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Summary: Background: Poor treatment adherence contributes to lower treatment completion and higher loss to follow-up among people with tuberculosis (PWTB). Medication monitors have shown some evidence of improved adherence. Methods: We conducted a cluster randomised trial in 18 primary health clinics in South Africa between May 2019–February 2022. Persons (aged ≥ 2 years) with drug-sensitive tuberculosis (DS-TB) were enrolled. All participants were provided with monitors which were silent in the standard of care (SoC) arm. In the intevention arm, weekly adherence reports were reviewed and participants received intensified support as appropriate (text, phone call, home visit, motivational counselling). The primary outcome was adherence, which was calculated as days box was opened (proxy for drug taken)/total expected treatment days as a binary variable (

Abstract Background Periods of droughts can lead to decreased food security, and altered behaviours, potentially affecting outcomes on antiretroviral therapy (ART) among persons with HIV (PWH). We investigated whether decreased rainfall is associated with adverse outcomes among PWH on ART in Southern Africa. Methods Data were combined from 11 clinical cohorts of PWH in Lesotho, Malawi, Mozambique, South Africa, Zambia, and Zimbabwe, participating in the International epidemiology Databases to Evaluate AIDS Southern Africa (IeDEA-SA) collaboration. Adult PWH who had started ART prior to 01/06/2016 and were in follow-up in the year prior to 01/06/2016 were included. Two-year rainfall from June 2014 to May 2016 at the location of each HIV centre was summed and ranked against historical 2-year rainfall amounts (1981–2016) to give an empirical relative percentile rainfall estimate. The IeDEA-SA and rainfall data were combined using each HIV centre’s latitude/longitude. In individual-level analyses, multivariable Cox or generalized estimating equation regression models (GEEs) assessed associations between decreased rainfall versus historical levels and four separate outcomes (mortality, CD4 counts 400 copies/mL, and > 12-month gaps in follow-up) in the two years following the rainfall period. GEEs were used to investigate the association between relative rainfall and monthly numbers of unique visitors per HIV centre. Results Among 270,708 PWH across 386 HIV centres (67% female, median age 39 [IQR: 32–46]), lower rainfall than usual was associated with higher mortality (adjusted Hazard Ratio: 1.18 [95%CI: 1.07–1.32] per 10 percentile rainfall rank decrease) and unsuppressed viral loads (adjusted Odds Ratio: 1.05 [1.01–1.09]). Levels of rainfall were not strongly associated with CD4 counts 12-month gaps in care. HIV centres in areas with less rainfall than usual had lower numbers of PWH visiting them (adjusted Rate Ratio: 0.80 [0.66–0.98] per 10 percentile rainfall rank decrease). Conclusions Decreased rainfall could negatively impact on HIV treatment behaviours and outcomes. Further research is needed to explore the reasons for these effects. Interventions to mitigate the health impact of severe weather events are required.

Summary: Background: While acute SARS-CoV-2 infection and associated inflammation resulted in substantial morbidity and mortality during the COVID-19 pandemic, particularly in unvaccinated patients, long-term effects of SARS-CoV-2 exposure for reactivation of latent oncogenic herpesviruses, such as KSHV, is unknown. Methods: We performed a longitudinal observational cross-sectional study on 407 non-hospitalised adult HIV-infected (CD4 count

Abstract Background South Africa bears a large HIV burden with 7.8 million people with HIV (PWH). However, due to suboptimal antiretroviral therapy (ART) adherence and retention in care, only 66% of PWH in South Africa are virally suppressed. Standard care only allows for suboptimal adherence detection when routine testing indicates unsuppressed virus. Several adherence interventions are known to improve HIV outcomes, yet few are implemented in routinely due to the resources required. Therefore, determining scalable evidence-based adherence support interventions for resource-limited settings (RLS) is a priority. The multiphase optimization strategy (MOST) framework allows for simultaneous evaluation of multiple intervention components and their interactions. We propose to use MOST to identify the intervention combination with the highest levels of efficacy and cost-effectiveness that is feasible and acceptable in primary care clinics in Cape Town. Methods We will employ a fractional factorial design to identify the most promising intervention components for inclusion in a multi-component intervention package to be tested in a future randomized controlled trial. We will recruit 512 participants initiating ART between March 2022 and February 2024 in three Cape Town clinics and evaluate acceptability, feasibility, and cost-effectiveness of intervention combinations. Participants will be randomized to one of 16 conditions with different combinations of three adherence monitoring components: rapid outreach following (1) unsuppressed virus, (2) missed pharmacy refill collection, and/or (3) missed doses as detected by an electronic adherence monitoring device; and two adherence support components: (1) weekly check-in texts and (2) enhanced peer support. We will assess viral suppression (

Digital adherence technologies (DATs) have emerged as an alternative to directly observed therapy (DOT) for supervisions of tuberculosis (TB) treatment. We conducted a meta-analysis of implementation feedback obtained from people with TB and health care workers (HCWs) involved in TB REACH Wave 6-funded DAT evaluation projects. Projects administered standardized post-implementation surveys based on the Capability, Opportunity, Motivation, Behavior (COM-B) model to people with TB and their health care workers. The surveys included questions on demographics and technology use, Likert scale questions to assess capability, opportunity, and motivation to use DAT and open-ended feedback. We summarized demographic and technology use data descriptively, generated pooled estimates of responses to Likert scale questions within each COM-B category for people with TB and health care workers using random effects models, and performed qualitative analysis of open-ended feedback using a modified framework analysis approach. The analysis included surveys administered to 1290 people with TB and 90 HCWs across 6 TB REACH-funded projects. People with TB and HCWs had an overall positive impression of DATs with pooled estimates between 4·0 to 4·8 out of 5 across COM-B categories. However, 44% of people with TB reported taking TB medications without reporting dosing via DATs and 23% reported missing a dose of medication. Common reasons included problems with electricity, network coverage, and technical issues with the DAT platform. DATs were overall perceived to reduce visits to clinics, decrease cost, increase social support, and decrease workload of HCWs. DATs were acceptable in a wide variety of settings. However, there were challenges related to the feasibility of using current DAT platforms. Implementation efforts should concentrate on ensuring access, anticipating, and addressing technical challenges, and minimizing additional cost to people with TB.

Objectives The tuberculosis (TB) MATE study evaluated whether a differentiated care approach (DCA) based on tablet-taking data from Wisepill evriMED digital adherence technology could improve TB treatment adherence. The DCA entailed a stepwise increase in adherence support starting from short message service (SMS) to phone calls, followed by home visits and motivational counselling. We explored feasibility of this approach with providers in implementing clinics.Design Between June 2020 and February 2021, in-depth interviews were conducted in the provider’s preferred language, audiorecorded, transcribed verbatim and translated. The interview guide included three categories: feasibility, system-level challenges and sustainability of the intervention. We assessed saturation and used thematic analysis.Setting Primary healthcare clinics in three provinces of South Africa.Participants We conducted 25 interviews with 18 staff and 7 stakeholders.Results Three major themes emerged: First, providers were supportive of the intervention being integrated into the TB programme and were eager to be trained on the device as it helped to monitor treatment adherence. Second, there were challenges in the adoption system such as shortage of human resources which could serve as a barrier to information provision once the intervention is scaled up. Healthcare workers reported that some patients received incorrect SMS’s due to delays in the system that contributed to distrust. Third, DCA was considered as a key aspect of the intervention by some staff and stakeholders since it allowed for support based on individual needs.Conclusions It was feasible to monitor TB treatment adherence using the evriMED device and DCA. To ensure successful scale-up of the adherence support system, emphasis will need to be placed on ensuring that the device and the network operate optimally and continued support on adhering to treatment which will enable people with TB to take ownership of their treatment journey and help overcome TB-related stigma.Trial registration number Pan African Trial Registry PACTR201902681157721.

BackgroundGlobally, the most significant risk factors for adverse COVID-19 outcome are increasing age and cardiometabolic comorbidities. However, underlying coinfections may modulate COVID-19 morbidity and mortality, particularly in regions with high prevalence of infectious diseases.MethodsWe retrospectively analyzed serum samples for IgG antibodies against the common circulating coronaviruses HCoV-NL63, HCoV-229E, HCoV-OC43 and HCoV-HKU1 from non-hospitalized and hospitalized confirmed COVID-19 patients recruited during the first (June-August 2020) and second (October 2020-June 2021) COVID-19 wave in Cape Town, South Africa. Patients were grouped according to COVID-19 disease severity: Group 1: previously SARS-CoV-2 infected with positive serology and no symptoms (n=94); Group 2: acutely SARS-CoV-2 infected, hospitalized for COVID-19 and severe symptoms (n=92).ResultsThe overall anti-HCoV IgG seroprevalence in the entire patient cohort was 60.8% (95% CI: 53.7 – 67.8), with 37.1% HCoV-NL63 (95% CI: 30 – 44), 30.6% HCoV-229E (95% CI: 24 – 37.3), 22.6% HCoV-HKU1 (95% CI: 16.6 – 28.6), and 21.0% HCoV-OC43 (95% CI: 15.1 – 26.8). We observed a significantly higher overall HCoV presence (72.3% versus 48.9%) and coinfection frequency (43.6% versus 19.6%) in group 1 compared to group 2 patients with significantly higher presentation of HCoV-NL63 (67.0% versus 6.6%) and HCoV-HKU1 (31.1% versus 14.1%). However, only antibody titers for HCoV-NL63 were significantly higher in group 1 compared to group 2 patients (p< 0.0001, 1.90 [95% CI: 0.62 – 2.45] versus 1.32 [95% CI: 0.30 – 2.01]) which was independent of the participants’ HIV status. Logistic regression analysis revealed significantly protective effects by previous exposure to HCoV-NL63 [p< 0.001, adjusted OR = 0.0176 (95% CI: 0.0039 – 0.0786)], while previous HCoV-229E exposure was associated with increased COVID-19 severity [p = 0.0051, adjusted OR = 7.3239 (95% CI: 1.8195–29.4800)].ConclusionWe conclude that previous exposure to multiple common coronaviruses, and particularly HCoV-NL63, might protect against severe COVID-19, while no previous HCoV exposure or single infection with HCoV-229E might enhance the risk for severe COVID-19. To our knowledge, this is the first report on HCoV seroprevalence in South Africa and its possible association with cross-protection against COVID-19 severity.

BackgroundThe introduction of digital adherence technologies (DATs) such as medication monitors in tuberculosis (TB) programmes supports treatment adherence among people with tuberculosis (PWTB). We evaluated the acceptability of using medication monitors (Wisepill evriMED) prompting a stepwise differentiated care approach (DCA), involving short message service (SMS), phone calls, home visits and motivational counselling, among PWTB in South Africa.MethodsWe conducted 62 in-depth interviews with participants in local languages across three provinces (January-October 2020), purposively selected by treatment month, adherence history and gender. Interviews were audio recorded, transcribed verbatim and translated. Using a deductive approach and the Theoretical Framework for Acceptability (TFA), we explored acceptability across the sample attributes.ResultsPWTB across adherence histories showed a positive attitude to using the evriMED device and receiving the DCA support. PWTB described the SMS reminders and phone calls as effective reminders, though home visits were less acceptable, due to perceived stigma. Despite willingness to participate in the intervention, the large size of the monitor and sound of the alarm drew attention, potentially causing embarrassment and stigma. Due to perceived stigma, some PWTB adapted the intervention by leaving the monitor at home after removing the pills to ensure that someone else tracked usage, while the PWTB used alternative reminders such as cell phones to take their medication.ConclusionAlthough PWTB showed a positive attitude towards the intervention, perceived stigma contributed to participants adapting their lifestyle to meet treatment adherence requirements without using the monitor. However, the medication monitor was a tool that seemed to prompt this personal change in behaviour. Achieving people-centered TB care, including the introduction of DATs, will require that TB programmes incorporate PWTB insights to maximize their use and effectiveness.

Abstract Background Young people including adolescents face barriers to healthcare and increased risk of poor sexual and reproductive health (SRH), which are exacerbated in humanitarian settings. Our systematic review assessed the evidence on SRH interventions for young people including adolescents in humanitarian settings, strategies to increase their utilisation and their effects on health outcomes. Methods We searched peer-reviewed and grey literature published between 1980 and 2018 using search terms for adolescents, young people, humanitarian crises in low- and middle- income countries and SRH in four databases and relevant websites. We analysed literature matching pre-defined inclusion criteria using narrative synthesis methodology, and appraised for study quality. Findings We found nine peer-reviewed and five grey literature articles, the majority published post-2012 and mostly high- or medium-quality, focusing on prevention of unintended pregnancies, HIV/STIs, maternal and newborn health, and prevention of sexual and gender-based violence. We found no studies on prevention of mother-to-child transmission (PMTCT), safe abortion, post-abortion care, urogenital fistulae or female genital mutilation (FGM). Thirteen studies reported positive effects on outcomes (majority were positive changes in knowledge and attitudes), seven studies reported no effects in some SRH outcomes measured, and one study reported a decrease in number of new and repeat FP clients. Strategies to increase intervention utilisation by young people include adolescent-friendly spaces, peer workers, school-based activities, and involving young people. Discussion Young people, including adolescents, continue to be a neglected group in humanitarian settings. While we found evidence that some SRH interventions for young people are being implemented, there are insufficient details of specific intervention components and outcome measurements to adequately map these interventions. Efforts to address this key population’s SRH needs and evaluate effective implementation modalities require urgent attention. Specifically, greater quantity and quality of evidence on programmatic implementation of these interventions are needed, especially for comprehensive abortion care, PMTCT, urogenital fistulae, FGM, and for LGBTQI populations and persons with disabilities. If embedded within a broader SRH programme, implementers and/or researchers should include young people-specific strategies, targeted at both girls/women and boys/men where appropriate, and collect age- and sex-disaggregated data to help ascertain if this population’s diverse needs are being addressed.

In South Africa, high exposure to SARS-CoV-2 occurs primarily in densely populated, low-income communities, which are additionally burdened by highly prevalent Human Immunodeficiency Virus (HIV). With the aim to assess SARS-CoV-2 seroprevalence and its association with HIV-related clinical parameters in non-hospitalized patients likely to be highly exposed to SARS-CoV-2, this observational cross-sectional study was conducted at the Gugulethu Community Health Centre Antiretroviral clinic between October 2020 and June 2021, after the first COVID-19 wave in South Africa and during the second and beginning of the third wave. A total of 150 adult (median age 39 years [range 20–65 years]) HIV-infected patients (69% female; 31% male) were recruited. 95.3% of the cohort was on antiretroviral therapy (ART), had a median CD4 count of 220 cells/µL (range 17–604 cells/µL) and a median HIV viral load (VL) of 49 copies/mL (range 1–1,050,867 copies/mL). Furthermore, 106 patients (70.7%) were SARS-CoV-2 seropositive, and 0% were vaccinated. When stratified for HIV VL, patients with uncontrolled HIV viremia (HIV VL > 1000 copies/mL) had significantly higher odds of SARS-CoV-2 seropositivity than patients with HIV VL < 1000 copies/mL, after adjusting for age, sex and ART status (p = 0.035, adjusted OR 2.961 [95% CI: 1.078–8.133]). Although the cause–effect relationship could not be determined due to the cross-sectional study design, these results point towards a higher risk of SARS-CoV-2 susceptibility among viremic HIV patients, or impaired HIV viral control due to previous co-infection with SARS-CoV-2.

Worldwide, non-adherence to tuberculosis (TB) treatment is problematic. Digital adherence technologies (DATs) offer a person-centered approach to support and monitor treatment. We explored adherence over time while using DATs. We conducted a meta-analysis on anonymized longitudinal adherence data for drug-susceptible (DS) TB (n = 4515) and drug-resistant (DR) TB (n = 473) populations from 11 DAT projects. Using Tobit regression, we assessed adherence for six months of treatment across sex, age, project enrolment phase, DAT-type, health care facility (HCF), and project. We found that DATs recorded high levels of adherence throughout treatment: 80% to 71% of DS-TB patients had ≥90% adherence in month 1 and 6, respectively, and 73% to 75% for DR-TB patients. Adherence increased between month 1 and 2 (DS-TB and DR-TB populations), then decreased (DS-TB). Males displayed lower adherence and steeper decreases than females (DS-TB). DS-TB patients aged 15–34 years compared to those >50 years displayed steeper decreases. Adherence was correlated within HCFs and differed between projects. TB treatment adherence decreased over time and differed between subgroups, suggesting that over time, some patients are at risk for non-adherence. The real-time monitoring of medication adherence using DATs provides opportunities for health care workers to identify patients who need greater levels of adherence support.