Associations between antiretroviral regimen and changes in blood pressure: results from the D2EFT study.

In this randomised, controlled study in 14 low- and middle-income countries, individuals taking dolutegravir with darunavir/ritonavir for 48 weeks had a greater increase in systolic and diastolic blood pressure than individuals taking two nucleoside reverse transcriptase with darunavir/ritonavir. The difference remained significant after controlling for confounding factors including weight gain.

Influence of CYP2B6 and CYP3A4 polymorphisms on the virologic and immunologic responses of patients treated with efavirenz-containing regimen.

OBJECTIVES: The main objective of this study was to evaluate the effect of CYP2B6 and CYP3A4 polymorphisms on the virological and immunologic responses of HIV patients. A total of 153 HIV-positive patients were enlisted for the study. PATIENTS AND METHODS: Viral load and median CD4 T cell counts were evaluated at baseline and month 6 (M6). Samples were identified using TaqMan genotyping assays. RESULTS: The AG in CYP2B6 rs2279343 was associated with VLS compared to homozygous AA. In the dominant model, the AG/GG genotypes were associated with VLS compared to the AA genotype. Moreover, in overdominant model, the AG genotype was associated with VLS compared to AA/GG. Regarding immunological response, only the AG in SNP rs2279343 CYP2B6 was associated with an increase in CD4 cell count between baseline and M6. In CYP2B6 rs3745274, the CD4 cell count at M6 was higher than that of baseline for GG carriers and for GT carriers. In CYP3A4 rs2740574, the TC carriers showed a higher median CD4 count at M6 compared to that of the baseline count, as well as for CC carriers. The best genotypes combination associated with CD4 cell count improvement were AA/AG in SNP rs2279343 and GG/GT in SNP rs3745274. CONCLUSION: Our findings support the fact that CYP2B6 rs2279343 could help in the prediction of VLS and both SNPs rs3745274 and rs2279343 in CYP2B6 and CYP3A4 rs2740574 were associated with immune recovery in Malian HIV-positive patients.

Study presence of COVID-19 (SARS-CoV-2) in the sweat of patients infected with Covid-19.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) disease, which started in Wuhan, Chin, has now become a public health challenge in most countries around the world. Proper preventive measures are necessary to prevent the spread of the virus to help control the pandemic. Because, SARS-CoV-2 is new, its transmission route has not been fully understood. In this study, we aimed to investigate the presence of SARS-CoV-2 in the sweat secretion of COVID-19 patients. Sweat specimens of 25 COVID- 19 patients were collected and tested for SARS-CoV-2 RNA by Real-time Polymerase Chain Reaction (RT-PCR) method. After RNA extraction and cDNA amplification, all samples were examined for the presence of ORF-1ab and N genes related to COVID-19. Results annotated by Realtime PCR machines software based on Dynamic algorithm. The results of this study showed the absence of SARS-CoV-2 in the sweat samples taken from the foreheads of infected people. Therefore, it can be concluded that the sweat of patients with COVID- 19 cannot transmit SARS-CoV-2. However they can be easily contaminated with other body liquids.

Genetic polymorphism of drug metabolism enzymes (GSTM1, GSTT1 and GSTP1) in the healthy Malian population.

Glutathione S-transferase genes, known to be highly polymorphic, are implicated in the process of phase II metabolism of many substrates, including xenobiotics, anticancer and anti-infective drugs. The detoxification activity is linked to individual genetic makeup. Therefore, the identification of alleles and genotypes in these genes within a population may help to better design genetic susceptibility and pharmacogenetic studies. We performed the present study to establish the frequencies of the GSTM1, GSTT1, and GSTP1 c. 313A > G (rs1695) polymorphisms in 206 individuals of the Malian healthy population. GSTM1 and GSTT1 were genotyped by using multiplex polymerase chain reaction, whereas genotypes of GSTP1 were identified by polymerase chain reaction followed by restriction fragment length polymorphism. The frequencies of GSTM1-null and GSTT1-null genotypes were respectively 24.3 and 41.3%. The observed genotype frequencies for GSTP1 were 25.73% homozygous wild-type AA, 49.03% heterozygous AG and 25.24% homozygous mutant GG. The frequency of GSTP1-A allele was 50.24% versus 49.76% for the GSTP1-G allele. The distribution of these three genes was homogeneous between men and women (p > 0.05). We found no statistical association between the presence of a particular profile of GSTM1 or GSTT1 with the genotypes of GSTP1 (p > 0.05). Nevertheless, we noticed that the majority of the individuals harboring the GSTM1-present or the GSTT1-present harbor also the GSTP1-AG genotype. In addition, the triple genotype GSTM1-present/GSTT1-present/AG was the most frequent with 25.2%. Our findings will facilitate future studies regarding genetic associations of multifactorial diseases and pharmacogenetic, thus opening the way to personalized medicine in our population.

Efavirenz and Lopinavir Levels in HIV-Infected Women and Their Nursing Infants, in Mali.

Limited data are currently available on antiretroviral pharmacokinetics in breast milk (BM) and in breastfed infants' blood. To explore these parameters in patients in Mali, we measured plasma antiretroviral levels in human immunodeficiency virus (HIV)-infected mothers and their breastfed infants over 6 months. We specifically analyzed the concentrations of efavirenz (EFV) and lopinavir (LPV) in the plasma of mothers living with HIV and their breastfed infants. Blood samples were collected at delivery and at month 1, 3, and 6 postpartum. EFV and LPV concentrations were measured by liquid chromatography-tandem mass spectrometry. HIV-1 RNA load was measured by Abbott M2000RT RealTime System at delivery and 6 months postpartum for mothers, and at 3 and 6 months postbirth for infants. The median duration of antiretroviral therapy at study inclusion was 57 months [interquartile range (IQR), 0-168 months]. The median EFV ratios of infant plasma/maternal plasma (MP) were 0.057 at month 1, 0.072 at month 3, and 0.048 at month 6. During the study period, the median BM/MP ratio of EFV was 1.16 (IQR, 0.96-20.62), which corresponds to a relative infant dose of 2.46% of the recommended weight-adjusted pediatric EFV dose at month 6. The apparent infant clearance of EFV was 0.146 l/h per kilogram at month 6. The LPV concentrations in the plasma of all infants were undetectable. No drug-related adverse reaction or toxicity was observed in any of the infants. The two women who presented a viral load of >50 copies/ml at month 6 had undetectable plasma drug concentrations at the same period. This study showed that breastfed infants received a low level of EFV but not LPV from their treated mothers.

Laboratory Response to 2014 Ebola Virus Outbreak in Mali.

Aware of the rapid spread of Ebola virus (EBOV) during the current West African epidemic, Mali took several proactive steps to rapidly identify cases within its borders. Under the Mali International Center for Excellence in Research program, a collaboration between the National Institute of Allergy and Infectious Diseases and the Malian Ministry of Higher Education and Scientific Research established a national EBOV diagnostic site at the University of Sciences, Techniques and Technologies of Bamako in the SEREFO Laboratory. Two separate introductions of EBOV occurred in Mali from neighboring Guinea, but both chains of transmission were quickly halted, and Mali was declared "Ebola free" on 18 January 2015 and has remained so since. The SEREFO Laboratory was instrumental in the success of Mali's Ebola response by providing timely and accurate diagnostics. As of today, the SEREFO Laboratory has tested 103 samples from 88 suspected cases, 10 of which were EBOV positive, since the Ebola diagnostics unit started in April 2014. The establishment of Ebola diagnostics in the SEREFO Laboratory, safety precautions, and diagnostics are described.

Molecular identification of Mycobacterium bovis from cattle and human host in Mali: expanded genetic diversity.

BACKGROUND: Bovine tuberculosis (BTB) is a contagious, debilitating human and animal disease caused by Mycobacterium bovis, a member of the Mycobacterium tuberculosis complex. The study objective were to estimate the frequency of BTB, examine genetic diversity of the M. bovis population in cattle from five regions in Mali and to determine whether M. bovis is involved in active tuberculosis (TB) in humans. Samples from suspected lesions on cattle at the slaughterhouses were collected. Mycobacterial smear, culture confirmation, and spoligotyping were used for diagnosis and species identification. Mycobacterium DNA from TB patients was spoligotyped to identify M. bovis. RESULTS: In total, 675 cattle have been examined for lesions in the five regions of Mali. Out of 675 cattle, 79 specimens presented lesions and then examined for the presence of M. bovis. Thus, 19 (24.1 %) were identified as M. bovis; eight (10.1 %) were non-tuberculous Mycobacterium (NTM). Nineteen spoligotype patterns were identified among 79 samples with five novel patterns. One case of M. bovis (spoligotype pattern SB0300) was identified among 67 TB patients. CONCLUSION: This study estimates a relatively true proportion of BTB in the regions of Mali and reveals new spoligotype patterns.

[Ear tuberculosis concomitant with pulmonary localization in an HIV-immunosuppressed patient, in Bamako, Mali]. / Tuberculose auriculaire concomitante à une localisation pulmonaire chez un patient immunodéprimé par le VIH, à Bamako, Mali.

Introduction/Rationale: Tuberculosis remains a major public health issue. It is an opportunistic pathology, very common in HIV-immunocompromised persons, classifying it at the WHO stage 4. Ear tuberculosis remains a rare and under-diagnosed clinical form. We report here a case of ear tuberculosis concomitant with pulmonary localization in an HIV-immunosuppressed person on triple antiretroviral therapy aged 32 years hospitalized in Bamako (Mali) to discuss the diagnostic and therapeutic difficulties posed by this rare localization. Description of the case: The patient had a chronic productive cough, otalgia and right chronic purulent otorrhea. The search for acid-resistant bacilli was positive for direct examination in gastric casing fluid and swabbing of the ear pus, confirming the diagnosis of tuberculosis. Anti-tuberculosis treatment instituted for 6 months associated with adjuvants resulted in complete healing of the patient. Discussion/conclusion: Although rare, ear localization must be actively sought. Etiological treatment must be instituted upon confirmation of the diagnosis to avoid complications and sequelae.

Neuromeningeal Cryptococcosis and Tuberculosis Coinfection in Bamako: A One-Year Case Series.

Cryptococcosis and tuberculosis are life-threatening opportunistic infections that occur in apparently immunocompetent or severely immunocompromised individuals worldwide. As both infections are strongly linked to HIV infection, they may share certain clinical manifestations, and the interaction of their treatments should be considered. However, despite their similarity, concurrent tuberculosis and cryptococcal infections have rarely been reported in West Africa. Herein, we present 3 cases of neuromeningeal cryptococcosis and lung tuberculosis coinfection collected prospectively over a year at the Department of Infectious Diseases of the Point G Teaching Hospital in Bamako. Two patients had HIV disease, and the third patient had no underlying immunosuppressive illnesses. Thus, active screening for tuberculosis and cryptococcosis, particularly in individuals with HIV, can reduce misdiagnosis and ensure appropriate coinfection management. Moreover, this may reduce mortality due to AIDS-related opportunistic infections in resource-limited settings.

Adverse Drug Reactions to Antiretroviral Therapy: Frequency, Type, and Risk Factors in Children in Mali.

OBJECTIVE: The aim of our study was to evaluate the frequency, type, and risk factors associated with adverse drug reactions (ADRs) in HIV-positive children with adherence to antiretroviral therapy (ART) at the Unit of Care and Accompaniment for People Living With HIV (USAC) of Bamako. METHODS: A cross-sectional study was conducted at USAC of Bamako from May 1, 2014, to July 31, 2015. We included children aged 1 to 14 years with at least 6 months of ARV treatment initiated at USAC, with or without ADRs. Data collection was based on information collected from parents and clinical/biological assessments. RESULTS: Median age of participants was 36 months and female sex was predominant (54.8%). Poor adherence during the study was observed in 15% of cases. Of patients in the study, 52% had a CD4 count less than 350 cells/mm3 at the time of adverse events. In bivariate analysis, we found that participants with adherence to ART tended to be younger than those with non-adherence to ART (36 vs 72 months, p = 0.093). In multivariable analysis, prophylactic treatment was the only factor marginally associated with ART adherence in HIV patients (p = 0.09). No other adverse biological effects or clinical conditions were associated with ART adherence in this study. CONCLUSIONS: In this study we found that ADRs were frequent in HIV-positive patients but less frequent in ART-adherent HIV-positive children. Therefore, it is essential to regularly monitor children receiving ARVs to detect and treat the complications associated with these therapies according to ART adherence.

Assessment of lung injury severity using ultrasound in critically ill COVID-19 patients in resource limited settings.

BACKGROUND: Lung ultrasound is a non-invasive tool available at the bedside for the assessment of critically ill patients. The objective of this study was to evaluate the usefulness of lung ultrasound in assessing the severity of SARS-CoV-2 infection in critically-ill patients in a low-income setting. METHODS: We conducted a 12-month observational study in a university hospital intensive care unit (ICU) in Mali, on patients admitted for COVID-19 as diagnosed by a positive polymerase chain reaction for SARS-CoV-2 and/or typical lung computed tomography scan findings. RESULTS: The inclusion criteria was met by 156 patients with a median age of 59 years. Almost all patients (96%) had respiratory failure at admission and many needed respiratory support (121/156, 78%). The feasibility of lung ultrasound was very good, with 1802/1872 (96%) quadrants assessed. The reproducibility was good with an intra-class correlation coefficient of elementary patterns of 0.74 (95% CI 0.65, 0.82) and a coefficient of repeatability of lung ultrasound score < 3 for an overall score of 24. Confluent B lines were the most common lesions found in patients (155/156). The overall mean ultrasound score was 23 ± 5.4, and was significantly correlated with oxygen saturation (Pearson correlation coefficient of - 0.38, p < 0.001). More than half of the patients died (86/156, 55.1%). The factors associated with mortality, as shown by multivariable analysis, were: the patients' age; number of organ failures; therapeutic anticoagulation, and lung ultrasound score. CONCLUSION: Lung ultrasound was feasible and contributed to characterize lung injury in critically-ill COVID-19 patients in a low income setting. Lung ultrasound score was associated with oxygenation impairment and mortality.

Long-Term Benefits from Early Antiretroviral Therapy Initiation in HIV Infection.

BACKGROUND: For people with HIV and CD4+ counts >500 cells/mm3, early initiation of antiretroviral therapy (ART) reduces serious AIDS and serious non-AIDS (SNA) risk compared with deferral of treatment until CD4+ counts are <350 cells/mm3. Whether excess risk of AIDS and SNA persists once ART is initiated for those who defer treatment is uncertain. METHODS: The Strategic Timing of AntiRetroviral Treatment (START) trial, as previously reported, randomly assigned 4684 ART-naive HIV-positive adults with CD4+ counts .500 cells/mm3 to immediate treatment initiation after random assignment (n = 2325) or deferred treatment (n= 2359). In 2015, a 57% lower risk of the primary end point (AIDS, SNA, or death) for the immediate group was reported, and the deferred group was offered ART. This article reports the follow-up that continued to December 31, 2021. Cox proportional-hazards models were used to compare hazard ratios for the primary end point from randomization through December 31, 2015, versus January 1, 2016, through December 31, 2021. RESULTS: Through December 31, 2015, approximately 7 months after the cutoff date from the previous report, the median CD4+ count was 648 and 460 cells/mm3 in the immediate and deferred groups, respectively, at treatment initiation. The percentage of follow-up time spent taking ART was 95% and 36% for the immediate and deferred groups, respectively, and the time-averaged CD4+ difference was 199 cells/mm3. After January 1, 2016, the percentage of follow-up time on treatment was 97.2% and 94.1% for the immediate and deferred groups, respectively, and the CD4+ count difference was 155 cells/mm3. After January 1, 2016, a total of 89 immediate and 113 deferred group participants experienced a primary end point (hazard ratio of 0.79 [95% confidence interval, 0.60 to 1.04] versus hazard ratio of 0.47 [95% confidence interval, 0.34 to 0.65; P<0.001]) before 2016 (P=0.02 for hazard ratio difference). CONCLUSIONS: Among adults with CD4+ counts >500 cells/mm3, excess risk of AIDS and SNA associated with delaying treatment initiation was diminished after ART initiation, but persistent excess risk remained. (Funded by the National Institute of Allergy and Infectious Diseases and others.).

Gut Microbiota and Human Body Interactions; Its Impact on Health: A Review.

Gut microbiota (GM), as an organ of the human body, has a particular and autonomous function that is related to it. This review aims to investigate human intestinal and gut microbiota interaction and its impact on health. As a creation referable database about this dynamic and complex organ, several comprehensive projects are implemented by using culture-dependent (culturomics), culture- independent methods (e.g., metagenomics, mathematics model), and Gnotobiological together. This study was done by searching PubMed, Scopus and Google scholar database in the gut, health microbiota, and interaction keywords. The first acquired microbiota during pregnancy or childbirth is colonized in the gut by using specific and non-specific mechanisms. Its structure and shape reach relative stability with selection pressure along with host development until adulthood and keeps its resilience against external or internal variables depending on the host's genetics and negative feedback. According to research, individuals have 2 functional group microbiotas, including the core (common between vast majorities human) and flexible (transient population) microbiome. The most important role of the GM in the human body can be summarized in three basic landscapes: metabolic, immune system, and gut-brain axis interaction. So, the loss of microbial population balance will lead to disorder and disease.

[Neuromeningeal cryptococcosis in an HIV-negative patient with pulmonary tuberculosis in the Infectious and tropical diseases department of the University teaching hospital Point G of Bamako, Mali]. / Cryptococcose neuroméningée chez une patiente séronégative pour le VIH atteinte de tuberculose pulmonaire au service de Maladies infectieuses et tropicales du CHU du Point G de Bamako, Mali.

Neuromeningeal cryptococcosis and pulmonary tuberculosis are respectively serious mycotic and bacterial infections occurring in a subject regardless of its HIV serological status. We report here a case of neuromeningeal cryptococcosis associated with pulmonary tuberculosis and malnutrition in an HIV-seronegative patient with a CD4 count of 750/mm3, to highlight some particularities opposed to certain literatures. This is an 18-year-old patient, housewife, from Bamako, admitted in the Infectious and tropical diseases department of the University teaching hospital Point G of Bamako on March 13, 2022 for fever and impaired consciousness. Her symptomatology appears to have gradually set in over a month, preceded by headache resistant to paracetamol, jet vomiting and irregular dry cough, initially treated with ceftriaxone, artesunate and paracetamol for confirmed malaria and suspicion of bacterial meningitis before admission. In whom no known medical-surgical history, no use of topical corticosteroids, no immunosuppressive therapy, no alcohol or tobacco, and no immunosuppressive pathology was found. The diagnoses of neuromeningeal cryptococcosis, pulmonary tuberculosis and undernutrition were retained in view of clinical and microbiological arguments. Diabetes, sickle cell disease, viral hepatitis B and C, kidney failure and cancer, which are immunosuppressive pathologies, were not found. She was successfully treated with first-line oral antituberculous drugs and fluconazole infusion. Three interests are drawn from this clinical case: neuromeningeal cryptococcosis is not only the prerogative of HIV-positive subjects, a high CD4 count does not always mean immunocompetence and fluconazole is an effective therapeutic alternative for neuromeningeal cryptococcosis.

Bacteriocins: Recent Advances in its Application as an Antimicrobial Alternative.

Due to the emergence and development of antibiotic resistance in the treatment of bacterial infections, efforts to discover new antimicrobial agents have increased. One of these antimicrobial agents is a compound produced by a large number of bacteria called bacteriocin. Bacteriocins are small ribosomal polypeptides that can exert their antibacterial effects against bacteria close to their producer strain or even non-closely-relatedstrains. Adequate knowledge of the structure and functional mechanisms of bacteriocins and their spectrum of activity, as well as knowledge of the mechanisms of possible resistance to these compounds, will lead to further development of their use as an alternative to antibiotics. Furthermore, most bacteria that live in the gastrointestinal tract (GIT) have the ability to produce bacteriocins, which spread throughout the GIT. Despite antimicrobial studies in vitro, our knowledge of bacteriocins in the GIT and the migration of these bacteriocins from the epithelial barrier is low. Hence, in this study, we reviewed general information about bacteriocins, such as classification, mechanism of action and resistance, emphasizing their presence, stability, and spectrum of activity in the GIT.

Postbiotics as the key mediators of the gut microbiota-host interactions.

The priority of the Sustainable Development Goals for 2022 is to reduce all causes related to mortality. In this regard, microbial bioactive compounds with characteristics such as optimal compatibility and close interaction with the host immune system are considered a novel therapeutic approach. The fermentation process is one of the most well-known pathways involved in the natural synthesis of a diverse range of postbiotics. However, some postbiotics are a type of probiotic response behavior to environmental stimuli that usually play well-known biological roles. Also, postbiotics with unique structure and function are key mediators between intestinal microbiota and host cellular processes/metabolic pathways that play a significant role in maintaining homeostasis. By further understanding the nature of parent microbial cells, factors affecting their metabolic pathways, and the development of compatible extraction and identification methods, it is possible to achieve certain formulations of postbiotics with special efficiencies, which in turn will significantly improve the performance of health systems (especially in developing countries) toward a wide range of acute/chronic diseases. The present review aims to describe the fundamental role of postbiotics as the key mediators of the microbiota-host interactions. Besides, it presents the available current evidence regarding the interaction between postbiotics and host cells through potential cell receptors, stimulation/improvement of immune system function, and the enhancement of the composition and function of the human microbiome.

Raoultella planticola and urinary tract infection: The first laboratory-confirmed case in an HIV-infected patient in Mali.

Raoultella planticola is a Gram-negative, aerobic, non-motile bacterium, abundant in the environment, but rarely associated with pathology in humans. Notably, few urinary tract infections caused by R. planticola have been reported. To our knowledge, we are presenting here the first case of urinary tract infection caused by R. planticola in an HIV-infected individual. It is a 50-year-old female, with a history of HIV-1 infection treated for three years. At admission, her CD4 count was 70 cells/mL, and the main complaints were severe diarrhea and cough. She was diagnosed and treated for pulmonary tuberculosis (TB) and E. Coli enteritis. Initially, we observed a good evolution. However, on day 21 of hospitalization, she presented with fever and dysuria. Urinalysis revealed the presence of R. planticola with resistance to multiple antibiotics. We also detected that she has an HIV-2 but not HIV-1 infection. After receiving the right regimen, she was confirmed cured of her bacterial infections.

Incidence and Predictors of Imported Cases of COVID-19 in Burkina Faso.

BACKGROUND: To limit the spread of COVID-19 due to imported cases, Burkina Faso has set up quarantine measures for arriving passengers. We aimed to determine the incidence and predictors of imported cases of COVID-19 in Burkina Faso. METHODS: A prospective cohort study was performed using data from passengers arriving at the airport from April 9 to August 31, 2020. The data was extracted from the District Health Information Software 2 (DHIS2) platform. Cox regression was used to identify predictors of imported cases of COVID-19. RESULTS: Among 6,332 travelers who arrived in the study period, 173 imported cases (2.7%) were recorded. The incidence rate was 1.9 cases per 1,000 traveler-days (95%CI: 1.6-2.2 per 1,000). Passengers arriving in April (Adjusted hazard ratio [aHR] = 3.56; 95%CI: 1.62-7.81) and May (aHR = 1.92; 95% CI: 1.18-3.12) were more at risk of being tested positive compared to those arriving in August, as well as, passengers presenting with one symptom (aHR = 3.71; 95% CI: 1.63-8.43) and at least two symptoms (aHR = 10.82; 95% CI: 5.24-22,30) compared to asymptomatic travelers. CONCLUSIONS: The incidence of imported cases was relatively low in Burkina Faso between April and August 2020. The period of travel and the presence of symptoms at arrival predicted the risk of being tested positive to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). This is essential in the context of the high circulation of virus variants worldwide and the low local capacity to perform genotyping tests to strengthen the surveillance and screening capacities at the points of entry into the country.

Adaption of an ongoing clinical trial to quickly respond to gaps in changing international recommendations: the experience of D2EFT.

A rapidly changing landscape of antiretrovirals and their procurement at scale has permitted the evaluation of new optimised second-line antiretroviral therapy (ART) in low- and middle-income countries. D2EFT is an open-label randomised controlled non-inferiority phase IIIB/IV trial in people living with HIV-1 (PWH) whose first-line non-nucleoside reverse transcriptase inhibitor (NNRTI)-based ART is failing. At inception, it compared a standard of care of boosted darunavir with two nucleos(t)ide reverse transcriptase inhibitors (NRTIs) to the novel NRTI-sparing regimen of boosted darunavir with dolutegravir. Implemented in 2017, participating sites were across Africa, Asia and Latin America. Around the time of implementation, the World Health Organization updated its treatment guidelines and recommended scaling up tenofovir disoproxil fumarate-lamivudine-dolutegravir (TLD). This situation pushed D2EFT investigators to consider the impact of the roll-out of TLD on the D2EFT research question. The protocol team agreed it was important to study TLD in second-line when an NNRTI regimen was failing, and focused on options to expedite the work by studying the question within the existing trial and network. All key issues (statistical, programmatic and financial) were reviewed to assess the benefits and risks of adding a third arm to the ongoing study, as opposed to developing a new randomised clinical trial with the same control arm and within the same network. The development of a new trial was deemed to be longer than adding a third arm, and to create a challenging situation with two competing clinical trials at the same sites which would slow down recruitment and impair both trials. On the other hand, adding a third arm would be demanding in terms of operationalisation, increased sample size and statistical biases to control. The optimal strategy was deemed to be the addition of a third arm, arriving retrospectively at a simplified multi-arm multi-stage clinical trial design to achieve statistical validity. The D2EFT study maintains additional value in a quickly evolving second-line ART strategy allowed by the progress in global access to ART.

High SARS-CoV-2 Seroprevalence among Healthcare Workers in Bamako, Mali.

In Mali, a country in West Africa, cumulative confirmed COVID-19 cases and deaths among healthcare workers (HCWs) remain enigmatically low, despite a series of waves, circulation of SARS-CoV-2 variants, the country's weak healthcare system, and a general lack of adherence to public health mitigation measures. The goal of the study was to determine whether exposure is important by assessing the seroprevalence of anti-SARS-CoV-2 IgG antibodies in HCWs. The study was conducted between November 2020 and June 2021. HCWs in the major hospitals where COVID-19 cases were being cared for in the capital city, Bamako, Mali, were recruited. During the study period, vaccinations were not yet available. The ELISA of the IgG against the spike protein was optimized and quantitatively measured. A total of 240 HCWs were enrolled in the study, of which seropositivity was observed in 147 cases (61.8%). A continuous increase in the seropositivity was observed, over time, during the study period, from 50% at the beginning to 70% at the end of the study. HCWs who provided direct care to COVID-19 patients and were potentially highly exposed did not have the highest seropositivity rate. Vulnerable HCWs with comorbidities such as obesity, diabetes, and asthma had even higher seropositivity rates at 77.8%, 75.0%, and 66.7%, respectively. Overall, HCWs had high SARS-CoV-2 seroprevalence, likely reflecting a "herd" immunity level, which could be protective at some degrees. These data suggest that the low number of cases and deaths among HCWs in Mali is not due to a lack of occupational exposure to the virus but rather related to other factors that need to be investigated.