Understanding health systems challenges in providing Advanced HIV Disease (AHD) care in a hub and spoke model: a qualitative analysis to improve AHD care program in Malawi.

BACKGROUND: Despite tremendous progress in antiretroviral therapy (ART) and access to ART, many patients have advanced human immunodeficiency virus (HIV) disease (AHD). Patients on AHD, whether initiating ART or providing care after disengagement, have an increased risk of morbidity and mortality. The Elizabeth Glaser Pediatric AIDS Foundation (EGPAF) launched an enhanced care package using a hub-and-spoke model to optimize AHD care in Malawi. This model improves supply availability and appropriate linkage to care. We utilized a hub-and-spoke model to share health facility challenges and recommendations on the AHD package for screening and diagnosis, prophylaxis, treatment, and adherence support. METHODS: This qualitative study assessed the facility-level experiences of healthcare workers (HCWs) and lay cadres (LCs) providing AHD services to patients through an intervention package. The study population included HCWs and LCs supporting HIV care at four intervention sites. Eligible study participants were recruited by trained Research Assistants with support from the health facility nurse to identify those most involved in supporting patients with AHD. A total of 32 in-depth interviews were conducted. Thematic content analysis identified recurrent themes and patterns across participants' responses. RESULTS: While HCWs and LCs stated that most medications are often available at both hub and spoke sites, they reported that there are sometimes limited supplies and equipment to run samples and tests necessary to provide AHD care. More than half of the HCWs stated that AHD training sufficiently prepared them to handle AHD patients at both the hub and spoke levels. HCWs and LCs reported weaknesses in the patient referral system within the hub-and-spoke model in providing a linkage of care to facilities, specifically improper referral documentation, incorrect labeling of samples, and inconsistent availability of transportation. While HCWs felt that AHD registers were time-consuming, they remained motivated as they thought they provided better patient services. CONCLUSIONS: These findings highlight the importance of offering comprehensive AHD services. The enhanced AHD program addressed weaknesses in service delivery through decentralization and provided services through a hub-and-spoke model, improved supply availability, and strengthened linkage to care. Additionally, addressing the recommendations of service providers and patients is essential to improve the health and survival of patients with AHD.

Building Integrated Testing Programs for Infectious Diseases.

In the past 2 decades, testing services for diseases such as human immunodeficiency virus (HIV), tuberculosis, and malaria have expanded dramatically. Investments in testing capacity and supportive health systems have often been disease specific, resulting in siloed testing programs with suboptimal capacity, reduced efficiency, and limited ability to introduce additional tests or respond to new outbreaks. Emergency demand for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) testing overcame these silos and demonstrated the feasibility of integrated testing. Moving forward, an integrated public laboratory infrastructure that services multiple diseases, including SARS-CoV-2, influenza, HIV, tuberculosis, hepatitis, malaria, sexually transmitted diseases, and other infections, will help improve universal healthcare delivery and pandemic preparedness. However, integrated testing faces many barriers including poorly aligned health systems, funding, and policies. Strategies to overcome these include greater implementation of policies that support multidisease testing and treatment systems, diagnostic network optimization, bundled test procurement, and more rapid spread of innovation and best practices across disease programs.

Understanding gender differences of people with HIV newly diagnosed or returning to care with advanced HIV disease in Malawi: a qualitative study.

BACKGROUND: Despite tremendous progress in improving antiretroviral therapy (ART) access, advanced HIV disease (AHD) still remains a challenge globally. Reasons for delayed presentation to care and ART adherence may be affected by gender. We present qualitative study findings on gender differences in decisions for HIV testing and ART initiation/adherence in adults with AHD in Malawi. METHODS: We used a qualitative study design, interviewing 16 men and 16 women aged 18 years and above diagnosed with AHD in sites implementing an optimized package of AHD care, from December 2021-February 2022. We included study participants receiving AHD services for at least two months. We also interviewed 16 lay workers and 16 health care workers supporting people living with AHD. In-depths interviews (IDIs) were conducted in English or Chichewa by trained research assistants using semi-structured interview guides. A short-answer analysis was conducted, and findings were interpreted according to thematic areas. RESULTS: Both men and women reported stigma as a main barrier influencing their decision to test for HIV and to initiate and adhere to ART. Fear of side effects, insufficient food, and the need for more information were other barriers reported among men and women as well as perceived as barriers by HCWs. Men appear to have tested later for HIV and stated that they were waiting until experiencing significant symptoms before testing. According to clients and HCWs, men were also less inclined to initiate ART after a HIV diagnosis, whereas women were motivated to start treatment to remain healthy and care for the family. Both genders reported that treatment could be delayed if they were feeling healthy. Treatment fatigue was reported among all groups as the main reason to discontinue treatment. CONCLUSIONS: There were similarities and differences between genders in decision-making about HIV care. Concerns about stigma were important reasons for delay in HIV care in both genders. Motivations for accessing HIV treatment and care were different among men and women, pushing the need for gender-tailored counseling services and community messaging that educate both men and women on the benefits of initiating ART early, in turn reducing the number of people presenting with AHD. TRIAL REGISTRATION: NCT05510973, first registration 22/08/2022.

Integrating pediatric TB services into child healthcare services in Africa: study protocol for the INPUT cluster-randomized stepped wedge trial.

BACKGROUND: Tuberculosis is among the top-10 causes of mortality in children with more than 1 million children suffering from TB disease annually worldwide. The main challenge in young children is the difficulty in establishing an accurate diagnosis of active TB. The INPUT study is a stepped-wedge cluster-randomized intervention study aiming to assess the effectiveness of integrating TB services into child healthcare services on TB diagnosis capacities in children under 5 years of age. METHODS: Two strategies will be compared: i) The standard of care, offering pediatric TB services based on national standard of care; ii) The intervention, with pediatric TB services integrated into child healthcare services: it consists of a package of training, supportive supervision, job aids, and logistical support to the integration of TB screening and diagnosis activities into pediatric services. The design is a cluster-randomized stepped-wedge of 12 study clusters in Cameroon and Kenya. The sites start enrolling participants under standard-of-care and will transition to the intervention at randomly assigned time points. We enroll children aged less than 5 years with a presumptive diagnosis of TB after obtaining caregiver written informed consent. The participants are followed through TB diagnosis and treatment, with clinical information prospectively abstracted from their medical records. The primary outcome is the proportion of TB cases diagnosed among children < 5 years old attending the child healthcare services. Secondary outcomes include: number of children screened for presumptive active TB; diagnosed; initiated on TB treatment; and completing treatment. We will also assess the cost-effectiveness of the intervention, its acceptability among health care providers and users, and fidelity of implementation. DISCUSSION: Study enrolments started in May 2019, enrolments will be completed in October 2020 and follow up will be completed by June 2021. The study findings will be disseminated to national, regional and international audiences and will inform innovative approaches to integration of TB screening, diagnosis, and treatment initiation into child health care services. TRIAL RESISTRATION: NCT03862261, initial release 12 February 2019.

Cost of Providing Advanced HIV Disease Treatment Services through Malawi's Hub-and-Spoke Model.

Antimicrobial prophylaxis and treatment of opportunistic infections immediately before or at the start of antiretroviral therapy (ART) improves prognosis and decreases death rates among patients with advanced HIV disease (AHD). In this study, we estimated the average cost per patient receiving AHD services (PP) and per client retained (PR) at 12 months. The study population included children, adolescents, and adults enrolled in the AHD program at 13 hub and 19 spoke sites in Malawi. To evaluate the cost PP and PR, we divided the cost of providing AHD services at 12 months by the total number of patients who received these services and who were retained in AHD services care at 12 months, respectively. We enrolled 246 AHD patients, with 137 retained at 12 months. The cost of providing AHD services to 246 patients at 12 months was $59,063; cost PP was $240, and cost PR was $431. Drugs were the largest expenditure (30%), followed by travel for supportive supervision (24%), clinic visit costs (19%), site support personnel (8%), laboratory tests (7%), annualized training costs (6%), consumables (3%), and meetings (3%). The cost of ART was $11,754; however, ART would be provided regardless of whether the AHD package was in place. Any reduction in overall costs of AHD care will require coordination among procurement partners and negotiations with manufacturers to help reduce the prices of drugs and laboratory consumables. This calls for further improvement of efficiency and capacity of site-level staff to reduce costs related to supportive supervision.

Assessment of knowledge and self-efficacy among health professionals and clinical scientists following the Cameroon HIV/AIDS Research Forum (CAM-HERO 2022) research methodology and bioethics training.

To inform public health policymakers that the generation of local evidence-based knowledge is key. Research capacity in low- and middle-income countries (LMIC) to generate medical knowledge is often weak and insufficiently resourced and efforts to tackle these challenges are not standardized. Continuous research training can equip researchers with the required knowledge and research skills, but its effectiveness largely depends on the quality and pertinence of the training methods used. We aim to assess the effectiveness of the Cameroon HIV/AIDS Research Forum (CAM-HERO) 2022 Research Methodology and Bioethics Training with the objective to describe the knowledge gained and the self-efficacy of health professionals and clinical scientists. A survey was conducted during the one-day training among health professionals and clinical scientists. Participants took an online self-administered questionnaire before and after the training related to the topics taught. The questionnaire consisted of two parts: 1) 18 Multiple Choice Questions (MCQs) to assess knowledge and 2) Nine items to evaluate self-efficacy using a five-point Likert scale. Mean scores were calculated, analysed, and compared using paired t-test for the pre- and post-test results. A total of 30 participants (57% women) completed the socio-demographic form. The median age (IQR) of participants was 33.5 (13.3) years. We registered 38 respondents for the pre-test and 33 respondents for the post-test. There was a rise in knowledge mean score from 13.0 to 14.8 (p=0.001) and an improvement in the perception of self-efficacy with a mean score increase from 2.9 to 3.7 (p < 0.001). Knowledge and perception of self-efficacy on research methodology improved among participants after the training. These results suggest that the CAM-HERO 2022 training had an immediate positive impact on skills and self-efficacy. Hence, we recommend the implementation of this training on a larger scale, periodically, and with long-term follow-up to evaluate its impact.

Effect of COVID-19 on paediatric TB service delivery and patients' comfort receiving TB services in Cameroon and Kenya during COVID: a qualitative assessment.

BACKGROUND: The outbreak of COVID-19 has caused a setback to the gains achieved in tuberculosis (TB) control by impairing TB diagnosis, delaying treatment initiation and aggravating TB deaths. This study explored the effect of COVID-19 on paediatric TB services provided through the Catalysing Paediatric TB Innovations (CaP-TB) project among caregivers of children receiving TB services and healthcare workers (HCWs) providing TB services in Cameroon and Kenya. METHODS: From March to September 2021, in-depth interviews (44) were conducted with caregivers whose children under 5 years had gone through TB services and programme managers (10) overseeing the CaP-TB project. Focus group discussions were conducted with HCWs (07) and community health workers (04) supporting TB care services. Transcripts were coded and analysed by using MAXQDA V.12. RESULTS: The COVID-19 pandemic has caused fear and anxiety among HCWs and caregivers. This fear was motivated by stigma related to COVID-19 and affected the ability to screen patients for TB due to the similarity of symptoms with COVID-19. The health-seeking behaviour of patients was affected, as many caregivers avoided hospitals and those accessing the facilities concealed their sickness due to fear of testing positive or being vaccinated. In addition, COVID-19 mitigation strategies implemented by both government and health facilities to curb the spread of the virus limited patient access to paediatric healthcare services. These included temporary closure of health facilities due to COVID-19 infections among staff, transfer of services to other spaces, spacing out patient appointments and reduced time spent with patients. CONCLUSIONS: The outbreak of COVID-19 has induced fear and stigma that affected patients' health-seeking behaviour and provider attitudes towards paediatric TB service delivery. In addition, facility and governmental measures put in place to mitigate COVID-19 impact negatively affected paediatric service delivery. Training for health personnel, timely provision of personal protective equipments and appropriate communication strategies could help mitigate COVID-19 impact on paediatric TB service delivery.

Follow-up Outcomes of Children, Adolescents and Young People on Darunavir-Based Third-line Antiretroviral Therapy - Observational Cohort from Nine African Countries.

BACKGROUND: We assessed clinical outcomes among children, adolescents and young people (< 25 years) on darunavir-based antiretroviral therapy (ART) in nine sub-Saharan African countries. SETTING: Third-line ART centers in Cameroon, Eswatini, Kenya, Lesotho, Nigeria, Rwanda, Uganda, Zambia and Zimbabwe. METHODS: From January 2019 to December 2022, we collected data from a cohort of children, adolescents and young people receiving third-line ART from 9 sub-Saharan African countries. Data on treatment continuity, viral suppression, death and clinic transfers were extracted from medical records and summarized. Cox proportional hazards models were used to identify factors independently associated with retention in care. RESULTS: Of 871 participants enrolled, median age 14.8 (range: 0.2 - 24.7) years, 488 (56.0%) male; 809 (92.9%) [median duration of follow-up of 28.3 months (IQR:17.5 - 45.2)] had final outcomes after initiating third-line ART. Of these, 711 (87.9%) were alive and in care at the end of study follow-up, 29 (3.6%) died, 30 (3.7%) transferred to other facilities, and 39 (4.8%) were lost to follow-up. Retention in care was less likely among males compared to females (aHR: 0.85, 95%CI 0.72-1.0), and in 10-14-year-olds compared to younger children. Adolescents (15-19 years) had higher mortality compared to children <10 years of age (aSHR: 4.20, 95% CI 1.37-12.87). Viral suppression was seen in 345/433 (79.7%), 249/320 (77.8%), and 546/674 (81.0%) patients with results at 6, 12 months and study end, respectively. CONCLUSION: A high proportion of children and young people receiving third-line ART in Sub-Saharan Africa, remain in care, and attain viral suppression during follow-up.

Improving COVID-19 contact tracing and testing of exposed individuals in Cameroon using digital health technology: a cluster randomised trial.

Background: Contact tracing was described as a key strategy to contribute to controlling the spread of severe acute respiratory syndrome of Coronavirus 2 (SARS-CoV-2) but implementing it can be a challenge. Digitalisation of contact tracing is among the proposed solutions being explored in sub-Saharan African settings. We assessed the effectiveness of a digital tool to expand SARS-CoV-2 testing in exposed individuals in Cameroon. Methods: We conducted a cluster-randomised (1:1) trial in eight health districts, including 22 facilities and SARS-CoV-2 testing units, randomly assigned to a digital (intervention) or standard (control) contact tracing approach. The intervention consisted of a contact tracing module added to the digital platform "Mamal PRO" used for monitoring and coordination of Coronavirus Disease 2019 pandemic response in Cameroon. The primary outcome was the proportion of contacts declared by SAR-CoV-2 index patients who were successfully traced and tested for SARS-CoV-2 evaluated with a Poisson regression model with cluster adjustment. This study is registered with ClinicalTrials.gov (NCT05684887). Findings: Between October 18, 2022, and March 31, 2023, we enrolled 164 index patients in the intervention arm and 149 in the control arm, who identified 854 and 849 contacts, respectively. In the intervention arm, 93.8% (801/854) of identified contacts were successfully reached by the tracing unit versus 54.5% (463/849) in the control arm. The intervention significantly increased the likelihood of successfully tracing contacts (adjusted relative risks (RR) 1.72 [95% CI: 1.00-2.95], p = 0.049). The median (interquartile range, IQR) time to successfully tracing contacts was 0 days [IQR: 0, 1] in the intervention and 1 day [IQR: 0, 2] in the control arm. In the intervention arm, 21.3% (182/854) of identified contacts received SARS-CoV-2 testing compared to 14.5% (123/849) in the control arm (adjusted RR 1.47 [95% CI: 0.44-4.90], p = 0.530). Interpretation: Digitalising the contact tracing process improved exposure notification and facilitated the tracing of a greater number of contacts of individuals infected with SARS-CoV-2 in resource-limited settings. Funding: The study was funded by FIND, United Kingdom (FCDO 40105983), Switzerland (81066910), Netherlands (SDD 4000004160), Canada (DFATD 7429348), The Kingdom of Saudi Arabia (FIND-ACT-A DX PARTNERSHIP 20.08.2020), The Rockefeller Foundation (2020 HTH 059), Germany (BMZ Covid-19 Diagnostic and Surveillance Response 27.07.2021), Australia (DFAT 76442), Kuwait (M239/2020), The Government of Portugal and Partners (ANF, BCP, CGF, APIFARMA) and The BlackRock Foundation (Grant Agreement as of April 20, 2022).

Rapid antiretroviral therapy initiation in patients with advanced HIV disease: 6-month outcomes of an observational cohort evaluation in Lesotho.

For adults and adolescents, the World Health Organization defines advanced HIV disease (AHD) as a CD4 (cluster of differentiation 4) count of <200 cells/mm3 or a clinical stage 3 or 4 event. We describe clinical outcomes in a cohort of AHD patients at two regional hospitals in Lesotho. From November 2018-June 2019, we prospectively enrolled eligible patients (≥15 years) not on antiretroviral therapy (ART) presenting with WHO-defined AHD into a differentiated model of care for AHD (including rapid ART initiation) and followed them for six months. All patients received Tuberculosis (TB) symptom screening with further diagnostic testing; serum cryptococcal antigen (CrAg) screening was done for CD4 <100 cells/mm3 or WHO clinical stage 3 or 4. Medical record data were abstracted using visit checklist forms. Categorical and continuous variables were summarized using frequencies, percentages, and means, respectively. Kaplan-Meier was used to estimate survival. Of 537 HIV-positive patients screened, 150 (27.9%) had AHD of which 109 were enrolled. Mean age was 38 years and 62 (56.9%) were men. At initial clinic visit, 8 (7.3%) were already on treatment and 33% (36/109) had presumptive TB per symptom screening. Among 39/109 (40.2%) patients screened for CrAg at initial visit, five (12.8%) were CrAg-positive. Among 109 enrolled, 77 (70.6%) initiated ART at their initial clinic visit, while 32 delayed ART initiation (median delay: 14 days). Of the 109 participants enrolled, 76 (69.7%) completed the 6-month follow-up, 17 (15.6%) were lost to follow-up, 5 (4.6%) transferred to other health facilities and 11 (10.1%) died. The 6-month survival was 87.4%; among 74 patients with a viral load result, 6-month viral suppression (<1,000 copies/ml) was 85.1%. Our study found that even after the implementation of Test and Treat of ART in 2016 in Lesotho, over 25% of patients screened had AHD. Patients with AHD had a high prevalence of TB and CrAg positivity, underscoring the need to assess for AHD and rapidly initiate ART within a package of AHD care for optimal patient outcomes.

Research for Health Care and Policy on HIV/AIDS: proceedings of the third edition of the Cameroon HIV Research (CAM-HERO) 2022, Kribi, Cameroon, from 1st to 3rd December 2022.

Cameroon is committed to reaching HIV epidemic control through coordinated efforts by the Ministry of Public Health, the National AIDS Control Committee, bilateral/multilateral institutions and implementing partners. The third edition of the Cameroon HIV Research Forum (CAM-HERO) was held in Kribi from December 1st to 3rd, 2022, with the theme "Research for Health Care and Policy on HIV/AIDS." The conference brought together local and international scientists and clinicians, policymakers, and regulatory authorities to 1) disseminate HIV research findings and HIV policy; 2) foster operational research collaboration; 3) build research capacity through training on basics of research methods and CAM-HERO young investigator Awards; and 4) initiate a guideline for promoting HIV/AIDS research in Cameroon. The main activities included training on research methodology and basic principles in bioethics, presentations of selected abstracts, and awards for top research. A total of 35 abstracts (16 oral presentations, 16 posters, and 3 late-breaker-abstracts) were selected for presentation following a rigorous review. The conference ended with evidence-based recommendations and a way-forward statement for the development of a National Guide for HIV/AIDS research in Cameroon, with the aim of improving the quality and quantity of research agenda and projects nationwide.

Clinical outcomes among adolescents living with HIV in Kenya following initiation on antiretroviral treatment.

In Kenya, HIV/AIDS remains a leading cause of morbidity and mortality among adolescents living with HIV (ALHIV). Our study evaluated associations between demographic and healthcare factors and HIV treatment outcomes among ALHIV in care in Kenya. This retrospective cohort study evaluated the clinical outcomes of newly diagnosed ALHIV enrolled in HIV care during January 2017-June 2018 at 32 healthcare facilities in Homabay and Kakamega Counties. Demographic and clinical data were abstracted from patient clinical records and registers during the follow up study period January 2017-through May 2019. ALHIV were stratified by age (10-14 versus 15-19 years). Categorical variables were summarized using descriptive statistics; continuous variables were analyzed using mean values. The latest available treatment and virological outcomes for ALHIV were assessed. 330 ALHIV were included in the study (mean age 15.9 years; 81.8% female, 63.0% receiving HIV care at lower-level healthcare facilities). Most (93.2%) were initiated on ART within 14 days of diagnosis; 91.4% initiated EFV-based regimens. Of those on ART, only 44.6% were active on care at the end of the study period. Of those eligible for viral load testing, 83.9% were tested with 84.4% viral suppression rate. Retention in care was higher at higher-level facilities (67.5%) compared to lower-level facilities (28.6%). Factors associated with higher retention in care were school attendance (aRR = 1.453), receipt of disclosure support (aRR = 13.315), and receiving care at a high-level health facility (aRR = 0.751). Factors associated with viral suppression included older age (15-19 years) (aRR = 1.249) and pre-ART clinical WHO stage I/II (RR = .668). Viral suppression was higher among older ALHIV. Studies are needed to evaluate effective interventions to improve outcomes among ALHIV in Kenya.

Evidence for an enhanced HIV/AIDS policy and care in Cameroon: proceedings of the second Cameroon HIV Research Forum (CAM-HERO) 2021.

To attain the HIV 95-95-95 goals by 2030 in Cameroon, high quality research to inform policy and patient care is of utmost importance. In the context of limited workforce and resources, collaborations, sharing of locally-adapted strategies and other field experience, leveraging on existing and innovative platforms would facilitate a coordinated and optimal AIDS response at country level. The second edition of the Cameroon HIV Research Forum (CAM-HERO) conference took place both physically and virtually on November 18 and 19, 2021 in Kribi, on the theme "Research for Policy and Care". This scientific event brought together Cameroonian HIV/AIDS researchers, experienced clinicians and regulatory authorities to foster i) the dissemination of research findings and facilitate translation into policy, ii) operational research collaboration, iii) identification of new research areas, and iv) capacity building. To achieve the set objectives during this event, a consensus on research priorities for accelerating the achievement of three 95 HIV goals in Cameroon were summarized; meeting sessions included 31 abstract presentations, 13 discussions, and presentations on various aspects of HIV research including ethics, administrative procedures and needs for capacity building; training of young scientists on guidelines for research proposal development toward ethical clearance was done; and a platform for discussion between researchers and regulatory authorities was conducted around the design and setting-up of a national HIV/AIDS research agenda. CAM-HERO 2021 brought together HIV researchers, experts and junior scientists around major programmatic challenges, evidence to translate into practice, research priorities on HIV/AIDS. Collaborations were reinforced, capacities were strengthened, and footprints were established towards a consensus on a national HIV/AIDS research agenda.

Strategic site selection for placement of HIV early infant diagnosis point-of-care technology within a national diagnostic network in Lesotho.

BACKGROUND: New technologies for rapid point-of-care (POC) diagnostic tests hold great potential for improving the health outcomes of HIV-exposed infants. POC testing for HIV early infant diagnosis (EID) was introduced in Lesotho in late 2016. Here we highlight critical requirements for selecting routine POC EID sites to ensure a sustainable and optimised EID diagnostic network. INTERVENTION: Lesotho introduced POC EID in a phased approach that included assessments of national databases to identify sites with high test volumes, the creation of local networks of sites to potentially increase access to POC EID, and a standardised capacity assessment to determine site readiness. Potential site networks comprising 'hub' testing sites and 'spoke' specimen referring sites were created. LESSONS LEARNT: After determining optimal placement, a total of 29 testing facilities were selected for placement of POC EID to potentially increase access to 189 facilities through the use of a hub-and-spoke model. Site capacity assessments identified vital human resources and infrastructure capacity gaps that needed to be addressed before introducing POC EID and informed appropriate POC platform selection. RECOMMENDATIONS: POC placement involves more than just purchasing the testing platforms. Considering the relatively small proportion of sites that can be eligible for placement of a POC platform, utilising a hub-and-spoke model can maximise the number of health facilities served by a POC platform while reducing the necessary capacity building and infrastructure investments to fewer sites.

Community-based differentiated service delivery models incorporating multi-month dispensing of antiretroviral treatment for newly stable people living with HIV receiving single annual clinical visits: a pooled analysis of two cluster-randomized trials in southern Africa.

INTRODUCTION: Differentiated service delivery (DSD) models for HIV treatment decrease health facility visit frequency and limit healthcare facility-based exposure to severe acute respiratory syndrome coronavirus 2. However, two important evidence gaps include understanding DSD effectiveness amongst clients commencing DSD within 12 months of antiretroviral treatment (ART) initiation and amongst clients receiving only single annual clinical consultations. To investigate these, we pooled data from two cluster-randomized trials investigating community-based DSD in Zimbabwe and Lesotho. METHODS: Individual-level participant data of newly stable adults enrolled between 6 and 12 months after ART initiation were pooled. Both trials (conducted between August 2017 and July 2019) had three arms: Standard-of-care three-monthly ART provision at healthcare facilities (SoC, control); ART provided three-monthly in community ART groups (CAGs) (3MC) and ART provided six-monthly in either CAGs or at community-distribution points (6MC). Clinical visits were three-monthly in SoC and annually in intervention arms. The primary outcome was retention in care and secondary outcomes were viral suppression (VS) and number of unscheduled facility visits 12 months after enrolment. Individual-level regression analyses were conducted by intention-to-treat specifying for clustering and adjusted for country. RESULTS AND DISCUSSION: A total of 599 participants were included; 212 (35.4%), 128 (21.4%) and 259 (43.2%) in SoC, 3MC and 6MC, respectively. Few participants aged <25 years were included (n = 32). After 12 months, 198 (93.4%), 123 (96.1%) and 248 (95.8%) were retained in SoC, 3MC and 6MC, respectively. Retention in 3MC was superior versus SoC, adjusted risk difference (aRD) = 4.6% (95% CI: 0.7%-8.5%). Retention in 6MC was non-inferior versus SoC, aRD = 1.7% (95% CI: -2.5%-5.9%) (prespecified non-inferiority aRD margin -3.25%). VS was similar between arms, 99.3, 98.6 and 98.1% in SoC, 3MC and 6MC, respectively. Adjusted risk ratio's for VS were 0.98 (95% CI: 0.92-1.03) for 3MC versus SoC, and 0.98 (CI: 0.95-1.00) for 6MC versus SoC. Unscheduled clinic visits were not increased in intervention arms: incidence rate ratio = 0.53 (CI: 0.16-1.80) for 3MC versus SoC; and 0.82 (CI: 0.25-2.79) for 6MC versus SoC. CONCLUSIONS: Community-based DSD incorporating three- and six-monthly ART refills and single annual clinical visits were at least non-inferior to standard facility-based care amongst newly stable ART clients aged ≥25 years. ClinicalTrials.gov: NCT03238846 & NCT03438370.

Economic evaluation of differentiated service delivery models for HIV treatment in Lesotho: costs to providers and patients.

INTRODUCTION: Lesotho, the country with the second-highest HIV/AIDS prevalence (23.6%) in the world, has made considerable progress towards achieving the "95-95-95" UNAIDS targets, but recent success in improving treatment access to all known HIV positive individuals has severely strained existing healthcare infrastructure, financial and human resources. Lesotho also faces the challenge of a largely rural population who incur a significant time and financial burden to visit healthcare facilities. Using data from a cluster-randomized non-inferiority trial conducted between August 2017 and July 2019, we evaluated costs to providers and costs to patients of community-based differentiated models of multi-month delivery of antiretroviral therapy (ART) in Lesotho. METHODS: The trial of multi-month dispensing compared 12-month retention in care among three arms: conventional care, which required quarterly facility visits and ART dispensation (3MF); three-month community adherence groups (CAGs) (3MC) and six-month community ART distribution (6MCD). We first estimated the average total annual cost of providing HIV care and treatment followed by the total cost per patient retained 12 months after entry for each arm, using resource utilization data from the trial and local unit costs. We then estimated the average annual cost to patients in each arm with self-reported questionnaire data. RESULTS: The average total annual cost of providing HIV care and treatment per patient was the highest in the 3MF arm ($122.28, standard deviation [SD] $23.91), followed by 3MC ($114.20, SD $23.03) and the 6MCD arm ($112.58, SD $21.44). Per patient retained in care, the average provider cost was $125.99 (SD $24.64) in the 3MF arm and 6% to 8% less for the other two arms ($118.38, SD $23.87 and $118.83, SD $22.63 for the 3MC and 6MCD respectively). There was a large reduction in patient costs for both differentiated service delivery arms: from $44.42 (SD $12.06) annually in the 3MF arm to $16.34 (SD $5.11) annually in the 3MC (63% reduction) and $18.77 (SD $8.31) annually in 6MCD arm (58% reduction). CONCLUSIONS: Community-based, multi-month models of ART in Lesotho are likely to produce small cost savings to treatment providers and large savings to patients in Lesotho. Patient cost savings may support long-term adherence and retention in care.

Adverse Pregnancy Outcomes Among HIV-positive Women in the Era of Universal Antiretroviral Therapy Remain Elevated Compared With HIV-negative Women.

BACKGROUND: Without treatment, HIV infection in pregnant women is associated with adverse pregnancy outcomes. We compared adverse pregnancy outcomes among HIV-positive women on antiretroviral therapy (ART) and HIV-negative women who enrolled for antenatal care in selected health facilities in Maseru district, Lesotho. METHODS: We enrolled a cohort of HIV-positive and HIV-negative women at their first antenatal visit and followed them through delivery. Study data on miscarriage, stillbirth, preterm birth, low birth weight and birth defects were collected through participant interviews and medical record abstraction. We used the Rao-Scott χ2 test and the t test to assess differences in characteristics and outcomes between HIV-positive and HIV-negative women and generalized estimating equations for multivariable analysis. RESULTS: A total of 614 HIV-positive and 390 HIV-negative pregnant women were enrolled in the study with delivery information on 571 (93.1%) and 352 (90.3%) respectively. In the delivery cohort, the median age at enrolment was 28 years for HIV-positive women and 23 years for HIV-negative women with median gestational ages of 20 and 21 weeks, respectively. A total of 149 singleton pregnancies had documented adverse pregnancy outcomes; 33 (9.6%) HIV-negative pregnancies and 116 (20.6%) HIV-positive pregnancies. Compared with their HIV-negative counterparts, HIV-positive women were more likely to experience an adverse pregnancy outcome, adjusted odds ratio (AOR) 2.6 [95% confidence interval (CI): 1.71-3.97]; an intrauterine death (miscarriage or stillbirth), AOR 2.64 [95% CI: 1.25-5.49]; or a low birth weight delivery, AOR 1.89 [95% CI: 1.16-3.09]. CONCLUSION: Adverse pregnancy outcomes remained 2-3 times higher among HIV-positive women compared with HIV-negative women despite universal ART.

Out-of-Facility Multimonth Dispensing of Antiretroviral Treatment: A Pooled Analysis Using Individual Patient Data From Cluster-Randomized Trials in Southern Africa.

BACKGROUND: Out-of-facility multi-month dispensing (MMD) is a differentiated service delivery model which provides antiretroviral treatment (ART) at intervals of up to 6 monthly in the community. Limited randomized evidence investigating out-of-facility MMD is available. We evaluated participant outcomes and compared out-of-facility MMD models using data from cluster-randomized trials in Southern Africa. SETTING: Eight districts in Zimbabwe and Lesotho. METHODS: Individual-level participant data from 2 cluster-randomized trials that included stable adults receiving ART at 60 facilities were pooled. Both trials had 3 arms: ART collected 3-monthly at healthcare facilities (3MF, control); ART provided three-monthly in community ART groups (CAGs) (3MC); and ART provided 6-monthly in either CAGs or on an individual provider-patient basis (6MC). Participant retention, viral suppression and incidence of unscheduled facility visits were compared. RESULTS: Ten thousand one hundred thirty-six participants were included, 3817 (37.7%), 2893 (28.5%) and 3426 (33.8%) in arms 3MF, 3MC and 6MC, respectively. After 12 months, retention was non-inferior for 3MC (95.7%) vs. 3MF (95.0%) {adjusted risk difference (aRD) = 0.3 [95% confidence interval (CI): -0.8 to 1.4]}; and 6MC (95.1%) vs. 3MF [aRD = -0.2 (95% CI: -1.4 to 1.0)]. Retention was greater amongst intervention arm participants in CAGs versus 6MC participants not in CAGs, aRD = 1.5% (95% CI: 0.2% to 2.9%). Viral suppression was excellent (≥98%) and unscheduled facility visits were not increased in the intervention arms. CONCLUSIONS: Three and 6-monthly out-of-facility MMD was non-inferior versus facility-based care for stable ART patients. Out-of-facility 6-monthly MMD should incorporate small group peer support whenever possible. CLINICALTRIAL REGISTRATION: ClinicalTrials.gov NCT03238846 and NCT03438370.

24-Month HIV-free survival among HIV-exposed Infants in Lesotho: the PEAWIL cohort study.

INTRODUCTION: Following the implementation of the provision of lifelong antiretroviral therapy to all HIV-positive pregnant or breastfeeding women for prevention of mother-to-child transmission (PMTCT) of HIV by the Kingdom of Lesotho in 2013, we assessed the effectiveness of this approach by evaluating 24-month HIV-free survival among HIV-exposed infants (HEIs). METHODS: We conducted a prospective observational cohort study that enrolled HIV-positive and HIV-negative pregnant women, with follow-up of women and their infants for 24 months after delivery. Participant recruitment started in June 2014 and follow-up ended in September 2018. Trained nurses collected study information through patient interviews and chart abstraction at enrolment and every three to six months thereafter. Maternal HIV testing, infant mortality, HIV transmission and HIV-free survival rates were computed using Kaplan-Meier estimation. Cox regression hazard models were used to identify factors associated with infant HIV infection and death. RESULTS: Between June 2014 and February 2016, we enrolled 653 HIV-positive and 941 HIV-negative pregnant women. Twenty-seven HIV-negative women acquired HIV during follow-up. Ultimately, 634 liveborn HEI (382 (52%) male, 303 (48%) female, 3 missing) and 839 who remained HIV-unexposed (HUIs) (409 (49.0%) male, 426 (51.0%) female, 4 missing) were followed; 550 HEIs and 701 HUIs completed the 24-month follow-up period. Of 607 (95.7%) HEIs who were tested for HIV at least once during follow-up, 17 were found to be HIV-positive. Two (9.5%) of 21 infants born to mothers who acquired HIV infection during follow-up were HIV-positive compared to 15 (2.4%) of 613 HEI born to women with known HIV infection. The risk of HIV transmission from HIV-positive mothers to their infants by 24 months of age was 2.9% (95% CI: 1.8 to 4.7). The estimated 24-month mortality rate among HEIs was 6.0% (95% CI: 4.4 to 8.2) compared to 3.8% (95% CI: 2.6 to 5.3) among HUIs (Log-rank p = 0.065). HIV-free survival at 24 months was 91.8% (95% CI: 89.2 to 93.7). Lower maternal age and birth weight were independently associated with increased HIV infection or death of infants. CONCLUSIONS: The implementation of lifelong ART for PMTCT in the Lesotho public health system resulted in low HIV transmission, but survival of HEI remains lower than their HIV uninfected counterparts.

18-24-month HIV-free survival as measurement of the effectiveness of prevention of mother-to-child transmission in the context of lifelong antiretroviral therapy: Results of a community-based survey.

INTRODUCTION: Population-based HIV-free survival at 18-24 months of age among HIV-exposed infants in high prevalence settings in the era of treatment for all is largely unknown. We conducted a community-based survey to determine outcomes of HIV-exposed infants at 18-24 months in Lesotho. METHODS: Between November 2015 and December 2016, we conducted a survey among households with a child born 18-24 months prior to data collection. Catchment areas from 25 health facilities in Butha-Buthe, Maseru, Mohale's Hoek and Thaba-Tseka districts were randomly selected using probability proportional to size sampling. Consecutive households were visited and eligible consenting caregivers and children were enrolled. Rapid HIV antibody testing was performed on mothers of unknown HIV status (never tested or tested HIV-negative >3 months prior) and their children, and to children born to known HIV-positive mothers. Information on demographics, health-seeking behavior, HIV, and mortality were captured for mothers and children, including those who died. The difference in survival between subgroups was determined using the log-rank test. RESULTS: Of the 1,852 mothers/caregivers enrolled, 570 mothers were HIV-positive. The mother-to-child HIV transmission rate was 5.7% [95% CI: 4.0-8.0]. The mortality rate was 2.6% [95% CI: 1.6-4.2] among HIV-exposed children compared to 1.4% (95% CI: 0.9-2.3) among HIV-unexposed children. HIV-free survival was 91.8% [95% CI: 89.2-93.8] among HIV-exposed infants. Disclosure of mother's HIV status (aOR = 4.9, 95% CI: 1.3-18.2) and initiation of cotrimoxazole prophylaxis in the child (aOR = 3.9, 95% CI: 1.2-12.6) were independently associated with increased HIV-free survival while child growth problems (aOR = 0.2, 95% CI: 0.09-0.5) were independently associated with reduced HIV-free survival. CONCLUSION: Even in the context of lifelong antiretroviral therapy among pregnant and breastfeeding women, HIV has a significant effect on survival among HIV-exposed children compared to unexposed children. Lesotho has not reached elimination of HIV transmission from mother to child.