A trial of nurturing care among children who are HIV-exposed and uninfected in eSwatini.

INTRODUCTION: Children who are HIV-exposed and uninfected (CHEU) are a growing population at potential risk of poor neurocognitive development. We tested a nurturing care intervention on children's neurocognitive development and maternal depressive symptoms (primary) with mediation through caregiving activities (secondary). METHODS: This study was conducted among six intervention and nine comparison antenatal-care/prevention of vertical transmission (ANC/PVT) HIV clinics in eSwatini. We enrolled pregnant women and measured infant development at 9 and 18 months. mothers2mothers (m2m) designed and implemented the clinic-home-community-based intervention. We measured infants' neurodevelopment, maternal depressive symptoms and caregiving activities with the Mullen Scales of Early Learning (MSEL), Edinburgh Postnatal Depression Scale, HOME Inventory and Family Care Indicators. We fitted linear mixed effects regression models with clinic random effects to compare intervention versus comparison arms, and generalised structural equation models to evaluate mediation, adjusting for confounders. RESULTS: Mother-infant pairs (n = 429) participated between January 2016 through May 2018. Socio-demographic characteristics were balanced between arms except for higher rates of peri-urban versus rural residence and single versus married mothers in the comparison group. The 18 month retention was 82% (180/220) intervention, 79% (166/209) comparison arm, with 25 infant deaths. Intervention MSEL scores were significantly, and modestly, higher in receptive language (55.7 [95% CI 54.6, 56.9] vs. 53.7 [95% CI 52.6, 54.8]), expressive language (42.5 [95% CI 41.6, 39.8] vs. 40.8 [95% CI 39.8, 41.7]) and composite MSEL (85.4 [95% CI 83.7, 84.5] vs. 82.7 [95% CI 81.0, 84.5]), with no difference in maternal depressive symptoms or in observations of mother-child interactions. Intervention book-sharing scores were higher (0.63 vs. 0.41) and mediated the effect on MSEL scores (indirect effect, p-values ≤ 0.024). The direct effects on visual reception and expressive language scores were significantly higher in the intervention compared to the comparison arm (coefficients 1.93 [95% CI 0.26, 3.60] and 1.66 [95% CI 0.51, 2.79, respectively]). CONCLUSIONS: Nurturing care interventions can be integrated into ANC/PVT clinic-home-community programmes. The intervention, mediated through interactive caregiving activities, increased language development scores among CHEU. Partnering with a local team, m2m, to design and implement a culturally relevant intervention illustrates the ability to impact parent-child play and learning activities that are associated with children's neurodevelopment.

Behavioral Determinants of Routine Health Information System Data Use in Senegal: A Qualitative Inquiry Based on the Integrated Behavioral Model.

Routine health information system (RHIS) data are essential in driving decision making and planning in health systems as well as health programs. However, despite their importance, these data are underutilized, and the underlying individual-level facilitators and barriers to use remain understudied. In this research, we applied the Integrated Behavior Model (IBM) to examine how attitudes toward RHIS data, perceived norms concerning RHIS data use, and the ability to use RHIS data influence the demand and use of RHIS data among stakeholders in Senegal. Using data from interviews with respondents working at national levels of malaria, HIV, and TB control programs in Senegal, we used a framework analysis approach to apply the IBM behavioral constructs and identify their linkages to RHIS data use. We found that attitudes about the quality, availability, and relevance of RHIS data for decision making were important in driving data use among respondents. Institutional expectations, organizational protocols, policies, and practices around RHIS data ultimately shape social norms around the use of the data. Although we found that perceived ability and self-efficacy to use RHIS data were not barriers to RHIS data use among stakeholders at the strategic levels of their respective organizations, these were reported to be barriers at lower levels of the health system. Low perceived control of the RHIS data production process ultimately reduced RHIS data use for decision making among the strategic-level respondents. We recommend context-specific reexamination of existing RHIS interventions with a renewed emphasis on behavioral aspects of data use. The IBM can help guide practitioners, policy makers, and academics to address multiple socioecological factors that influence data use behavior when recommending RHIS and data use solutions.

A data quality assessment of the first four years of malaria reporting in the Senegal DHIS2, 2014-2017.

BACKGROUND: As the global burden of malaria decreases, routine health information systems (RHIS) have become invaluable for monitoring progress towards elimination. The District Health Information System, version 2 (DHIS2) has been widely adopted across countries and is expected to increase the quality of reporting of RHIS. In this study, we evaluated the quality of reporting of key indicators of childhood malaria from January 2014 through December 2017, the first 4 years of DHIS2 implementation in Senegal. METHODS: Monthly data on the number of confirmed and suspected malaria cases as well as tests done were extracted from the Senegal DHIS2. Reporting completeness was measured as the number of monthly reports received divided by the expected number of reports in a given year. Completeness of indicator data was measured as the percentage of non-missing indicator values. We used a quasi-Poisson model with natural cubic spline terms of month of reporting to impute values missing at the facility level. We used the imputed values to take into account the percentage of malaria cases that were missed due to lack of reporting. Consistency was measured as the absence of moderate and extreme outliers, internal consistency between related indicators, and consistency of indicators over time. RESULTS: In contrast to public facilities of which 92.7% reported data in the DHIS2 system during the study period, only 15.3% of the private facilities used the reporting system. At the national level, completeness of facility reporting increased from 84.5% in 2014 to 97.5% in 2017. The percentage of expected malaria cases reported increased from 76.5% in 2014 to 94.7% in 2017. Over the study period, the percentage of malaria cases reported across all districts was on average 7.5% higher (P < 0.01) during the rainy season relative to the dry season. Reporting completeness rates were lower among hospitals compared to health centers and health posts. The incidence of moderate and extreme outlier values was 5.2 and 2.3%, respectively. The number of confirmed malaria cases increased by 15% whereas the numbers of suspected cases and tests conducted more than doubled from 2014 to 2017 likely due to a policy shift towards universal testing of pediatric febrile cases. CONCLUSIONS: The quality of reporting for malaria indicators in the Senegal DHIS2 has improved over time and the data are suitable for use to monitor progress in malaria programs, with an understanding of their limitations. Senegalese health authorities should maintain the focus on broader adoption of DHIS2 reporting by private facilities, the sustainability of district-level data quality reviews, facility-level supervision and feedback mechanisms at all levels of the health system.

Prevalence of depression among HIV-positive pregnant women and its association with adherence to antiretroviral therapy in Addis Ababa, Ethiopia.

BACKGROUND: Vertical transmission of HIV remains one of the most common transmission modes. Antiretroviral therapy (ART) decreases the risk of transmission to less than 2%, but maintaining adherence to treatment remains a challenge. Some of the commonly reported barriers to adherence to ART include stress (physical and emotional), depression, and alcohol and drug abuse. Integrating screening and treatment for psychological problem such as depression was reported to improve adherence. In this study, we sought to determine the prevalence of depression and its association with adherence to ART among HIV-positive pregnant women attending antenatal care (ANC) clinics in Addis Ababa, Ethiopia. METHODS: We conducted a cross-sectional survey from March through November 2018. Participants were conveniently sampled from 12 health institutions offering ANC services. We used the Patient Health Questionnaire-9 (PHQ-9) to screen for depression and the Center for Adherence Support Evaluation (CASE) Adherence index to evaluate adherence to ART. Descriptive statistics was used to estimate the prevalence of depression during third-trimester pregnancy and nonadherence to ART. A bivariate logistic regression analysis was used to get significant predictors for each of the two outcome measures. The final multivariable logistic regression analysis included variables with a P<0.25 in the bivariate logistic regression model; statistical significance was evaluated at P<0.05. RESULTS: We approached 397 eligible individuals, of whom 368 (92.7%) participated and were included in the analysis. Of the total participants, 175(47.6%) had depression. The participants' overall level of adherence to ART was 82%. Pregnant women with low income were twice more likely to have depression (AOR = 2.10, 95%CI = 1.31-3.36). Women with WHO clinical Stage 1 disease were less likely to have depression than women with more advanced disease (AOR = 0.16, 95%CI = 0.05-0.48). There was a statistically significant association between depression and nonadherence to ART (P = 0.020); nonadherence was nearly two times higher among participants with depression (AOR = 1.88, 95%CI = 1.08-3.27). CONCLUSION: We found a high prevalence of depression among HIV-positive pregnant women in the selected health facilities in Addis Ababa, and what was more concerning was its association with higher rates of nonadherence to ART adversely affecting the outcome of their HIV care. We recommend integrating screening for depression in routine ANC services.

The role of men in antenatal care and preventing HIV transmission from mothers to infants in Gambella region, Ethiopia.

Prevention of vertical transmission of HIV has evolved over the past two decades. Although public health agencies advocate for male involvement in such interventions, their role in the prevention of vertical transmission of HIV remains limited. This study aims to explore the role of men in antenatal care and prevention of vertical transmission of HIV in the Gambella region of Ethiopia. The study was conducted among the Nuer and Anuak communities in Gambella region. Participants included female antenatal care attendees at two health centers, men who were husbands, local health extension workers of the catchment villages, and health care providers and managers. Data were collected using focus group discussions, in-depth interviews, and key informant interviews. Recordings were transcribed, coded, and analysed using thematic approaches. MAXQDA version 11 was used to facilitate data organization and reduction. Findings showed that men in Gambella are not expected to accompany their wives to health facilities or encourage them to visit the facilities in connection to pregnancy. Participants reported that men rarely visit health facilities with their partners, and they are largely unaware of the connection between antenatal care during pregnancy and prevention of mother to child transmission of HIV. Participants indicated that women's attendance at health facilities during pregnancy is not a common practice, and if they do visit them in connection to pregnancy there may be suspicion she has HIV. In this cultural context, men do not have a role in the health care of their wives during pregnancy. Men's engagement may be further lessened by the common perception that visiting a health facility in connection to pregnancy is associated with HIV.

Key informant perspectives on the challenges and opportunities for using routine health data for decision-making in Senegal.

BACKGROUND: Increasing the performance of routine health information systems (RHIS) is an important policy priority both globally and in Senegal. As RHIS data become increasingly important in driving decision-making in Senegal, it is imperative to understand the factors that determine their use. METHODS: Semi-structured interviews were conducted with 18 high- and mid-level key informants active in the malaria, tuberculosis and HIV programmatic areas in Senegal. Key informants were employed in the relevant divisions of the Senegal Ministry of Health or nongovernmental / civil society organizations. We asked respondents questions related to the flow, quality and use of RHIS data in their organizations. A framework approach was used to analyze the qualitative data. RESULTS: Although the respondents worked at the strategic levels of their respective organizations, they consistently indicated that data quality and data use issues began at the operational level of the health system before the data made its way to the central level. We classify the main identified barriers and facilitators to the use of routine data into six categories and attempt to describe their interrelated nature. We find that data quality is a central and direct determinant of RHIS data use. We report that a number of upstream factors in the Senegal context interact to influence the quality of routine data produced. We identify the sociopolitical, financial and system design determinants of RHIS data collection, dissemination and use. We also discuss the organizational and infrastructural factors that influence the use of RHIS data. CONCLUSIONS: We recommend specific prescriptive actions with potential to improve RHIS performance in Senegal, the quality of the data produced and their use. These actions include addressing sociopolitical factors that often interrupt RHIS functioning in Senegal, supporting and motivating staff that maintain RHIS data systems as well as ensuring RHIS data completeness and representativeness. We argue for improved coordination between the various stakeholders in order to streamline RHIS data processes and improve transparency. Finally, we recommend the promotion of a sustained culture of data quality assessment and use.

Predictors of Virologic Failure Among a Cohort of HIV-infected Children in Southern Ethiopia.

BACKGROUND: Optimal care for children with HIV infection includes timely assessment of treatment failure. Using HIV viral load to define treatment failure remains a challenge in resource-limited settings. METHODS: Children with HIV infection who were already on or starting first-line antiretroviral therapy were enrolled and followed over time. We examined clinical and immunologic predictors of virologic failure (VF), defined as consecutive viral load measurements > 1000 copies/mL (VF). Children were followed every 6 months with clinical assessments, immunologic assays and viral load testing until treatment failure or up to 18 months. RESULTS: Of the 484 children with complete data, we observed a prevalence of 15% who had VF at enrollment, and 18 who developed VF over 10.5 person-years of follow-up for an incidence of 4.97 [95% CI: 3.04-7.70) per 100 person-years. Lower adherence, lower CD4 T-cell count, lower white blood cells count, lower platelets and a lower glomerular filtration rate were all associated with increased VF. However, in a multivariable analysis, renal function (estimated glomerular filtration rate < 90 mL/min), odds ratio: 11.5 (95% CI: 1.5-63.7), and lower adherence, odds ratio: 3.9 (95% CI: 1.1-13.4), were the only factors associated with development of VF. CONCLUSIONS: We identified a significant risk of VF in children with HIV infection in a prospective cohort study in southern Ethiopia and limited predictive value of clinical variables for VF. This provides further evidence that rapid and reliable viral load testing is needed to adequately address the HIV epidemic, along with implementation of adherence interventions in sub-Saharan Africa.

Adolescents living with HIV are at higher risk of death and loss to follow up from care: Analysis of cohort data from eight health facilities in Ethiopia.

BACKGROUND: There are limited data on the treatment outcomes of adolescents living with HIV. Our objective was to compare mortality and loss to follow up (LTFU) rates between adolescent and younger age groups at enrollment in care. METHODS: This was a retrospective cohort study carried out in eight health facilities in two regions of Ethiopia. Adolescents (age 10-14 and 15-19 year) and children (age 0-9 year) enrolled in chronic HIV care between 2005 and 2013 constituted the study population. We reviewed the individual patient charts between March and June 2014 and updated the data on the status of each patient through December 2015. We used death and loss-to-follow up as primary endpoints and used the Cox-regression analysis where age, categorized as adolescent versus child, was the main predictor variable. RESULTS: Of 2058 participants studied, 52.1% were adolescents. The cohort contributed 2422 person-years of observation (PYO) during the pre-ART follow-up, whereas 1531 patients put on ART contributed 5984 PYO. Of those put on ART, 209 (13.7%) LTFU and 92 (6%) deaths were reported. Adolescents in age group 15-19 yr had the highest risk of LTFU [adjusted hazard ratio, aHR (95% CI) = 3.1 2.1, 5.0 ] followed by those in age group 10-14 yr (aHR = 1.5 [0.9, 2.3]) compared with children aged 0-9 yr. Mortality hazard was significantly higher among younger adolescents (aHR = 2.8 [1.4, 5.4]) and older adolescents (aHR = 2.3 [1.1, 4.9]) compared with children. CONCLUSIONS: Adolescents are at higher risk of mortality and LTFU as compared to children ages 0-9. Younger adolescents and children had similar LTFU rates. Narrow age band disaggregated analysis can serve as useful guide for tailoring interventions to the specific needs of different age groups.

Establishing a Multicenter Longitudinal Clinical Cohort Study in Ethiopia: Advanced Clinical Monitoring of Antiretroviral Treatment Project.

BACKGROUND: The purpose of this paper is to describe the establishment of the Advanced Clinical Monitoring of ART Project in Ethiopia for monitoring and evaluation of the longitudinal effectiveness of the ART program and to show the opportunities it presents. This cohort was established in response to the 2005 call by WHO for establishing additional mechanisms for stronger monitoring of ART and the need for creating the platform to generate evidence to guide the care given for the ever increasing number of patients on ART in Ethiopia. METHOD: A participatory and multi-stage process which started from a consensus building workshop and steered by a mother protocol as well as guiding documents which dictated the degree of engagement and expectations was followed. The primary and secondary aims of the study were agreed upon. A multi-site longitudinal observational clinical cohort was established by a consortium of stakeholders including seven Ethiopian medical schools and their affiliated referral hospitals, John Hopkins University, Ethiopian Public Health Institute, Ministry of Science and Technology, US Centers for Disease Prevention and Control - CDC-Ethiopia, and the Federal Ministry of Health. Adult and adolescent cohorts covering the age range of 14+ years) and pediatric cohorts covering those below age 14 years were the two main cohorts. During the initial recruitment of these cohorts information was extracted from existing documents for a total of 2,100 adult participants. In parallel, a prospective cohort of 1,400 adult and adolescent patients were enrolled for ART initiation and follow-up. Using similar recruitment procedures, a total of 120 children were enrolled in each of retrospective and prospective cohorts. Replacement of participants were made in subsequent years based on lost follow up and death rates to maintain adequacy of the sample to be followed-up. ACHIEVEMENTS: Between January 2005 and August 2013 a total of 4,339 patients were followed for a median of 41.6 months and data on demographic characteristics, baseline and ongoing clinical features, hospitalization history, medication and laboratory information were collected. 39,762 aliquots and 25,515 specimens of plasma and dryblood-spots respectively were obtained and stored longitudinally from October 2009 to August 2013. The project created a research platform for researchers, policy and decision makers. Moreover, it encouraged local and international investigators to identify and answer clinically and programmatically relevant research questions using the available data and specimens. Calls for concept notes paired with multiple trainings to stimulate investigators to conduct analyses further boosted the potential for doing research. CONCLUSIONS: A comprehensive and resourceful mechanism for scientific inquiry was established to support the national HIV/ART program. With meaningful involvement and defined roles, establishment of a study, which involved multiple institutions and investigators, was possible. Since ACM is the largest multi-site clinical cohort of patients on antiretroviral treatment in Ethiopia-which can be used for research and for improving clinical management-considering options to sustain the project is crucial.

Associations Between Khat Use and HIV Risk and Status Among Voluntary Counseling and Testing Center Clients in Addis Ababa, Ethiopia.

OBJECTIVES: Ethiopia is 1 of 15 countries that account for nearly 75% of all people living with HIV. Khat use, a common practice in Ethiopia and sub-Saharan Africa, has gained attention as a potential risk factor for HIV. Our objective was to evaluate associations between khat use and demographic and risk-taking characteristics (alcohol use, sexual behavior), and also associations between HIV status and these characteristics among voluntary counseling and testing clients in Addis Ababa, Ethiopia. METHODS: This cross-sectional study was conducted among Pro Pride voluntary counseling and testing center clients, aged 18 to 49 years, from November 2009 to March 2010. All clients were approached, and 98.8% of these (684) completed a self-administered questionnaire. Associations between khat use, alcohol use, multiple sexual partners, and HIV status were assessed using logistic regression models. RESULTS: Using khat in the past 90 days (current khat use) was significantly associated with being Muslim, being male, alcohol use, and having a greater number of sex partners in one's lifetime. The adjusted odds of current khat use was almost 7-fold higher in those having 4 or more sexual partners in their lifetime (adjusted odds ratio 6.89, 95% confidence interval 3.87, 12.25) as compared with those with 1 or none. HIV-positive status was significantly associated with age, employment, marital status, number of sex partners in one's lifetime, and khat use. Having used khat in one's lifetime, but not currently, past khat use, was associated with over a 2-fold increased adjusted odds (adjusted odds ratio 2.64, 95% confidence interval 1.13, 6.19) of being HIV-infected. CONCLUSIONS: Our findings highlight associations between current khat use and the modifiable factors of number of lifetime sexual partners and alcohol use. In addition, we observed the association between HIV status and past khat use after adjusting for age, marital status, and number of sex partners in one's lifetime.

Cohort profile: improving treatment of HIV-infected Ethiopian children through better detection of treatment failure in southern Ethiopia.

PURPOSE: The Ethiopian Paediatric HIV Cohort (EPHIC) was established to identify clinical and laboratory predictors of virological treatment failure to ultimately develop a clinical-immunological prediction rule with area under the curve of >0.80 for detecting first-line antiretroviral therapy failure (ARTF). It will also assess the performance of the current WHO guidelines for detection of first-line ARTF in children. PARTICIPANTS: Using a prospective cohort design, HIV-infected children and adolescents below the age of 18 years are followed every 6 months with a set of clinical and laboratory parameters at 6 hospitals in southern Ethiopia. For inclusion in the cohort, children should be on or are initiating first-line antiretroviral therapy (ART) and are not on second-line ART. Virological treatment failure is taken as the gold standard for the diagnosis of treatment failure. FINDINGS TO DATE: From October 2015 through April 2016, 628 children have been enrolled from 6 different HIV treatment centres across southern Ethiopia. The mean age at enrolment was 11.1 years and 47.6% were girls. Many of the children (88.6%) were at WHO Clinical stage 1 at time of enrolment. At enrolment, the mean duration on first-line ART was 45 months. Substitution of ART drugs was performed to nearly half (42.6%) of the cohort. Adherence as assessed with the Visual Analogue Scale was high (mean, 94.4%; SD=11.9). The median CD4 count of the cohort at enrolment was 741 with 3.1% having a value consistent with ARTF. FUTURE PLANS: Regular data uploads from the 6 hospitals in southern Ethiopia enable this cohort to be followed prospectively. The cohort will be completed in September 2017. The successful completion of this study will allow for better targeting of viral-load testing to those at highest risk in resource-poor settings and provide clinicians and policymakers with a practical prediction rule. ETHICS APPROVAL: SNNPR Regional Health Bureau Institutional Review Board.

Cost-effectiveness of Diagnostic Algorithms for Tuberculosis in Children Less Than 5 Years of Age.

BACKGROUND: The objective of this analysis was to assess the cost-effectiveness of TB diagnosis using microscopic observation drug susceptibility (MODS), Xpert MTB/RIF (Xpert) and empiric treatment for all patients, in addition to current clinical diagnostic practices in children less than 5 years of age in a national tuberculosis (TB) referral hospital in Uganda. METHODS: A decision analysis was conducted from the healthcare perspective, with a primary outcome of incremental cost-effectiveness expressed as cost per year of life gained (YLG). RESULTS: Cost-effectiveness of the algorithms depended strongly on 3 variables: the prevalence of TB, probability of death if TB was untreated and accuracy of existing diagnostic algorithms. Xpert and MODS had similar cost-effectiveness profiles and were preferred in settings where the prevalence of TB and probability of death from untreated TB were low. As the underlying probability of TB disease and death increased, treating all children with clinically suspected disease became more cost-effective. In settings where the probability that an untreated child will die of TB-whether a result of high prevalence of TB or high mortality from untreated TB-treating all children for TB is likely to be the most cost-effective approach until better diagnostic tests can be developed. CONCLUSIONS: The cost-effectiveness of diagnostic tools for TB in children depends on the population, natural history of untreated TB and existing diagnostic practices. In settings where the risk of TB death is high, empiric treatment of all children for TB should be considered until a more sensitive, low-cost diagnostic test is available.

Predictors of Infant Age at Enrollment in Early Infant Diagnosis Services in Kenya.

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.

Improving early infant HIV diagnosis in Kenya: study protocol of a cluster-randomized efficacy trial of the HITSystem.

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.

Collaboratively reframing mental health for integration of HIV care in Ethiopia.

BACKGROUND: Integrating mental health with general medical care can increase access to mental health services, but requires helping generalists acquire a range of unfamiliar knowledge and master potentially complex diagnostic and treatment processes. METHOD: We describe a model for integrating complex specialty care with generalist/primary care, using as an illustration the integration of mental health into hospital-based HIV treatment services in Ethiopia. Generalists and specialists collaboratively developed mental health treatments to fit the knowledge, skills and resources of the generalists. The model recognizes commonalities between mental health and general medical care, focusing on practical interventions acceptable to patients. It was developed through a process of literature review, interviews, observing clinical practice, pilot trainings and expert consultation. Preliminary evaluation results were obtained by debriefing generalist trainees after their return to their clinical sites. RESULTS: In planning interviews, generalists reported discomfort making mental health diagnoses but recognition of symptom groups including low mood, anxiety, thought problems, poor child behaviour, seizures and substance use. Diagnostic and treatment algorithms were developed for these groups and tailored to the setting by including possible medical causes and burdens of living with HIV. First-line treatment included modalities familiar to generalists: empathetic patient-provider interactions, psychoeducation, cognitive reframing, referral to community supports and elements of symptom-specific evidence-informed counselling. Training introduced basic skills, with evolving expertise supported by job aides and ongoing support from mental health nurses cross-trained in HIV testing. Feedback from trainees suggested the programme fit well with generalists' settings and clinical goals. CONCLUSIONS: An integration model based on collaboratively developing processes that fit the generalist setting shows promise as a method for incorporating complex, multi-faceted interventions into general medical settings. Formal evaluations will be needed to compare the quality of care provided with more traditional approaches and to determine the resources required to sustain quality over time.

Beneficial effect of isoniazid preventive therapy and antiretroviral therapy on the incidence of tuberculosis in people living with HIV in Ethiopia.

BACKGROUND: IPT with or without concomitant administration of ART is a proven intervention to prevent tuberculosis among PLHIV. However, there are few data on the routine implementation of this intervention and its effectiveness in settings with limited resources. OBJECTIVES: To measure the level of uptake and effectiveness of IPT in reducing tuberculosis incidence in a cohort of PLHIV enrolled into HIV care between 2007 and 2010 in five hospitals in southern Ethiopia. METHODS: A retrospective cohort analysis of electronic patient database was done. The independent effects of no intervention, "IPT-only," "IPT-before-ART," "IPT-and-ART started simultaneously," "ART-only," and "IPT-after-ART" on TB incidence were measured. Cox-proportional hazards regression was used to assess association of treatment categories with TB incidence. RESULTS: Of 7,097 patients, 867 were excluded because they were transferred-in; a further 823 (12%) were excluded from the study because they were either identified to have TB through screening (292 patients) or were on TB treatment (531). Among the remaining 5,407 patients observed, IPT had been initiated for 39% of eligible patients. Children, male sex, advanced disease, and those in Pre-ART were less likely to be initiated on IPT. The overall TB incidence was 2.6 per 100 person-years. As compared to those with no intervention, use of "IPT-only" (aHR = 0.36, 95% CI = 0.19-0.66) and "ART-only" (aHR = 0.32, 95% CI = 0.24-0.43) were associated with significant reduction in TB incidence rate. Combining ART and IPT had a more profound effect. Starting IPT-before-ART (aHR = 0.18, 95% CI = 0.08-0.42) or simultaneously with ART (aHR = 0.20, 95% CI = 0.10-0.42) provided further reduction of TB at ∼ 80%. CONCLUSIONS: IPT was found to be effective in reducing TB incidence, independently and with concomitant ART, under programme conditions in resource-limited settings. The level of IPT provision and effectiveness in reducing TB was encouraging in the study setting. Scaling up and strengthening IPT service in addition to ART can have beneficial effect in reducing TB burden among PLHIV in settings with high TB/HIV burden.

Pooled individual data analysis of 5 randomized trials of infant nevirapine prophylaxis to prevent breast-milk HIV-1 transmission.

BACKGROUND: In resource-limited settings, mothers infected with human immunodeficiency virus type 1 (HIV-1) face a difficult choice: breastfeed their infants but risk transmitting HIV-1 or not breastfeed their infants and risk the infants dying of other infectious diseases or malnutrition. Recent results from observational studies and randomized clinical trials indicate daily administration of nevirapine to the infant can prevent breast-milk HIV-1 transmission. METHODS: Data from 5396 mother-infant pairs who participated in 5 randomized trials where the infant was HIV-1 negative at birth were pooled to estimate the efficacy of infant nevirapine prophylaxis to prevent breast-milk HIV-1 transmission. Four daily regimens were compared: nevirapine for 6 weeks, 14 weeks, or 28 weeks, or nevirapine plus zidovudine for 14 weeks. RESULTS: The estimated 28-week risk of HIV-1 transmission was 5.8% (95% confidence interval [CI], 4.3%-7.9%) for the 6-week nevirapine regimen, 3.7% (95% CI, 2.5%-5.4%) for the 14-week nevirapine regimen, 4.8% (95% CI, 3.5%-6.7%) for the 14-week nevirapine plus zidovudine regimen, and 1.8% (95% CI, 1.0%-3.1%) for the 28-week nevirapine regimen (log-rank test for trend, P < .001). Cox regression models with nevirapine as a time-varying covariate, stratified by trial site and adjusted for maternal CD4 cell count and infant birth weight, indicated that nevirapine reduces the rate of HIV-1 infection by 71% (95% CI, 58%-80%; P < .001) and reduces the rate of HIV infection or death by 58% (95% CI, 45%-69%; P < .001). CONCLUSIONS: Extended prophylaxis with nevirapine or with nevirapine and zidovudine significantly reduces postnatal HIV-1 infection. Longer duration of prophylaxis results in a greater reduction in the risk of infection.

Khat use among HIV voluntary counselling and testing centre clients in Ethiopia.

Khat (Catha edulis, a natural stimulant), has been used in Ethiopia for centuries. Over the past few decades, however, its use has dramatically increased, with recent research linking khat use to HIV status. Using qualitative methods, we explored the individual and micro-environmental characteristics of khat use and the social and physical contexts influencing type, acceptability and consequences of khat use. Among khat chewers attending an HIV voluntary counselling and testing centre in Addis Ababa, Ethiopia, we found that chewing typically starts at an early age (15-18 years). The majority of users are young (aged 18-35) and chew for pleasure, primarily in social settings. Over 25 types of khat, with varying effects were reported. Approximately half of the participants perceived khat to enhance sexual desire, while the rest claimed the effect on sexual desire to be the opposite. Alcohol use among chewers was high. Our findings suggest the need for culturally appropriate interventions that highlight the factors associated with khat use and the potential interplay between khat, alcohol and risky sexual behaviour.

PEPFAR scale-up of pediatric HIV services: innovations, achievements, and challenges.

HIV/AIDS has had a profound impact on children around the world since the start of the epidemic. There are currently 3.4 million children under the age of 15 years living with HIV globally, and more than 450,000 children currently receiving lifesaving antiretroviral treatment. This article describes efforts supported by the President's Emergency Plan for AIDS Relief (PEPFAR) to expand access to treatment for children living with HIV in high-burden countries. The article also highlights a series of case studies that illustrate the impact that the PEPFAR initiative has had on the pediatric HIV epidemic. Through its support of host governments and partner organizations, the PEPFAR initiative has expanded HIV testing and treatment for pregnant women to reduce vertical transmission of HIV, increased access to early infant diagnosis for HIV-exposed infants, improved training and resources for clinicians who provide pediatric care and antiretroviral treatment, and, through public-private partnerships with pharmaceutical manufacturers, helped increase the number of medications available for the treatment of HIV-infected children in resource-limited settings.

Use of dried-blood-spot samples and in-house assays to identify antiretroviral drug resistance in HIV-infected children in resource-constrained settings.

Monitoring HIV drug resistance is an important component of the World Health Organization's global HIV program. HIV drug resistance testing is optimal with commercially available clinically validated test kits using plasma; however, that type of testing may not be feasible or affordable in resource-constrained settings. HIV genotyping from dried blood spots (DBS) with noncommercial (in-house) assays may facilitate the capture of HIV drug resistance outcomes in resource-constrained settings but has had varying rates of success. With in-house assays for HIV reverse transcriptase, we evaluated the yield of genotyping DBS samples collected from HIV-infected children who were enrolled in two clinical trials conducted in sub-Saharan Africa (median HIV viral load, 5.88 log(10) HIV RNA copies/ml; range, 4.04 to 6.99). Overall, HIV genotypes were obtained for 94 (89.5%) of 105 samples tested (95% and 84% from clinical trials #1 and #2, respectively); however, successful analysis of 15 (16.1%) of the 94 samples required repeat testing using a different set of primers on previously synthesized cDNA. The yield of genotyping was lower on the DBS that were stored suboptimally from clinical trial #2 (56% versus 88% for optimally stored). Concordance with plasma genotypes derived using a clinically validated, commercial kit-based assay (ViroSeq HIV-1 genotyping system) was also assessed in a subset of children with paired testing. For 34 samples with paired DBS and plasma genotypes, there was 100% concordance for major drug resistance mutations. DBS genotyping using in-house assays provides an alternative for antiretroviral drug resistance testing in children in resource-constrained regions but may require region-specific optimization before widespread use.