The scope of the antimicrobial resistance challenge.

Each year, an estimated 7·7 million deaths are attributed to bacterial infections, of which 4.95 million are associated with drug-resistant pathogens, and 1·27 million are caused by bacterial pathogens resistant to the antibiotics available. Access to effective antibiotics when indicated prolongs life, reduces disability, reduces health-care expenses, and enables access to other life-saving medical innovations. Antimicrobial resistance undoes these benefits and is a major barrier to attainment of the Sustainable Development Goals, including targets for newborn survival, progress on healthy ageing, and alleviation of poverty. Adverse consequences from antimicrobial resistance are seen across the human life course in both health-care-associated and community-associated infections, as well as in animals and the food chain. The small set of effective antibiotics has narrowed, especially in resource-poor settings, and people who are very young, very old, and severely ill are particularly susceptible to resistant infections. This paper, the first in a Series on the challenge of antimicrobial resistance, considers the global scope of the problem and how it should be measured. Robust and actionable data are needed to drive changes and inform effective interventions to contain resistance. Surveillance must cover all geographical regions, minimise biases towards hospital-derived data, and include non-human niches.

Need assessment for HIV drug resistance testing and landscape of current and future technologies in low- and middle-income countries.

Resistance to antiretroviral drugs used to treat HIV is an important and evolving concern, particularly in low- and middle-income countries (LMICs) which have been impacted to the greatest extent by the HIV pandemic. Efforts to monitor the emergence and transmission of resistance over the past decade have shown that drug resistance-especially to the nucleoside analogue and non-nucleoside reverse transcriptase inhibitors-can (and have) increased to levels that can jeopardize the efficacy of available treatment options at the population level. The global shift to integrase-based regimens as the preferred first-line therapy as well as technological advancements in the methods for detecting resistance have had an impact in broadening and diversifying the landscape of and use case for HIV drug resistance testing. This review estimates the potential demand for HIV drug resistance tests, and surveys current testing methodologies, with a focus on their application in LMICs.

Global knowledge gaps on antimicrobial resistance in the human health sector: A scoping review.

OBJECTIVES: To identify and summarize existing global knowledge gaps on antimicrobial resistance (AMR) in human health, focusing on the World Health Organization (WHO) bacterial priority pathogens, Mycobacterium tuberculosis, and selected fungi. METHODS: We conducted a scoping review of gray and peer-reviewed literature, published in English from January 2012 through December 2021, that reported on the prevention, diagnosis, treatment, and care of drug-resistant infections. We extracted relevant knowledge gaps and, through an iterative process, consolidated those into thematic research questions. RESULTS: Of 8409 publications screened, 1156 were included, including 225 (19.5%) from low- and middle-income countries. A total of 2340 knowledge gaps were extracted, in the following areas: antimicrobial research and development, AMR burden and drivers, resistant tuberculosis, antimicrobial stewardship, diagnostics, infection prevention and control, antimicrobial consumption and use data, immunization, sexually transmitted infections, AMR awareness and education, policies and regulations, fungi, water sanitation and hygiene, and foodborne diseases. The knowledge gaps were consolidated into 177 research questions, including 78 (44.1%) specifically relevant to low- and middle-income countries and 65 (36.7%) targeting vulnerable populations. CONCLUSION: This scoping review presents the most comprehensive compilation of AMR-related knowledge gaps to date, informing a priority-setting exercise to develop the WHO Global AMR Research Agenda for the human health sector.

Associated factors for mortality in a COVID-19 colombian cohort: is the third wave relevant when Mu variant was predominant epidemiologically?

OBJECTIVES: To evaluate the association between Colombia's third wave when the Mu variant was predominant epidemiologically (until 75%) in Colombia and COVID-19 all-cause in-hospital mortality. METHODS: In this retrospective cohort, we included hospitalized patients ≥18 years with SARS-CoV-2 infection between March 2020 to September 2021 in ten hospitals from three cities in Colombia. Description analysis, survival, and multivariate Cox regression analyses were performed to evaluate the association between the third epidemic wave and in-hospital mortality. RESULTS: A total of 25,371 patients were included. The age-stratified time-to-mortality curves showed differences according to epidemic waves in patients ≥75 years (log-rank test p = 0.012). In the multivariate Cox analysis, the third wave was not associated with increased mortality relative to the first wave (aHR 0.95; 95%CI 0.84-1.08), but there was an interaction between age ≥75 years and the third wave finding a lower HR for mortality (aHR 0.56, 95%CI 0.36-0.86). CONCLUSIONS: We did not find an increase in in-hospital mortality during the third epidemic wave in which the Mu variant was predominant in Colombia. The reduced hazard in mortality in patients ≥75 years hospitalized in the third wave could be explained by the high coverage of SARS-CoV-2 vaccination in this population and patients with underlying conditions.

Antimicrobial resistance in patients with COVID-19: a systematic review and meta-analysis.

BACKGROUND: Frequent use of antibiotics in patients with COVID-19 threatens to exacerbate antimicrobial resistance. We aimed to establish the prevalence and predictors of bacterial infections and antimicrobial resistance in patients with COVID-19. METHODS: We did a systematic review and meta-analysis of studies of bacterial co-infections (identified within ≤48 h of presentation) and secondary infections (>48 h after presentation) in outpatients or hospitalised patients with COVID-19. We searched the WHO COVID-19 Research Database to identify cohort studies, case series, case-control trials, and randomised controlled trials with populations of at least 50 patients published in any language between Jan 1, 2019, and Dec 1, 2021. Reviews, editorials, letters, pre-prints, and conference proceedings were excluded, as were studies in which bacterial infection was not microbiologically confirmed (or confirmed via nasopharyngeal swab only). We screened titles and abstracts of papers identified by our search, and then assessed the full text of potentially relevant articles. We reported the pooled prevalence of bacterial infections and antimicrobial resistance by doing a random-effects meta-analysis and meta-regression. Our primary outcomes were the prevalence of bacterial co-infection and secondary infection, and the prevalence of antibiotic-resistant pathogens among patients with laboratory-confirmed COVID-19 and bacterial infections. The study protocol was registered with PROSPERO (CRD42021297344). FINDINGS: We included 148 studies of 362 976 patients, which were done between December, 2019, and May, 2021. The prevalence of bacterial co-infection was 5·3% (95% CI 3·8-7·4), whereas the prevalence of secondary bacterial infection was 18·4% (14·0-23·7). 42 (28%) studies included comprehensive data for the prevalence of antimicrobial resistance among bacterial infections. Among people with bacterial infections, the proportion of infections that were resistant to antimicrobials was 60·8% (95% CI 38·6-79·3), and the proportion of isolates that were resistant was 37·5% (26·9-49·5). Heterogeneity in the reported prevalence of antimicrobial resistance in organisms was substantial (I2=95%). INTERPRETATION: Although infrequently assessed, antimicrobial resistance is highly prevalent in patients with COVID-19 and bacterial infections. Future research and surveillance assessing the effect of COVID-19 on antimicrobial resistance at the patient and population level are urgently needed. FUNDING: WHO.

Antibiotic resistance associated with the COVID-19 pandemic: a systematic review and meta-analysis.

BACKGROUND: COVID-19 and antimicrobial resistance (AMR) are two intersecting global public health crises. OBJECTIVE: We aimed to describe the impact of the COVID-19 pandemic on AMR across health care settings. DATA SOURCE: A search was conducted in December 2021 in WHO COVID-19 Research Database with forward citation searching up to June 2022. STUDY ELIGIBILITY: Studies evaluating the impact of COVID-19 on AMR in any population were included and influencing factors were extracted. Reporting of enhanced infection prevention and control and/or antimicrobial stewardship programs was noted. METHODS: Pooling was done separately for Gram-negative and Gram-positive organisms. Random-effects meta-analysis was performed. RESULTS: Of 6036 studies screened, 28 were included and 23 provided sufficient data for meta-analysis. The majority of studies focused on hospital settings (n = 25, 89%). The COVID-19 pandemic was not associated with a change in the incidence density (incidence rate ratio 0.99, 95% CI: 0.67-1.47) or proportion (risk ratio 0.91, 95% CI: 0.55-1.49) of methicillin-resistant Staphylococcus aureus or vancomycin-resistant enterococci cases. A non-statistically significant increase was noted for resistant Gram-negative organisms (i.e. extended-spectrum beta-lactamase, carbapenem-resistant Enterobacterales, carbapenem or multi-drug resistant or carbapenem-resistant Pseudomonas aeruginosa or Acinetobacter baumannii, incidence rate ratio 1.64, 95% CI: 0.92-2.92; risk ratio 1.08, 95% CI: 0.91-1.29). The absence of reported enhanced infection prevention and control and/or antimicrobial stewardship programs initiatives was associated with an increase in gram-negative AMR (risk ratio 1.11, 95% CI: 1.03-1.20). However, a test for subgroup differences showed no statistically significant difference between the presence and absence of these initiatives (p 0.40). CONCLUSION: The COVID-19 pandemic may have hastened the emergence and transmission of AMR, particularly for Gram-negative organisms in hospital settings. But there is considerable heterogeneity in both the AMR metrics used and the rate of resistance reported across studies. These findings reinforce the need for strengthened infection prevention, antimicrobial stewardship, and AMR surveillance in the context of the COVID-19 pandemic.

An international observational study to assess the impact of the Omicron variant emergence on the clinical epidemiology of COVID-19 in hospitalised patients.

Background: Whilst timely clinical characterisation of infections caused by novel SARS-CoV-2 variants is necessary for evidence-based policy response, individual-level data on infecting variants are typically only available for a minority of patients and settings. Methods: Here, we propose an innovative approach to study changes in COVID-19 hospital presentation and outcomes after the Omicron variant emergence using publicly available population-level data on variant relative frequency to infer SARS-CoV-2 variants likely responsible for clinical cases. We apply this method to data collected by a large international clinical consortium before and after the emergence of the Omicron variant in different countries. Results: Our analysis, that includes more than 100,000 patients from 28 countries, suggests that in many settings patients hospitalised with Omicron variant infection less often presented with commonly reported symptoms compared to patients infected with pre-Omicron variants. Patients with COVID-19 admitted to hospital after Omicron variant emergence had lower mortality compared to patients admitted during the period when Omicron variant was responsible for only a minority of infections (odds ratio in a mixed-effects logistic regression adjusted for likely confounders, 0.67 [95% confidence interval 0.61-0.75]). Qualitatively similar findings were observed in sensitivity analyses with different assumptions on population-level Omicron variant relative frequencies, and in analyses using available individual-level data on infecting variant for a subset of the study population. Conclusions: Although clinical studies with matching viral genomic information should remain a priority, our approach combining publicly available data on variant frequency and a multi-country clinical characterisation dataset with more than 100,000 records allowed analysis of data from a wide range of settings and novel insights on real-world heterogeneity of COVID-19 presentation and clinical outcome. Funding: Bronner P. Gonçalves, Peter Horby, Gail Carson, Piero L. Olliaro, Valeria Balan, Barbara Wanjiru Citarella, and research costs were supported by the UK Foreign, Commonwealth and Development Office (FCDO) and Wellcome [215091/Z/18/Z, 222410/Z/21/Z, 225288/Z/22/Z]; and Janice Caoili and Madiha Hashmi were supported by the UK FCDO and Wellcome [222048/Z/20/Z]. Peter Horby, Gail Carson, Piero L. Olliaro, Kalynn Kennon and Joaquin Baruch were supported by the Bill & Melinda Gates Foundation [OPP1209135]; Laura Merson was supported by University of Oxford's COVID-19 Research Response Fund - with thanks to its donors for their philanthropic support. Matthew Hall was supported by a Li Ka Shing Foundation award to Christophe Fraser. Moritz U.G. Kraemer was supported by the Branco Weiss Fellowship, Google.org, the Oxford Martin School, the Rockefeller Foundation, and the European Union Horizon 2020 project MOOD (#874850). The contents of this publication are the sole responsibility of the authors and do not necessarily reflect the views of the European Commission. Contributions from Srinivas Murthy, Asgar Rishu, Rob Fowler, James Joshua Douglas, François Martin Carrier were supported by CIHR Coronavirus Rapid Research Funding Opportunity OV2170359 and coordinated out of Sunnybrook Research Institute. Contributions from Evert-Jan Wils and David S.Y. Ong were supported by a grant from foundation Bevordering Onderzoek Franciscus; and Andrea Angheben by the Italian Ministry of Health "Fondi Ricerca corrente-L1P6" to IRCCS Ospedale Sacro Cuore-Don Calabria. The data contributions of J.Kenneth Baillie, Malcolm G. Semple, and Ewen M. Harrison were supported by grants from the National Institute for Health Research (NIHR; award CO-CIN-01), the Medical Research Council (MRC; grant MC_PC_19059), and by the NIHR Health Protection Research Unit (HPRU) in Emerging and Zoonotic Infections at University of Liverpool in partnership with Public Health England (PHE) (award 200907), NIHR HPRU in Respiratory Infections at Imperial College London with PHE (award 200927), Liverpool Experimental Cancer Medicine Centre (grant C18616/A25153), NIHR Biomedical Research Centre at Imperial College London (award IS-BRC-1215-20013), and NIHR Clinical Research Network providing infrastructure support. All funders of the ISARIC Clinical Characterisation Group are listed in the appendix.

Resistance levels to non-nucleoside reverse transcriptase inhibitors among pregnant women with recent HIV infection in Malawi.

BACKGROUND: Information on HIV drug resistance (HIVDR) prevalence in people newly diagnosed with HIV is limited. We implemented a cross-sectional study to estimate HIVDR prevalence among pregnant women recently infected with HIV in Malawi. METHODS: The HIVDR study was nested within a routine antenatal clinic (ANC) sentinel surveillance survey. Dried blood spot samples were tested for recent infection using a limiting antigen antibody assay together with HIV viral load testing. HIV-1 protease and reverse transcriptase were sequenced using Sanger sequencing. Drug susceptibility was predicted using Stanford HIVdb algorithm (version 8.9). Weighted analysis was performed in Stata 15.1. RESULTS: Of the 21,642 pregnant women enrolled in the ANC survey, 8.4% (1826/21,642) tested HIV positive. Of these, 5.0% (92/1826) had recent HIV infection, and 90.2% (83/92) were tested by PCR. The amplification and sequencing success rate was 57.8% (48/83). The prevalence of any HIVDR was 14.6% (5/45) (95% CI: 4.7-36.8%), all of which indicated HIVDR to nonnucleoside reverse transcriptase inhibitors (NNRTIs). HIVDR to nucleoside reverse transcriptase inhibitors was 7.9% (2/45) (95% CI: 1.4-34.6%). Resistance to protease inhibitors currently in use in Malawi was not observed. CONCLUSIONS: Despite the low number of cases with presumed TDR, our study hints that resistance to NNRTIs was high, above the 10% target for regimen change. Further investigation is needed to establish the exact magnitude of presumed TDR among women recently infected with HIV. These findings support the transition to an integrase inhibitor-based first-line regimen for patients initiating or on ART.

The First 110,593 COVID-19 Patients Hospitalised in Lombardy: A Regionwide Analysis of Case Characteristics, Risk Factors and Clinical Outcomes.

Objectives: To describe the monthly distribution of COVID-19 hospitalisations, deaths and case-fatality rates (CFR) in Lombardy (Italy) throughout 2020. Methods: We analysed de-identified hospitalisation data comprising all COVID-19-related admissions from 1 February 2020 to 31 December 2020. The overall survival (OS) from time of first hospitalisation was estimated using the Kaplan-Meier method. We estimated monthly CFRs and performed Cox regression models to measure the effects of potential predictors on OS. Results: Hospitalisation and death peaks occurred in March and November 2020. Patients aged ≥70 years had an up to 180 times higher risk of dying compared to younger patients [70-80: HR 58.10 (39.14-86.22); 80-90: 106.68 (71.01-160.27); ≥90: 180.96 (118.80-275.64)]. Risk of death was higher in patients with one or more comorbidities [1: HR 1.27 (95% CI 1.20-1.35); 2: 1.44 (1.33-1.55); ≥3: 1.73 (1.58-1.90)] and in those with specific conditions (hypertension, diabetes). Conclusion: Our data sheds light on the Italian pandemic scenario, uncovering mechanisms and gaps at regional health system level and, on a larger scale, adding to the body of knowledge needed to inform effective health service planning, delivery, and preparedness in times of crisis.

Developing a priority global research agenda for antimicrobial resistance in the human health sector: protocol for a scoping review.

INTRODUCTION: To accelerate the response to the public health threat by antimicrobial resistance (AMR), the WHO is developing a Global Research Agenda for AMR in the human health sector that aims to provide a global and transparent assessment of priority knowledge gaps related to critical bacteria-including Mycobacterium tuberculosis-and fungi that inform control and response strategies to tackle AMR by 2030. A literature scoping review represents the first phase in a stepwise process, and we hereby outline the protocol to review current knowledge gaps and research questions on AMR in the human health sector. METHODS AND ANALYSIS: This literature scoping review will follow the Arksey and O'Malley (2005) methodology and will include: (1) a hand search to identify relevant WHO guidelines and documents suggested by the WHO Steering Group for the AMR Global Research Agenda; (2) a grey literature search through a stakeholder mapping process and google searches of organisational websites; (3) a systematic search of relevant systematic reviews through bibliographic databases (PubMed, Embase and Web of Science); (4) screening of the reference lists of included studies. We will include relevant publications from the last 10 years (January 2012 to December 2021). Two researchers separately will review the yielded citations to determine eligibility based on predefined criteria. Relevant research questions with attributes will be extracted using a tool developed through an iterative process by the research team. Each identified research question will be classified and aggregated according to a conceptual framework (ie, 'knowledge matrix'), composed of three themes (ie, Prevention, Diagnosis and Care & Treatment) and four cross-cutting domains (ie, Descriptive, Discovery, Development, Delivery). We will present numerical and thematic summaries of the knowledge matrix. A qualitative content analysis is out of the scope of this protocol. ETHICS AND DISSEMINATION: The scoping review process will only involve identification, selection and analysis of documents available for use in the public domain, and will not include any personal information on individuals, therefore ethical approval is not required. The findings will be disseminated through a peer-reviewed publication and stakeholder meetings.

Epidemiology of HIV drug resistance in low- and middle-income countries and WHO global strategy to monitor its emergence.

PURPOSE OF REVIEW: This review summarises the latest information of the epidemiology of HIV drug resistance (HIVDR) in low- and middle-income countries and the updated WHO global strategy for HIVDR surveillance and monitoring. RECENT FINDINGS: Finding from recent national-representative surveys show a rise in pretreatment drug resistance (PDR) to reverse transcriptase inhibitors and especially to the class of nonnucleoside reverse transcriptase inhibitors. Levels of PDR are especially high in infants <18 months and adults reporting prior exposure to antiretrovirals. Although viral suppression rates are generally high and increasing among adults on antiretroviral therapy, those with unsuppressed viremia have high levels of acquired drug resistance (ADR). Programmatic data on HIVDR to integrase-transfer-inhibitor resistance is scarce, highlighting the need to increase integrase-inhibitors resistance surveillance. As the landscape of HIV prevention, treatment and monitoring evolves, WHO has also adapted its strategy to effectively support countries in preventing and monitoring the emergence of HIVDR. This includes new survey methods for monitoring resistance emerging from patients diagnosed with HIV while on preexposure prophylaxis, and a laboratory-based ADR survey leveraging on remnant viral load specimens which are expected to strengthen dolutegravir-resistance surveillance. SUMMARY: Monitoring HIVDR remains pivotal to ensure countries attain and sustain the global goals for ending HIV as a public health threat by 2030.

Clinical features of, and risk factors for, severe or fatal COVID-19 among people living with HIV admitted to hospital: analysis of data from the WHO Global Clinical Platform of COVID-19.

BACKGROUND: WHO has established a Global Clinical Platform for the clinical characterisation of COVID-19 among hospitalised individuals. We assessed whether people living with HIV hospitalised with COVID-19 had increased odds of severe presentation and of in-hospital mortality compared with individuals who were HIV-negative and associated risk factors. METHODS: Between Jan 1, 2020, and July 1, 2021, anonymised individual-level data from 338 566 patients in 38 countries were reported to WHO. Using the Platform pooled dataset, we performed descriptive statistics and regression analyses to compare outcomes in the two populations and identify risk factors. FINDINGS: Of 197 479 patients reporting HIV status, 16 955 (8·6%) were people living with HIV. 16 283 (96.0%) of the 16 955 people living with HIV were from Africa; 10 603 (62·9%) were female and 6271 (37·1%) were male; the mean age was 45·5 years (SD 13·7); 6339 (38·3%) were admitted to hospital with severe illness; and 3913 (24·3%) died in hospital. Of the 10 166 people living with HIV with known antiretroviral therapy (ART) status, 9302 (91·5%) were on ART. Compared with individuals without HIV, people living with HIV had 15% increased odds of severe presentation with COVID-19 (aOR 1·15, 95% CI 1·10-1·20) and were 38% more likely to die in hospital (aHR 1·38, 1·34-1·41). Among people living with HIV, male sex, age 45-75 years, and having chronic cardiac disease or hypertension increased the odds of severe COVID-19; male sex, age older than 18 years, having diabetes, hypertension, malignancy, tuberculosis, or chronic kidney disease increased the risk of in-hospital mortality. The use of ART or viral load suppression were associated with a reduced risk of poor outcomes; however, HIV infection remained a risk factor for severity and mortality regardless of ART and viral load suppression status. INTERPRETATION: In this sample of hospitalised people contributing data to the WHO Global Clinical Platform for COVID-19, HIV was an independent risk factor for both severe COVID-19 at admission and in-hospital mortality. These findings have informed WHO immunisation policy that prioritises vaccination for people living with HIV. As the results mostly reflect the data contribution from Africa, this analysis will be updated as more data from other regions become available. FUNDING: None. TRANSLATION: For the French translation of the abstract see Supplementary Materials section.

The prevalence of pre-treatment and acquired HIV drug resistance in Vietnam: a nationally representative survey, 2017-2018.

INTRODUCTION: Monitoring the population-level emergence and transmission of HIV drug resistance (HIVDR) is necessary for supporting public health programmes. This study provides a nationally representative prevalence estimate of HIVDR in people initiating antiretroviral therapy (ART) and estimates of acquired HIVDR and viral load (VL) suppression in people who have received it for 12 or ≥48 months in Vietnam. METHODS: The study was conducted between September 2017 and March 2018 following World Health Organization guidance. Thirty ART clinics were randomly sampled using probability proportional to size sampling from a total of 367 ART clinics in the country. RESULTS AND DISCUSSION: In total, 409 patients initiating ART were enrolled into the survey of pre-treatment HIVDR. The prevalence of any pre-treatment HIVDR was 5.8% (95% CI 3.4-9.5%), and the prevalence of non-nucleoside reverse transcriptase inhibitor resistance was 3.4% (95% CI 1.8-6.2%). Four hundred twenty-nine patients on ART for 12±3 months and 723 patients on ART for ≥48 months were enrolled into the surveys of acquired HIVDR. The prevalence of VL suppression (defined as <1000 copies/ml) in patients on ART for 12±3 and ≥48 months was 95.5% (95% CI 91.3-97.8%) and 96.1% (95% CI 93.2-97.8%), respectively. Among individuals with viral non-suppression, any HIVDR was detected in 11/14 (weighted prevalence 74.3%) of those on ART for 12±3 months and in 24/27 (weighted prevalence 88.5%) of those receiving ART for ≥48 months. CONCLUSIONS: This nationally representative study of HIVDR found high levels of VL suppression among those on ART for 12 and ≥48 months. Overall, high levels of VL suppression at both time points suggested good adherence among patients receiving ART and quality of treatment services in Vietnam. CLINICAL TRIAL NUMBER: Not applicable.

Drivers of HIV-1 drug resistance to non-nucleoside reverse-transcriptase inhibitors (NNRTIs) in nine southern African countries: a modelling study.

INTRODUCTION: The rise of HIV-1 drug resistance to non-nucleoside reverse-transcriptase inhibitors (NNRTI) threatens antiretroviral therapy's long-term success (ART). NNRTIs will remain an essential drug for the management of HIV-1 due to safety concerns associated with integrase inhibitors. We fitted a dynamic transmission model to historical data from 2000 to 2018 in nine countries of southern Africa to understand the mechanisms that have shaped the HIV-1 epidemic and the rise of pretreatment NNRTI resistance. METHODS: We included data on HIV-1 prevalence, ART coverage, HIV-related mortality, and survey data on pretreatment NNRTI resistance from nine southern Africa countries from a systematic review, UNAIDS and World Bank. Using a Bayesian hierarchical framework, we developed a dynamic transmission model linking data on the HIV-1 epidemic to survey data on NNRTI drug resistance in each country. We estimated the proportion of resistance attributable to unregulated, off-programme use of ART. We examined each national ART programme's vulnerability to NNRTI resistance by defining a fragility index: the ratio of the rate of NNRTI resistance emergence during first-line ART over the rate of switching to second-line ART. We explored associations between fragility and characteristics of the health system of each country. RESULTS: The model reliably described the dynamics of the HIV-1 epidemic and NNRTI resistance in each country. Predicted levels of resistance in 2018 ranged between 3.3% (95% credible interval 1.9-7.1) in Mozambique and 25.3% (17.9-33.8) in Eswatini. The proportion of pretreatment NNRTI resistance attributable to unregulated antiretroviral use ranged from 6% (2-14) in Eswatini to 64% (26-85) in Mozambique. The fragility index was low in Botswana (0.01; 0.0-0.11) but high in Namibia (0.48; 0.16-10.17), Eswatini (0.64; 0.23-11.8) and South Africa (1.21; 0.83-9.84). The combination of high fragility of ART programmes and high ART coverage levels was associated with a sharp increase in pretreatment NNRTI resistance. CONCLUSIONS: This comparison of nine countries shows that pretreatment NNRTI resistance can be controlled despite high ART coverage levels. This was the case in Botswana, Mozambique, and Zambia, most likely because of better HIV care delivery, including rapid switching to second-line ART of patients failing first-line ART.

Overview of SARS-CoV-2 infection in adults living with HIV.

Around 2·5 million deaths and more than 110 million COVID-19 cases have been reported globally. Although it initially appeared that HIV infection was not a risk factor for COVID-19 or more severe disease, more recent large studies suggest that people living with HIV (particularly with low CD4 cell counts or untreated HIV infection) might have a more severe clinical course than those who are HIV-negative. Moreover, the COVID-19 pandemic has disrupted HIV prevention and treatment services worldwide, creating huge challenges to the continuity of essential activities. We have reviewed the most relevant features of COVID-19 in people living with HIV and highlighted topics where further research is required.

Guidelines are needed for studies of pre-treatment HIV drug resistance: a methodological study.

BACKGROUND: The expansion of access to antiretroviral therapy (ART) has been accompanied by an increase in pre-treatment drug resistance (PDR). While it is critical to monitor the increasing prevalence of PDR across countries and populations to inform optimal regimen selection, the completeness of reporting is often suboptimal, limiting the interpretation and generalizability of the results. Indeed, there is no formal guidance on how studies investigating the prevalence of drug resistance should be reported. Thus, we sought to determine the completeness of reporting in studies of PDR and the factors associated with sub-optimal reporting to ascertain the need for guidelines. METHODS: As part of a systematic review on the global prevalence of PDR in key populations (men who have sex with men, sex workers, transgender people, people who inject drugs and people in prisons), we searched 10 electronic databases until January 2019. We extracted information on selected study characteristics useful for interpreting prevalence data. Data were extracted in duplicate. Analyses of variance and correlation were used to explore factors that may explain the number of items reported. RESULTS: We found 650 studies of which 387 were screened as full text and 234 were deemed eligible. The included studies were published between 1997 and 2019 and included a median of 239 (quartile 1 = 101; quartile 3 = 778) participants. Most studies originated from high-income countries (125/234; 53.0%). Of 23 relevant data items, including study design, setting, participant sociodemographic characteristics, HIV risk factors, type of resistance test conducted, definition of resistance, the mean (standard deviation) number of items reported was 13 (2.2). We found that more items were reported in studies published more recently (r = 0.20; p < 0.002) and in studies at low risk of bias (F [2231] = 8.142; p < 0.001). CONCLUSIONS: Incomplete reporting in studies on PDR makes characterising levels of PDR in subpopulations across countries challenging. Hence, guidelines are needed to define a minimum set of variables to be included in such studies.