During the COVID-19 pandemic, the South African Centralized Chronic Medicines Dispensing and Distribution (CCMDD) programme, adapted to include extended 12-month antiretroviral therapy (ART) prescriptions, 3-months ART refills and earlier eligibility criteria at 6-months after ART initiation. We aimed to explore the experiences of healthcare workers (HCWs) in implementing these adaptations, and to understand the overall impact of COVID-19 on CCMDD. We conducted semi-structured in-depth interviews with HCWs in eThekwini District clinics, KwaZulu-Natal, South Africa. Interviews were audio-recorded, transcribed, translated, and analysed thematically. Between 18 February and 13 December 2022, we conducted 21 interviews with nurses, doctors, pharmacists, clinic managers and a community pick-up-point staff member. There were mixed perceptions about COVID-19 adaptations to CCMDD. HCWs reported that COVID-19 adaptations to CCMDD helped keep clients away from clinics, reducing exposure to COVID-19, minimizing queues, alleviating client frustration, and easing workload, which enabled more focused attention on clients with greater needs. Clients reportedly preferred 12-month prescriptions as it gave them independence. However, HCWs were concerned about clients' ART adherence, potential to miss out on clinical input, and difficulties aligning annual viral load results, during the 12 months without clinic attendance. The extended eligibility and multi-month dispensing were acceptable to HCWs, but concerns were expressed about non-adherence and stock shortages. Challenges, including staff shortages due to sickness, increased workload, inadequate training, HCWs' distrust in clients' ability to manage their health autonomously, and staff's limited involvement in decisions about the adaptations, impacted on their implementation. While HCWs reported benefits of 12-month prescribing, extended eligibility and multi-month dispensing in CCMDD, long-term implementation would require addressing concerns about impacts on adherence, alignment of annual viral loads and timely follow up. Prioritizing HCW input in decision-making processes and enhancing provider-client interactions will be pivotal in ensuring the effectiveness of CCMDD adaptations.
BACKGROUND Routinely recorded primary care data have been used for many years by sentinel networks for surveillance. More recently, real world data have been used for a wider range of research projects to support rapid, inexpensive clinical trials. Because the partial national lockdown in the United Kingdom due to the coronavirus disease (COVID-19) pandemic has resulted in decreasing community disease incidence, much larger numbers of general practices are needed to deliver effective COVID-19 surveillance and contribute to in-pandemic clinical trials. OBJECTIVE The aim of this protocol is to describe the rapid design and development of the Oxford Royal College of General Practitioners Clinical Informatics Digital Hub (ORCHID) and its first two platforms. The Surveillance Platform will provide extended primary care surveillance, while the Trials Platform is a streamlined clinical trials platform that will be integrated into routine primary care practice. METHODS We will apply the FAIR (Findable, Accessible, Interoperable, and Reusable) metadata principles to a new, integrated digital health hub that will extract routinely collected general practice electronic health data for use in clinical trials and provide enhanced communicable disease surveillance. The hub will be findable through membership in Health Data Research UK and European metadata repositories. Accessibility through an online application system will provide access to study-ready data sets or developed custom data sets. Interoperability will be facilitated by fixed linkage to other key sources such as Hospital Episodes Statistics and the Office of National Statistics using pseudonymized data. All semantic descriptors (ie, ontologies) and code used for analysis will be made available to accelerate analyses. We will also make data available using common data models, starting with the US Food and Drug Administration Sentinel and Observational Medical Outcomes Partnership approaches, to facilitate international studies. The Surveillance Platform will provide access to data for health protection and promotion work as authorized through agreements between Oxford, the Royal College of General Practitioners, and Public Health England. All studies using the Trials Platform will go through appropriate ethical and other regulatory approval processes. RESULTS The hub will be a bottom-up, professionally led network that will provide benefits for member practices, our health service, and the population served. Data will only be used for SQUIRE (surveillance, quality improvement, research, and education) purposes. We have already received positive responses from practices, and the number of practices in the network has doubled to over 1150 since February 2020. COVID-19 surveillance has resulted in tripling of the number of virology sites to 293 (target 300), which has aided the collection of the largest ever weekly total of surveillance swabs in the United Kingdom as well as over 3000 severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) serology samples. Practices are recruiting to the PRINCIPLE (Platform Randomised trial of INterventions against COVID-19 In older PeopLE) trial, and these participants will be followed up through ORCHID. These initial outputs demonstrate the feasibility of ORCHID to provide an extended national digital health hub. CONCLUSIONS ORCHID will provide equitable and innovative use of big data through a professionally led national primary care network and the application of FAIR principles. The secure data hub will host routinely collected general practice data linked to other key health care repositories for clinical trials and support enhanced in situ surveillance without always requiring large volume data extracts. ORCHID will support rapid data extraction, analysis, and dissemination with the aim of improving future research and development in general practice to positively impact patient care. INTERNATIONAL REGISTERED REPORT DERR1-10.2196/19773
The global public health community has set ambitious treatment targets to end the HIV/AIDS pandemic. With the notable absence of a cure, the goal of HIV treatment is to achieve sustained suppression of an HIV viral load, which allows for immunological recovery and reduces the risk of onward HIV transmission.
We analyzed the STREAM (Simplifying HIV TREAtment and Monitoring) study to determine risk factors associated with HIV viraemia and poor retention 18 months after initiation of antiretroviral therapy (ART).
Abstract Introduction There is an urgent need for more efficient models of differentiated antiretroviral therapy (ART) delivery for people living with HIV (PLHIV), with the World Health Organization calling for evidence to guide whether annual ART prescriptions and consultations (12M scripts) should be recommended in global guidelines. We assessed the association between 12M scripts (allowed temporarily during the COVID-19 pandemic) versus standard 6-month prescriptions and clinical review (6M scripts) and clinical outcomes. Methods We performed a retrospective cohort study using routine, de-identified data from 59 public clinics in KwaZulu-Natal, South Africa. We included PLHIV aged > 18 years with a recent suppressed viral load (VL) who had been referred for community ART delivery with 6M or 12M scripts. We used modified Poisson regression to compare 12-month retention-in-care (not >90 days late for any visit) and viral suppression (<50 copies/mL) between prescription groups. Results Among 27,148 PLHIV referred for community ART between Jun-Dec 2020, 42.6% received 6M scripts and 57.4% 12M scripts. The median age was 39 years (interquartile range [IQR] 33-46) and 69.4% were women. Age, gender, prior community ART use and time on ART were similar in the two groups. However, more of the 12M script group had a dolutegravir-based regimen (60.0% versus 46.3%). The median (IQR) number of clinic visits in the 12 months of follow-up was 1(1-1) in the 12M group and 2(2-3) in the 6M group. Retention at 12 months was 94.6% (95% confidence interval [CI] 94.2%-94.9%) among those receiving 12M scripts and 91.8% (95% CI 91.3%-92.3%) among those with 6M scripts. 17.1% and 16.9% of clients in the 12M and 6M groups were missing follow-up VL data, respectively. Among those with VLs, 91.0% (95% CI 90.5%-91.5%) in the 12M group and 89.7% (95% CI 89.0%-90.3%) in the 6M group were suppressed. After adjusting for age, gender, ART regimen, time on ART, prior community ART use and calendar month, retention (adjusted risk ratio [aRR]: 1.03, 95% CI 1.01-1.05) and suppression (aRR: 1.01, 95% CI 1.00-1.02) were similar in the prescription groups. Conclusions Wider use of 12M scripts could reduce clinic visits without impacting short-term clinical outcomes.
Abstract Introduction There is little data on long‐term implementation and outcomes for people living with HIV (PLHIV) in differentiated antiretroviral therapy (ART) delivery programmes. We aimed to analyse usage patterns of and associated treatment outcomes in a community ART programme, within the Centralized Chronic Medicines Dispensing and Distribution programme, in South Africa over 3.5 years. Methods We performed a retrospective cohort study among PLHIV on first‐line ART who were eligible for community ART delivery between October 2016 and March 2019, from 56 urban clinics in KwaZulu‐Natal, South Africa. Follow‐up ended in March 2020. We measured referral rates and, among those referred, we characterized patterns of community ART usage using group‐based trajectory modelling following referral. We used survival analysis to measure the association between community ART usage and loss‐to‐care (no visit for ≥365 days) and logistic regression to measure the association between community ART usage and viraemia (≥50 copies/ml). Results Among the 80,801 patients eligible for community ART, the median age was 36 years, 69.8% were female and the median (interquartile range [IQR]) follow‐up time was 22 (13–31) months. In total, 49,961 (61.8%) were referred after a median of 6 (IQR 2–13) months from first eligibility. After referral, time spent in community ART varied; 42% remained consistently in community ART, 15% returned to consistent clinic‐based care and the remaining 43% oscillated between community ART and clinic‐based care. Following referral, the incidence of loss‐to‐care was 3.93 (95% confidence interval [CI]: 3.71–4.15) per 100 person‐years during periods of community ART usage compared to 5.75 (95% CI: 5.28–6.25) during clinic‐based care. In multivariable models, community ART usage was associated with a 36% reduction in the hazards of loss‐to‐care (adjusted hazard ratio: 0.64 [95% CI: 0.57–0.72]). The proportion of patients who became viraemic after first community ART referral was 5.2% and a 10% increase in time in community ART was associated with a 3% reduction in odds of viraemia (adjusted odds ratio: 0.97 [95% CI: 0.95–0.99]). Conclusions Community ART usage patterns vary considerably, while clinical outcomes were good. Promoting consistent community ART usage may reduce clinic burden and the likelihood of patients being lost to care, while sustaining viral suppression.
The effect of the COVID-19 pandemic on HIV outcomes in low-income and middle-income countries is poorly described. We aimed to measure the impact of the 2020 national COVID-19 lockdown on HIV testing and treatment in KwaZulu-Natal, South Africa, where 1·7 million people are living with HIV.In this interrupted time series analysis, we analysed anonymised programmatic data from 65 primary care clinics in KwaZulu-Natal province, South Africa. We included data from people testing for HIV, initiating antiretroviral therapy (ART), and collecting ART at participating clinics during the study period, with no age restrictions. We used descriptive statistics to summarise demographic and clinical data, and present crude summaries of the main outcomes of numbers of HIV tests per month, ART initiations per week, and ART collection visits per week, before and after the national lockdown that began on March 27, 2020. We used Poisson segmented regression models to estimate the immediate impact of the lockdown on these outcomes, as well as post-lockdown trends.Between Jan 1, 2018, and July 31, 2020, we recorded 1 315 439 HIV tests. Between Jan 1, 2018, and June 15, 2020, we recorded 71 142 ART initiations and 2 319 992 ART collection visits. We recorded a median of 41 926 HIV tests per month before lockdown (January, 2018, to March, 2020; IQR 37 838-51 069) and a median of 38 911 HIV tests per month after lockdown (April, 2020, to July, 2020; IQR 32 699-42 756). In the Poisson regression model, taking into account long-term trends, lockdown was associated with an estimated 47·6% decrease in HIV testing in April, 2020 (incidence rate ratio [IRR] 0·524, 95% CI 0·446-0·615). ART initiations decreased from a median of 571 per week before lockdown (IQR 498-678), to 375 per week after lockdown (331-399), with an estimated 46·2% decrease in the Poisson regression model in the first week of lockdown (March 30, 2020, to April 5, 2020; IRR 0·538, 0·459-0·630). There was no marked change in the number of ART collection visits (median 18 519 visits per week before lockdown [IQR 17 074-19 922] vs 17 863 visits per week after lockdown [17 509-18 995]; estimated effect in the first week of lockdown IRR 0·932, 95% CI 0·794-1·093). As restrictions eased, HIV testing and ART initiations gradually improved towards pre-lockdown levels (slope change 1·183/month, 95% CI 1·113-1·256 for HIV testing; 1·156/month, 1·085-1·230 for ART initiations).ART provision was generally maintained during the 2020 COVID-19 lockdown, but HIV testing and ART initiations were heavily impacted. Strategies to increase testing and treatment initiation should be implemented.Wellcome Trust, Africa Oxford Initiative.
Background The HIV protease inhibitor lopinavir, boosted with ritonavir, has been used off-label to treat COVID-19. We aimed to synthesize the clinical evidence for lopinavir/ ritonavir as a treatment for COVID-19. Methods We performed a rapid review by searching databases including PubMed, GoogleScholar, medRxiv, ClinicalTrials.gov and the Cochrane COVID-19 Study Register, for COVID-19 studies comparing outcomes between patients who did and did not receive lopinavir/ritonavir. The quality of evidence was assessed using the GRADE criteria. Results We identified five completed randomized controlled trials (RCTs) and 14 retrospective cohort studies. Two large RCTs of 5,040 and 2,771 hospitalized adults with COVID-19 found no evidence that lopinavir/ritonavir influenced the primary outcome of mortality, or secondary outcomes including progression to mechanical ventilation or time to discharge. Results remained similar in all subgroup analyses including by age, gender, baseline ventilation and time since symptom onset. The three smaller RCTs ( n=86–199) also found no evidence of a benefit in the primary outcomes of time to clinical improvement or time to viral clearance. The 14 observational studies included between 50 and 415 participants, and were limited by a lack of adjustment for potential confounding variables. The majority of these studies found no evidence that lopinavir/ritonavir was associated with improved mortality or other clinical outcomes, although results regarding viral clearance were mixed. Conclusions Good evidence from large clinical trials does not support using lopinavir/ritonavir to treat COVID-19 amongst hospitalized patients.
Background Colchicine has been proposed as a COVID-19 treatment. Aim To determine whether colchicine reduces time to recovery and COVID-19-related admissions to hospital and/or deaths among people in the community. Design and setting Prospective, multicentre, open-label, multi-arm, randomised, controlled, adaptive platform trial (PRINCIPLE). Method Adults aged ≥65 years or ≥18 years with comorbidities or shortness of breath, and unwell for ≤14 days with suspected COVID-19 in the community, were randomised to usual care, usual care plus colchicine (500 µg daily for 14 days), or usual care plus other interventions. The co-primary endpoints were time to first self-reported recovery and admission to hospital/death related to COVID-19, within 28 days, analysed using Bayesian models. Results The trial opened on 2 April 2020. Randomisation to colchicine started on 4 March 2021 and stopped on 26 May 2021 because the prespecified time to recovery futility criterion was met. The primary analysis model included 2755 participants who were SARS-CoV-2 positive, randomised to colchicine ( n = 156), usual care ( n = 1145), and other treatments ( n = 1454). Time to first self-reported recovery was similar in the colchicine group compared with usual care with an estimated hazard ratio of 0.92 (95% credible interval (CrI) = 0.72 to 1.16) and an estimated increase of 1.4 days in median time to self-reported recovery for colchicine versus usual care. The probability of meaningful benefit in time to recovery was very low at 1.8%. COVID-19-related admissions to hospital/deaths were similar in the colchicine group versus usual care, with an estimated odds ratio of 0.76 (95% CrI = 0.28 to 1.89) and an estimated difference of −0.4% (95% CrI = −2.7 to 2.4). Conclusion Colchicine did not improve time to recovery in people at higher risk of complications with COVID-19 in the community.
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