Resistance-informed versus empirical management of viraemia in children and adolescents with HIV in Lesotho and Tanzania (GIVE MOVE trial): a multisite, open-label randomised controlled trial.

BACKGROUND: Children and adolescents with HIV taking antiretroviral therapy (ART) have high rates of viraemia. We assessed if genotypic resistance testing (GRT) to inform onward treatment improved treatment outcomes in Lesotho and Tanzania, two countries with little access to GRT. METHODS: The Genotype-Informed Versus Empirical Management of Viremia (GIVE MOVE) open-label, parallel-group randomised controlled trial enrolled children and adolescents with HIV between the ages of 6 months and 19 years, taking ART, and with a viral load at least 400 copies per mL. Participants were recruited from ten clinical centres and hospitals in Lesotho and Tanzania. Participants were electronically randomly allocated 1:1 to receive either GRT with expert recommendation (GRT group) or repeat viral-load testing and empirical onward treatment (usual care group). Participants and study staff were not masked, but the endpoint committee and laboratory staff conducting viral-load testing were. Participants in both groups received at least three sessions of enhanced adherence counselling, and in the GRT group, blood for GRT assessed via Sanger sequencing was drawn at enrolment. The composite primary endpoint was death, hospitalisation, a new WHO HIV clinical stage 4 event, or not having documented viral suppression of less than 50 copies per mL at 36 weeks in the modified intention-to-treat population, which excluded participants who were retrospectively found to be ineligible after randomisation. Serious adverse events were analysed in the modified intention-to-treat population. The trial was registered with ClinicalTrials.gov (NCT04233242) and the trial status is completed. FINDINGS: Between March 3, 2020, and July 5, 2022, 286 participants were enrolled and 284 were included in the modified intention-to-treat analysis (144 in the GRT group and 140 in the usual care group). Of these participants, 158 (56%) were female and 126 (44%) were male. Five (3%) in the GRT group and four (3%) in the usual care group did not complete follow-up but were included in the primary analysis. The median age across both groups was 14 years (IQR 9-16). The composite primary endpoint occurred in 67 (47%) participants in the GRT group and 73 (52%) in the usual care group (adjusted odds ratio 0·79 [95% CI 0·49 to 1·27]; adjusted risk difference -0·06 [95% CI -0·17 to 0·06]; p=0·34); all participants reaching the composite primary endpoint had no documented viral suppression at 36 weeks. No deaths were recorded, and only one clinical stage 4 event requiring hospitalisation occurred (in the usual care group); this was the only serious adverse event recorded in the study. INTERPRETATION: GRT-informed management did not significantly improve treatment outcomes for children and adolescents with viraemia while taking ART. FUNDING: Fondation Botnar, Swiss National Science Foundation, and Gottfried and Julia Bangerter-Rhyner Foundation. TRANSLATIONS: For the Sesotho and Swahili translations of the abstract see Supplementary Materials section.

Characteristics, consent patterns, and challenges of randomized trials using the Trials within Cohorts (TwiCs) design A scoping review.

OBJECTIVE: Trials within Cohorts (TwiCs) is a pragmatic design approach that may overcome frequent challenges of traditional randomized trials such as slow recruitment, burdensome consent procedures, or limited external validity. This scoping review aims to identify all randomized controlled trials using the TwiCs design and to summarize their design characteristics, ways to obtain informed consent, output, reported challenges and mitigation strategies. STUDY DESIGN AND SETTING: Systematic search of Medline, Embase, Cochrane, trial registries and citation tracking up to December 2022. TwiCs were defined as randomized trials embedded in a cohort with post-randomization consent for the intervention group and no specific post-randomization consent for the usual care control group. Information from identified TwiCs were extracted in duplicate from protocols, publications, and registry entries. We analyzed the information descriptively and qualitatively to highlight methodological challenges and solutions related to non-uptake of interventions and informed consent procedure. RESULTS: We identified a total of 46 TwiCs conducted between 2005 and 2022 in 14 different countries by a handful of research groups. The most common medical fields were oncology (11/46; 24%), infectious diseases (8/46;17%), and mental health (7/46; 15%). A typical TwiCs was investigator-initiated (46/46;100%), publicly funded (36/46; 78%), and recruited outpatients (27/46; 59%). Excluding eight pilot trials, only 16/38 (42%) TwiCs adjusted their calculated sample size for non-uptake of the intervention, anticipating a median non-uptake of 25% (interquartile range 10%-32%) in the experimental arm. Seventeen TwiCs (45%) planned analyses to adjust effect estimates for non-uptake. Regarding informed consent, we observed three patterns: 1) three separate consents for cohort participation, randomization, and intervention (17/46; 37%); 2) combined consent for cohort participation and randomization and a separate intervention consent (10/46; 22%); and 3) consent only for cohort participation and intervention (randomization consent not mentioned; 19/46; 41%). CONCLUSIONS: Existing TwiCs are globally scattered across a few research groups covering a wide range of medical fields and interventions. Despite the potential advantages, the number of TwiCs remains small. The variability in consent procedures and the possibility of substantial non-uptake of the intervention warrants further research to guide the planning, implementation, and analysis of TwiCs.

Antibody and T-cell response to bivalent booster SARS-CoV-2 vaccines in people with compromised immune function (COVERALL-3).

BACKGROUND: Bivalent mRNA vaccines, designed to combat emerging SARS-CoV-2 variants, incorporate ancestral strains and a new variant. Our study assessed the immune response in previously vaccinated individuals of the Swiss HIV Cohort Study (SHCS) and the Swiss Transplant Cohort Study (STCS) following bivalent mRNA vaccination. METHODS: Eligible SHCS and STCS participants received approved bivalent mRNA SARS-CoV-2 vaccines (mRNA-1273.214 or BA.1-adapted BNT162b2) within clinical routine. Blood samples were collected at baseline, 4 weeks, 8 weeks, and 6 months post vaccination. We analyzed the proportion of participants with anti-spike protein antibody response ≥1642 units/ml (indicating protection against SARS-CoV-2 infection), and in a subsample T-cell response (including mean concentrations), stratifying results by cohorts and population characteristics. RESULTS: In SHCS participants, baseline anti-spike antibody concentrations ≥1642 were observed in 87% (96/112), reaching nearly 100% at follow-ups. Among STCS participants, 58% (35/60) had baseline antibodies ≥1642, increasing to 80% at 6 months. Except for lung transplant recipients, all participants showed a five-fold increase in geometric mean antibody concentrations at 4 weeks and a reduction by half at 6 months. At baseline, T-cell responses were positive in 96% (26/27) of SHCS participants and 36% (16/45) of STCS participants (moderate increase to 53% at 6 months). Few participants reported SARS-CoV-2 infections, side-effects, or serious adverse events. CONCLUSIONS: Bivalent mRNA vaccination elicited a robust humoral response in individuals with HIV or solid organ transplants, with delayed responses in lung transplant recipients. Despite a waning effect, antibody levels remained high at 6 months and adverse events were rare.

Community-based management of arterial hypertension and cardiovascular risk factors by lay village health workers for people with controlled and uncontrolled blood pressure in rural Lesotho: joint protocol for two cluster-randomized trials within the ComBaCaL cohort study (ComBaCaL aHT Twic 1 and ComBaCaL aHT TwiC 2).

BACKGROUND: Arterial hypertension (aHT) is a major cause for premature morbidity and mortality. Control rates remain poor, especially in low- and middle-income countries. Task-shifting to lay village health workers (VHWs) and the use of digital clinical decision support systems may help to overcome the current aHT care cascade gaps. However, evidence on the effectiveness of comprehensive VHW-led aHT care models, in which VHWs provide antihypertensive drug treatment and manage cardiovascular risk factors is scarce. METHODS: Using the trials within the cohort (TwiCs) design, we are assessing the effectiveness of VHW-led aHT and cardiovascular risk management in two 1:1 cluster-randomized trials nested within the Community-Based chronic disease Care Lesotho (ComBaCaL) cohort study (NCT05596773). The ComBaCaL cohort study is maintained by trained VHWs and includes the consenting inhabitants of 103 randomly selected villages in rural Lesotho. After community-based aHT screening, adult, non-pregnant ComBaCaL cohort participants with uncontrolled aHT (blood pressure (BP) ≥ 140/90 mmHg) are enrolled in the aHT TwiC 1 and those with controlled aHT (BP < 140/90 mmHg) in the aHT TwiC 2. In intervention villages, VHWs offer lifestyle counseling, basic guideline-directed antihypertensive, lipid-lowering, and antiplatelet treatment supported by a tablet-based decision support application to eligible participants. In control villages, participants are referred to a health facility for therapeutic management. The primary endpoint for both TwiCs is the proportion of participants with controlled BP levels (< 140/90 mmHg) 12 months after enrolment. We hypothesize that the intervention is superior regarding BP control rates in participants with uncontrolled BP (aHT TwiC 1) and non-inferior in participants with controlled BP at baseline (aHT TwiC 2). DISCUSSION: The TwiCs were launched on September 08, 2023. On May 20, 2024, 697 and 750 participants were enrolled in TwiC 1 and TwiC 2. To our knowledge, these TwiCs are the first trials to assess task-shifting of aHT care to VHWs at the community level, including the prescription of basic antihypertensive, lipid-lowering, and antiplatelet medication in Africa. The ComBaCaL cohort and nested TwiCs are operating within the routine VHW program and countries with similar community health worker programs may benefit from the findings. TRIAL REGISTRATION: ClinicalTrials.gov NCT05684055. Registered on January 04, 2023.

Diphtheria in a Swiss Asylum Seeker Reception Centre: Outbreak Investigation and Evaluation of Testing and Vaccination Strategies.

Objectives: To describe a suspected diphtheria outbreak in a Swiss asylum seeker reception centre, and to analyse its management response regarding testing and vaccination. Methods: We retrospectively analysed clinical, microbiology, and case management data of all asylum seekers tested for C. diphtheriae between 28th August and 31st December 2022 while residing at the centre. Results are reported descriptively. Results: Among 265 individuals tested, ten cases of cutaneous diphtheria, one simultaneous respiratory and cutaneous case, and nine respiratory carriers were identified. Mass throat screening, targeted throat testing and targeted wound testing yielded 4.8%, 4.3%, and 17.4% positive results, respectively. No respiratory carrier was identified among cutaneous cases undergoing a throat swab, and no symptomatic case was identified among individuals with unspecific throat symptoms. Rates of vaccination implementation of newly arriving asylum seekers before and after the outbreak were low (17.5% and 15.5%, respectively), as were rates of targeted vaccination among cases and close contacts. Conclusion: We provide evidence for transmission both prior to arrival and within the setting, suboptimal practices and timeliness of testing, and implementation gaps in vaccination.

Infection prevention practice in home healthcare: a mixed-method study in two Swiss home healthcare organisations.

BACKGROUND: Infection prevention and control (IPC) research has long neglected the home healthcare sector with its unique challenges. This study aimed to gain an understanding of the barriers to the implementation of infection prevention practices relevant to this setting, the related attitudes, perceived relevance and priorities from the home healthcare worker perspective in Switzerland. METHODS: The mixed-method study involved semi-structured interviews (n = 18) and an anonymous web-based survey (n = 144) among nursing assistants and nurses from two home healthcare organizations in northwest Switzerland. Questions in both sub-studies focused on perceived challenges to infection prevention practices, perceived relevance, and related attitudes and mitigation strategies. Using an exploratory-sequential design, survey questions were designed to quantify and complement the findings from the interview study. RESULTS: Healthcare workers in these two organisations felt adequately protected, trained and supported by their organisations regarding IPC (survey agreement rates > 90%). General challenges to IPC in the home environment most agreed on were lack of cleanliness, lack of space, and the priorities of the patient to be respected (survey agreement rates 85.4%, 77.1%, and 70.8%, respectively). Practices and perceived challenges in the case of colonisation with multi-drug resistant organisms (MDRO) and potentially infectious diarrheal or respiratory illnesses varied highly regarding information transfer, use of protective equipment, and use and disinfection practices of multi-use equipment. Challenges to hand hygiene, sharps safety, waste management and decontamination of equipment did not feature as a prominent concern. CONCLUSIONS: This study is the first to characterise the implementation of infection prevention practices and the related challenges in home healthcare in Switzerland. Home healthcare workers describe various challenges related to infection prevention practices as largely manageable in their work routine, and generally show satisfaction with the support provided by their organisations regarding IPC precautions. Key findings regarding challenges amenable to interventions include uncertainty and inconsistency regarding the management of MDRO colonisation and acute illnesses, and gaps in information transfer. Those challenges may benefit from both organisational interventions and further research into the level of precautions that are appropriate to the home healthcare setting.

Emergence of acquired dolutegravir resistance in treatment-experienced people with HIV in Lesotho.

BACKGROUND: Since 2019, the World Health Organization has recommended dolutegravir-based antiretroviral therapy (ART) as the preferred regimen for HIV management. Large-scale programmatic transitioning to dolutegravir-based ART was subsequently implemented across Africa, often in the absence of recent viral load testing and without access to genotypic resistance testing (GRT) in case of viremia. METHODS: This study assessed for emerging dolutegravir resistance in the routine care Viral Load Cohort North-East Lesotho (VICONEL). We included pediatric and adult participants who changed from non-nucleoside transcriptase inhibitor- (NNRTI-) to dolutegravir-based ART and had at least one viral load assessment before and after the change. We sequenced available samples of participants fulfilling the additional virological criteria of having two viraemic episodes while taking dolutegravir, thereof at least one viral load ≥500 copies/mL taken ≥18 months after changing to dolutegravir. RESULTS: Among 15'349 participants, 157 (1.0%) met the virological criteria and GRT was successful for 85 (0.6%). Among these 85, eight (9.4%) had dolutegravir resistance, with two (2.4%) and six (7.1%) predicted to have intermediate and high-level dolutegravir resistance, respectively. One participant had two, two had one, and five had zero active drugs in their regimen. A GRT from before the change to dolutegravir is available for five of these eight participants: four had zero and one had one active drug in their NNRTI-based regimen. CONCLUSIONS: Nine percent of people with persistent or recurring HIV viremia ≥18 months after changing to dolutegravir-based ART had dolutegravir resistance. Detection and management of emerging dolutegravir resistance must be addressed across Africa.

Clinical Relevance of Human Immunodeficiency Virus Low-level Viremia in the Dolutegravir era: Data From the Viral Load Cohort North-East Lesotho (VICONEL).

Background: Human immunodeficiency virus low-level viremia (LLV) is associated with subsequent treatment failure at least with non nucleoside reverse transcriptase inhibitor (NNRTI)-containing antiretroviral therapy. Data on implications of LLV occurring under dolutegravir, which has largely replaced NNRTIs in Africa, are scarce, however. Methods: We included adults with human immunodeficiency virus in Lesotho who had ≥2 viral loads (VLs) taken after ≥6 months of NNRTI- or dolutegravir-based antiretroviral therapy. Within VL pairs, we assessed the association of viral suppression (<50 copies/mL) and low- and high-range LLV (50-199 and 200-999 copies/mL, respectively) with virological failure (≥1000 copies/mL) using a mixed-effects regression model. Participants could contribute VLs to the NNRTI and the dolutegravir group. Results: Among 18 550 participants, 12 216 (65.9%) were female and median age at first VL included was 41.2 years (interquartile range, 33.4-51.5). In both groups, compared with a suppressed VL, odds of subsequent virological failure were higher for low-range LLV (NNRTI: adjusted odds ratio; 95% confidence interval: 1.9; 1.4-2.4 and dolutegravir: 2.1; 1.3-3.6) and high-range LLV (adjusted odds ratio; 95% confidence interval, 4.2; 3.1-5.7 and 4.4; 2.4-7.9). Conclusions: In the dolutegravir era, LLV remains associated with virological failure, endorsing the need for close clinical and laboratory monitoring of those with a VL ≥50 copies/mL.

Community-based models of care for adolescent and adult depression, suicidal behavior, anxiety, trauma, and substance use in Africa: a scoping review.

Background: Community-based care (CBC), where care is delivered outside of the traditional health facility setting, has been proposed to narrow the mental health (MH) and substance use (SU) treatment gap in Africa. Objective: This scoping review aims to comprehensively summarize CBC models addressing adolescent and adult MH (depression, anxiety, trauma, suicidal behavior) and (non-tobacco) SU problems in Africa. Methods: We searched PsycINFO, Embase, Scopus, CINAHL, and Medline Ovid. Studies and protocols were included if they reported on CBC intervention's effects on MH or SU symptoms/ diagnoses, acceptability, feasibility, or patient engagement in care, regardless of whether the intervention itself was designed specifically for MH or SU. Results: Among 11,477 screened publications, 217 were eligible. Of the unique intervention studies (n = 206), CBC models were classified into the following approaches (non-mutually exclusive): psychotherapeutic (n = 144), social (n = 81), lifestyle/physical health (n = 55), economic (n = 26), and psychopharmacological (n = 2). While quantitative results suggest possible efficacy of CBC models, description of CBC location was often poor. Fewer interventions addressed suicidal behavior (n = 12), the needs of adolescents (n = 49), or used traditional healers or religious figures as providers (n = 3). Conclusion: Many CBC models have been tested on MH and SU in Africa and should be critically appraised and meta-analyzed in subsequent reviews, where possible.

HIV viral suppression in children and adolescents 2 years after transition to dolutegravir: a multicentre cohort study.

BACKGROUND: Treatment failure is common among children and adolescents with HIV. Antiretroviral therapy (ART) containing dolutegravir has recently been rolled out across Africa, though long-term real-world data in paediatric populations are lacking. Here, we report treatment outcomes among children and adolescents in Lesotho who transitioned from nonnucleoside reverse transcriptase inhibitor (NNRTI)-based to dolutegravir-based ART through 2 years' follow-up. METHODS: Data were derived from two open cohort studies in Lesotho. Children and adolescents aged less than 18 years who transitioned from NNRTI-based to dolutegravir-based ART at least 18 months before data closure were included. We report viral load results less than 12 months before, 12 (window: 6-17) months after, and 24 (window: 18-29) months after transition to dolutegravir. Associations of pretransition demographic and clinical factors with 24-month viraemia were assessed through multivariable logistic regression. RESULTS: Among 2126 included individuals, 1100 (51.7%) were female individuals, median age at transition to dolutegravir was 14.0 years [interquartile range (IQR) 11.5-15.8], and median time taking ART at transition was 7.6 years (IQR 4.4-10.6). Among those with a viral load result at the respective time points, viral suppression to less than 50 copies/ml was achieved by 1635 of 1973 (82.9%) less than 12 months before, 1846 of 2012 (91.8%) 12 months after, and 1725 of 1904 (90.6%) 24 months after transition to dolutegravir. Pretransition viraemia was associated with viraemia at 24 months, though more than 80% of individuals with pretransition viraemia achieved resuppression to less than 50 copies/ml at 24 months. CONCLUSION: The proportion of children and adolescents with viral suppression increased after transition to dolutegravir, though further progress is needed to reach global targets.

Same-day versus rapid ART initiation in HIV-positive individuals presenting with symptoms of tuberculosis: Protocol for an open-label randomized non-inferiority trial in Lesotho and Malawi.

BACKGROUND: In absence of contraindications, same-day initiation (SDI) of antiretroviral therapy (ART) is recommended for people testing HIV-positive who are ready to start treatment. Until 2021, World Health Organization (WHO) guidelines considered the presence of TB symptoms (presumptive TB) a contraindication to SDI due to the risk of TB-immune reconstitution inflammatory syndrome (TB-IRIS). To reduce TB-IRIS risk, ART initiation was recommended to be postponed until results of TB investigations were available, and TB treatment initiated if active TB was confirmed. In 2021, the WHO guidelines changed to recommending SDI even in the presence of TB symptoms without awaiting results of TB investigations based on the assumption that TB investigations often unnecessarily delay ART initiation, increasing the risk for pre-ART attrition from care, and noting that the clinical relevance of TB-IRIS outside the central nervous system remains unclear. However, this guideline change was not based on conclusive evidence, and it remains unclear whether SDI of ART or TB test results should be prioritized in people with HIV (PWH) and presumptive TB. DESIGN AND METHODS: SaDAPT is an open-label, pragmatic, parallel, 1:1 individually randomized, non-inferiority trial comparing two strategies for the timing of ART initiation in PWH with presumptive TB ("ART first" versus "TB results first"). PWH in Lesotho and Malawi, aged 12 years and older (re)initiating ART who have at least one TB symptom (cough, fever, night sweats or weight loss) and no signs of intracranial infection are eligible. After a baseline assessment, participants in the "ART first" arm will be offered SDI of ART, while those in the "TB results first" arm will be offered ART only after active TB has been confirmed or refuted. We hypothesize that the "ART first" approach is safe and non-inferior to the "TB results first" approach with regard to HIV viral suppression (<400 copies/ml) six months after enrolment. Secondary outcomes include retention in care and adverse events consistent with TB-IRIS. EXPECTED OUTCOMES: SaDAPT will provide evidence on the safety and effects of SDI of ART in PWH with presumptive TB in a pragmatic clinical trial setting. TRIAL REGISTRATION: The trial has been registered on clinicaltrials.gov (NCT05452616; July 11 2022).

Barriers and facilitators to infection prevention practices in home healthcare: a scoping review and proposed implementation framework.

Infection prevention and control (IPC) research has focused on the hospital setting, neglecting the rapidly expanding home healthcare (HHC) sector. Current infection prevention recommendations do not reflect the challenges specific to the HHC setting. This scoping review considered any original studies reporting on barriers or facilitators to infection prevention practices in the context of HHC. Study characteristics were mapped, and a descriptive content analysis was performed. Based on the findings we propose a framework of eight HHC setting characteristics relevant to infection prevention implementation. 33 studies fulfilled the eligibility criteria. A majority of studies addressed sharps injury or blood and body fluid exposure prevention (N=15) and the majority were conducted in the United States (N=23). Study methodologies employed were surveys (N=18), qualitative (N=11), direct observation (N=7), and one interventional study. The HHC setting characteristics relevant to infection prevention implementation were: the care process in the patient's immediate environment; the need to bring equipment and materials into the home; the provision and financing of equipment and materials; the use of patient space and facilities; the unique position of and the expectations towards HHC providers; working alone with little support; the intermittent nature of care; the attitudes of HHC providers formed by their work circumstances. Interventional studies generating higher-quality evidence for implementation are lacking. Furthermore, implementation of aseptic technique and the decontamination and reprocessing of equipment are poorly studied in the HHC setting and deserve more research interest. The proposed framework may guide future research and implementation work.

Implementing focused echocardiography and AI-supported analysis in a population-based survey in Lesotho: implications for community-based cardiovascular disease care models.

In settings where access to expert echocardiography is limited, focused echocardiography, combined with artificial intelligence (AI)-supported analysis, may improve diagnosis and monitoring of left ventricular hypertrophy (LVH). Sixteen nurses/nurse-assistants without prior experience in echocardiography underwent a 2-day hands-on intensive training to learn how to assess parasternal long axis views (PLAX) using an inexpensive hand-held ultrasound device in Lesotho, Southern Africa. Loops were stored on a cloud-drive, analyzed using deep learning algorithms at the University Hospital Basel, and afterwards confirmed by a board-certified cardiologist. The nurses/nurse-assistants obtained 756 echocardiograms. Of the 754 uploaded image files, 628 (83.3%) were evaluable by deep learning algorithms. Of those, results of 514/628 (81.9%) were confirmed by a cardiologist. Of the 126 not evaluable by the AI algorithm, 46 (36.5%) were manually evaluable. Overall, 660 (87.5%) uploaded files were evaluable and confirmed. Following short-term training of nursing cadres, a high proportion of obtained PLAX was evaluable using AI-supported analysis. This could be a basis for AI- and telemedical support in hard-to-reach areas with minimal resources.

Mycobacterium tuberculosis infection associated immune perturbations correlate with antiretroviral immunity.

Infection with Mycobacterium tuberculosis (MTB) remains one of the most important opportunistic infections in people with HIV-1 (PWH). While active Tuberculosis (TB) leads to rapid progression of immunodeficiency in PWH, the interaction between MTB and HIV-1 during the asymptomatic phase of both infections remains poorly understood. In a cohort of individuals with HIV (PWH) with and without suppressed HIV-1 viral load, the transcriptomic profiles of peripheral blood mononuclear cells (PBMC) clustered in individuals infected with Mycobacterium tuberculosis (MTB) compared to carefully matched controls. Subsequent functional annotation analysis disclosed alterations in the IL-6, TNF, and KRAS pathways. Notably, MTB-associated genes demonstrated an inverse correlation with HIV-1 viremia, evident at both on individual gene level and when employed as a gene score. In sum, our data show that MTB infection in PWH is associated with a shift in the activation state of the immune system, displaying an inverse relationship with HIV-1 viral load. These results could provide an explanation for the observed increased antiretroviral control associated with MTB infection in PWH.

Community-based models of care for management of type 2 diabetes mellitus among non-pregnant adults in sub-Saharan Africa: A scoping review.

INTRODUCTION: The prevalence of type 2 diabetes mellitus (T2DM) and associated morbidity and mortality are increasing in sub-Saharan Africa (SSA). To facilitate access to quality care and improve treatment outcomes, there is a need for innovative community care models and optimized use of non-physician healthcare workers bringing diagnosis and care closer to patients' homes. AIM: We aimed to describe with a scoping review different models of community-based care for non-pregnant adults with T2DM in SSA, and to synthesize the outcomes in terms of engagement in care, blood sugar control, acceptability, and end-organ damage. We further aimed to critically appraise the different models of care and compare community-based to facility-based care if data were available. METHODS: We searched Medline, Embase, Cumulative Index to Nursing and Allied Health Literature (CINAHL) and Scopus, supplemented with backward and forward citation searches. We included cohort studies, randomized trials and case-control studies that reported on non-pregnant individuals diagnosed with T2DM in SSA, who received a substantial part of care in the community. Only studies which reported at least one of our outcomes of interest were included. A narrative analysis was done, and comparisons made between community-based and facility-based models, where within-study comparison was reported. RESULTS: We retrieved 5,335 unique studies, four of which met our inclusion criteria. Most studies were excluded because interventions were facility-based; community care interventions described in the studies were only add-on features of a primarily facility-based care; and studies did not report outcomes of interest. The included studies reported on a total of 383 individuals with T2DM. Three different community care models were identified. 1) A community-initiated model where diagnosis, treatment and monitoring occurred primarily in the community. This model reported a higher linkage and engagement in care at 9 months compared to the corresponding facility model, but only slight reductions of average blood glucose levels at six months compared to baseline. 2) A facility-originated community model where after treatment initiation, a substantial part of follow-up was offered at community level. Two studies reported such a model of care, both had as core component home-delivery of medication. Acceptability of this approach was high. But neither study found improved T2DM control when compared to facility care 3) An eHealth model with high acceptability scores for both patients and care providers, and an absolute 1.76% reduction in average HbA1c levels at two months compared to baseline. There were no reported outcomes on end-organ damage. All four studies were rated as being at high risk for bias. CONCLUSION: Evidence on models of care for persons with T2DM in SSA where a substantial part of care is shifted to the community is scant. Whereas available literature indicates high acceptability of community-based care, we found no conclusive data on their effectiveness in controlling blood sugar and preventing complications. Evidence from larger scale studies, ideally randomized trials with clinically relevant endpoints is needed before roll-out of community-based T2DM care can be recommended in SSA.

Community-based type 2 diabetes care by lay village health workers in rural Lesotho: protocol for a cluster-randomized trial within the ComBaCaL cohort study (ComBaCaL T2D TwiC).

BACKGROUND: Type 2 diabetes (T2D) poses a growing public health burden, especially in low- and middle-income countries (LMICs). Task-shifting to lay village health workers (VHWs) and the use of digital clinical decision support systems (CDSS) are promising approaches to tackle the current T2D care gap in LMICs. However, evidence on the effectiveness of lay worker-led T2D care models, in which VHWs initiate and monitor drug treatment in addition to community-based screening and referral services, is lacking. METHODS: We are conducting a cluster-randomized trial nested within the Community-Based Chronic Disease Care Lesotho (ComBaCaL) cohort study (NCT05596773) using the trial within cohort (TwiC) design to assess the effectiveness of a VHW-led, CDSS-assisted T2D care model in rural Lesotho. Participants are non-pregnant members of the ComBaCaL cohort study with T2D. The ComBaCaL cohort study is conducted in approximately 100 villages in two rural districts in Lesotho and is managed by trained and supervised VHWs. In intervention villages, VHWs offer a community-based T2D care package including lifestyle counselling, first-line oral antidiabetic, lipid-lowering, and antiplatelet treatment guided by a tablet-based CDSS to participants who are clinically eligible, as well as treatment support to participants who prefer or clinically require facility-based T2D care. In control clusters, all participants will be referred to a health facility for T2D management. The primary endpoint is the mean glycosylated haemoglobin (HbA1c) 12 months after enrolment. Secondary endpoints include the 10-year risk for cardiovascular events estimated using the World Health Organization risk prediction tool. DISCUSSION: The trial was launched on May 13, 2023, and has enrolled 226 participants at the date of submission (October 6, 2023). To our knowledge, the trial is the first to assess task-shifting of T2D care to VHWs at the community level, including the prescription of first-line antidiabetic, lipid-lowering, and antiplatelet medication in sub-Saharan Africa, and will thus provide the missing evidence on the effectiveness of such a T2D care model in this setting. The study is operating within the established Lesotho VHW programme. Similar community health worker programmes which exist across sub-Saharan Africa may benefit from the findings. TRIAL REGISTRATION: ClinicalTrials.gov NCT05743387. Registered on February 24 2023.

High Rates of Undiagnosed Target Organ Damage Among Adults with Elevated Blood Pressure or Diabetes Mellitus in a Community-Based Survey in Lesotho.

INTRODUCTION: Prevalence of elevated blood pressure (BP) and diabetes mellitus (DM) is increasing in sub-Saharan Africa. Data on target organ damage such as retinopathy, left ventricular hypertrophy (LVH), renal impairment and peripheral neuropathy (PN) among persons with elevated BP and/or DM in sub-Saharan Africa remain scarce. AIM: To determine at community-level the prevalence of retinopathy, LVH, renal impairment, and PN among adults with elevated BP and/or DM, and assess the association of elevated BP and/or DM with target organ damage in Lesotho. METHODS: During a household-based survey, a sub-sample of adults with elevated BP (≥ 140/90 mmHg) and/or DM (glycosylated hemoglobin ≥ 6.5%), as well as comparators (BP < 140/90 mmHg, HbA1c < 6.5%) were screened for retinopathy, LVH, renal impairment, and PN. We used multivariable logistic regression for inferential analysis. RESULTS: Out of 6108 participants screened during the survey, 420 with elevated BP only, 80 with DM only, 61 with elevated BP and DM, and 360 comparators were assessed for target organ damage. Among those with elevated BP, and among those with DM with or without elevated BP, prevalence of retinopathy was 34.6% (89/257) and 14.4% (15/104); renal impairment was 45.0% (156/347) and 42.4% (56/132), respectively. Among those with elevated BP, 2.3% (7/300) and 65.7% (224/341) had LVH and left ventricular concentric remodeling, respectively. PN, only assessed among those with DM, was present in 32.6% (42/129). Elevated BP was associated with increased odds of retinopathy (aOR, 19.13; 95% CI, 8.52-42.94; P < 0.001) and renal impairment (aOR, 1.80; 95% CI, 1.27-2.55; P = 0.001). Presence of both elevated BP and DM was associated with an increased odds of retinopathy (aOR, 16.30; 95%CI, 5.69-46.68; P < 0.001), renal impairment (aOR, 2.55; 95% CI, 1.35-4.81; P = 0.004), and PN (aOR, 2.13; 95% CI, 1.04-4.38; P = 0.040). CONCLUSION: We found a high prevalence of undiagnosed target organ damage among adults with elevated BP and/or DM during community-based screening. These findings emphasize the importance of regular prevention and screening activities in this setting.

Head-to-head comparison of the WHO STEPwise approach with immediate unattended and delayed unattended automated blood pressure measurements during household-based screening: a diagnostic accuracy study in Lesotho.

Background: WHO introduced the STEPwise approach to surveillance (STEPS) to monitor trends in non-communicable diseases. For arterial hypertension, the STEPS protocol takes the average of the last two out of three standard blood pressure measurements (SBPM). This study assesses the diagnostic accuracy of SBPM, same-day and next-day unattended automated measurement (uABP), with 24 h ambulatory measurement (24 h-ABPM) as reference. Methods: This diagnostic accuracy study was done within a population-based household survey on cardiovascular risk factors in two districts in Northern Lesotho. Adults (aged ≥ 18 years) with elevated SBPM (defined as ≥140/90 mmHg), and 2:1 age- and sex-matched participants with normal SBPM during the survey were recruited. Following SBPM, first uABP readings were obtained on survey day. Afterwards, participants received a 24 h-ABPM device. Second uABP readings were taken 24 h later, after retrieval of the 24 h-ABPM. The main outcome was overall diagnostic accuracy of all screening measurements (SBPM, first uABP, and second uABP), determined using area under the receiver operating characteristic curve (AUROC), with 24 h-ABPM as a reference. Findings: Between November 2, 2021 and August 31, 2022, 275 participants (mean age 58 years (SD: 16 years), 163 (59%) female) were enrolled, 183 of whom had elevated and 92 had normal SBPM. Mean difference between systolic daytime 24 h-ABPM and screening measurements was highest for SBPM (mean difference: -13 mmHg; 95% CI: -14 to -11). Mean difference between diastolic daytime 24 h-ABPM and diastolic SBPM was -2 mmHg (95% CI: -4 to -1), whereas no difference was found for mean diastolic first uABP (mean difference: -1 mmHg; 95% CI: -2.0 to 0.3); and mean diastolic second uABP (mean difference: 1.0 mmHg; 95% CI: -0.4 to 2.3). White coat hypertension was highest with SBPM (55 [20%]), followed by first uABP (27 [9.8%]), and second uABP (18 [6.5%]). Using systolic daytime 24 h-ABPM as a reference, the uABPs had higher AUROC (first uABP: 87% [95% CI: 83-91]; second uABP: 88% [95% CI: 84-92]); SBPM: (79% [95% CI: 74-85]). This difference was significant between first uABP and SBPM (P = 0.0024), and between second uABP and SBPM (P = 0.0017). Interpretation: uABP had better diagnostic performance than SBPM. Integration of uABP into STEPS protocol should be considered. Funding: Swiss Agency for Development and Cooperation under the ComBaCaL project, and the World Diabetes Foundation.

Prevalence and determinants of cardiovascular risk factors in Lesotho: a population-based survey.

BACKGROUND: There are no recent data on the prevalence of cardiovascular risk factors (CVDRFs) in Lesotho. This study aims to assess the prevalence of CVDRFs and their determinants. METHODS: We conducted a household-based, cross-sectional survey among adults ≥18 y of age in 120 randomly sampled clusters in two districts. RESULTS: Among 6061 participants, 52.2% were female and their median age was 39 y (interquartile range 27-58). The overall prevalence of overweight, diabetes, elevated blood pressure (BP) and tobacco use was 39.9%, 5.3%, 21.6% and 24.9%, respectively. Among participants, 34.6% had none, 45.2% had one and 20.2% had two or more CVDRFs. Women were more likely to have two or more CVDRFs (20.7% vs 12.3%). Overall, 7.5% of participants had elevated total cholesterol, 52.7% had low high-density lipoprotein cholesterol and 1.6% had elevated low-density lipoprotein cholesterol. Among younger participants (18-29 y), 16.1% reported tobacco use, 28.6% were overweight, 1.5% had diabetes and 3.5% had elevated BP. Household wealth positively correlated with the prevalence of elevated BP, overweight and diabetes, whereas tobacco use was higher among people in the lowest three wealth quintiles. CONCLUSIONS: CVDRFs are highly prevalent in Lesotho across age and sex groups, underlining the importance of strengthening prevention and care programs in Lesotho and similar settings in southern Africa.

Two-Year Outcomes of Treatment-Experienced Adults After Programmatic Transitioning to Dolutegravir: Longitudinal Data From the VICONEL Human Immunodeficiency Virus Cohort in Lesotho.

In the Viral Load Cohort North-East Lesotho (VICONEL) human immunodeficiency virus cohort, 14 242 adults had transitioned from efavirenz- or nevirapine-based antiretroviral therapy (ART) to dolutegravir-based ART by October 2021. Rates of viral suppression to <50 copies/mL were 84.8%, 93.9%, and 95.4% before, 12 months after, and 24 months after transition, respectively. Sex, age, pretransition viral load, and treatment backbone correlated with 24-month viremia.