Effectiveness of Dolutegravir in People on Rifampin-Based Tuberculosis Treatment

Background: Tenofovir-lamivudine-dolutegravir (TLD) is the WHO-preferred first-line regimen for people with HIV, but drug-drug interactions between dolutegravir (DTG) and rifampin (RIF) require an additional 50mg DTG (TLD+50) in people receiving tuberculosis (TB)/HIV co-treatment. RIF is a key drug in TB treatment, but is a potent inducer of metabolizing enzymes and efflux transporters, which can markedly lower drug concentrations. There are limited data on the effectiveness of TLD+50 in people with TB/HIV from program settings. Method(s): We conducted a prospective, observational study at 12 sites in 6 countries (Haiti, Kenya, Malawi, South Africa, Uganda, Zimbabwe). Participants received concomitant TLD+50 and RIF-based TB treatment provided as standard of care by HIV and TB treatment programs. Primary outcome was HIV-1 RNA <1000 copies/mL (cpm) at end of TB treatment. New DTG resistance mutations were defined as those present at end of TB treatment but not present at start. Result(s): From 11/2019-6/2021, we enrolled 91 participants with TB/HIV, including 75 ART-naive participants (82%) starting TLD+50 after a median of 15 days on TB treatment, 10 ART-naive participants (11%) starting TLD+50 and RIF together, 5 (5%) starting TB treatment and changing to TLD+50 after a median of 3.3y on TLD, and 1 (1%) starting RIF and TLD+50 after changing from EFV/3TC/TDF. Median age was 37y (IQR 32-43), 35% were female, 100% cis-gender, median CD4 count was 120 cells/mm3 (IQR 50-295), 87% had HIV-1 RNA >1000 copies/mL. Two participants died during TB treatment (week 4 disseminated TB, week 12 suspected COVID-19), 1 interrupted TLD+50 due to jaundice;and 1 discontinued TB treatment due to drug-induced liver injury. Among 89 surviving participants, 6 were lost to follow-up and a further 10 had no HIV-1 RNA result due to missed or remote visits. Primary virologic outcome was therefore assessed in 73 (80%), of whom 69 (95%, Wald 95% CI 89-100%) had HIV-1 RNA <=1000 cpm;68 (93%) had HIV-1 RNA <200 cpm. No sex specific differences in viral suppression were observed. No DTG resistance mutations were detected among 4 participants with HIV-1 RNA >1000 cpm. Conclusion(s): Concomitant RIF-containing TB treatment and TLD+50 was welltolerated and achieved excellent viral suppression in a cohort of predominantly ART-naive people with TB/HIV. These multi-country data from program settings support feasibility and effectiveness of current treatment approaches for TB/ HIV co-infection.

Charting the ‘new normal’ in Canadian community pharmacy practice: scoping review

IntroductionTo identify the Canada-wide changes in community pharmacy practice in response to the COVID-19 pandemic and to assess what is currently being practiced.What are the emerging practices and regulations that keep community pharmacies safe (customers and professionals) during the COVID-19 pandemic and what are the implications of these changes?MethodsReview includes primary studies (i.e., experimental, quasi-experimental, observational, and qualitative study designs) and grey literature that broadly focused on policies, regulations, and recommendations developed for Canadian community pharmacies during the COVID-19 pandemic. Study s and full texts were screened for eligibility by two reviewers, independently. Data extraction of relevant studies were also done independently by two reviewers. All discrepancies were addressed through further discussion or adjudicated by a third reviewer. Presentation of the extracted data focuses on descriptive frequencies and thematic analysis and the results are presented in diagrammatic or tabular form, with a narrative summary of the findings.ResultsTeam members screened fifty-five citations and considered five to meet the inclusion criteria, with an additional 449 grey literature items. Pharmacists rely on regulatory and professional associations as their primary information source, yet corporate employers were found to offer better resources for communicating policies to pharmacists.1 In the pan-Canadian context, Health Canada granted pharmacists new permissions for prescribing, including extending and renewing prescriptions2 3 while simultaneously recommending that pharmacists should limit patient medication supplies.2 4 Although COVID-19 updates were regularly being sent by regulatory bodies and national associations, pharmacists were either unaware of where to find or did not understand available information.1 2 4 5DiscussionAs Canada emerges from the COVID-19 pandemic, there is a ‘new normal’ for community pharmacy practice, or an expanded role in the overall healthcare system. This review adds to the understanding of how pharmacies faced challenges of incorporating rapidly evolving information into practice, while maintaining client care and worker safety.ReferencesAustin Z, Gregory P. Resilience in the time of pandemic: the experience of community pharmacists during COVID-19. Research in Social and Administrative Pharmacy 2021;17(1):1867–75.Elbeddini A, Hooda N, Yang L. Role of Canadian pharmacists in managing drug shortage concerns amid the COVID-19 pandemic. Canadian Pharmacists Journal/Revue des Pharmaciens du Canada 2020;153(4):198–203.Merks P, Jakubowska M, Drelich E, Świeczkowski D, Bogusz J, Bilmin K, et al. The legal extension of the role of pharmacists in light of the COVID-19 global pandemic. Research in Social and Administrative Pharmacy 2021;17(1):1807–12.Elbeddini A, Botross A, Gerochi R, Gazarin M, Elshahawi A. Pharmacy response to COVID-19: lessons learnt from Canada. Journal of Pharmaceutical Policy and Practice 2020;13(1):1–8.Gregory PAM, Austin Z. COVID-19: how did community pharmacies get through the first wave? Canadian Pharmacists Journal/Revue des Pharmaciens du Canada 2020;153(5):243–51.

EFFICACY of TENOFOVIR-LAMIVUDINE-DOLUTEGRAVIR for INITIAL and FIRST-LINE SWITCH ART

Background: Single-tablet tenofovir disoproxil fumarate/lamivudine/dolutegravir (TLD) has been rapidly adopted as 1st-line ART for patients initiating treatment and switching from virally-suppressive NNRTI-based 1st regimens in PEPFAR programs. There are limited data, however, on effectiveness and emergence of resistance to TLD in programmatic settings where plasma HIV-1 RNA and drug resistance testing are not used widely. Methods: A prospective observational study is being performed at 13 ACTG sites in six countries (Haiti, Kenya, Malawi, South Africa, Uganda, Zimbabwe) coincident with TLD rollout to assess efficacy and emergence of HIV drug resistance following TLD for 1st, 2nd or 3rd-line ART. This report focuses on the 2 Groups that completed enrollment and 6 months of follow-up: Group 1b (Gp1b) participants on NNRTI-based ART for at least 6 months with HIV-1 RNA ≤1000 cps/mL before switch to TLD;and Group 4 (Gp4) ART-naïve participants initiating 1st-line TLD. The primary objective was to estimate the proportions of participants on TLD with HIV-1 RNA ≤1000 cps/mL and with new DTG resistance mutations at 6 months. Results:\From 10/2019-10/2020, we enrolled 600 participants who started TLD: 421 in Gp1b (median age 41years;80% female) and 179 in Gp4 (median age 35years;42% female). In Gp1b, median time on ART was 6.6y (IQR 3.3-10.3);88% were taking EFV with 3TC+TDF or FTC+TDF. In Gp4, median baseline HIV-1 RNA was 4.4 log10 cps/mL (IQR 3.5-5.1). Six participants in Gp1b (1.4%) and 6 in Gp4 (3.4%) discontinued TLD by 6 months, due to withdrawal or loss to follow-up (6 participants), adverse events considered related to TLD (4), and death (2;both Gp4;1 from TB, 1 unknown cause). Among participants followed on TLD to 6 months, 90% in Gp1b (373/415) and 86% in Gp4 (149/173) had a 6-month HIV-1 RNA result (missing values mainly due to COVID-related virtual visits). HIV-1 RNA ≤1000, <200 and <50 cps/mL was achieved in 99%, 98.4%, and 96% of participants in Gp1b and in 90%, 87.2%, and in 84.6% of Gp4, respectively (Table). A new mutation possibly selected by DTG was observed in 1 participant in Gp1b (T97AT) and none in Gp4. Conclusion: TLD was well tolerated and achieved excellent viral suppression in ART-naïve participants and in participants who switched from virally-suppressive 1st-line ART. An emerging InSTI mutation of uncertain significance was seen in only one participant. These data support early tolerability and efficacy of TLD transition in the public sector.

PEPFAR's response to the convergence of the HIV and COVID-19 pandemics in Sub-Saharan Africa

The COVID-19 pandemic reached the African continent in less than three months from when the first caseswere reported from mainland China. As COVID-19 preparedness and response plans were rapidly instituted across sub-Saharan Africa, many governments and donor organizations braced themselves for the unknown impact the COVID-19 pandemicwould have in under-resourced settings with high burdens of PLHIV. The potential negative impact of COVID-19 inthese countries is uncertain, but is estimated to contribute both directly and indirectly to the morbidity and mortality ofPLHIV, requiring countries to leverage existing HIV care systems to propel COVID-19 responses, while safeguarding PLHIVand HIV programme gains. In anticipation of COVID-19-related disruptions, PEPFAR promptly established guidance to rapidlyadapt HIV programmes to maintain essential HIV services while protecting recipients of care and staff from COVID-19. Thiscommentary reviews PEPFARs COVID-19 technical guidance and provides country-specific examples of programme adaptionsin sub-Saharan Africa.

Mental health & maltreatment risk of children with special educational needs during COVID-19.

BACKGROUND: Children with special educational needs (SEN) are more vulnerable during the COVID-19 pandemic with risk of poor mental wellbeing and child maltreatment. OBJECTIVE: To examine the impact of COVID-19 on the mental health of children with SEN and their maltreatment risk. PARTICIPANTS AND SETTING: 417 children with SEN studying at special schools and 25,427 children with typical development (TD) studying at mainstream schools completed an online survey in April 2020 in Hong Kong during school closures due to COVID-19. METHOD: Emotional/behavioural difficulties, quality of life and parental stress of children with SEN were compared with typically developed children using mixed effect model. Linear regression analyses were performed to explore factors associated with child emotional/behavioural difficulties and parental stress during the pandemic. Chi-square test was performed to detect the differences in maltreatment risk before and during COVID-19. RESULTS: Children with SEN had significantly poorer overall quality of life (68.05 vs 80.65, p < 0.01). 23.5% of children had at least one episode of severe physical assault and 1.9% experienced very severe physical assault during COVID-19. Rates of physical assault increased significantly (59.8% vs. 71.2% p < 0.001) while children with mental disorders had increased risk of severe physical assault comparing to those without mental disorders (RR = 1.58, ꭓ2 = 5.19 p = 0.023). CONCLUSION: Children with SEN had poorer mental health than typically developed children during the COVID-19 pandemic. Maltreatment risk for children with SEN is higher in comparison to pre-COVID-19 era. Surveillance of child maltreatment, continuity of medical and rehabilitation care to support children with SEN are essential during a disease pandemic.

Assessment of SARS-CoV-2 Immunity in Convalescent Children and Adolescents.

Persistence of protective immunity for SARS-CoV-2 is important against reinfection. Knowledge on SARS-CoV-2 immunity in pediatric patients is currently lacking. We opted to assess the SARS-CoV-2 adaptive immunity in recovered children and adolescents, addressing the pediatrics specific immunity towards COVID-19. Two independent assays were performed to investigate humoral and cellular immunological memory in pediatric convalescent COVID-19 patients. Specifically, RBD IgG, CD4+, and CD8+ T cell responses were identified and quantified in recovered children and adolescents. SARS-CoV-2-specific RBD IgG detected in recovered patients had a half-life of 121.6 days and estimated duration of 7.9 months compared with baseline levels in controls. The specific T cell response was shown to be independent of days after diagnosis. Both CD4+ and CD8+ T cells showed robust responses not only to spike (S) peptides (a main target of vaccine platforms) but were also similarly activated when stimulated by membrane (M) and nuclear (N) peptides. Importantly, we found the differences in the adaptive responses were correlated with the age of the recovered patients. The CD4+ T cell response to SARS-CoV-2 S peptide in children aged <12 years correlated with higher SARS-CoV-2 RBD IgG levels, suggesting the importance of a T cell-dependent humoral response in younger children under 12 years. Both cellular and humoral immunity against SARS-CoV-2 infections can be induced in pediatric patients. Our important findings provide fundamental knowledge on the immune memory responses to SARS-CoV-2 in recovered pediatric patients.

Hiv treatment/retention in sub-saharan africa before and during the covid-19 pandemic

Background: In sub-Saharan Africa (SSA), the COVID-19 pandemic and response has posed a challenge for HIV prevention, testing, and treatment. We used routinely collected President's Emergency Plan for AIDS Relief (PEPFAR) Monitoring, Evaluation, and Reporting (MER) data to assess potential loss to follow-up (LTFU) across PEPFAR countries in SSA before and during the pandemic to determine the impact of COVID-19 on HIV clinical treatment. Methods: Treatment and LTFU data for people living with HIV (PLHIV) aged 15+ from Oct - Dec 2019 (fiscal year[FY]20 quarter[Q]1;pre-COVID) and Apr - Jun 2020 (FY20Q3;during COVID-19) were extracted from two MER indicators: TX-CURR (PLHIV on treatment) and TX-ML (tracking outcomes of PLHIV potentially LTFU) for 18 countries in SSA. Aggregate indicator data are not linked. Data were disaggregated by age band (15-19, 20-29, 30-39, 40-49, 50+) and sex. Proportions of potential LTFU were calculated as total number of PLHIV with no known clinical contact since last expected contact divided by total PLHIV on treatment during the reporting quarter. Proportions of select outcomes of potential LTFU (Died, LTFU <3 months since last expected clinical contact, LTFU ≥3 months since last expected clinical contact) were calculated as total individual outcome divided by total LTFU. Analyses were disaggregated by reporting quarter, age band, and sex and paired t-tests were run to test for statistical significance between quarters. Results: Number of PLHIV LTFU was 644,380 in FY20Q1 and 740,112 in FY20Q3 across the 18 countries. Proportion of any LTFU outcome was 4.9% and 5.3% for the two quarters, respectively, and was higher overall among men and those aged 20-29, although not statistically significant (Table). Among all LTFU, an increase in deaths and in LTFU ≥3 months among men and a decrease in LTFU <3 months among women and all age bands were statistically significant. Conclusion: The proportion of LTFU <3 months decreased during the early months of the COVID-19 pandemic in SSA, which, in part, may be attributed to adaptations in HIV programming implemented to mitigate further transmission of COVID-19. These data give an initial indication that the COVID-19 pandemic may have implications for HIV treatment in the coming months and ongoing data review is critical.

“Flash blending” development finance: how to make aid donor-private sector partnerships help meet the SDGs

Aid donors, development advocates, and finance experts increasingly look to the private sector to fill the estimated $2.5 trillion annual Sustainable Development Goals financing gap, an amount likely to increase due to effects of COVID-19. Donors use a variety of partnerships with the private sector to realise development objectives. We use the term donor-private partnerships (DPPs) to describe the broad range of arrangements between donors and private-sector actors. Using ODA to leverage private finance, innovation testing, or service delivery, modalities include blended finance, de-risking instruments, public-private partnerships, and more. Does the reality match donors’ enthusiastic rhetoric? There are success stories but civil society actors and others question whether private-sector engagement in development reduces poverty and inequality, advances gender justice, and achieves environmental sustainability. There may be trade-offs between development and profit making. We present our research based on frameworks we developed to categorise and assess DPPs. We applied these to 20 partnerships involving nine donors and found that donors fail to sufficiently integrate development, human rights, and environmental standards. They inconsistently implement due diligence and risk management requirements, and impact assessments are inadequate. Our frameworks offer practitioners and academics valuable tools to examine how DPPs can advance sustainable development. © 2021 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.

Multilevel Factors Affecting Healthcare Workers' Perceived Stress and Risk of Infection During COVID-19 Pandemic.

Objectives: This study aimed to identify key factors affecting Healthcare workers (HCWs) perceived stress and risk of contracting COVID-19 among themselves and their family members during the pandemic. Methods: A cross-sectional online questionnaire study was conducted between 19 March and April 5, 2020 in Hong Kong. HCWs from public hospitals and private dentists, and their family members participated. Results: A total of 747 HCWs and 245 family members participated. Higher perceived stress in HCWs was associated with more negative changes in family relationship (p = 0.025). The HCWs' perceived stress, however, was positively associated with family cohesion (p = 0.033) and stress levels of family members (p < 0.001). The level of HCWs' satisfaction toward the hospital policies in response to the COVID-19 outbreak was associated with lower levels of perceived stress and risk of themselves or their family members contracting COVID-19. HCWs' previous frontline experience of SARS was significantly associated with less perceived risk of themselves or their family members contracting COVID-19. Conclusion: Hospital policies addressing HCWs' needs, frontline experience of SARS, and family relationship influenced psychological wellbeing of HCWs during the COVID-19 outbreak.

Saliva viral load better correlates with clinical and immunological profiles in children with coronavirus disease 2019.

BACKGROUND: Pediatric COVID-19 studies exploring the relationships between NPS and saliva viral loads, clinical and immunological profiles are lacking. METHODS: Demographics, immunological profiles, nasopharyngeal swab (NPS), and saliva samples collected on admission, and hospital length of stay (LOS) were assessed in children below 18 years with COVID-19. FINDINGS: 91 patients were included between March and August 20 20. NPS and saliva viral loads were correlated (r = 0.315, p = 0.01). Symptomatic patients had significantly higher NPS and saliva viral loads than asymptomatic patients. Serial NPS and saliva viral load measurements showed that the log10 NPS (r = -0.532, p < 0.001) and saliva (r = -0.417, p < 0.001) viral loads for all patients were inversely correlated with the days from symptom onset with statistical significance. Patients with cough, sputum, and headache had significantly higher saliva, but not NPS, viral loads. Higher saliva, but not NPS, viral loads were associated with total lymphopenia, CD3 and CD4 lymphopenia (all p < 0.05), and were inversely correlated with total lymphocyte (r = -0.43), CD3 (r = -0.55), CD4 (r = -0.60), CD8 (r = -0.41), B (r = -0.482), and NK (r = -0.416) lymphocyte counts (all p < 0.05). INTERPRETATION: Saliva viral loads on admission in children correlated better with clinical and immunological profiles than NPS.

Vulnerability and resilience in children during the COVID-19 pandemic.

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic is having a profound impact on the health and development of children worldwide. There is limited evidence on the impact of COVID-19 and its related school closures and disease-containment measures on the psychosocial wellbeing of children; little research has been done on the characteristics of vulnerable groups and factors that promote resilience. METHODS: We conducted a large-scale cross-sectional population study of Hong Kong families with children aged 2-12 years. Parents completed an online survey on family demographics, child psychosocial wellbeing, functioning and lifestyle habits, parent-child interactions, and parental stress during school closures due to COVID-19. We used simple and multiple linear regression analyses to explore factors associated with child psychosocial problems and parental stress during the pandemic. RESULTS: The study included 29,202 individual families; of which 12,163 had children aged 2-5 years and 17,029 had children aged 6-12 years. The risk of child psychosocial problems was higher in children with special educational needs, and/or acute or chronic disease, mothers with mental illness, single-parent families, and low-income families. Delayed bedtime and/or inadequate sleep or exercise duration, extended use of electronic devices were associated with significantly higher parental stress and more psychosocial problems among pre-schoolers. CONCLUSIONS: This study identifies vulnerable groups of children and highlights the importance of strengthening family coherence, adequate sleep and exercise, and responsible use of electronic devices in promoting psychosocial wellbeing during the COVID-19 pandemic.

A Comparison Between Chinese Children Infected with Coronavirus Disease-2019 and with Severe Acute Respiratory Syndrome 2003.

OBJECTIVES: To compare the clinical and laboratory features of severe acute respiratory syndrome 2003 (SARS) and coronavirus disease 2019 (COVID-19) in 2 Chinese pediatric cohorts, given that the causative pathogens and are biologically similar. STUDY DESIGN: This is a cross-sectional study reviewing pediatric patients with SARS (n = 43) and COVID-19 (n = 244) who were admitted to the Princess Margaret Hospital in Hong Kong and Wuhan Children's Hospital in Wuhan, respectively. Demographics, hospital length of stay, and clinical and laboratory features were compared. RESULTS: Overall, 97.7% of patients with SARS and 85.2% of patients with COVID-19 had epidemiologic associations with known cases. Significantly more patients with SARS developed fever, chills, myalgia, malaise, coryza, sore throat, sputum production, nausea, headache, and dizziness than patients with COVID-19. No patients with SARS were asymptomatic at the time of admission, whereas 29.1% and 20.9% of patients with COVID-19 were asymptomatic on admission and throughout their hospital stay, respectively. More patients with SARS required oxygen supplementation than patients with COVID-19 (18.6 vs 4.7%; P = .004). Only 1.6% of patients with COVID-19 and 2.3% of patients with SARS required mechanical ventilation. Leukopenia (37.2% vs 18.6%; P = .008), lymphopenia (95.4% vs 32.6%; P < .01), and thrombocytopenia (41.9% vs 3.8%; P < .001) were significantly more common in patients with SARS than in patients with COVID-19. The duration between positive and negative nasopharyngeal aspirate and the length in hospital stay were similar in patients with COVID-19, regardless of whether they were asymptomatic or symptomatic, suggesting a similar duration of viral shedding. CONCLUSIONS: Children with COVID-19 were less symptomatic and had more favorable hematologic findings than children with SARS.

Haematological and immunological data of Chinese children infected with coronavirus disease 2019.

Haematological and immunological data of children with COVID-19 infection is lacking. Between 21st January and 20th March 2020, 244 children who were confirmed to have COVID-19 infection and admitted to the Wuhan Children's Hospital, China were retrospectively reviewed. 193 children were considered as symptomatic, which was defined as having either the presence of clinical symptoms or the presence of CT thorax abnormalities. Their haematological and immunological profiles, including complete blood counts, lymphocyte subsets (T, B and NK cell counts), immunoglobulin (Ig) profiles (IgG, IgA and IgM) and cytokine profiles were analysed and compared between the symptomatic and asymptomatic groups. The median values and the interquartile ranges were calculated. Comparison was made using the Mann-Whitney U test. Children with symptomatic COVID-19 infection had significantly lower haemoglobin levels, but higher absolute lymphocyte and monocyte counts, IgG and IgA levels, as well as interleukin 6 (IL-6), IL-10, tumour necrosis factor alpha and interferon gamma levels. The obtained data will be utilized for further studies in comparing children and adults with COVID-19 infections in other parts of the world and with different severity .