Specific plasma microRNAs are associated with CD4 + T-cell recovery during suppressive antiretroviral therapy for HIV-1.

OBJECTIVE: This study investigated the association of plasma microRNAs before and during antiretroviral therapy (ART) with poor CD4 + T-cell recovery during the first year of ART. DESIGN: MicroRNAs were retrospectively measured in stored plasma samples from people with HIV (PWH) in sub-Saharan Africa who were enrolled in a longitudinal multicountry cohort and who had plasma viral-load less than 50 copies/ml after 12 months of ART. METHODS: First, the levels of 179 microRNAs were screened in a subset of participants from the lowest and highest tertiles of CD4 + T-cell recovery (ΔCD4) ( N  = 12 each). Next, 11 discordant microRNAs, were validated in 113 participants (lowest tertile ΔCD4: n  = 61, highest tertile ΔCD4: n  = 52). For discordant microRNAs in the validation, a pathway analysis was conducted. Lastly, we compared microRNA levels of PWH to HIV-negative controls. RESULTS: Poor CD4 + T-cell recovery was associated with higher levels of hsa-miR-199a-3p and hsa-miR-200c-3p before ART, and of hsa-miR-17-5p and hsa-miR-501-3p during ART. Signaling by VEGF and MET, and RNA polymerase II transcription pathways were identified as possible targets of hsa-miR-199a-3p, hsa-200c-3p, and hsa-miR-17-5p. Compared with HIV-negative controls, we observed lower hsa-miR-326, hsa-miR-497-5p, and hsa-miR-501-3p levels before and during ART in all PWH, and higher hsa-miR-199a-3p and hsa-miR-200c-3p levels before ART in all PWH, and during ART in PWH with poor CD4 + T-cell recovery only. CONCLUSION: These findings add to the understanding of pathways involved in persistent HIV-induced immune dysregulation during suppressive ART.

Preparing healthcare facilities in sub-Saharan Africa for future outbreaks: insights from a multi-country digital self-assessment of COVID-19 preparedness.

BACKGROUND: Despite previous experience with epidemics, African healthcare systems were inadequately prepared and substantially impacted by the coronavirus disease 2019 (COVID-19) pandemic. Limited information about the level of COVID-19 preparedness of healthcare facilities in Africa hampers policy decision-making to fight future outbreaks in the region, while maintaining essential healthcare services running. METHODS: Between May-November 2020, we performed a survey study with SafeCare4Covid - a free digital self-assessment application - to evaluate the COVID-19 preparedness of healthcare facilities in Africa following World Health Organization guidelines. The tool assessed (i) COVID-19-related capabilities with 31 questions; and (ii) availability of essential medical supplies with a 23-supplies checklist. Tailored quality improvement plans were provided after assessments. Information about facilities' location, type, and ownership was also collected. RESULTS: Four hundred seventy-one facilities in 11 African countries completed the capability assessment; 412 also completed the supplies checklist. The average capability score on a scale of 0-100 (n=471) was 58.0 (interquartile range 40.0-76.0), and the average supplies score (n=412) was 61.6 (39.0-83.0). Both scores were significantly lower in rural (capability score, mean 53.6 [95%CI:50.3-57.0]/supplies score, 59.1 [55.5-62.8]) versus urban facilities (capability score, 65.2 [61.7-68.7]/supplies score, 70.7 [67.2-74.1]) (P<0.0001 for both comparisons). Likewise, lower scores were found for public versus private clinics, and for primary healthcare centres versus hospitals. Guidelines for triage and isolation, clinical management of COVID-19, staff mental support, and contact tracing forms were largely missing. Handwashing stations were partially equipped in 33% of facilities. The most missing medical supply was COVID-19 specimen collection material (71%), while 43% of facilities did not have N95/FFP2 respirators and 19% lacked medical masks. CONCLUSIONS: A large proportion of public and private African facilities providing basic healthcare in rural areas, lacked fundamental COVID-19-related capabilities and life-saving personal protective equipment. Decentralization of epidemic preparedness efforts in these settings is warranted to protect healthcare workers and patients alike in future epidemics. Digital tools are of great value to timely measure and improve epidemic preparedness of healthcare facilities, inform decision-making, create a more stakeholder-broad approach and increase health-system resilience for future disease outbreaks.

Stability in care and risk of loss to follow-up among clients receiving community health worker-led differentiated HIV care: Results from a prospective cohort study in northern Tanzania.

BACKGROUND: HIV services in Tanzania are facility-based but facilities are often overcrowded. Differentiated care models (DCM) have been introduced into the National Guidelines. We piloted a Community Health Worker (CHW)-led HIV treatment club model (CHW-DCM) in an urban region, and assessed its effectiveness in comparison to the standard of care (SoC, facility-based model), in terms of stability in care, loss to follow-up (LTFU) and treatment adherence. METHODS: In two clinics in the Shinyanga region, clients established on ART (defined as stable clients by national guidelines as on first-line ART >6 months, undetectable viral load, no opportunistic infections or pregnancy, and good adherence) were offered CHW-DCM. This prospective cohort study included all stable clients who enrolled in CHW-DCM between July 2018 and March 2020 (CHW-DCM) and compared them to stable clients who remained in SoC during that period. Multivariable Cox regression models were used to analyse factors associated with continued stability in care and the risk of LTFU during 18 months of follow-up; treatment adherence was assessed by pill count and compared using Chi-square tests. RESULTS: Of 2472 stable clients, 24.5% received CHW-DCM and 75.5% SoC. CHW-DCM clients were slightly older (mean 42.8 vs. 37.9 years) and more likely to be female (36.2% vs. 32.2%). Treatment adherence was better among CHW-DCM than SoC: 96.6% versus 91.9% and 98.5% versus 92.2%, respectively (both p = 0.001). SoC clients were more likely to not remain stable over time than CHW-DCM (adjusted Hazard ratio [AHR] = 2.68; 95% CI: 1.86-3.90). There was no difference in LTFU (adjusted hazard ratio [AHR] = 1.54; 95%CI: 0.82-2.93). CONCLUSION: Clients attending CHW-DCM demonstrated better stability in care and treatment adherence than SoC, and the risk of LTFU was not increased. These findings demonstrate the potential of CHW in delivering community-based HIV services in the local Tanzanian context. These results could be used to extend this CHW-DCM model to similar settings.

Developing contents for a digital adherence tool: A formative mixed-methods study among children and adolescents living with HIV in Tanzania.

Optimal adherence (>95%) to antiretroviral treatment (ART) remains a challenge among children and adolescents living with HIV (CALHIV). Digital adherence tools (DAT) with reminder cues have proven feasible among adult people living with HIV (PLHIV), with some concerns about the risk of HIV status disclosure. We aimed to assess the needs, contents and acceptability of an SMS-based DAT among CALHIV. We first conducted a survey to understand potential barriers to using DAT among CALHIV, then tested the DAT intervention among purposively selected participants. The DAT intervention included using the Wisepill device, receiving daily reminder SMS and receiving adherence reports on how they had taken medication in the past month. The content of the reminder SMS differed over time from asking if the medication was taken to a more neutral SMS like "take care". Afterwards, we conducted exit interviews, in-depth interviews, and focus-group discussions. We analysed quantitative findings descriptively and used thematic content analysis for qualitative data. We included 142 children and 142 adolescents in the survey, and 20 of each used the intervention. Eighty-five percent (121/142) of surveyed participants indicated they would like to receive reminder SMS. Most of them (97/121-80%) of children and 94/121(78%) of adolescents would prefer to receive daily reminders. Participants who used the DAT mentioned to be happy to use the device. Ninety percent of them had good experience with receiving reminders and agreed that the SMS made them take medication. However, 25% experienced network problems. Participants preferred neutral reminder SMSs that did not mention the word 'medication', but preserved confidentiality. The provided adherence reports inspired participants to improve their adherence. None of the participants experienced unwanted disclosure or stigmatisation due to DAT. However, 5% of adolescents were concerned about being monitored daily. This study showed that DAT is acceptable and provided insight of the needed SMS content for a customized DAT for CALHIV.

Reduced incidence of respiratory, gastrointestinal and malaria infections among children during the COVID-19 pandemic in Western Kenya: An analysis of facility-based and weekly diaries data.

Background: Epidemics can cause significant disruptions of essential health care services. This was evident in West-Africa during the 2014-2016 Ebola outbreak, raising concerns that COVID-19 would have similar devastating consequences for the continent. Indeed, official facility-based records show a reduction in health care visits after the onset of COVID-19 in Kenya. Our question is whether this observed reduction was caused by lower access to health care or by reduced incidence of communicable diseases resulting from reduced mobility and social contacts. Methods: We analysed monthly facility-based data from 2018 to 2020, and weekly health diaries data digitally collected by trained fieldworkers between February and November 2020 from 342 households, including 1974 individuals, in Kisumu and Kakamega Counties, Kenya. Diaries data was collected as part of an ongoing longitudinal study of a digital health insurance scheme (Kakamega), and universal health coverage implementation (Kisumu). We assessed the weekly incidence of self-reported medical symptoms, formal and informal health-seeking behaviour, and foregone care in the diaries and compared it with facility-based records. Linear probability regressions with household fixed-effects were performed to compare the weekly incidence of health outcomes before and after COVID-19. Results: Facility-based data showed a decrease in health care utilization for respiratory infections, enteric illnesses, and malaria, after start of COVID-19 measures in Kenya in March 2020. The weekly diaries confirmed this decrease in respiratory and enteric symptoms, and malaria / fever, mainly in the paediatric population. In terms of health care seeking behaviour, our diaries data find a temporary shift in consultations from health care centres to pharmacists / chemists / medicine vendors for a few weeks during the pandemic, but no increase in foregone care. According to the diaries, for adults the incidence of communicable diseases/symptoms rebounded after COVID-19 mobility restrictions were lifted, while for children the effects persisted. Conclusions: COVID-19-related containment measures in Western Kenya were accompanied by a decline in respiratory infections, enteric illnesses, and malaria / fever mainly in children. Data from a population-based survey and facility-based records aligned regarding this finding despite the temporary shift to non-facility-based consultations and confirmed that the drop in utilization of health care services was not due to decreased accessibility, but rather to a lower incidence of these infections.

Experiences on the Utility and Barriers of Telemedicine in Healthcare Delivery in Kenya.

Introduction: Telemedicine is the provision of health services over a distance using information communication technology devices. Telemedicine is emerging as a promising component of healthcare care delivery worldwide, accelerated by the COVID-19 pandemic. This study assessed the factors promoting uptake, barriers, and opportunities for telemedicine among doctors in Kenya. Methodology. A semiquantitative, cross-sectional online survey was conducted among doctors in Kenya. During a month, between February and March 2021, 1,200 doctors were approached by email and WhatsApp, of whom 13% responded. Findings. A total of 157 interviewees participated in the study. The general usage of telemedicine was 50%. Seventy-three percent of doctors reported using a mix of in-person care and telemedicine. Fifty percent reported using telemedicine to support physician-to-physician consultations. Telemedicine had limited utility as a standalone clinical service. The inadequate information communication technology infrastructure was the most reported barrier to telemedicine, followed by a cultural resistance to using technology to deliver healthcare services. Other notable barriers were the high cost of initial setup limited skills among patients, limited skills among doctors, inadequate funding to support telemedicine services, weak legislative/policy framework, and lack of dedicated time for telemedicine services. The COVID-19 pandemic increased the uptake of telemedicine in Kenya. Conclusion: The most extensive use of telemedicine in Kenya supports physician-to-physician consultations. There is limited single use of telemedicine in providing direct clinical services to patients. However, telemedicine is regularly used in combination with in-person clinical services, allowing for continuity of clinical services beyond the physical hospital infrastructure. With the widespread adoption of digital technologies in Kenya, especially mobile telephone technologies, the growth opportunities for telemedicine services are immense. Numerous mobile applications will improve access capabilities for both service providers and users and bridge the gaps in care.

Readiness of Ghanaian health facilities to deploy a health insurance claims management software (CLAIM-it).

INTRODUCTION: Inadequate, inefficient and slow processing of claims are major contributors to the cost of health insurance schemes, and therefore undermining their sustainability. This study uses the Technology, Organisation and Environment (TOE) framework to examine the preparedness of health facilities of the Christian Health Association of Ghana (CHAG) to implement a digital mobile health insurance claims processing software (CLAIM-it), which aims to increase efficiency. METHODS: The study used a cross-sectional mixed method design to collect data (technology and human capital capacity and baseline operational performance of claims management) from a sample of 20 CHAG health facilities across Ghana. While quantitative data was analysed using simple descriptive statistics statistics (frequencies, mean, minimum and maximum values), qualitative interviews were recorded, transcribed and abstracted into two major themes that were reported to re-enforce the quantitative findings. RESULTS: The quantitative results revealed challenges including inadequate computers and accessories, adequate numbers and skills for claims processing, poor intranets and internet access, absence of a robust post-implementation support system and inadequate standard operating procedures (SOPs) for seamless automation of claims processing. In addition to the above, the qualitative results emphasised the need to make CLAIM-it more flexible and capable of being integrated into third-party softwares. Notwithstanding the challenges, decision-makers in CHAG health facilities see the CLAIM-it software as having better functionality and superior capabilities compared to existing claims processing systems in Ghana. CONCLUSION: Notwithstanding the challenges, the CLAIM-it software is more likely to be adopted by decision-makers, given the positive perception in terms of superior functionality. It is important that key actors in claims management at the National Health Insurance collaborate with relevant stakeholders to adopt the CLAIM-it software for claims processing and management in Ghana.

A digital mobile health platform increasing efficiency and transparency towards universal health coverage in low- and middle-income countries.

In low-and middle-income countries, achieving universal health coverage remains challenging due to insufficient, temporary and fragmented funding as well as limited accessibility to quality healthcare. Leveraging a mobile health platform can be a powerful tool to address these problems. This paper demonstrates how analysing data collected from a mobile health platform helps optimize healthcare provider networks, monitor patient flows and assess the quality and equitability of access to care. The COVID-19 pandemic reinforces the importance of real-time data on health-seeking behaviour. Between 2018 and 2019, as a Kenyan universal health coverage pilot was being planned, Kisumu County, with support from PharmAccess Foundation, implemented household-level digital registration for healthcare and collected socio-economic and healthcare claims data using the M-TIBA platform. In total, 273,350 Kisumu households enrolled. The claims data showed many patients visit higher-level facilities for ailments, that can be treated at primary care levels, unnecessarily. High-level estimate of the disease burden at participating facilities revealed rampant overprescription of pertinent medicines for highly prevalent malaria and respiratory tract infections, exemplifying clinical management deficiencies. M-TIBA data allowed tracking of individual patient trajectories. Analyses of data are shown at the aggregate level. The paper shows how mobile health platforms can be used to generate valuable insights into access to and quality of care. Funding for healthcare can be united through mobile health platforms, limiting the fragmentation in funding. They can be useful for funders, health managers and policymakers to improve the implementation of universal health coverage programs in low-and middle-income countries.

Community- and facility-based HIV testing interventions in northern Tanzania: Midterm results of Test & Treat Project.

Test & Treat Project offers universal HIV testing and access to antiretroviral treatment in Northern Tanzania. The current cross-sectional study provides midterm results on HIV testing and counseling activities through community outreaches and facility-based services. A total 255,329 HIV tests were performed: 198,451 (77.7%) during testing campaigns in the villages, 12,592 (4.9%) during special events outreach and 44,286 (17.4%) in the health facilities. Females represented 53.8% (23,809) among those tested in the health facilities, while males were the majority in the community (54.4%, 114,835). Over one third of tests (n = 104,605, 41%) were performed among first-time testers. The overall HIV positivity rate was 1.2%, ranging from 0.7% in the community to 3.8% in the health facilities and decreased over time. Using a multivariable analysis, a positive test result was associated with age ≥ 50 years (PR 1.22, 95% CI 1.11 to 1.34), with female gender (PR 1.61, 95% CI 1.50 to 1.73), being tested in health facilities (PR 5.00, 95% CI 4.65 to 5.36) and for the first time (PR 1.86, 95% CI 1.73 to 2.00). The estimated proportion of PLHIV who knew their status of the project area increased by 28.6% (from 35.7% to 64.3%) and 11.1% (from 57.7% to 68.8%) in the project areas of Shinyanga and Simiyu regions respectively. Reaching the first UNAIDS 90 target by the end of this project seems possible. Future strategies should focus on improving PITC coverage, implementing more targeted testing modalities, together with current universal community-based approach.

Exploring the mechanisms behind HIV drug resistance in sub-Saharan Africa: conceptual mapping of a complex adaptive system based on multi-disciplinary expert insights.

BACKGROUND: HIV drug resistance (HIVDR) continues to threaten the effectiveness of worldwide antiretroviral therapy (ART). Emergence and transmission of HIVDR are driven by several interconnected factors. Though much has been done to uncover factors influencing HIVDR, overall interconnectedness between these factors remains unclear and African policy makers encounter difficulties setting priorities combating HIVDR. By viewing HIVDR as a complex adaptive system, through the eyes of multi-disciplinary HIVDR experts, we aimed to make a first attempt to linking different influencing factors and gaining a deeper understanding of the complexity of the system. METHODS: We designed a detailed systems map of factors influencing HIVDR based on semi-structured interviews with 15 international HIVDR experts from or with experience in sub-Saharan Africa, from different disciplinary backgrounds and affiliated with different types of institutions. The resulting detailed system map was conceptualized into three main HIVDR feedback loops and further strengthened with literature evidence. RESULTS: Factors influencing HIVDR in sub-Saharan Africa and their interactions were sorted in five categories: biology, individual, social context, healthcare system and 'overarching'. We identified three causal loops cross-cutting these layers, which relate to three interconnected subsystems of mechanisms influencing HIVDR. The 'adherence motivation' subsystem concerns the interplay of factors influencing people living with HIV to alternate between adherence and non-adherence. The 'healthcare burden' subsystem is a reinforcing loop leading to an increase in HIVDR at local population level. The 'ART overreliance' subsystem is a balancing feedback loop leading to complacency among program managers when there is overreliance on ART with a perceived low risk to drug resistance. The three subsystems are interconnected at different levels. CONCLUSIONS: Interconnectedness of the three subsystems underlines the need to act on the entire system of factors surrounding HIVDR in sub-Saharan Africa in order to target interventions and to prevent unwanted effects on other parts of the system. The three theories that emerged while studying HIVDR as a complex adaptive system form a starting point for further qualitative and quantitative investigation.

Digital health systems strengthening in Africa for rapid response to COVID-19.

The COVID-19 pandemic has painfully exposed the constraints of fragile health systems in low- and middle-income countries, where global containment measures largely set by high-income countries resulted in disproportionate collateral damage. In Africa, a shift is urgently needed from emergency response to structural health systems strengthening efforts, which requires coordinated interventions to increase access, efficiency, quality, transparency, equity, and flexibility of health services. We postulate that rapid digitalization of health interventions is a key way forward to increase resilience of African health systems to epidemic challenges. In this paper we describe how PharmAccess' ongoing digital health system interventions in Africa were rapidly customized to respond to COVID-19. We describe how we developed: a COVID-19 App for healthcare providers used by more than 1,000 healthcare facilities in 15 African countries from May-November 2020; digital loans to support private healthcare providers with USD 20 million disbursed to healthcare facilities impacted by COVID-19 in Kenya; a customized Dutch mobile COVID-19 triage App with 4,500 users in Ghana; digital diaries to track COVID-19 impacts on household expenditures and healthcare utilization; a public-private partnership for real-time assessment of COVID-19 diagnostics in West-Kenya; and an expanded mobile phone-based maternal and child-care bundle to include COVID-19 adapted services. We also discuss the challenges we faced, the lessons learned, the impact of these interventions on the local healthcare system, and the implications of our findings for policy-making. Digital interventions bring efficiency due to their flexibility and timeliness, allowing co-creation, targeting, and rapid policy decisions through bottom-up approaches. COVID-19 digital innovations allowed for cross-pollinating the interests of patients, providers, payers, and policy-makers in challenging times, showing how such approaches can pave the way to universal health coverage and resilient healthcare systems in Africa.

Pre-exposure prophylaxis for transgender women and men who have sex with men: qualitative insights from healthcare providers, community organization-based leadership and end users in coastal Kenya.

Transgender women (TW) and men who have sex with men (MSM) in Kenya are disproportionately affected by human immunodeficiency virus (HIV) and would benefit substantially from pre-exposure prophylaxis (PrEP). We conducted focus group discussions (FGDs) with healthcare providers (HCPs) and TW/MSM leadership and in-depth interviews (IDIs) with PrEP-experienced MSM and TW to learn about perceived and actual barriers to PrEP programming. Eleven HCP and 10 TW/MSM leaders participated in FGDs before PrEP roll-out (January 2018) and 12 months later. Nineteen PrEP end-users (11 MSM and 8 TW) participated in IDIs. Topic guides explored PrEP knowledge, HIV acquisition risk, gender identity, motivation for PrEP uptake and adherence and PrEP-dispensing venue preferences. Braun and Clarke thematic analysis was applied. Four themes emerged: limited preparedness of HCPs to provide PrEP to TW and MSM, varied motivation for PrEP uptake and persistence among end users, lack of recognition of TW by HCPs and suggestions for PrEP programming improvement from all stakeholders. Providers' reluctance to prescribe PrEP to TW and distrust of TW towards providers calls for interventions to improve the capacity of service environments and staff HIV preventive care. Alternative locations for PrEP provision, including community-based sites, may be developed with TW/MSM leaders.

Public-private partnership to rapidly strengthen and scale COVID-19 response in Western Kenya.

Introduction: In Africa almost half of healthcare services are delivered through private sector providers. These are often underused in national public health responses. To support and accelerate the public sector's COVID-19 response, we facilitated recruitment of additional private sector capacity by initiating a public-private partnership (PPP) in Kisumu County, Kenya. In this manuscript we demonstrate this PPP's performance. Methods: COVID-19 diagnostic testing formed the basis for a PPP between Kenyan Medical Research Institute (KEMRI), Department of Health Kisumu County, PharmAccess Foundation, and local faith-based and private healthcare facilities: COVID-Dx. First phase COVID-Dx was implemented from June 01, 2020, to March 31, 2021 in Kisumu County, Kenya. Trained laboratory technologists in participating healthcare facilities collected nasopharyngeal and oropharyngeal samples from patients meeting the Kenyan MoH COVID-19 case definition. Healthcare workers in participating facilities collected patient clinical data using a digitized MoH COVID-19 Case Identification Form. We shared aggregated results from these data via (semi-) live dashboards with all relevant stakeholders through their mobile phones and tablets. Statistical analyses were performed using Stata 16 to inform project processes. Results: Nine private facilities participated in the project. A patient trajectory was developed from case identification to result reporting, all steps supported by a semi-real time digital dashboard. A total of 4,324 PCR tests for SARS-CoV-2 were added to the public response, identifying 425 positives, accounting for 16% of all COVID-19 tests performed in the County over the given time-period. Geo-mapped and time-tagged information on incident cases was depicted on Google maps through PowerBI-dashboards and fed back to policymakers for informed rapid decision making. Preferential COVID-19 testing was performed on health workers at risk, with 1,009 tests performed (up to 43% of all County health workforce). Conclusion: We demonstrate feasibility of rapidly increasing the public health sector COVID-19 response through coordinated private sector efforts in an African setting. Our PPP intervention in Kisumu, Kenya was based on a joint testing strategy and demonstrated that semi-real time digitalization of patient trajectories can gain significant efficiencies, linking public and private healthcare efforts, increasing transparency, support better quality health services and informing policy makers to target interventions.

Connected diagnostics to improve accurate diagnosis, treatment, and conditional payment of malaria services in Kenya.

BACKGROUND: In sub-Saharan Africa, the material and human capacity to diagnose patients reporting with fever to healthcare providers is largely insufficient. Febrile patients are typically treated presumptively with antimalarials and/or antibiotics. Such over-prescription can lead to drug resistance and involves unnecessary costs to the health system. International funding for malaria is currently not sufficient to control malaria. Transition to domestic funding is challenged by UHC efforts and recent COVID-19 outbreak. Herewith we present a digital approach to improve efficiencies in diagnosis and treatment of malaria in endemic Kisumu, Kenya: Connected Diagnostics. The objective of this study is to evaluate the feasibility, user experience and clinical performance of this approach in Kisumu. METHODS: Our intervention was performed Oct 2017-Dec 2018 across five private providers in Kisumu. Patients were enrolled on M-TIBA platform, diagnostic test results digitized, and only positive patients were digitally entitled to malaria treatment. Data on socio-demographics, healthcare transactions and medical outcomes were analysed using standard descriptive quantitative statistics. Provider perspectives were gathered by 19 semi-structured interviews. RESULTS: In total 11,689 febrile patients were digitally tested through five private providers. Malaria positivity ranged from 7.4 to 30.2% between providers, significantly more amongst the poor (p < 0.05). Prescription of antimalarials was substantially aberrant from National Guidelines, with 28% over-prescription (4.6-63.3% per provider) and prescription of branded versus generic antimalarials differing amongst facilities and correlating with the socioeconomic status of clients. Challenges were encountered transitioning from microscopy to RDT. CONCLUSION: We provide full proof-of-concept of innovative Connected Diagnostics to use digitized malaria diagnostics to earmark digital entitlements for correct malaria treatment of patients. This approach has large cost-saving and quality improvement potential.

Patient-incurred costs in a differentiated service delivery club intervention compared to standard clinical care in Northwest Tanzania.

INTRODUCTION: Placing all clients with a positive diagnosis for HIV on antiretroviral therapy (ART) has cost implications both for patients and health systems, which could, in turn, affect feasibility, sustainability and uptake of new services. Patient-incurred costs are recognized barriers to healthcare access. Differentiated service delivery (DSD) models in general and community-based care in particular, could reduce these costs. We aimed to assess patient-incurred costs of a community-based DSD intervention (clubs) compared to clinic-based care in the Shinyanga region, Tanzania. METHODS: Cross-sectional survey among stable ART patients (n = 390, clinic-based; n = 251, club-based). For each group, we collected socio-demographic, income and expenditure data between May and August 2019. We estimated direct and indirect patient-incurred costs. Direct costs included out-of-pocket expenditures. Indirect costs included income loss due to time spent during transport, accessing services and off work during illness. Cost drivers were assessed in multivariate regression models. RESULTS: Overall, costs were significantly higher among clinic participants. Costs (USD) per year for clinic versus club were as follows: 11.7 versus 4.17 (p < 0.001) for direct costs, 20.9 versus 8.23 (p < 0.001) for indirect costs and 32.2 versus 12.4 (p < 0.001) for total costs. Time spent accessing care and time spent in illness (hours/year) were 38.3 versus 13.8 (p < 0.001) and 16.0 versus 6.69 (p < 0.001) respectively. The main cost drivers included transportation (clinic vs. club: 67.7% vs. 44.1%) for direct costs and income loss due to time spent accessing care (clinic vs. club: 60.4% vs. 56.7%) for indirect costs. Factors associated with higher total costs among patients attending clinic services were higher education level (coefficient [95% confidence interval]) 20.9 [5.47 to 36.3]) and formal employment (44.2 [20.0 to 68.5). Differences in mean total costs remained significantly higher with formal employment, rural residence, in addition to more frequent visits among clinic participants. The percentage of households classified as having had catastrophic expenditures in the last year was low but significantly higher among clinic participants (10.8% vs. 5.18%, p = 0.014). CONCLUSIONS: Costs incurred by patients accessing DSD in the community are significantly lower compared to those accessing standard clinic-based care. DSD models could improve access, especially in resource-limited settings.

Exploring Sustainability in the Era of Differentiated HIV Service Delivery in Sub-Saharan Africa: A Systematic Review.

INTRODUCTION: The World Health Organization recommends differentiated service delivery (DSD) to support resource-limited health systems in providing patient-centered HIV care. DSD offers alternative care models to clinic-based care for people living with HIV who are stable on antiretroviral therapy (ART). Despite good patient-related outcomes, there is limited evidence of their sustainability. Our review evaluated the reporting of sustainability indicators of DSD interventions conducted in sub-Saharan Africa (SSA). METHODS: We searched PubMed and EMBASE for studies conducted between 2000 and 2019 assessing DSD interventions targeting HIV-positive individuals who are established in ART in sub-Saharan Africa. We evaluated them through a comprehensive sustainability framework of constructs categorized into 6 domains (intervention design, process, external environment, resources, organizational setting, and people involvement). We scored each construct 1, 2, or 3 for no, partial, or sufficient level of evidence, respectively. Interventions with a calculated sustainability score (overall and domain-specific) of >90% or domain-specific median score >2.7 were considered likely to be sustainable. RESULTS: Overall scores ranged from 69% to 98%. Top scoring intervention types included adherence clubs (98%) and community ART groups (95%) which comprised more than half of interventions. The highest scoring domains were design (2.9) and organizational setting (2.8). The domains of resources (2.4) and people involvement (2.3) scored lowest revealing potential areas for improvement to support DSD sustainability. CONCLUSIONS: With the right investment in stakeholder involvement and domestic funding, DSD models generally show potential for sustainability. Our results could guide informed decisions on which DSD intervention is likely to be sustainable per setting and highlight areas that could motivate further research.

High patient acceptability but low coverage of provider-initiated HIV testing among adult outpatients with symptoms of acute infectious illness in coastal Kenya.

BACKGROUND: Only approximately one in five adults are offered HIV testing by providers when seeking care for symptoms of acute illness in Sub-Saharan Africa. Our aims were to estimate testing coverage and identify predictors of provider-initiated testing and counselling (PITC) and barriers to PITC implementation in this population. METHODS: We assessed HIV testing coverage among adult outpatients 18-39 years of age at four public and two private health facilities in coastal Kenya, during a 3- to 6-month surveillance period at each facility. A subset of patients who reported symptoms including fever, diarrhoea, fatigue, body aches, sore throat or genital ulcers were enrolled to complete a questionnaire independently of PITC offer. We assessed predictors of PITC in this population using generalised estimating equations and identified barriers to offering PITC through focus group discussion with healthcare workers (HCW) at each facility. RESULTS: Overall PITC coverage was 13.7% (1600 of 11,637 adults tested), with 1.9% (30) testing positive. Among 1,374 participants enrolled due to symptoms, 378 (27.5%) were offered PITC and 352 (25.6%) were tested, of whom 3.7% (13) tested positive. Among participants offered HIV testing, 93.1% accepted it; among participants not offered testing, 92.8% would have taken an HIV test if offered. The odds of completed PITC were increased among older participants (adjusted odds ratio [aOR] 1.7, 95% confidence interval [CI] 1.4-2.1 for 30-39 years, relative to 18-24 years), men (aOR 1.3, 95% CI 1.1-1.7); casual labourers (aOR 1.3, 95% CI 1.0-1.7); those paying by cash (aOR 1.2, 95% CI 1.0-1.4) or insurance (aOR 3.0, 95% CI 1.5-5.8); participants with fever (aOR 1.5, 95% CI 1.2-1.8) or genital ulcers (aOR 4.0, 95% CI 2.7-6.0); and who had tested for HIV >1 year ago (aOR 1.4, 95% CI 1.0-2.0) or had never tested (aOR 2.2, 95% CI 1.5-3.1). Provider barriers to PITC implementation included lack of HCW knowledge and confidence implementing guidelines, limited capacity and health systems constraints. CONCLUSION: PITC coverage was low, though most patients would accept testing if offered. Missed opportunities to promote testing during care-seeking were common and innovative solutions are needed.

Plasma Inflammatory Biomarkers Predict CD4+ T-cell Recovery and Viral Rebound in HIV-1 Infected Africans on Suppressive Antiretroviral Therapy.

This multicountry prospective study investigated whether persistent systemic inflammation, measured by 8 plasma biomarkers, in HIV-1-infected Africans during suppressive antiretroviral therapy (ART) (viral load <50 copies/mL), was associated with CD4+ T-cell recovery and viral rebound (>1000 copies/mL) during long-term treatment. On-ART sCD14 and C-reactive protein concentrations were inversely associated with subsequent CD4+ T-cell counts. Risk of viral rebound was increased for participants with higher on-ART CXCL10 concentrations and reduced for those with a greater sCD163 decline during the first year of ART. Persistent systemic inflammation predicted CD4+ T-cell recovery and viral rebound, warranting further mechanistic research in relation to clinical outcomes.

The impact of HIV-1 subtypes on virologic and immunologic treatment outcomes at the Lagos University Teaching Hospital: A longitudinal evaluation.

INTRODUCTION: HIV is a highly diverse virus with significant genetic variability which may confer biologic differences that could impact on treatment outcomes. MATERIALS AND METHODS: We studied the association between HIV subtypes and immunologic and virologic outcomes in a longitudinal cohort of 169 patients on combination antiretroviral therapy. Participants were followed up for 5 years. Demographic data, CD4 cell count and viral loads (VL) were extracted from medical records. Whole protease gene and codon 1-300 of the reverse transcriptase gene were sequenced and analysed. RESULTS: Sixty-four percent of participants were females with a median age of 35 years. Twelve different subtypes were observed, the commonest being CRF 02_AG (55.0%) and subtypes G (23.1%). All subtypes showed steady rise in CD4 count and there was no difference in proportion who achieved CD4+ cell count rise of ≥100 cells/µL from baseline within 12 months' post-initiation of ART, or ≥350 cells/µL at 60 months' post-initiation. Median time to attaining a rise of ≥350 cells/µL was 24 months (6-48 months). The proportion that achieved undetectable VL at month 6 and 12 post-initiation of ART were comparable across subtypes. At end of 5th year, there was no statistical difference in proportion with virologic failure. CONCLUSION: No association between HIV subtypes and immunologic or virologic response to therapy was observed, suggesting that current first-line ART may have similar efficacy across subtype predominating in South-West Nigeria.