HIV-positive Infants Research Articles

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

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

HIV-exposed infant follow-up in Mozambique: formative research findings for the design of a cluster randomized controlled trial to improve testing and ART initiation

BackgroundEarly infant diagnosis (EID) of HIV-exposed and initiation of HIV-positive infants on anti-retroviral therapy (ART) requires a well-coordinated cascade of care. Loss-to-follow-up (LTFU) can occur at multiple steps and effective EID is impeded by human resource constraints, difficulty with patient tracking, and long waiting periods. The objective of this research was to conduct formative research to guide the development of an intervention to improve the pediatric HIV care cascade in central Mozambique. The study was conducted in Manica and Sofala Provinces where the adult HIV burden is higher than the national average. The research focused on 3 large clinics in each province, along the highly populated Beira corridor.MethodsThe research was conducted in 2014 over 3 months at six facilities and consisted of 1) patient flow mapping and collection of health systems data from postpartum, child-at-risk, and ART service registries, 2) measurement of clinic waiting times, and 3) patient and health worker focus groups.ResultsHIV testing and ART initiation coverage for mothers tends to be high, but EID and pediatric ART initiation are hampered by lack of patient tracking, long waiting times, and inadequate counseling to navigate the care cascade. About 76% of HIV-positive infants were LTFU and did not initiate ART.ConclusionsEffective interventions to reduce LTFU in EID and improve pediatric ART initiation should focus on patient tracking, active follow-up of defaulting patients, reduction in EID turn-around times for PCR results, and initiation of ART by nurses in child-at-risk services.Trial registrationRetrospectively registered, ISRCTN67747315, July 24, 2019.

The Prevalence of HIV-Positive Infants Born to HIV-Positive Mothers Attended at the University of Gondar Specialized Hospital Anti-Retroviral Therapy Services, Northwest Ethiopia, 2018.

IntroductionThe human immunodeficiency virus (HIV) attacks the human immune cells and affects their function. It is the highest burden that occurs in a developing country. Ethiopia is one of the top ten countries in the world, which has a high burden of HIV-infected children. Even if the country works hard on the PMCT program, still there is challenging on MTCT reduction.ObjectiveThe purpose of this study was to assess the prevalence of HIV-positive infants born to HIV-positive mothers attending anti-retroviral treatment (ART) services at the University of Gondar specialized hospital, Gondar, northwest Ethiopia, 2018.MethodsA retrospective chart review study was conducted from February to April 2018, among HIV-exposed infants who born to HIV-positive mothers in ART service at the University of Gondar specialized hospital. A systematic sampling method was applied to select study participants. Data were entered into EPI info version 7 statistical software and transferred to SPSS version 20 for analysis.ResultsIn this study, 239 participants were enrolled, with a 98.8% response rate. The prevalence of HIV-positive infants born to HIV-positive mothers was 5.5% with a 95% CI (3.0–8.5%). Of the mothers, 77.1% were within 25–35 years of age range. Of the total infants, 56.8% were males. From these HIV-positive infants, 13 (5.5%) were born from age ranges of 25–35years old mothers, 9(3.8%) were females, 8(3.4%) were 6–11 months old, 13 (5.5%) were post-term gestation, and 13 (5.5%) were maternal CD4+ less than 350/mm3.Conclusion and RecommendationsThe prevalence of HIV-positive infants born to HIV-positive mothers in this study was lower than the previous 10.2%. To reduce such infant HIV infection to zero, it needs proactive action from stakeholders, health professionals, and the community at large.

Implementation of an active case management network to identify HIV-positive infants and accelerate the initiation of antiretroviral therapy, Thailand 2015 to 2018.

IntroductionEarly initiation of antiretroviral therapy (ART) can reduce HIV‐related morbidity and mortality in HIV‐positive infants. We implemented an Active Case Management Network to promote early ART initiation Aiming for Cure (ACC) in August 2014. We describe ACC implementation, early infant diagnosis (EID) coverage and ART initiation during August 2014 to July 2018 compared with a national EID survey during October 2007 to September 2011 (pre‐ACC).MethodsThailand's 2014 HIV Treatment Guidelines recommend that HIV‐exposed infants have HIV polymerase chain reaction (PCR) testing at birth, one month and at two to four months. Testing is done at 14 national HIV PCR laboratories. When an HIV‐positive infant (HIV PCR+) is identified, PCR laboratory staff send the result to the hospital staff responsible for the infant's care and to the national laboratory case manager (CM). As part of ACC, the national laboratory CM alerts a regional CM who contacts the hospital staff caring for the infant to offer technical support with ART initiation and ART adherence. CMs enter clinical, demographic and laboratory data into the national ACC database. We analysed the ACC data from August 2014 to July 2018 to assess the ACC's impact on EID coverage, ART initiation and time‐to‐ART initiation.ResultsThe uptake of EID increased from 64% (pre‐ACC) to >95% in 2018 (ACC). The number of HIV‐positive infants born declined from 429 cases (pre‐ACC) to 267 cases (ACC). Median age at the first‐positive PCR declined from 75 days (pre‐ACC) to 60 days (ACC); P < 0.001. Among 429 infants diagnosed before ACC was started, 241 (56%) received ART; during ACC, 235 (88%) of 267 HIV‐positive infants received ART. The median age at ART initiation declined from 282 days before ACC to 83 days during ACC (P < 0.001) and the median time from blood collection to ART initiation declined from 168 days before ACC to 23 days during ACC (P < 0.001).ConclusionsAn innovative case management network (ACC) has been established in Thailand and results suggest that the network is promoting EID and early ART initiation. The ACC model, using case‐managed PCR notification and follow‐up, may speed ART initiation in other settings.

Epidemiology of HIV Infection Among HIV-Exposed Infants, Nairobi County, Kenya, 2015

Objective:To characterize human immunodeficiency virus (HIV)-positive infants among HIV-exposed infants (HEIs) in Nairobi County for public health action.Methods:We conducted a retrospective review of records of HEIs’ HIV polymerase chain reaction (PCR) results in Nairobi County in 2015, excluding confirmatory PCR-positive results. HIV-exposed infant registry data were entered into Microsoft Excel and descriptive and associative statistics were calculated with OpenEpi software.Results:A total of 5802 HEI records were analyzed, with a median age of 4.5 (interquartile range, 8.5) months; 342 (5.9%) tested positive, 51% were female, and 4420 (76.2%) were seen at maternal and child health clinics. Standard highly active antiretroviral therapy intervention was given to 184 (60.3%) of the mothers of exposed infants, and 178 (53%) of the HIV-positive infants received active antiretroviral therapy. A total of 3464 (59.7%) HEIs had PCR done within the first 2 months, and 119 (3.4%) tested positive. The average turnaround time for PCR samples was 28 ± 22 days, and a total of 191 (3.3%) HIV-positive HEIs were exclusively breastfed for the first 6 months of life.Conclusion:The recorded mother-to-child transmission (MTCT) rate of 5.9% in Nairobi County is lower than the 2015 national rate, which suggests the Nairobi prevention of mother-to-child transmission efforts are moderately effective. However, results from this study show that Kenya will struggle to meet the MTCT 2020 target rate of <5%.

Factors affecting acceptance of at-birth point of care HIV testing among providers and parents in Kenya: A qualitative study.

BackgroundAt-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.MethodsWe 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.ResultsMost 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.DiscussionWhile 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.

Uptake of care and treatment amongst a national cohort of HIV positive infants diagnosed at primary care level, South Africa

BackgroundLoss to follow-up after a positive infant HIV diagnosis negates the potential benefits of robust policies recommending immediate triple antiretroviral therapy initiation in HIV positive infants. Whilst the diagnosis and follow-up of HIV positive infants in urban, specialized settings is easier to institutionalize, there is little information about access to care amongst HIV positive children diagnosed at primary health care clinic level. We sought to understand the characteristics of HIV positive children diagnosed with HIV infection at primary health care level, across all provinces of South Africa, their attendance at study-specific exit interviews and their reported uptake of HIV-related care. The latter could serve as a marker of knowledge, access or disclosure.MethodsSecondary analysis of data gathered about HIV positive children, participating in an HIV-exposed infant national observational cohort study between October 2012 and September 2014, was undertaken. HIV infected children were identified by total nucleic acid polymerase chain reaction using standardized procedures in a nationally accredited central laboratory. Descriptive analyses were conducted on the HIV positive infant population, who were treated as a case series in this analysis. Data from interviews conducted at baseline (six-weeks post-delivery) and on study exit (the first visit following infant HIV positive diagnosis) were analysed.ResultsOf the 2878 HIV exposed infants identified at 6 weeks, 1803 (62.2%), 1709, 1673, 1660, 1680 and 1794 were see at 3, 6, 9, 12, 15 and 18 months respectively. In total, 101 tested HIV positive (67 at 6 weeks, and 34 postnatally). Most (76%) HIV positive infants were born to single mothers with a mean age of 26 years and an education level above grade 7 (76%). Although only 33.7% of pregnancies were planned, 83% of mothers reported receiving antiretroviral drugs to prevent MTCT. Of the 44 mothers with a documented recent CD4 cell count, the median was 346.8 cell/mm3. Four mothers (4.0%) self-reported having had TB. Only 59 (58.4%) HIV positive infants returned for an exit interview after their HIV diagnosis; there were no statistically significant differences in baseline characteristics between HIV positive infants who returned for an exit interview and those who did not. Amongst HIV positive infants who returned for an exit interview, only two HIV positive infants (3.4%) were reportedly receiving triple antiretroviral therapy (ART). If we assume that all HIV positive children who did not return for their exit interview received ART, then ART uptake amongst these HIV positive children < 18 months would be 43.6%.ConclusionsEarly ART uptake amongst children aged 15 months and below was low. This raises questions about timely, early paediatric ART uptake amongst HIV positive children diagnosed in primary health care settings. Qualitative work is needed to understand low and delayed paediatric ART uptake in young children, and more work is needed to measure progress with infant ART initiation at primary care level since 2014.

Prevalence of HIV-1 drug resistance amongst newly diagnosed HIV-infected infants age 4\u20138\u2009weeks, enrolled in three nationally representative PMTCT effectiveness surveys, South Africa: 2010, 2011\u201312 and 2012\u201313

BackgroundSouth Africa (SA) has expanded efforts to reduce mother-to-child transmission of HIV (MTCT) to less than 2% at six weeks after birth and to less than 5% at 18 months postpartum by 2016. Despite improved antiretroviral regimens and coverage between 2001 and 2016, there is little data on infant HIV drug resistance. This paper tracks the prevalence of HIV drug resistance patterns amongst HIV infected infants from three nationally representative studies that assessed the effectiveness of national programs to prevent MTCT (PMTCT). The first study was conducted in 2010 (under the dual therapy PMTCT policy), the second from 2011 to 12 (PMTCT Option A policy) and the third from 2012 to 13 (PMTCT Option A policy). From 2010 to 2013, infant non-nucleoside reverse transcriptase inhibitor (NNRTI) exposure increased from single dose to daily throughout breastfeeding; maternal nucleoside reverse transcriptase inhibitor (NRTI) and NNRTI exposure increased with initiation of NNRTI-and NRTI- containing triple antiretroviral therapy (ART) earlier in gestation and at higher CD4 cell counts.MethodsThree nationally representative surveys were conducted in 2010, 2011–12 and 2012–13. During the surveys, mothers with known, unknown, or no exposure to antiretrovirals for PMTCT and their infants were included, and MTCT was measured. For this paper, infant dried blood spots (iDBS) from HIV PCR positive infants aged 4–8 weeks, with consent for additional iDBS testing, were analysed for HIV drug resistance at the National Institute of Communicable Diseases (NICD), SA, using an in-house assay validated by the Centers for Disease Control and Prevention (CDC). Total viral nucleic acid was extracted from 2 spots and amplified by nested PCR to generate a ~ 1 kb amplicon that was sequenced using Sanger sequencing technologies. Sequence assembly and editing was performed using RECall v3.ResultsOverall, HIV-1 drug resistance was detected in 51% (95% Confidence interval (CI) [45–58%]) of HIV PCR positive infants, 37% (95% CI [28–47%]) in 2010, 64% (95% CI [53–74%]) in 2011 and 63% (95% CI [47–77%]) in 2012 (p < 0.0001), particularly to the NNRTI drug class. Pooled analyses across all three surveys demonstrated that infants whose mothers received ART showed the highest prevalence of resistance (74%); 26% (21/82) of HIV PCR positive infants with no or undocumented antiretroviral drug (ARV) exposure harboured NNRTI resistance.ConclusionsThese data demonstrate increasing NNRTI resistance amongst newly-diagnosed infants in a high HIV prevalence setting where maternal ART coverage increased across the years, starting earlier in gestation and at higher CD4 cell counts. This is worrying as lifelong maternal ART coverage for HIV positive pregnant and lactating women is increasing. Also of concern is that resistant virus was detected in HIV positive infants whose mothers were not exposed to ARVs, raising questions about circulating resistant virus. Numbers in this group were too small to assess trends over the three years.

Treatment outcomes among HIV-positive orphaned and non-orphaned children on antiretroviral therapy in Johannesburg, South Africa.

Limited research investigating treatment outcomes for HIV-positiveorphans compared with non-orphans has shown mixed results, with several studies indicating that HIV-positive orphans are at greater risk of delayed access to HIV care and poor antiretroviral therapy (ART) adherence, while other data suggest that ART outcomes of orphans can be similar to those of non-orphans. Understanding the impact of orphan status on short-term ART outcomes could improve targeted intervention strategies, and subsequent long-term treatment and developmental outcomes, for HIV-positiveinfants, children and adolescents. To evaluate the relationship between orphan status and ART outcomes among HIV-positive infants, children and adolescents initiating ART at two large public sector HIV clinics in Johannesburg, South Africa. This was a retrospective cohort study of HIV-positivechildren aged &lt;18 years initiating standard first-line ART between June 2004 and May 2013. Using propensity scores, orphans and non-orphans were matched for age, sex, World Health Organization stage and ART regimen. The effect of orphanhood on attrition from care (all-cause mortality and loss to follow-up) was evaluated using Cox proportional hazards regression analysis, and its effect on having a detectable viral load (≥400 copies/mL) at 12 months on ART using binomial regression analysis with modified Poisson distribution. A total of 251 (29.4%) orphans (maternal, paternal or both) and 603 (70.6%) non-orphans were included at ART initiation. Following multiple imputation for missing data and propensity score matching, 222 orphans and 222 non-orphans were included. Orphans had a median age of 8.0 years (interquartile range (IQR) 4.9 - 10.7) and non-orphans 7.4 years (IQR 4.2 - 10.2). A total of 12 (5.4%) orphans and 33 (14.9%) non-orphans experienced attrition from care during the first 12 months on ART (adjusted hazard ratio 0.32, 95% confidence interval (CI) 0.17 - 0.63). Among those alive and in care, with a viral load at 12 months on ART, 18.0% of orphans (33/183) and 14.8% of non-orphans (24/162) had a detectable viral load (adjusted risk ratio 1.15, 95% CI 1.04 - 1.28). Orphans were less likely than non-orphans to experience attrition, but among those in care at 12 months, orphans were more likely to have detectable viral loads. Lower attrition among orphans may be due to their being in institutional or foster care, ensuring that they make their visits; however, their higher rates of non-suppression may result from lack of psychosocial support or stigma resulting in struggles to adhere. Additional research investigating age-specific outcomes will be important to elucidate these effects further.

Missed opportunities for early infant diagnosis of HIV in rural North-Central Nigeria: A cascade analysis from the INSPIRE MoMent study.

BackgroundEarly identification of HIV-infected infants for treatment is critical for survival. Efficient uptake of early infant diagnosis (EID) requires timely presentation of HIV-exposed infants, same-day sample collection, and prompt release of results. The MoMent (Mother Mentor) Nigeria study investigated the impact of structured peer support on EID presentation and maternal retention. This cascade analysis highlights missed opportunities for EID and infant treatment initiation during the study.MethodsHIV-infected pregnant women and their infants were recruited at 20 rural Primary Healthcare Centers. Routine infant HIV DNA PCR testing was performed at centralized laboratories using dried blood spot (DBS) samples ideally collected by age two months. EID outcomes data were abstracted from study case report forms and facility registers. Descriptive statistics summarized gaps and missed opportunities in the EID cascade.ResultsOut of 497 women enrolled, delivery data was available for 445 (90.8%), to whom 415 of 455 (91.2%) infants were live-born. Out of 408 live-born infants with available data, 341 (83.6%) presented for DBS sampling at least once. Only 75.4% (257/341) were sampled, with 81.7% (210/257) sampled at first presentation. Only 199/257 (77.4%) sampled infants had results available up to 28 months post-collection. Two (1.0%) of the 199 infants tested HIV-positive; one infant died before treatment initiation and the other was lost to follow-up.ConclusionsWhile nearly 85% of infants presented for sampling, there were multiple missed opportunities, largely due to health system and not necessarily patient-level failures. These included infants presenting without being sampled, presenting multiple times before samples were collected, and getting sampled but results not forthcoming. Finally, neither of the two HIV-positive infants were linked to treatment within the follow-up period, which may have led to the death of one. To facilitate patient compliance and HIV-free infant survival, quality improvement approaches should be optimized for EID commodity availability, consistent DBS sample collection, efficient processing/result release, and prompt infant treatment initiation.

Determinants of HIV Positive Infants Treatment Gaps in the Centre Region

Determinants of HIV Positive Infants Treatment Gaps in the Centre Region

HIV testing at birth: Are we getting it right?

BackgroundBirth polymerase chain reaction (PCR) testing improves early detection of HIV and allows for early treatment initiation. National guidelines exist, but it is unknown whether these are being implemented correctly.ObjectivesTo determine whether HIV-exposed infants at the Mangaung University Community Partnership Programme Community Health Centre (MUCPP CHC) received PCR tests at birth, if HIV-positive infants were initiated on treatment, if follow-up dates were scheduled and the percentage of mothers or caregivers who returned to collect the results.MethodsThe study was a retrospective descriptive file audit (1304 files) of births from 01 January to 31 December 2016 at MUCPP CHC. The study sample was 428 infants born to HIV-positive mothers. The birth register was used to collect the infants’ HIV PCR test barcodes. The birth and 10-week PCR results were retrieved from an electronic database at the Virology Department, University of the Free State.ResultsIn total, 375 infants received a birth PCR test (87.6%) of which 4 (1.1%) tested HIV positive and 327 (87.2%) negative. Follow-up tests were not scheduled. However, 145 (44.3%) HIV-negative infants returned for a 10-week test. Irrespective of the PCR birth result, 157 (36.7%) infants were brought for a 10-week follow-up test at which time 3 (1.9%) tested positive and 151 (96.2%) negative.ConclusionThe majority of HIV-exposed infants received a PCR test at birth; however, the clinic is below the national target (90%) for HIV testing. A record-keeping system of infants’ visits does not exist at MUCPP CHC, making it impossible to determine whether HIV-positive infants were started on antiretroviral treatment.

PG-9 Predictors of final HIV status outcome for HIV-exposed infants at 18 months of age in 10 Nigerian states

Introduction: There were an estimated 37,000 new child HIV infections in Nigeria in 2016, the highest globally. For Nigeria, 6 week and final mother-to-child transmission of HIV (MTCT) rates are estimated at 13.1% and 23.0%, respectively. The UNAIDS has targeted final MTCT rates of &lt;2% and &lt;5% among non-breastfeeding and breastfeeding infants, respectively. Data on 18-month final outcomes among HIV-Exposed Infants (HEI) in Nigeria is scarce. We evaluated for predictors of HIV status among HEI at 18 months of life in 10 Nigerian states. Methods: This retrospective, cross-sectional study collected data from 96 PEPFAR-supported health facilities supported by the Institute of Human Virology Nigeria in 10 Nigerian states between October 2014 and September 2015. Only HEI with a first DNA PCR result at ≥4–6 weeks, and a rapid HIV antibody test result at ≥18 months of age were included. Data including residence, birth weight, breastfeeding status, and maternal ART access were collected for analysis. Multivariate logistic regression (adjusted odds ratios [aORs] evaluated for predictors of HIV test positivity at 18 months. Results: A total of 2405 HEI from the 96 facilities were included in the study. Median birthweight was 3 kg (IQR 1.2–6.1), and at final testing was 10 kg (IQR 5.5–15). Of the 2405 HEI negative at first DNA PCR test and tested at ≥18 months, 68 (2.8%) were positive. After a minimum of 18 months of age, 51 (75%) of the 68 HIV-positive infants were alive on ART; 7 (10%) had died, 4 (6%) were lost to follow-up and 6 (9%) had transferred out to other facilities for care. Infant birth weight of ≥2.5 kg (AOR 0.40, P = 0.009), urban residence (OR 0.45, P = 0.008) and exclusive breastfeeding (OR 0.04, P &lt; 0.001) protected against MTCT; maternal non-initiation/utilization of antenatal/in-labor ART (OR 9.59, P &lt; 0.001) correlated with MTCT. Conclusions: The final HIV positivity rate of 2.8% in our cohort is lower than the national estimates, which is encouraging. However, this should be interpreted with caution: the HIV status of HEI seen at the study facilities who did not present for early and/or final testing was not available and thus not evaluated. Nevertheless, supported by our findings, we recommend strengthening universal maternal access to ART, ideally in the pre-conception and prenatal stages. This should be prioritized especially for rural women living with HIV. Furthermore, our findings correlate with the nationally-recommended 6-months of exclusive infant breastfeeding. We acknowledge that data from non-presenting HEI are also needed to devise interventions for universal uptake of early and final HIV testing. We expect that as Option B plus is scaled up in Nigeria, more women would access and be maintained on ART through their first and subsequent pregnancies, thereby reducing the gaps in maternal-infant HIV service uptake.

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.

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.

Effect of point-of-care early infant diagnosis on antiretroviral therapy initiation and retention of patients.

We measured the effect of point-of-care (POC) early infant HIV testing on antiretroviral therapy initiation rates and retention in care among infants in Mozambique. A cluster-randomized trial was conducted in 16 primary healthcare centres providing either on-site POC arm (n = 8) or referred laboratory [standard-of-care (SOC) arm; n = 8] infant HIV testing. The primary outcomes were the proportion of HIV-positive infants initiating antiretroviral therapy within 60 days of sample collection, and the proportion of HIV-positive infants who initiated antiretroviral therapy that were retained in care at 90 days of follow-up. The proportion of HIV-positive infants initiating antiretroviral therapy within 60 days of sample collection was 89.7% (157 of 175) for the POC arm and 12.8% (13 of 102) for the SOC arm [relative risk (RR)(adj) 7.34; P < 0.001]. The proportion of HIV-positive infants who initiated antiretroviral therapy that were retained in care at 90 days of follow-up was 61.6% (101 of 164) for the POC arm and 42.9% (21 of 49) for the SOC arm [RR(adj) 1.40; P < 0.027]. The median time from sample collection to antiretroviral therapy initiation was less than 1 day (interquartile range: 0-1) for the POC arm and 127 days (44-154; P < 0.001) for the SOC arm. POC infant HIV testing enabled clinics to more rapidly diagnose and provide treatment to HIV-infected infants. This reduced opportunities for pretreatment loss to follow-up and enabled a larger proportion of infants to receive test results and initiate antiretroviral therapy. The benefits of faster HIV diagnosis and antiretroviral treatment may also improve early retention in care.

Performance of point-of-care birth HIV testing in primary health care clinics: An observational cohort study.

BackgroundFailure to timely diagnose HIV in infants is a major barrier for scaling-up paediatric antiretroviral treatment (ART). WHO recommends birth testing for earlier diagnosis and to improve test coverage, but current diagnosis takes 2–3 weeks to complete, thereby limiting the ability of care givers to provide follow-on care, especially in low-resource settings. We evaluated the benefit of implementing rapid diagnosis of HIV at birth in primary health care maternity wards in Mozambique.Methods and findingsInfants born to HIV-infected mothers delivering consecutively at eight primary health care clinics were tested within 24 hours of delivery using on-site POC (Alere q HIV1/2 Detect) and standard laboratory (Roche COBAS AmpliPrep/TaqMan HIV-1 qualitative assay v2.0) testing. Infants were also tested at 4–6 weeks of age with both assays. Of 2,350 HIV-exposed infants enrolled in this implementation research study, 33 tested HIV-positive at birth on both assays. Sensitivity and specificity of POC testing compared with laboratory testing at birth were 100% (95% CI 89·4–100·0) and 100% (95% CI 99·8–100·0), respectively. At 4–6 weeks of age, 61 infants were identified as HIV-positive; of these 29 (47·5%) had a positive test at birth. Testing at both birth and 4–6 weeks identified 71 HIV-positive infants compared with 61 infants by testing at 4–6 weeks alone, a 16% increase. Two infants tested positive at birth but tested HIV-negative during follow-up.ConclusionsAdding POC birth testing to the 4–6 week screen may increase access to HIV diagnosis and expedite ART initiation in primary health care settings within low resource settings. Guidance on appropriate confirmatory HIV testing algorithms for birth testing is needed.

Postpartum maternal mental health is associated with cognitive development of HIV-exposed infants in Zimbabwe: a cross-sectional study

ABSTRACTThis study examines the cognitive profiles of infants born to HIV positive mothers in Zimbabwe. Caregivers with HIV exposed infants delivered in 30 clinics in two areas of Zimbabwe were recruited to the study. Of the 574 study participants, 562 caregiver-infant dyads with a biological HIV +ve mother and infant aged 0–24 months were interviewed. All infants were tested by a trained administrator for cognitive development on the Mullen Scales of Early Learning (MSEL). The Edinburgh Postnatal Depression Scale and Parental Stress Index-Short Form were completed by the mothers together with infant and caregiver socioeconomic characteristics. Linear regression models were used to relate cognitive development scores to maternal stress scores, maternal depression scores and infant HIV status adjusting for infant and caregiver characteristics, as well as socioeconomic factors. Higher maternal depression scores were associated with lower overall infant cognitive scores (adjusted mean difference (aMD) = −0.28; CI 95%:−0.50 to −0.06; p = 0.01) and in the expressive language (aMD = −0.14; CI 95%:−0.27 to −0.01; p = 0.04), fine motor skills (aMD = −0.17; CI 95%: −0.33 to −0.01; p = 0.03), gross motor (aMD = −0.22; CI 95%:−0.40 to −0.04; p = 0.02), and visual reception (aMD = −0.22; CI 95%:−0.40 to −0.05; p = 0.01) domains. Higher maternal stress was associated with poorer overall infant cognitive scores (aMD = −0.11; CI 95%:−0.20 to −0.02; p = 0.02) and in the specific domains of expressive language (aMD = −0.07; CI 95%:−0.12 to −0.01; p = 0.01), gross motor skills (aMD = −0.12; CI 95%:−0.18 to −0.05; p < 0.01) and visual reception (aMD = −0.09; CI 95%:−0.16 to −0.02; p = 0.02). Comparisons between the small number of HIV positive infants (n = 16) and the HEU infants (n = 381) showed the latter to have higher mean gross motor scores (50.3 vs. 40.6; p = 0.01). There was no evidence of difference by HIV status in the other MSEL domains or overall mean cognitive scores. Our findings demonstrate the association between maternal mood and stress levels and child cognitive functioning, particularly in expressive language and visual reception development. Although cross sectional data cannot shed light on the direction of this association, the study suggests that interventions to address maternal stress and depression symptoms may prove to be beneficial.

Barriers to antiretroviral therapy initiation for HIV-positive children aged 2–18 months in Swaziland

Although early antiretroviral therapy (ART) reduces HIV-related mortality in children by up to 75%, almost half of HIV-positive children younger than 1 year old in Swaziland do not initiate ART. This study was conducted to identify barriers to early ART initiation among HIV-positive infants. This was a case-control study among HIV-positive infants, aged 2 to 18 months, who either did not initiate ART (cases), or initiated ART (controls), during 18 months after testing. Multivariable logistic regression showed that infants who visited the clinic every month, or every 2 months, were 5.78 and 6.20 times more likely to initiate ART than those who visited less often (OR 5.78, 95% CI 1.82–18.33 and OR 6.20, 95% CI 1.30–29.60 respectively). Children who lived ≤30 and 31–60 minutes from the nearest clinic were 84% and 79% less likely respectively to initiate ART (OR 0.16, 95% CI 0.03–0.78 and OR 0.21, 95% CI 0.04–0.98) compared with those who lived more than 60 minutes away. Children who received immunisation after 6 months were 22.59 times more likely to initiate ART (OR 22.59, 95% CI 7.00–21.72) than those who did not. Infants of caregivers who had excellent or good relationships with their healthcare provider were 4.32 times more likely to initiate ART (OR 4.32, 95% CI 1.01–18.59) than those of caregivers who had average or poor relationships with healthcare providers. The significant predictors of ART initiation identified in this study should be regarded as priority areas for intervention among HIV-positive women in Swaziland.

Closing the gaps to eliminate mother-to-child transmission of HIV (MTCT) in South Africa: Understanding MTCT case rates, factors that hinder the monitoring and attainment of targets, and potential game changers

Background. Ninety percent of the world’s HIV-positive pregnant women live in 22 countries. These 22 countries, including South Africa (SA) have prioritised the elimination of mother-to-child transmission of HIV (EMTCT). Since 2016 all 22 countries recommend lifelong antiretroviral treatment for all HIV-positive pregnant and lactating women. To measure South African national, provincial and district-level progress towards attaining EMTCT, we analysed the number of in utero (IU) paedatric HIV infections per 100 000 live births (IU case rate), and synthesised factors hindering the monitoring of EMTCT progress and attainment from the viewpoint of provincial and district-level healthcare managers and implementers. We highlight potential innovations to strengthen health systems and improve EMTCT programme delivery. Methods. We reviewed national-, provincial- and district-level birth HIV testing data from routine National Health Laboratory Services (NHLS) records between April 2016 and March 2017. To obtain a qualitative perspective from healthcare managers and implementers, we synthesised information from the nine 2016 provincial-level EMTCT stock-taking workshops. These workshops involve key provincial and district-level staff, mentors and supporting partners. Lastly, we highlight potential innovations presented at these workshops to overcome operational challenges. Results. The national IU mother-to-child transmission (MTCT) rate was 0.9%, which translated to an IU case rate of 245 HIV-positive neonates per 100 000 live births. Provincial IU percent MTCT risk ranged from 0.6% to 1.3%, with IU case rates ranging between 168 and 325 cases per 100 000 live births. District-level IU percent MTCT risk ranged from 0.4% to 1.9%. Potential game changers include: pre-conception counselling to optimise maternal-partner health, weekly dissemination of HIV polymerase chain reaction (PCR) and viral load reports from the NHLS to specific individuals who trace mothers and infants needing care, use of ward-based outreach teams and community caregivers to trace HIV-infected mothers and their infants to link them into care, inclusion of a unique identifier in patient-held infant Road to Health booklets to facilitate infant tracing and continuous quality improvement (CQI) processes within facilities and districts and implementation of an HIV-positive baby tool to understand the characteristics and risks of HIV-positive infants. On an ecological level, provinces and districts using community-based approaches and CQI methodology seemed to have lower MTCT and IU case rates. Conclusions. More quantitative analyses are needed to understand what proportion of the success can be attributed to community-based and CQI approaches and the impact of the potential game changers on progress towards EMTCT.