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Background: The HITSystem efficacy trial showed significant improvements in early infant diagnosis retention, return and notification of infant test results, and earlier antiretroviral therapy (ART) initiation compared with standard-of-care early infant diagnosis services in Kenya. This study aimed to analyse data from the HITSystem trial to assess the cost-effectiveness of the intervention in Kenya., Methods: In this analysis, we extrapolated results from the HITSystem cluster randomised controlled trial to model early infant diagnosis outcomes and cost-effectiveness if the HITSystem was scaled up nationally in Kenya, compared with standard-of-care outcomes. We used a micro-costing method to collect cost data, which were analysed from a health-system perspective, reflecting the investment required to add HITSystem to existing early infant diagnosis services and infrastructure. The base model used to calculate cost-effectiveness was deterministic and calculated the progression of infants through early infant diagnosis. Differences in progression across study arms were used to establish efficacy outcomes. The number of life-years gained per infant successfully initiating ART were based on the Cost Effectiveness of Preventing AIDS Complications model in east Africa. HITSystem cost data were integrated into the model, and the incremental cost-effectiveness ratio was calculated in terms of cost per life-year gained. Sensitivity analyses were done using the deterministic model with triangular stochastic probability functions for key model parameters added. The number of life-years gained was discounted at 3% and costs were adjusted to 2021 values., Findings: The cost per life-year gained from the HITSystem was US$82·72. Total cost for national HITSystem coverage in Kenya was estimated to be around $2·6 million; covering 82 230 infants exposed to HIV at a cost of $31·38 per infant and a yield of 1133 infants receiving timely ART, which would result in 31 189 life-years gained. With sensitivity analyses, the cost per life-year gained varied from $40·13 to $215·05. 90% of model values across iterations ranged between $55·58 (lower 5% threshold) and $132·38 (upper 95% threshold)., Interpretation: The HITSystem would be very cost-effective in Kenya and can optimise the return on the existing investment in the national early infant diagnosis programme., Funding: The US National Institute of Child Health and Human Development., Competing Interests: Declaration of interests We declare no competing interests., (Copyright © 2023 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY-NC-ND 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Background: Prevention of mother-to-child HIV transmission (PMTCT) services in Kenya can be strengthened through the delivery of relevant and culturally appropriate SMS messages., Methods: This study reports on the results of focus groups conducted with pre and postnatal women living with HIV (5 groups, n = 40) and their male partners (3 groups, n = 33) to elicit feedback and develop messages to support HIV+ women's adherence to ART medication, ANC appointments and a facility-based birth. The principles of message design informed message development., Results: Respondents wanted ART adherence messages that were low in verbal immediacy (ambiguous), came from an anonymous source, and were customized in timing and frequency. Unlike other studies, low message immediacy was prioritized over customization of message content. For retention, participants preferred messages with high verbal immediacy-direct appointment reminders and references to the baby-sent infrequently from a clinical source., Conclusion: Overall, participants favored content that was brief, cheerful, and emotionally appealing., (© 2021. The Author(s).)

Background: In Kenya, standard early infant diagnosis (EID) with polymerase chain reaction (PCR) testing at 6-week postnatal achieves early treatment initiation (<12 weeks) in <20% of HIV+ infants. Kenya's new early infant diagnosis guidelines tentatively proposed adding PCR testing at birth, pending results from pilot studies., Methods: We piloted birth testing at 4 Kenyan hospitals between November 2017 and November 2018. Eligible HIV-exposed infants were offered both point-of-care and PCR HIV testing at birth (window 0 to <4 weeks) and 6 weeks (window 4-12 weeks). We report the: proportion of infants tested at birth, 6-week, and both birth and 6-week testing; median infant age at results; seropositivity and antiretroviral therapy initiation., Results: Final sample included 624 mother-infant pairs. Mean maternal age was 30.4 years, 73.2% enrolled during antenatal care and 89.9% had hospital deliveries. Among the 590 mother-infants pairs enrolled before 4 weeks postnatal, 452 (76.6%) completed birth testing before 4 weeks, with 360 (79.6%) testing within 2 weeks, and 178 (39.4%) before hospital discharge (0-2 days). Mothers were notified of birth PCR results at a median infant age of 5.4 weeks. Among all 624 enrolled infants, 575 (92.1%) were tested during the 6-week window; 417 (66.8%) received testing at both birth and 6-weeks; and 207 received incomplete testing (93.3% only 1 PCR and 6.7% no PCR). Four infants were diagnosed with HIV, and 3 infants were initiated on antiretroviral therapy early, before 12 weeks of age., Conclusions: Uptake of PCR testing at birth was high and a majority of infants received repeat testing at 6 weeks of age., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2021 The Author(s). Published by Wolters Kluwer Health, Inc.)

We assessed the preliminary impact of the adapted HIV Infant Tracking System (HITSystem v2.0) intervention on prevention of mother-to-child transmission (PMTCT) outcomes using a matched cluster randomized design in two Kenyan government hospitals. Between November 2017 and June 2019, n = 157 pregnant women with HIV were enrolled and followed from their first PMTCT appointment until 12-weeks postpartum. Data from 135 women were analyzed (HITSystem 2.0: n = 53, standard of care (SOC): n = 82), excluding eight deaths, eight pregnancy losses, and six transfers/moves. The primary outcome, complete PMTCT retention, is an aggregate measure of attendance at all scheduled antenatal appointments, hospital-based delivery, and infant HIV-testing before 7-weeks postnatal. HITSystem 2.0 participants were more likely to receive complete PMTCT services compared to SOC (56.6% vs. 17.1% p < 0.001). In multivariate modeling, HITSystem 2.0 was the strongest predictor of complete PMTCT retention (aOR 5.7, [1.2-90.8], p = 0.032). SOC participants had 1.91 increased hazard rate of PMTCT disengagement; (aHR 6.8, [2.2-21.1]; p < 0.001).

Male involvement in prevention of mother to child transmission of HIV (PMTCT) care improves maternal and child outcomes. We conducted a mixed-methods study at two Kenyan government hospitals. We quantitatively assessed women's expectations and preferences for male partner involvement in PMTCT and male partner attendance at PMTCT appointments. Qualitative interviews with women during the postpartum period assessed types of support women received from their male partners. At enrollment, most participants wanted (75%) and expected (69%) male partners to attend appointments; yet, only 9% had a male partner attend any appointments. Most women agreed that their partner would: support them financially (81%), help follow doctor's guidance (61%), support a hospital-based delivery (85%), and want to receive text messages (68%). Expectations and preferences varied by women's characteristics, most notably experiences with mistreatment, disclosure status, and knowledge of male partner's HIV status. In qualitative interviews, instrumental (financial) support was the most frequently discussed type of support. Male partners also provided informational support by reminding women of medication or appointments. Women reported a variety of ways in which their male partners supported them through PMTCT; however, there was a gap between women's expectation for male partner attendance and the level of male attendance achieved.

We sought to understand the sequence of testing and treatment among nine infants offered both conventional and point-of-care testing and diagnosed as HIV-positive by 6 months of age in Kenya. One infant received per protocol testing and treatment. Patient-level (late presentation and disengagement), provider-level (reluctance and error/oversight) and system-level (stock outs, errors) challenges delayed diagnosis and treatment. Early point-of-care testing can streamline testing; however, challenges mitigate benefits., Competing Interests: The authors have no conflicts of interest to disclose. The authors declare that they have no conflict of interest., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Early infant diagnosis (EID) establishes the presence of HIV infection in HIV-exposed infants and children younger than 18 months of age. EID services are hospital-based, and thus fail to capture HIV-exposed infants who are not brought to the hospital for care. Point-of-care (POC) diagnostic systems deployed in the community could increase the proportion tested and linked to treatment, but little feasibility and acceptability data is available., Methods: Semi-structured interviews (n = 74) were conducted by a Kenyan team with community members (Community Health Workers/Volunteers [CHW/CHV], Traditional Birth Attendants [TBAs], community leaders) and parents of HIV-exposed infants at four study sites in Kenya to elicit feedback on the acceptability and feasibility of community-based POC HIV testing., Results: Participants described existing community health resources that could be leveraged to support integration of community-based POC HIV testing; however, the added demand placed on CHW/CHV could pose a challenge. Participants indicated that other potential barriers (concerns about confidentiality, disclosure, and HIV stigma) could be overcome with strong engagement from trusted community leaders and health providers, community sensitization, and strategic location and timing of testing. These steps were seen to improve acceptability and maximize the recognized benefits (rapid results, improved reach) of community-based testing., Conclusion: Community members felt that with strategic planning and engagement, community-based POC HIV testing could be a feasible and acceptable strategy to overcome the existing barriers of hospital-based EID., Competing Interests: The authors have declared that no competing interests exist.

Background: Testing 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., Methods: Four 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)., Results: Of 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., Discussion: At 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., Competing Interests: The authors have declared that no competing interests exist.

Objective: Early initiation of antiretroviral therapy (ART, before 12 weeks of age) among infants living with HIV reduces infant mortality and slows disease progression. However, inefficiencies in early infant diagnosis processes prevents timely ART initiation among infants living with HIV in Kenya. This study assesses predictors of early ART initiation among infants living with HIV in Kenya., Design: We retrospectively reviewed data from 96 infants living with HIV born between January 2013 and June 2017 at 6 Kenyan government hospitals., Methods: The primary outcome was infant receipt of ART by 12 weeks of age. We assessed bivariable and multivariable predictors of ART initiation by 12 weeks of age., Results: Among 96 infants living with HIV, 82 (85.4%) infants initiated ART at a median infant age of 17.1 weeks. Of the 82 infants who started ART, only 17 (20.7%) initiated ART by 12 weeks of age. In multivariable logistic regression analyses, testing per national guidelines (< 7 weeks of age) (aOR 40.14 [3.96-406.97], p = 0.002), shorter turnaround time for result notification (≤ 4 weeks) (aOR 11.30 [2.02-63.34], p = 0.006), and ART initiation within 3 days of mother notification (aOR 7.32 [1.41-38.03], p = 0.006) were significantly associated with ART initiation by 12 weeks of age., Conclusion: Current implementation of early infant diagnosis services in Kenyan only achieves targets for early ART initiation in one-fifth of infants with HIV. Strengthening services to support earlier infant testing and streamlined processes for early infant diagnosis may increase the proportion of infants who receive timely ART.

Background: At-birth and point-of-care (POC) HIV testing are emerging strategies to streamline infant HIV diagnosis and expedite ART initiation for HIV-positive infants. The purpose of this qualitative study was to evaluate factors influencing the provision and acceptance of at-birth POC testing among both HIV care providers and parents of HIV-exposed infants in Kenya., Methods: We conducted semi-structured interviews with 26 HIV care providers and 35 parents of HIV-exposed infants (including 23 mothers, 6 fathers, and 3 mother-father pairs) at four study hospitals prior to POC implementation. An overview of best available evidence related to POC was presented to participants prior to each interview. Interviews probed about standard EID services, perceived benefits and risk of at-birth and POC testing, and suggested logistics of providing at-birth and POC. Interviews were audio recorded, translated (if necessary), and transcribed verbatim. Using the Transdisciplinary Model of Evidence Based Practice to guide analysis, transcripts were coded based on a priori themes related to environmental context, patient characteristics, and resources., Results: Most providers (24/26) and parents (30/35) held favorable attitudes towards at-birth POC testing. The potential for earlier results to improve infant care and reduce parental anxiety drove preferences for at-birth POC testing. Parents with unfavorable views towards at-birth POC testing preferred standard testing at 6 weeks so that mothers could heal after birth and have time to bond with their newborn before-possibly-learning that their child was HIV-positive. Providers identified lack of resources (shortage of staff, expertise, and space) as a barrier., Discussion: While overall acceptability of at-birth POC testing among HIV care providers and parents of HIV-exposed infants may facilitate uptake, barriers remain. Applying a task-shifting approach to implementation and ensuring providers receive training on at-birth POC testing may mitigate provider-related challenges. Comprehensive counseling throughout the antenatal and postpartum periods may mitigate patient-related challenges., Competing Interests: The authors have declared that no competing interests exist.

The HIV Infant Tracking System (HITSystem) is an eHealth intervention to improve early infant diagnosis (EID) through alerts to providers and text messages to mothers. This study explored mothers' experiences receiving standard and HITSystem-enhanced EID services to assess perceived intervention benefits, acceptability, and opportunities for improvement. This qualitative study was embedded within a cluster-randomized control trial to evaluate the HITSystem at six Kenyan government hospitals (3 intervention, 3 control). We conducted semi-structured interviews with 137 mothers attending EID follow-up visits. Compared to control sites, participants at HITSystem sites described enhanced EID quality; HITSystem-generated texts informed them of result availability and retesting needs, provided cues-to-action for clinic attendance, and engendered opportunities for patient support. They described improved EID efficiency through shorter waiting periods for results and fewer hospital visits. Participants reported high satisfaction with EID and acceptability of text messages; however, modifications to ensure text delivery, increase repeat testing reminders, include low literacy content options, and provide encouraging messages were suggested. These user experience data suggest improvements in EID at HITSystem sites when compared with control sites.

Early infant diagnosis (EID) involves age-specific tracking and testing of HIV-exposed infants during the first 18 months of life and rapid initiation of life-saving treatment for those infected. In Kenya, pre-2013 data estimate EID lost to follow-up (LTFU) at 39-65%, yet no study has documented LTFU rates and predictors throughout the EID cascade since Option B+ fundamentally changed services by placing all HIV-positive expectant mothers on lifelong treatment. Using an explanatory mixed-method design, we assessed LTFU rates and predictors among 870 mother-infant dyads enrolled in EID in six urban/peri-urban Kenyan government hospitals. Mothers completed baseline surveys, and dyads were tracked through EID. We selected 12 baseline variables and modeled odds of LTFU at 9 and 18 months using mixed logistic regression. Qualitative interviews were conducted with 61 mothers to assess barriers and facilitators to completing EID. Thematically coded transcripts were used to interpret quantitative predictors of LTFU. By the 18-month test, 145 dyads (22%) were LTFU, with three-quarters of LTFU occurring between 9- and 18-month tests. Odds of LTFU at 18 months decreased by 10% for each additional year of maternal age and by 66% with HIV status disclosure. Qualitative data revealed how disclosure facilitated essential social support for EID completion and how older mothers attributed maturity and life experience to successful engagement in care. Findings suggest LTFU rates in Kenya have declined, but gaps remain in ensuring universal coverage. Efforts to improve retention should focus on increasing support for younger mothers and those who have not disclosed their HIV status.

Delays in traditional HIV DNA PCR testing for early infant diagnosis (EID) at 6 weeks of age result in late antiretroviral treatment (ART). Birth point of care (POC) testing is an emerging strategy with the potential to streamline EID services. We elicited providers' recommendations for introducing birth POC testing to guide strategies in Kenya and similar settings. We conducted formative interviews with 26 EID providers from four Kenyan hospitals prior to POC implementation. Providers discussed the need for comprehensive training, covering both EID and POC-specific topics for all key personnel. Providers highlighted equipment considerations, such as protocols for maintenance and safe storage. Providers emphasized the need for maternal counseling to ensure patient acceptance and most agreed that specimen collection for birth POC testing should occur in the maternity department and supported a multidisciplinary approach. Though most providers supported ART initiation based on a positive birth POC result, a few expressed concerns with result validity. To maximize implementation success, provider training, equipment security, maternal counseling, and logistics of testing must be planned and communicated to providers.

Background: 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., Methods: 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., Findings: 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., Interpretation: 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., Funding: National Institute of Child Health and Human Development., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

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.

Despite the importance of early detection to signal lifesaving treatment initiation for HIV+ infants, early infant diagnosis (EID) services have received considerably less attention than other aspects of prevention of mother to child transmission care. This study draws on baseline data from an on-going cluster randomized study of an intervention to improve EID services at six government hospitals across Kenya. Two logistic regressions examined potential predictors of "on time" (infant ≤6 weeks of age) vs. "late" (≥7 weeks) and "on time" versus "very late" (≥12 weeks) EID engagement among 756 mother-infant pairs. A quarter of the infants failed to get "on time" testing. Predictors of "on time" testing included being informed about EID by providers when pregnant, perceiving less HIV stigma, and mother's level of education. Predictors of "very late" testing (≥12 weeks of age) included not being informed about EID by providers when pregnant and living farther from services. Findings highlight the importance of ensuring that health care providers actively and repeatedly inform HIV+ mothers of the availability of EID services, reduce stigma by frequently communicating judgment free support, and assisting mothers in early planning for accessing EID services. Extra care should be focused on engaging mothers with less formal education who are at increased risk for seeking "late" EID testing. This study offers clear targets for improving services so that all HIV-exposed infants can be properly engaged in EID services, thus increasing the potential for the best possible outcomes for this vulnerable population., Competing Interests: The authors have no conflict to disclose.

Objectives: Guided by the RE-AIM model, we describe preliminary data and lessons learned from multiple serial implementations of an eHealth intervention to improve early infant diagnosis (EID) of HIV in Kenya., Methods: We describe the reach, effectiveness, adoption, implementation and maintenance of the HITSystem, an eHealth intervention that links key stakeholders to improve retention and outcomes in EID. Our target community includes mother-infant pairs utilizing EID services and government health care providers and lab personnel. We also explore our own role as program and research personnel supporting the dissemination and scale up of the HITSystem in Kenya., Results: Key findings illustrate the importance of continual adaptation of the HITSystem interface to accommodate varied stakeholders' workflows in different settings. Surprisingly, technology capacity and internet connectivity posed minimal short-term challenges. Early and sustained ownership of the HITSystem among stakeholders proved critical to reach, effectiveness and successful adoption, implementation and maintenance., Conclusions: Preliminary data support the ability of the HITSystem to improve EID outcomes in Kenya. Strong and sustained collaborations with stakeholders improve the quality and reach of eHealth public health interventions., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Background: Early infant diagnosis among human immunodeficiency virus (HIV)-exposed infants is a critical component of prevention of mother-to-child transmission programs. Barriers to early infant diagnosis include poor uptake, low retention at designated re-testing intervals, delayed test results, passive systems of communication, and poor linkage to treatment. This study will evaluate the HIV Infant Tracking System (HITSystem), an eHealth intervention that streamlines communication and accountability between the key early infant diagnosis stakeholders: HIV+ mothers and their HIV-exposed infants, healthcare providers, and central laboratory personnel. It is hypothesized that the HITSystem will significantly improve early infant diagnosis retention at 9 and 18 months postnatal and the timely provision of services., Methods/design: Using a phased cluster-randomized controlled trial design, we will evaluate the impact of the HITSystem on eight primary benchmarks in the 18-month long cascade of care for early infant diagnosis. Study sites are six government hospitals in Kenya matched on geographic region, resource level, and patient volume. Early infant diagnosis outcomes of mother-infant dyads (n = 120 per site) at intervention hospitals (n = 3) where the HITSystem is deployed at baseline will be compared to the matched control sites providing standard care. After allowing for sufficient time for enrollment and 18-month follow-up of dyads, the HITSystem will be deployed at the control sites in the end of Year 3. Primary outcomes are retention among mother-infant dyads, initiation of antiretroviral therapy among HIV-infected infants, and the proportion of services delivered within the optimal time window indicated by national and study guidelines. Satisfaction interviews with participants and providers will inform intervention improvements. Cost-effectiveness analyses will be conducted to inform the sustainability of the HITSystem. Hypothesized outcomes include significantly higher retention throughout the 18-month early infant diagnosis process, significantly more services provided on-time at intervention sites, and a potential savings to the healthcare system., Discussion: This study will evaluate the public health impact of the HITSystem to improve critical early infant diagnosis outcomes in low-resource settings. Cost-effectiveness analyses will inform the feasibility of scale-up in other settings., Trial Registration: ClinicalTrials.gov: NCT02072603.

Background: Nucleic-acid-testing (NAT) to diagnose HIV infection in children under age 18 months provides a barrier to HIV-testing in exposed children from resource-constrained settings. The ultrasensitive HIV-p24-antigen (Up24) assay is cheaper and easier to perform and is sensitive (84-98%) and specific (98-100%). The cut-point optical density (OD) selected for discriminating between positive and negative samples may need assessment due to regional differences in mother-to-child HIV-transmission rates., Objectives: We used receiver operator characteristics (ROC) curves and logistic regression analyses to assess the effect of various cut-points on the diagnostic performance of Up24 for HIV-infection status among HIV-exposed children. Positive and negative predictive values at different rates of disease prevalence were also estimated., Study Design: A study of Up24 testing on dried blood spot (DBS) samples collected from 278 HIV-exposed Haitian children, 3-24-months of age, in whom HIV-infection status was determined by NAT on the same DBS card., Results: The sensitivity and specificity of Up24 varied by the cut-point-OD value selected. At a cut-point-OD of 8-fold the standard deviation of the negative control (NCSD), sensitivity and specificity of Up24 were maximized [87.8% (95% CI, 83.9-91.6) and 92% (95% CI, 88.8-95.2), respectively]. In lower prevalence settings (5%), positive and negative predictive values of Up24 were maximal (75.9% and 98.8%, respectively) at a cut-point-OD that was 15-fold the NCSD., Conclusions: In low prevalence settings, a high degree of specificity can be achieved with Up24 testing of HIV-exposed children when a higher cut-point OD is used; a feature that may facilitate more frequent use of Up24 antigen testing for HIV-exposed children., (Copyright © 2011 Elsevier B.V. All rights reserved.)