Adolescents' implicit and explicit attitudes toward their peers with genetic conditions.

INTRODUCTION: Previous research has demonstrated that children lacking knowledge about genetic disorders may have harmful attitudes toward people with disabilities, but disability awareness can successfully modify these attitudes. We explored adolescents' implicit and explicit attitudes toward peers with genetic conditions to determine whether improved genetics/genomics literacy can mitigate the impact of ableism in this population. METHODS: English-speaking adolescents (10-18 years) from British Columbia were invited to complete a Disability Attitudes Implicit Association Test (DA-IAT) and participate in a semi-structured focus group centering on a fictionalized vignette about an adolescent with Down syndrome. We used pragmatism as an analytical paradigm. Descriptive and inferential statistics were used to analyze DA-IAT and sociodemographic data; phronetic iterative analysis with constant comparison as a coding strategy for transcripts; and interpretive description to develop a conceptual model. RESULTS: Twenty-two adolescents completed the DA-IAT and participated in one of four focus groups. Participants had a statistically significant implicit preference for non-disabled people (D-score = 0.72, SD = 0.44; t = 7.18, p < .00001). They demonstrated greater diversity in their explicit attitudes during the focus groups. Although participants articulated a positive attitude toward improved genetics education, results demonstrate their belief that social and personal interactions with disabled peers would be essential to address negative perceptions. CONCLUSIONS: This study lays important groundwork to understand, explain, and influence the negative attitudes of adolescents toward individuals with disabilities. Findings will be used to inform the design of interventions that address biased perceptions of people with genetic disorders, with the goal of reducing prejudices and improving social interactions.

Negative clinic experiences as a barrier to care for people with HIV and their impact on patient preferences for intervention support: a qualitative study in Cape Town, South Africa.

We conducted qualitative research among people with HIV (PWH) and care providers in Cape Town, South Africa to understand the impact of negative clinic experiences on adherence and support preferences. In-depth interviews were conducted with 41 patients with an unsuppressed viral load or a treatment gap, and focus group discussions with physicians, nurses, counselors, and community health workers. Questions addressed treatment history and adherence barriers, then participants evaluated evidence-based adherence interventions for potential scale up. Inductive analysis examined care experiences and corresponding preference for intervention options. More than half of PWH described negative experiences during clinic visits, including mistreatment by staff and clinic administration issues, and these statements were corroborated by providers. Those with negative experiences in care stated that fear of mistreatment led to nonadherence. Most patients with negative experiences preferred peer support groups or check-in texts to clinic-based interventions. We found that PWH's negative clinic experiences were a primary reason behind nonadherence and influenced preferences for support mechanisms. These findings emphasize the importance of HIV treatment adherence interventions at multiple levels both in and outside of the clinic, and providing more comprehensive training to providers to better serve PWH in adherence counseling, especially those who are most vulnerable..

Reactivation of Kaposi's sarcoma-associated herpesvirus (KSHV) by SARS-CoV-2 in non-hospitalised HIV-infected patients.

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 <350 cells/µL) patients attending antiretroviral therapy services in Gugulethu, South Africa, from October 2020 to April 2023. FINDINGS: KSHV seroprevalence was 53.5%; the quarterly SARS-CoV-2 seroprevalence increased from 76.2% (before roll-out of COVID-19 vaccinations) to 94.9%, with 32.2% being self-reportedly vaccinated against COVID-19. Over the course of recruitment, the quarterly percentage of patients with detectable KSHV viral load (VL) in the peripheral blood increased from 3.3% to 69.2%. The presence of KSHV VL was significantly associated with SARS-CoV-2 RBD antibody titers in unvaccinated (median RBD IgG OD 1.24 [IQR 0.82-2.42] in non-reactivated versus 2.83 [IQR 1.08-4.72] in reactivated patients, p = 0.0030) but not in vaccinated patients (median RBD IgG OD 5.13 [IQR 4.11-6.36] in non-reactivated versus 4.53 [IQR 2.90-5.92] in reactivated patients, p = 0.086). Further logistic regression revealed significantly higher odds of KSHV reactivation in unvaccinated, previously SARS-CoV-2 exposed patients (p = 0.015, adjusted OR 1.28 [95% CI: 1.05-1.55]), but not vaccinated patients (p = 0.080, adjusted OR 0.83 [95% CI: 0.67-1.02]). Interestingly, detectable KSHV VL was not associated with increased inflammatory markers such as C-reactive protein and interleukin-6. INTERPRETATION: High, and most likely repeated, exposure to SARS-CoV-2 in unvaccinated individuals may have long-term consequences for reactivation of KSHV infection as shown here in the context of HIV-infected patients with impaired immune functions. Post-pandemic prevention and/or monitoring strategies of potential KSHV-associated pathologies in high-risk patients with immunodeficiencies are therefore highly recommended. FUNDING: This research was funded by the EDCTP2 programme (Training and Mobility Action TMA2018SF-2446).

Associations of inter-annual rainfall decreases with subsequent HIV outcomes for persons with HIV on antiretroviral therapy in Southern Africa: a collaborative analysis of cohort studies.

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 < 200 cells/mm3, viral loads > 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 < 200 cell/mm3 or > 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.

Emotional Intelligence and Resilience "PROGRAM" Improves Wellbeing and Stress Management Skills in Preclinical Medical Students.

Purpose: The purpose of this study was to determine if implementation of a new educational curriculum focusing on Emotional Intelligence (EI) and Resilience improved second year medical student scores in these areas. Methods: Our EI-Resilience curriculum was offered as an elective for second year medical students to voluntarily enroll in. The elective consisted of six 2-hour sessions taught by a single faculty member over eight months. Sessions focused on development of EI skills and teaching a Resilience "PROGRAM" (Positive thinking, Reframing, Optimism, Gratitude, Reflection, Altruism, Meaning). Participants' EI levels were assessed before and after the elective using the Bar-On Emotional Quotient Inventory 2.0 (EQ-i 2.0). Results: Over a period of 2 years, 70 students participated in the elective. The overall mean EI score significantly improved after the educational elective (100.05 ± 12.94 versus 108.14 ±12.36, p < 0.001). Compared to the baseline scores, there was significant improvement in all EI components, including all five composite scales, all fifteen content subscales, and the well-being score (all p < 0.05). In a post-intervention survey assessing student perception of the elective, most students found the elective to be helpful (95%, 64/67), most students felt the elective should continue to be available for future students (95%, 64/67), and most would recommend the elective to other students (93%, 62/67). Conclusion: An EI-Resilience curriculum offered as an elective to second year medical students was well received by students. Our outcomes showed significant improvement in students' EI scores and all sub-scores, including all components of the stress management composite and well-being score. Teaching EI skills and Resilience strategies in the preclinical setting might be an opportune time for this type of educational intervention.

Acceptability of using the medication monitor and experience of a differentiated care approach for TB treatment adherence among people living with TB in South Africa.

BACKGROUND: The 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. METHODS: We 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. RESULTS: PWTB 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. CONCLUSION: Although 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.

Acceptability and feasibility of digital adherence technologies for drug-susceptible tuberculosis treatment supervision: A meta-analysis of implementation feedback.

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.

Protocol for an evaluation of adherence monitoring and support interventions among people initiating antiretroviral therapy in Cape Town, South Africa-a multiphase optimization strategy (MOST) approach using a fractional factorial design.

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 (<50 copies/mL) at 24 months as the primary outcome; acceptability, feasibility, fidelity, and other implementation outcomes; and cost-effectiveness. We will use logistic regression models to estimate intervention effects with an intention-to-treat approach, employ descriptive statistics to assess implementation outcomes, and determine an optimal intervention package. DISCUSSION: To our knowledge, ours will be the first study to use the MOST framework to determine the most effective combination of HIV adherence monitoring and support intervention components for implementation in clinics in a RLS. Our findings will provide direction for pragmatic, ongoing adherence support that will be key to ending the HIV epidemic. TRIAL REGISTRATION: ClinicalTrials.gov NCT05040841. Registered on 10 September 2021.

Acceptability and Feasibility of Providing Adherence Feedback Based on Tenofovir Diphosphate in Dried Blood Spots: Results from a Pilot Study Among Patients and Providers in Cape Town, South Africa.

Tenofovir diphosphate (TFV-DP) concentrations in dried blood spots (DBS) predict viral breakthrough, but their use remains understudied in real-world clinic settings. This pilot study examined acceptability, feasibility, and initial adherence outcomes of providing adherence feedback using TFV-DP concentrations on patient- and provider-levels in Cape Town, South Africa. We enrolled 60 persons with HIV (PWH) receiving tenofovir-containing ART attending a primary health clinic. They were randomized 1:1 to an intervention receiving TFV-DP concentration feedback by research staff vs. no feedback at monthly visits for 4 months. Acceptability among medical providers and level of clinical follow-up of TFV-DP results was examined. Patient acceptability was assessed descriptively. Mean electronic adherence (EA), as measured by WisePill device, and TFV-DP in DBS were compared between the two arms. All participants in the intervention group (100%) reported finding TFV-DP feedback helpful and 86% reported changing adherence behaviors. Medical providers indicated high acceptability of incorporating TFV-DP concentration feedback into the clinic, yet among 29 results < 1000 fmol/punch, only 2 were reviewed with no follow-up actions performed. In the intervention arm, mean TFV-DP concentrations were significantly higher (t = 2.5, p < .01) during follow-up and EA in upper quartile (96-100%) was greater compared to controls (x2 = 7.8, p ≤ .05). This study found high acceptability among patients for receiving adherence feedback based on TFV-DP concentrations. TFV-DP and EA data demonstrated greater adherence in the intervention group. Providers indicated high acceptability of incorporating TFV-DP feedback into the clinic, but few providers reviewed results, which could impact clinic-level feasibility.

Qualitative study exploring the feasibility of using medication monitors and a differentiated care approach to support adherence among people receiving TB treatment in South Africa.

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.

Comparing Predictive Ability of Two Objective Adherence Measures in a Community-Based Cohort on Antiretroviral Therapy in South Africa: Tenofovir Diphosphate Concentrations and Electronic Adherence Monitors.

BACKGROUND: Electronic adherence (EA) and tenofovir diphosphate (TFV-DP) in dried blood spots (DBS) are objective measures of antiretroviral therapy (ART) adherence. We characterized the association between these measures in a prospective cohort of persons with HIV (PWH) on ART. SETTING: Four primary health clinics in Cape Town, South Africa. METHODS: We enrolled 250 virally suppressed PWH receiving tenofovir-based ART. We collected EA data, monthly viral load, and TFV-DP in DBS for 12 months. We used logistic regression to estimate the adjusted odds ratio (aOR) and 95% confidence intervals (CIs) for future viral breakthrough (VB) (>400 copies/mL) for each adherence measure. Receiver operating characteristics (ROCs) provided the predictive power of these measures. RESULTS: Participants had a median (IQR) age of 34 (27-42); 78% were women. Twenty-one (8%) developed VB. Logistic regression showed that when percent EA and TFV-DP concentrations increased, the odds of VB decreased. This relationship was consistent at the time of VB (aOR of 0.41 [95% CI: 0.25 to 0.66] for TFV-DP and aOR of 0.64 [95% CI: 0.54 to 0.76] for EA) and for up to 2 months before VB. Both adherence measures predicted future VB at both 1 month and 2 months before viral load measurement. CONCLUSION: We established that 2 objective adherence measures, EA and TFV-DP in DBS, have a positive association with, and are both strongly predictive of, VB in a community-based South African cohort on ART. Future research is needed to determine the feasibility of implementing these adherence measures in resource-limited settings to facilitate adherence interventions.

Perspectives of people living with HIV and health workers about a point-of-care adherence assay: a qualitative study on acceptability.

Current antiretroviral therapy (ART) adherence monitoring is premised on patients' self-reported adherence behaviour (prone to recall error) and verified by blood viral load measurement (which can delay results). A newly developed Urine Tenofovir Rapid Assay (UTRA) assesses tenofovir in urine at point-of-care and is a novel tool to test and immediately respond to adherence levels of people living with HIV (PLHIV). We explored PLHIV and health workers' initial perceptions about integrating the UTRA into routine medical care for adherence support. We conducted a series of once-off in-depth qualitative interviews with PLHIV (n = 25) and health workers (n = 5) at a primary care health facility in Cape Town, South Africa. Data analysis involved descriptive summaries of key emergent themes with illustrative case examples. We applied a deductive, outcomes-driven analytic approach to the summaries using the Implementation Outcomes Framework proffered by Proctor et al. (2011). The three relevant concepts from this framework that guided our evaluation were: acceptability, appropriateness, and feasibility. We found positive perceptions about the UTRA from many PLHIV and health worker participants. Many PLHIV reported that the immediate results offered by the UTRA could enable them to have constructive discussions with health workers on how to resolve adherence challenges in real-time. Few PLHIV reported concerns that drinking alcohol could affect their UTRA results. Many health workers reported that the UTRA could help them identify patients at risk of treatment failure and immediately intervene through counselling, though some relayed that they would support the UTRA's implementation if more staff members could be added in their busy facility. Overall, these findings show that the UTRA was widely perceived to be acceptable and actionable by many PLHIV and health workers in the study.

Urine tenofovir-monitoring predicts HIV viremia in patients treated with high genetic-barrier regimens.

OBJECTIVE: Access to viral load measurements is constrained in resource-limited settings. A lateral flow urine tenofovir (TFV) rapid assay (UTRA) for patients whose regimens include TFV offers an affordable approach to frequent adherence monitoring. DESIGN: We conducted a cross-sectional study of patients to assess the utility of UTRA to predict virologic failure, defined as a viral load greater than 400 copies/ml. METHODS: We assessed urine TFV among 113 participants at increased risk of viral failure (who had previous viral failure on this regimen or had previously been ≥30 days out of care), comparing low genetic-barrier efavirenz (EFV) regimens (n = 60) to dolutegravir (DTG)-boosted or ritonavir-boosted protease inhibitor (PI/r)-based high genetic-barrier regimens (n = 53). Dried blood spots (DBS) for TFV-diphosphate and plasma for TFV concentrations were collected, with drug resistance assessed if viral failure present. RESULTS: Among 113 participants, 17 of 53 received DTG or PI/r had viral failure at the cross-sectional visit, with 11 (64.7%) demonstrating an undetectable urine TFV; the negative-predictive value (NPV) of undetectable UTRA for viral failure was 85% (34/40); none of the 16 sequenced had dual class drug resistance. In those treated with EFV regimens the sensitivity was lower, as only 1 (4.8%) of 21 with viral failure had an undetectable UTRA (P < 0.001). CONCLUSIONS: Urine tenofovir-testing had a high negative-predictive value for viral failure in patients treated with DTG or ritonavir-boosted protease inhibitor regimens, where viral failure was largely explained by poor drug adherence. Frequent monitoring with inexpensive lateral flow urine TFV testing should be investigated prospectively in between viral load visits to improve viral load suppression on DTG-based first-line therapy in resource-limited settings.

Sequential Lonsdaleite to Diamond Formation in Ureilite Meteorites via In Situ Chemical Fluid/Vapor Deposition.

Ureilite meteorites are arguably our only large suite of samples from the mantle of a dwarf planet and typically contain greater abundances of diamond than any known rock. Some also contain lonsdaleite, which may be harder than diamond. Here, we use electron microscopy to map the relative distribution of coexisting lonsdaleite, diamond, and graphite in ureilites. These maps show that lonsdaleite tends to occur as polycrystalline grains, sometimes with distinctive fold morphologies, partially replaced by diamond + graphite in rims and cross-cutting veins. These observations provide strong evidence for how the carbon phases formed in ureilites, which, despite much conjecture and seemingly conflicting observations, has not been resolved. We suggest that lonsdaleite formed by pseudomorphic replacement of primary graphite shapes, facilitated by a supercritical C-H-O-S fluid during rapid decompression and cooling. Diamond + graphite formed after lonsdaleite via ongoing reaction with C-H-O-S gas. This graphite > lonsdaleite > diamond + graphite formation process is akin to industrial chemical vapor deposition but operates at higher pressure (∼1-100 bar) and provides a pathway toward manufacture of shaped lonsdaleite for industrial application. It also provides a unique model for ureilites that can reconcile all conflicting observations relating to diamond formation.

SARS-CoV-2 Infection Is Associated with Uncontrolled HIV Viral Load in Non-Hospitalized HIV-Infected Patients from Gugulethu, South Africa.

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.

Time Trend Analysis of Tuberculosis Treatment While Using Digital Adherence Technologies-An Individual Patient Data Meta-Analysis of Eleven Projects across Ten High Tuberculosis-Burden Countries.

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.

Patients' and Providers' Views on Optimal Evidence-Based and Scalable Interventions for Individuals at High Risk of HIV Treatment Failure: Sequential Explorations Among Key Stakeholders in Cape Town, South Africa.

To support translation of evidence-based interventions into practice for HIV patients at high risk of treatment failure, we conducted qualitative research in Cape Town, South Africa. After local health officials vetted interventions as potentially scalable, we held 41 in-depth interviews with patients with elevated viral load or a 3-month treatment gap at community clinics, followed by focus group discussions (FGDs) with 20 providers (physicians/nurses, counselors, and community health care workers). Interviews queried treatment barriers, solutions, and specific intervention options, including motivational text messages, data-informed counseling, individual counseling, peer support groups, check-in texts, and treatment buddies. Based on patients' preferences, motivational texts and treatment buddies were removed from consideration in subsequent FGDs. Patients most preferred peer support groups and check-in texts while individual counseling garnered the broadest support among providers. Check-in texts, peer support groups, and data-informed counseling were also endorsed by provider sub-groups. These strategies warrant attention for scale-up in South Africa and other resource-constrained settings.

Tenofovir diphosphate in dried blood spots predicts future viremia in persons with HIV taking antiretroviral therapy in South Africa.

OBJECTIVES: Tenofovir diphosphate (TFV-DP) in dried blood spots (DBS) is used as a biomarker of antiretroviral therapy (ART) adherence. Recent treatment studies have shown that TFV-DP predicts future viremia in persons with HIV (PWH) but there are few data from high-burden settings. We investigated whether TFV-DP in DBS predicts future viral breakthrough in South African PWH. DESIGN: Prospective observational cohort. METHODS: We enrolled 250 adults receiving tenofovir-containing regimens, currently virally suppressed (<50 copies/ml) but at risk of future viral breakthrough, from four primary health clinics in Cape Town. Paired viral load and DBS for TFV-DP were collected monthly for 12 months. Viral breakthrough was the first confirmed viral load greater than 400 copies/ml. Logistic regression estimated the odds ratio (OR) and 95% confidence intervals for future viral breakthrough at the next visit. RESULTS: Participants provided 2944 paired DBS and viral load samples. Median (IQR) age was 34 (27-42) years; median duration on ART at study entry was 11 (4-12) months;78% were women. Twenty-one (8%) participants developed viral breakthrough. Participants with TFV-DP 400 fmol/punch or less had an adjusted OR of 16.1 (95% CI: 3.9-67.4; P < 0.001) for developing viral breakthrough 1 month later compared with participants with TFV-DP greater 800 fmol/punch. CONCLUSION: TFV-DP in DBS strongly predicted future viral breakthrough in a clinical cohort of South African PWH. A biomarker able to identify PWH at risk for future viral breakthrough has the potential to improve health outcomes through timely intervention. Future studies exploring the clinical use of TFV-DP in DBS in conjunction with viral load in ART monitoring are warranted.

Drug Resistance, Rather than Low Tenofovir Levels in Blood or Urine, Is Associated with Tenofovir, Emtricitabine, and Efavirenz Failure in Resource-Limited Settings.

The high cost of viral load (VL) testing limits its use for antiretroviral therapy (ART) adherence support. A low-cost lateral flow urine tenofovir (TFV) rapid assay predicts pre-exposure prophylaxis breakthroughs, but has not yet been investigated in HIV treatment. We therefore evaluated its utility in a pilot cross-sectional study of TFV-containing ART recipients at an increased risk of virologic failure (VF). Participants who had a treatment interruption ≥30 days or had ≥1 episode of viremia (VL ≥400 copies/mL) in the previous year were recruited from a public health setting in Cape Town, South Africa. Self-reported adherence data were collected, the urine TFV assay performed, and concurrent TFV-diphosphate analyzed in dried blood spots. VL testing was done concurrently and, if viremic, genotypic HIV drug resistance testing was performed. Of 48 participants, 18 (37.5%) had VL (>400 copies/mL) at the time of the study, including 16 of 39 receiving efavirenz (EFV), 2 of 6 receiving protease inhibitors, and 0 of 3 receiving dolutegravir. Resistance testing succeeded in 17/18, of which 14 had significant mutations compromising ≥2 agents of the current EFV-based regimen. Of these 14, all had detected urine TFV. Urine TFV was undetectable in two out of three without regimen-relevant resistance; p = .02. In participants on EFV-based regimens returning to care, VF was largely due to viral resistance, where detectable urine TFV had 100% sensitivity (14/14 participants) in predicting resistance. Conversely, when undetectable, the urine-based assay could be used to preclude participants with poor adherence from undergoing costly HIV drug resistance testing.