected women who delivered low birth weight newborn were 20.9% (111/531) versus 16.5% (1910/11.546) in HIV negative patients (p = 0.016). CD4 T cell counts low than 350 T cells count were strongly associated to LBW (p = 0.000; RR = 3.03; 95% CI [1.89 - 3.16]). There is no significant association between ART that was initiated during pregnancy (p = 0.061, RR = 0.02; CI 95% (1.02 - 1.99)) or during delivery (p = 0.571; RR = 1.01; CI 95% (0.10 - 3.02)) and LBW delivery. In multivariate analysis ART regimens containing protease inhibitor (PI) were lone regimens associated with LBW ((p = 0.030; RR = 1.001; 95% confidence interval [1.28 - 3.80]). Very low birth weight was statistically associated to women HIV infection (adjusted relative risk, 2.02; p = 0.000; 95% confidence interval (2.17 - 4.10)). There is no significant difference between mother to child HIV transmission rate in the two HIV-infected pregnant women (10 infected children in group 2: MTCT rate 4.5%) and 3 infected children in group 1 (MTCT rate: 2.7%) (p = 0.56; RR, 0.59; CI 95% (0.18 - 4.39)). In multivariate analysis, LBW was associated with infant death (p = 0.001; RR = 2.04; CI 95% [1.04 - 5.05]). The median weight of infant at the moment of death in group 1 was 851 g (IQR: 520 - 1833 g). Significant relationship was found between infant death among LBW newborn with mother WHO stage 2 (p = 0.004; adjusted RR = 3.22; CI 95% [2.25 - 6.00]), CD4 T cells count < 350 cells/mm3 (p = 0.005; RR = 2.81; CI 95% [1.20 - 4.11]), PI regimens (p = 0.030; RR = 1.00; CI 95% [1.28 - 3.80]). Conclusion: We confirm increased risk of low birth weight and mother HIV-1 infection and we identified strongest association between mortality in infant born to HIV-1 infected mother and LBW.

Participation in a clinical trial of a text messaging intervention is associated with increased infant HIV testing: A parallel-cohort randomized controlled trial.

ObjectiveText messages significantly improve uptake of infant HIV testing in clinical trial contexts. Women who were excluded from a randomized trial in Kenya were followed to create a comparison between women who were enrolled and did not receive the study SMS intervention and women who were screened but not enrolled.DesignParallel-cohort randomized controlled trial analysis.MethodsWe compared time to infant HIV testing between women in three groups: the Trial SMS group, the Trial Control group, and the Comparison Cohort comprised of women who were screened but not enrolled.ResultsOf the 1,115 women screened, 388 (35%) were eligible for trial enrollment, and were randomized to receive either intervention text messages (Trial SMS; N = 195) or continue usual care (Trial Control; N = 193). Among 727 women not enrolled in the study (Comparison Cohort), we obtained infant HIV testing data from clinic records for 510 (70%). The cumulative probability of infant HIV testing was highest in the Trial SMS group (92.0%; 95% CI 87.5–95.3), followed by the Trial Control group (85.1%; 95% CI 79.5–89.8), and lowest among women in the Comparison Cohort (43.4%; 95% CI 39.2–47.8).ConclusionsBoth the Trial SMS group and the Trial Control group were significantly more likely to have their infants tested for HIV compared to the Comparison Cohort, providing evidence of a “clinical trial effect.” This analysis suggests that SMS interventions should be implemented as an adjunct to consistent and engaged delivery of basic health services.

WAYS TO ELIMINATION OF MOTHER-TO-CHILD TRANSMISSION OF HIV

Aim. The article addresses the progress in elimination of mother-to-child transmission of HIV in the Russian Federation. The authors reviewed the available data on the current situation and identified opportunities to reduce the risk of mother-to-child transmission of HIV. Materials and methods. The basic HIV statistics for 2017 from the federal public health watchdog Rospotrebnadzor and the Russia's ministry of health were analysed. The findings included several important aspects. Results. In 2017, women constituted a substantial proportion of population living with HIV, both among all cases and among new HIV infections (37%-38%). The number of new HIV cases among women was growing every year and by 2017 increased 62% compared to 2010. In 28 regions of the Russian Federation, more than 1% of pregnant women were HIV positive. Across the whole monitoring period (from 1987), 177,663 pregnancies complicated by HIV infection and ended in delivery were registered in Russia by the end of 2017, including 14,969 such pregnancies in 2017 alone. In 2017, 91.0% of pregnant women living with HIV took ART during pregnancy, 94.7% received it in labour. 98.7% of new-borns were given antiretroviral therapy as prevention. However, a three-stage chemoprophylaxis was provided to only 89.1% of mother-child pairs. It was revealed that 1,635 motherchild pairs (10.9%) missed at least one of prevention stages. The main reason for incomplete prevention was the late diagnosis of HIV infection in mothers. The viral load before delivery was not suppressed in 25.8% of HIV-positive pregnant women whose pregnancies were completed in 2017 (2,527 women were tested for viral load and 1,342 did not take antiretroviral drugs during pregnancy). 708 children born to HIV-positive mothers were diagnosed HIV positive in 2017 of whom, however, only 235 were born that year. Calculations showed that in 2017 the risk of vertical HIV transmission amounted to 2.3%, which were 348 new-born babies. A significant number of children (35,579 born in different years) did not undergo a final HIV test. 3.9% of all HIV-infected children born to HIV-positive women had contracted HIV through breastfeeding. There was also a trend towards increasing the number of HIV transmissions this way. The article reveals that in the cohort of children born women, the death rate is higher. So in 2017 mortality among infants born to HIV-positive mothers was 1.5 times higher, while perinatal mortality was twice as high as in the general population. Conclusion. The study showed that in order to improve the situation concerning vertical transmission of HIV, it is necessary to solve a number of tasks related to low threshold programmes aimed at access to surveillance, treatment and retention in care for women, especially those of at-risk of HIV. The ways to achieve the goal are early infant HIV diagnosis in first two months of new-borns' life, urgent final laboratory examination of older children exposed to HIV at birth, determination and elimination of factors leading to increased infant mortality, breast-feeding counselling, as well as improvements in statistical methods.

Field evaluation of near point of care Cepheid GeneXpert HIV-1 Qual for early infant diagnosis.

BackgroundAccess to point-of-care HIV testing shortens turn-around times, time to diagnosis and reduces loss to follow-up hence minimizing barriers to early linkage to care and treatment among HIV infected infants. Currently samples for early infant HIV diagnosis are sent to centralized testing facilities which are few and located only at specific regions in Kenya. However, there are Point of Care (POC) early infant diagnosis [EID] technologies elsewhere such as SAMBA and ALERE-Q that are yet to be evaluated in Kenya despite the urgent need for data to inform policy formulation regarding EID. The Cepheid GeneXpert HIV-1 Qual (GeneXpert) technology for POC EID offers a great opportunity to minimize HIV associated morbidity, mortality and loss to follow-up through decentralization of early infant HIV testing to the clinics. This technology also allows for same-day results thus facilitating prompt linkage to care.MethodsWe evaluated the GeneXpert HIV Qual EID POC in Homabay County against the standard of care platform, Roche CAP/CTM HIV-1 qualitative PCR, using dried blood spots (DBS). Between February—July 2016, DBS samples were collected from HIV exposed children <18 months of age enrolled in a cross-sectional study. Samples were collected by qualified nurse counselors, and were tested by trained technicians using field based GeneXpert and conventional laboratory based Roche CAP/CTM HIV-1 qualitative PCR. Sensitivity and specificity were determined.ResultsOverall, 3,814 mother/infant pairs were included in the study, out of which 921 infants were HIV exposed as per the mothers’ HIV status and based on the infant’s HIV rapid test. A total of 969 PCR tests were performed, out of which 30 (3.3%) infants were concordantly positive using both platforms. GeneXpert HIV-1 Qual yielded a sensitivity of 94.1% and specificity of 99.8% with an overall error rate of 0.7%.ConclusionOur findings show that GeneXpert HIV-1 Qual performs well compared to CAP/CTM using DBS samples, suggesting that this technology may be adopted in decentralized laboratories as a near POC device. It may contribute to prompt diagnosis of HIV exposed infants hence enabling early linkage to care, thus advancing further gains in EID.

The Effect of the Prevention of Mother to Child Transmission Strategies on the Prevalence of HIV in HIV-Exposed Infants in Rivers State, Nigeria

Background: The Scourge of HIV is still severe in Sub-Saharan Africa, Nigeria has the highest burden. Mother to Child Transmission is an important source of this disease. The WHO Option B plus strategy for prevention of mother to child transmission of HIV has been adopted in many communities including ours, we undertook this study to assess the efficacy of this programme in our setting. Methods: A retrospective review of laboratory requests and results for Early Infant diagnosis at Rivers State University Teaching Hospital PCR laboratory was done. Patients samples were delivered as DBS and tested with RT-PCR technology using Cobas Taqman version 1.5 (Roche Molecular Systems, Branchburg, NJ, USA). Results: Two hundred and three HIV-Exposed Infants (HEI) were tested in the period, 98(48.3%) of them were tested by the 2nd month of life, 158(78.3%) of them had received some form of ART after birth. Majority of the mothers 112(70.4%) were receiving ART for the first time in the index pregnancy. Nine (4.4%) of the HEI had positive EID results, the major predictor of EID result was maternal use of ART. Conclusion: The PMTCT programme is effective in preventing transmission, maternal use of ART during pregnancy and early EID testing by the second month of life are key components that have helped to control the disease in HEI in our study. Steps should be taken to strengthen health education among women of reproductive age and link mothers from the PMTCT service to EID services promptly. Funding Statement: This study was not funded. Declaration of Interests: Each of the authors have no conflict of interest to declare. Ethics Approval Statement: This study was approved the the Rivers State Health Research Ethics Committee.

611. Placental Pathology and Neonatal Outcomes in Pregnancies of Perinatally vs. Nonperinatally HIV-Infected Women

BackgroundPerinatally HIV-infected (PHIV) women are reaching childbearing age, but little is known about the impact of long-term exposure to HIV and antiretroviral therapy on pregnancy outcomes of PHIV women, including the impact on neonatal health and placental pathology.MethodsWe performed a retrospective cohort analysis over a 10-year period (2007–2017) of PHIV women, matched by age and date of delivery in 1:2 ratio, to behaviorally HIV-infected women (BHIV). The primary maternal outcome variable included virologic suppression (viral load ≤ 400 copies/mL) at delivery. Secondary outcome variables included hospital length of stay (LOS), mode of delivery, infectious (chorioamnionitis, funisitis) and vascular (vasculitis) placental complications based on histopathological analysis of placental specimen (composite variable). The primary neonatal outcome was preterm birth (<37 weeks); secondary neonatal outcomes included APGAR scores and infant HIV status. Primary and secondary maternal and neonatal outcomes were compared between PHIV and BHIV women. Logistic regression models measured the association between primary maternal and neonatal outcomes and perinatal status, adjusting for age and race.ResultsA total of 60 deliveries were evaluated during the study period (20 from women with PHIV and 40 from BHIV). Women with PHIV were significantly younger (20 vs. 29, P < 0.05) and less likely to be suppressed at delivery (55% vs. 90%, P < 0.05) compared with women with BHIV. A total of 19 women experienced placental pathologies but no differences were found by perinatal status (31% vs. 36%, P = 0.7, among PHIV and BHIV, respectively). Other than viral suppression, there were no significant differences among maternal and neonatal outcomes of interest by mode of HIV acquisition. In the multivariable regression, women with PHIV were significantly less likely to be suppressed after adjusting for age and race (AOR 0.07, 95% CI 0.01–0.80). There was no significant difference for preterm birth.ConclusionWomen with PHIV were significantly less likely to be suppressed at delivery but did not experience other complications at birth. Neonatal outcomes were similar among women with PHIV and BHIV.Disclosures All authors: No reported disclosures.

Progress in the performance of HIV early infant diagnosis services in Zambia using routinely collected data from 2006 to 2016

BackgroundEarly diagnosis and treatment initiation of HIV-infected infants can greatly reduce the risk of infant mortality. The WHO recommends testing HIV-exposed infants at 6 weeks of age and immediate initiation of antiretroviral therapy if positive. This study aimed to determine the feasibility of using an electronic health records system to evaluate the performance of Zambia’s HIV Early Infant Diagnosis services.MethodsA retrospective analysis of routinely collected data from the Zambian SmartCare database was performed for the period January 2006 to December 2016. The study population includes all HIV-infected infants (n = 32,593) registered during this period on treatment for HIV. Univariable logistic regression was conducted to identify factors associated with later infant testing and treatment initiation.ResultsThe mean age at infant HIV test decreased from 10.10 months in 2006 to 3.49 months in 2016. Infants born in 2015 were almost 4 times more likely to be tested under 2 months of age compared to infants born in 2006 (OR: 3.72, p-value: < 0.001). The mean time from diagnosis to treatment initiation decreased from 220 days in 2006 to 9 days in 2015. There was substantial regional variability with infants in the provinces of Copperbelt, Luapula and Southern performing best in outcomes and Eastern, Lusaka and Western performing the worst.ConclusionsHIV-exposed infants born more recently have significantly better outcomes than infants born a decade ago in Zambia, which could be as a result of increased attention and funding for HIV programmes.

National estimates and risk factors associated with early mother-to-child transmission of HIV after implementation of option B+: a cross-sectional analysis

Routine data from Malawi's prevention of mother-to-child transmission (MTCT) option B+ programme suggest high uptake of antiretroviral therapy (ART) among pregnant women. Malawi's Ministry of Health led the National Evaluation of Malawi's PMTCT Program to obtain nationally representative data on maternal ART coverage and prevention of MTCT effectiveness. Here, we present the early transmission data for infants aged 4-12 weeks. We used a multistage cluster design to recruit a nationally representative sample of HIV-exposed infants and their mothers in Malawi. Between October 16, 2014, and May 17, 2016, we screened for HIV in all mothers attending an under-5 vaccination or outpatient sick-child clinic with infants aged 4-26 weeks at 54 health facilities selected across ten districts and four regional sampling zones. Infants with mothers identified as HIV-infected were enrolled in the cohort. We calculated weighted MTCT rates for only the subset of infants aged 4-12 weeks at screening, thereby capturing MTCT from early pregnancy, to delivery, and early breastfeeding. We collected data on maternal and infant demographics and self-reported use of HIV services, ART, and antenatal clinics. We tested HIV-exposed infants for the virus and assessed associations of certain variables with infant HIV status. We confirmed HIV exposure in 3542 (10·4%) of 33 980 mother (guardian)-infant pairs with infants aged 4-26 weeks. Of those, 2530 (2514 mothers and 16 guardians) had infants aged 4-12 weeks at the time of screening (2498 singlets and 32 twins). We excluded 25 infants from the analysis because no information was available about their HIV status. 91·3% (95% CI 85·6-96·9) of mothers were on ART during pregnancy. The MTCT rate was 3·7% (2·3-6·0) overall and ranged from 1·4% (0·4-4·4) in women who initiated ART before pregnancy to 19·9% (13·4-28·6) in women not on ART. In multivariable logistic regression analysis, the odds of early MTCT were higher in mothers starting ART post partum (adjusted odds ratio 16·7, 95% CI 1·6-171·5; p=0·022) and in those not on ART with an unknown HIV status during pregnancy (19·1, 8·5-43·0; p<0·0001) than in mothers on ART before pregnancy. Among HIV-exposed infants, 98·0% (95% CI 96·9-99·1) were reported by the mother to have received infant nevirapine prophylaxis, and only 45·6% (34·8-56·4) were already enrolled in an exposed infant HIV care clinic at the time of study screening. These data suggest that Malawi's decentralisation of ART services has resulted in higher ART coverage and lower early MTCT. However, the uptake of services for HIV-exposed infants remains suboptimal. President's Emergency Plan for AIDS Relief.

Pre- and post-natal macronutrient supplementation for HIV-positive women in Tanzania: Effects on infant birth weight and HIV transmission.

ObjectiveTo determine if a protein-calorie supplement (PCS) plus a micronutrient supplement (MNS) improves outcomes for HIV-infected lactating women and their infants.DesignRandomized, controlled trial.SettingDar es Salaam, TanzaniaSubjects, participantsPregnant HIV-infected women enrolled in PMTCT programs who intended to breastfeed for 6 months.InterventionRandomization 1:1 to administration of a PCS plus MNS versus MNS alone among 96 eligible women beginning in the third trimester and continuing for 6 months of breast-feeding.Main outcome measure(s)Primary: infant weight at 3 months. Secondary: maternal BMI at 6 months.ResultsPCS resulted in significant increases in daily energy intake compared to MNS at all time points (range of differences: +388–719 Kcal); and increases in daily protein intake (range of differences: +22–33 gm). Infant birth weight (excluding twins) was higher in the PCS than MNS groups: 3.30 kg vs 3.04 kg (p = 0.04). Infant weight at 3 months did not differ between PCS and MNS groups: 5.63 kg vs 5.99 kg (p = 0.07). Maternal BMI at 6 months did not differ between PCS and MNS groups: 24.3 vs 23.8 kg/m2 (p = 0.68). HIV transmission occurred in 0 infants in the PCS group vs 4 in the MNS group (p = 0.03).ConclusionsIn comparison to MNS the PCS + MNS intervention was well tolerated, increased maternal energy and protein intake, and increased infant birth weight, but not weight at 3 months or maternal BMI at 6 months. Reduced infant HIV transmission in the PCS + MNS group was observed.Trial registrationClinical Trials.Gov NCT01461863.

Evaluation of the HIV Infant Tracking System (HITSystem) to optimise quality and efficiency of early infant diagnosis: a cluster-randomised trial in Kenya

The HIV Infant Tracking System (HITSystem) is a web-based intervention linking providers of early infant diagnosis, laboratory technicians, and mothers and infants to improve outcomes for HIV-exposed infants. We aimed to evaluate the efficacy of the HITSystem on key outcomes of early infant diagnosis. We did a cluster-randomised trial at six hospitals in Kenya, which were matched on geographic region, resource level, and volume of patients (high, medium, and low). We randomly allocated hospitals within a matched pair to either the HITSystem (intervention; n=3) or standard of care (control; n=3). A random number generator was used to assign clusters. Investigators were unaware of the randomisation process. Eligible participants were mothers aged 18 years or older with an infant younger than 24 weeks presenting for their first early infant diagnosis appointment. The primary outcome was complete early infant diagnosis retention, which was defined as receipt of all indicated age-specific interventions until 18 months post partum (for HIV-negative infants) or antiretroviral therapy initiation (for HIV-positive infants). Analysis was per protocol in all randomised pairs judged eligible, excluding infant deaths and those who moved or were transferred to another health facility. Modified intention-to-treat sensitivity analyses judged all infant deaths and transfers as incomplete early infant diagnosis retention. Separate multivariable logistic regression analyses were done with intervention group, hospital volume, and significant covariates as fixed effects. This trial is registered with ClinicalTrials.gov, number NCT02072603; the trial has been completed. Between Feb 16, 2014, and Dec 31, 2015, 895 mother-infant pairs were enrolled. Of these, 87 were judged ineligible for analysis, 26 infants died, and 92 pairs moved or were transferred to another health facility. Thus, data from 690 mother-infant pairs were analysed, of whom 392 were allocated to the HITSystem and 298 to standard of care. Mother-infant pairs were followed up to Sept 30, 2017. Infants diagnosed as HIV-positive were followed up for a median of 2·1 months (IQR 1·6-4·8) and HIV-negative infants were followed up for a median of 17·0 months (IQR 16·6-17·6). Infants enrolled in the HITSystem were significantly more likely to receive complete early infant diagnosis services compared with those assigned standard of care (334 of 392 [85%] vs 180 of 298 [60%]; adjusted odds ratio [OR] 3·7, 95% CI 2·5-5·5; p<0·0001). No intervention effect was recorded at high-volume hospitals, but strong effects were seen at medium-volume and low-volume hospitals. Modified intention-to-treat analyses for complete early infant diagnosis were also significant (334 of 474 [70%] vs 180 of 334 [54%]; adjusted OR 2·0, 95% CI 1·4-2·7; p<0·0001). No adverse events related to study participation were reported. The HITSystem intervention is effective and feasible to implement in low-resource settings. The HITSystem algorithms have been modified to include HIV testing at birth, and an adapted HITSystem 2.0 version is supporting HIV-positive pregnant women to prevent perinatal transmission and optimise maternal and infant outcomes. National Institute of Child Health and Human Development.

Mother–baby dyads enrolled in PMTCT care in western Kenya: characteristics and implications for ART programmes

The objective of the study was to establish the mother–baby pair characteristics that contribute to vertical transmission of HIV and elucidate on remediation. We assessed for factors increasing the odds of HIV transmission in children born to HIV-infected mothers in western Kenya. We used a retrospective study which reviewed routinely collected data of 1 028 mother–baby pairs enrolled in a prevention of mother-to-child transmission (PMTCT) programme in western Kenya from January to December 2015. We compared the transmission rates amongst mothers known to have a positive HIV status before conception (known positives/KPs) versus the transmission amongst those who were newly diagnosed during maternal and child health (MCH) clinic attendance (new positives/NPs). We compared the socio-demographic and clinical characteristics of the mothers using chi square and Kruskal–Wallis tests at 95% confidence interval (CI). We assessed for factors associated with the infants’ HIV status using a logistic regression model. The results revealed that 60% (622) of the mothers were KPs, and that KPs and NPs had mother-to-child transmission (MTCT) rates of 5.5% and 20.7% respectively. Close to 90% of the NP Mothers were at an early HIV clinical stage at enrolment and 40% were enrolled after delivery. The infants of NPs were enrolled at a mean age of 18.3 weeks compared to 6.6 weeks for the infants of the KPs. On adjusted multivariable analysis, child's age at enrolment (AOR = 1.05, 95%CI = 1.036–1.064) and mother's status at conception (AOR = 1.96, 95%CI = 1.042–3.664) were significantly associated with the infant's HIV status. None of the HIV infected infants had received nevirapine prophylaxis. Most of the mothers enrolling into the PMTCT programme have a known HIV-positive status, however, NPs are the largest contributors to continued MTCT.

Evaluating outcomes of mother-infant pairs using dolutegravir for HIV treatment during pregnancy.

Objectives:Dolutegravir (DTG), a second-generation integrase inhibitor, is an effective treatment for HIV but its safety and efficacy are not well established in pregnancy. Here, we assess maternal and infant outcomes of mother–infant pairs using DTG-containing regimens during pregnancy.Methods:We performed a retrospective cohort analysis of pregnant women with HIV on DTG from two urban clinics in the United States, 2015–2018. Maternal outcomes included viral suppression (viral load of <20 copies/ml prior to delivery), development of resistance, and tolerability to DTG. Infant outcomes included preterm delivery (birth at <37 weeks), small for gestational age (SGA, weight <10th percentile), infant HIV status at birth, birth defect(s), and Appearance, Pulse, Grimace, Activity, Respiration (APGAR) scores. We performed a trend analysis to assess DTG use over time.Results:A total of 66 women used DTG during pregnancy and the proportion on DTG increased each year: in 2015, 8% (5/60) of women were on DTG, versus 22% (15/67) in 2016, 42% (30/71) in 2017, and 59% (16/27) in 2018 (P < 0.05). Among women who delivered (n = 57), 77.2% were undetectable at delivery. There were no drug resistance and no reported side effects during pregnancy. Infants had a mean APGAR score of 8 (SD 1.5) at 1 min and 9 (SD 0.8) at 5 min; 31.6% were born prematurely and 15.8% were SGA, and 2 infants had a birth defect. No cases of HIV transmission occurred.Conclusion:Our findings suggest that DTG can be an effective treatment during pregnancy. Infant outcomes (preterm deliveries and birth defects) need to be investigated in larger studies.