HIV primary drug resistance and associated HIV risk factors among HIV positive blood donors in Brazil from 2007 to 2017.

BACKGROUND: Acquisition of HIV primary drug resistant (PDR) infection can lead to poor virologic and clinical outcomes in individuals and hampers public health efforts in epidemic control. Monitoring PDR in HIV-positive blood donors can be used to inform nationwide trends in the spread of drug-resistant HIV strains. METHODS: We conducted a cross-sectional study using genetic sequence analysis to assess HIV pol sequences, PDR, and risk factors for infection using audio computer-assisted structured interviews in four large blood centers in Brazil from 2007 to 2017. RESULTS: Of 716 HIV-positive blood donors, 504 (70.4%) were successfully sequenced. HIV clade B (73.2%) was the most prevalent subtype, followed by a mix of non-B (21.2%) sub-types. A twofold increase (from 4% to 8%) in recombinants prevalence was observed during the study period. Sixty-four (12.7%) presented PDR. Overall, HIV PDR prevalence remained stable during the study period. Drug resistance mutations for non-nucleoside reverse transcriptase inhibitors were found in 39 (7.7%) donors, while for nucleoside reverse transcriptase inhibitors were found in 26 (5.1%), and for protease inhibitors in 24 (4.8%) of HIV-infected donors. We did not find statistically significant differences in demographics, behavioural risk factors, or HIV genotypes when comparing volunteers with and without PDR. CONCLUSION: The HIV PDR rate among donors remained stable during the study period. HIV-positive blood donors can be an informative population to monitor primary HIV resistance and ultimately may help to increase the knowledge and awareness of HIV risk factors and PDR.

Drug resistance-associated mutations in antiretroviral treatment-naïve and -experienced patients in Kuwait.

The identification of human immunodeficiency virus (HIV) mutations leading to drug resistance enables patient-specific adaptation of the treatment regimen and predicts the risk of transmission of drug-resistant HIV. In this study, we report for the first time the prevalence in Kuwait of non-polymorphic resistance-associated mutations (RAMs) in patients under first-line antiretroviral therapy. Viral RNA was extracted from plasma samples of 64 treatment-naïve (untreated) and 64 treatment-experienced patients. The HIV-1 load was determined by real-time RT-PCR. The protease- and reverse transcriptase-encoding regions were analyzed by subtyping, and for drug resistance. The HIV-1 load at sampling in treatment-naïve patients ranged from 1.61 x 104 to 1.91 x 106 copies/ml, whereas that in treatment-experienced patients ranged from bitors (PIs) and NNRTIs. These results necessitate efforts to be made for reducing emergence of resistance-associated mutations in treated patients, and highlight the need for continuous monitoring of drug resistance patterns in Kuwait.

The emerging threat of pre-extensively drug-resistant tuberculosis in West Africa: preparing for large-scale tuberculosis research and drug resistance surveillance.

BACKGROUND: Drug-resistant tuberculosis (TB) is a global public health problem. Adequate management requires baseline drug-resistance prevalence data. In West Africa, due to a poor laboratory infrastructure and inadequate capacity, such data are scarce. Therefore, the true extent of drug-resistant TB was hitherto undetermined. In 2008, a new research network, the West African Network of Excellence for Tuberculosis, AIDS and Malaria (WANETAM), was founded, comprising nine study sites from eight West African countries (Burkina Faso, The Gambia, Ghana, Guinea-Bissau, Mali, Nigeria, Senegal and Togo). The goal was to establish Good Clinical Laboratory Practice (GCLP) principles and build capacity in standardised smear microscopy and mycobacterial culture across partnering laboratories to generate the first comprehensive West African drug-resistance data. METHODS: Following GCLP and laboratory training sessions, TB isolates were collected at sentinel referral sites between 2009-2013 and tested for first- and second-line drug resistance. RESULTS: From the analysis of 974 isolates, an unexpectedly high prevalence of multi-drug-resistant (MDR) strains was found in new (6 %) and retreatment patients (35 %) across all sentinel sites, with the highest prevalence amongst retreatment patients in Bamako, Mali (59 %) and the two Nigerian sites in Ibadan and Lagos (39 % and 66 %). In Lagos, MDR is already spreading actively amongst 32 % of new patients. Pre-extensively drug-resistant (pre-XDR) isolates are present in all sites, with Ghana showing the highest proportion (35 % of MDR). In Ghana and Togo, pre-XDR isolates are circulating amongst new patients. CONCLUSIONS: West African drug-resistance prevalence poses a previously underestimated, yet serious public health threat, and our estimates obtained differ significantly from previous World Health Organisation (WHO) estimates. Therefore, our data are reshaping current concepts and are essential in informing WHO and public health strategists to implement urgently needed surveillance and control interventions in West Africa.

Cost-efficient HIV-1 drug resistance surveillance using multiplexed high-throughput amplicon sequencing: implications for use in low- and middle-income countries.

OBJECTIVES: Increased trends of primary drug resistance mutations (DRMs) among treatment-naive HIV-1-infected patients in low- and middle-income countries (LMICs) and the non-availability of pre-antiretroviral therapy (ART) genotypic resistance testing (GRT) may severely affect future therapeutic outcomes. The main objective of this study was therefore to develop a simplified, cost- and labour-efficient but high-throughput GRT protocol to be applied in the large-scale surveillance of DRMs in LMICs. PATIENTS AND METHODS: Ninety-six therapy-naive HIV-1-infected patients belonging to three cohorts were included: Indian patients followed at St John's Medical College Hospital, Bangalore, India (n = 49); East Africans (n = 21), who had migrated to Sweden; and Caucasians (n = 26) living in Sweden. GRT by population sequencing (GRT-PS) on individual plasma samples and GRT by next-generation sequencing (GRT-NGS) on equimolar multiplexed samples (n = 24) using Illumina MiSeq were performed. RESULTS: The multiplexing procedure was shown to be technically feasible and gave high-quality reads independent of whether HIV-1 subtype C or B was analysed. GRT-NGS detected all the DRMs found by GRT-PS. Additional clinically important low-abundance (<20% of the viral population) major DRMs (e.g. K101E, K103N, Y181C and M184V) were detected by GRT-NGS but not by GRT-PS. The frequency of low-abundance DRMs was higher among East African compared with Indian and Caucasian individuals. CONCLUSIONS: Our high-throughput next-generation sequencing with a multiplexed amplicon is a cost-efficient and promising approach for the large-scale surveillance of primary DRMs in LMICs where routine pre-ART GRT is not the standard of care. This strategy may be useful in optimizing future therapeutic regimens in those settings.

Epidemiologic analysis of antimicrobial resistance in hospital departments in China from 2022 to 2023.

Bacterial drug resistance monitoring in hospitals is a crucial aspect of healthcare management and a growing concern worldwide. In this study, we analysed the bacterial drug resistance surveillance in our hospital from 2022 Q1 to 2023 Q2. The main sampling sources were respiratory, blood, and urine-based, and the main clinical infections were respiratory and genitourinary in nature. Specimens were inoculated and cultured; bacterial strains were isolated using a VITEK® 2 Compact 60-card automatic microorganism identifier (bioMerieux, Paris, France) and their matching identification cards were identified, and manual tests were supplemented for strain identification. The most common Gram-positive bacteria detected were Staphylococcus aureus, followed by Enterococcus faecalis (E. faecalis), Staphylococcus epidermidis (S. epidermidis), and Staphylococcus haemolyticus (S. haemolyticus). The most common Gram-negative bacteria detected were Escherichia coli, Klebsiella pneumoniae, and Pseudomonas aeruginosa. The most prevalent multidrug-resistant bacteria were those producing extended-spectrum beta-lactamases, followed by methicillin-resistant Staphylococcus aureus, followed by carbapenem-resistant Enterobacterales. This study suggests that the prevention and control of infections in the respiratory and genitourinary systems should be the focus of anti-infective work and that the use of antimicrobials should be reduced and regulated to prevent the emergence and spread of resistant bacteria.

Surveillance of multidrug-resistant tuberculosis in Taiwan, 2008-2019.

BACKGROUND: Drug-resistant tuberculosis (DR-TB) is a major contributor to global cases of antimicrobial resistance and remains a public health challenge. To understand the extent and trend of DR-TB under an enhanced multidrug-resistant TB (MDR-TB) management program, we conducted a population-based retrospective study of 1511 Taiwanese MDR-TB cases reported from 2008 to 2019. METHODS: We obtained patient demographics and clinical and bacteriological information from the National TB Registry and the Infectious Disease Notification System. RESULTS: Of the 1511 MDR-TB patients, 941 were new cases, 485 were previously treated, and 85 had an unknown history of treatment. The male to female ratio was 2.75, and the median age of the patients was 57 years (IQR: 45-72). We observed a significant decline in MDR-TB cases, with annual percentage change (APC) of -4.17%. However, new and previously treated MDR-TB cases had APCs of -1.41% and -9.18%, respectively. The rates of MDR-TB resistance to ethambutol, streptomycin and pyrazinamide were 47.2%, 42.4% and 28.9%, respectively, whereas the rates of resistance to fluoroquinolones and second-line injectable drugs (SLIDs) were 4.1-7.1%, 9.0-14.1%; and the rate of extensively drug-resistant TB was 1.9%, respectively. Furthermore, we observed a decreasing trend of resistance to SLIDs (APCs -7.0% to -8.2%) in new cases and a significant decreasing trend of resistance to moxifloxacin (-24.6%) and levofloxacin (-23.3%) in previously treated cases. CONCLUSION: The decreasing trend of MDR-TB and resistance to second-line drugs suggested that our programmatic management of TB was effective and that the impact on TB control was profound.

HIV Drug Resistance in Adults Initiating or Reinitiating Antiretroviral Therapy in Uruguay-Results of a Nationally Representative Survey, 2018-2019.

The first nationally representative cross-sectional HIV drug resistance (HIVDR) survey was conducted in Uruguay in 2018-2019 among adults diagnosed with HIV and initiating or reinitiating antiretroviral therapy (ART). Protease, reverse transcriptase, and integrase genes of HIV-1 were sequenced. A total of 206 participants were enrolled in the survey; 63.2% were men, 85.7% were >25 years of age, and 35.6% reported previous exposure to antiretroviral (ARV) drugs. The prevalence of HIVDR to efavirenz or nevirapine was significantly higher (OR: 1.82, p < 0.001) in adults with previous ARV drug exposure (20.3%, 95% CI: 18.7-22.0%) compared to adults without previous ARV drug exposure (12.3%, 11.0-13.8%). HIVDR to any nucleoside reverse transcriptase inhibitors was 10.3% (9.4-11.2%). HIVDR to ritonavir-boosted protease inhibitors was 1.5% (1.1-2.1%); resistance to ritonavir-boosted darunavir was 0.9% (0.4-2.1%) among adults without previous ARV drug exposure and it was not observed among adults with previous ARV drug exposure. Resistance to integrase inhibitors was 12.7% (11.7-13.8%), yet HIVDR to dolutegravir, bictegravir, and cabotegravir was not observed. The high level (>10%) of HIVDR to efavirenz highlights the need to accelerate the transition to the WHO-recommended dolutegravir-based ART. Access to dolutegravir-based ART should be prioritised for people reporting previous ARV drug exposure.

High Level of Pretreatment and Acquired Human Immunodeficiency Virus Drug Resistance in El Salvador: A Nationally Representative Survey, 2018-2019.

Background: Human immunodeficiency virus drug resistance (HIVDR) can negatively impact the effectiveness of antiretroviral therapy (ART). We aimed to estimate the prevalence of pretreatment HIVDR (PDR) among ART initiators and the prevalence of viral load (VL) suppression and acquired HIVDR among individuals receiving ART for 12 ± 3 months (ADR12) and ≥48 months (ADR48) in El Salvador. Methods: Nationally representative cross-sectional PDR, ADR12 and ADR48 surveys were conducted among adults with HIV from October 2018 to August 2019, following World Health Organization-recommended methods. Demographic and clinic data and blood specimens were collected. Results: Two hundred sixty participants were enrolled in the PDR survey, 230 in ADR12 and 425 in ADR48. Twenty-seven percent (95% confidence interval [CI], 17.1%-39.9%) of ART initiators had PDR to efavirenz or nevirapine. The prevalence of VL suppression was 88.8% (95% CI, 83.1%-92.8%) in ADR12 and 80.5% (95% CI, 76.6%-84.0%) in ADR48 surveys. Among people with HIV receiving a first-line nonnucleoside reverse transcriptase inhibitor (NNRTI)-based ART regimens and with unsuppressed VL, the prevalence of ADR to efavirenz or nevirapine was 72.0% (95% CI, 32.3%-93.3%) and 95.0% (68.5%-99.4%) in the ADR12 and ADR28 surveys, respectively. ADR12 to boosted protease inhibitors (PI/r) or integrase strand transfer inhibitors (INSTIs) was not observed. ADR48 was 1.3% (95% CI, 0.2%-9.6%) and 2.1% (0.3%-13.7%), respectively. Conclusions: Programmatic improvements in ART delivery are urgently needed in El Salvador to address the high levels of resistance to efavirenz or nevirapine among ART initiators and the low VL suppression prevalence among individuals on treatment.

Brazilian network for HIV Drug Resistance Surveillance (HIV-BresNet): a survey of treatment-naive individuals.

INTRODUCTION: In Brazil, more than 487,450 individuals are currently undergoing antiretroviral treatment. In order to monitor the transmission of drug-resistant strains and HIV subtype distribution in the country, this work aimed to estimate its prevalence and to characterize the nationwide pretreatment drug resistance in individuals recently diagnosed with HIV between 2013 and 2015. METHODS: The HIV threshold survey methodology (HIV-THS, WHO) targeting antiretroviral-naive individuals with recent HIV diagnosis was utilized, and subjects were selected from 51 highly populated cities in all five Brazilian macroregions. The HIV pol genotypic test was performed by genomic sequencing. RESULTS: We analysed samples from 1568 antiretroviral-naive individuals recently diagnosed with HIV, and the overall transmitted drug resistance (TDR) prevalence was 9.5% (150 sequences). The regional prevalence of resistance according to Brazilian geographical regions was 9.4% in the northeast, 11.2% in the southeast, 6.8% in the central region, 10.2% in the north and 8.8% in the south. The inhibitor-specific TDR prevalence was 3.6% for nucleoside reverse transcriptase inhibitors (NRTIs), 5.8% for non-nucleoside reverse transcriptase inhibitors (NNRTIs) and 1.6% for protease inhibitors (PIs); 1.0% of individuals presented resistance to more than one class of inhibitors. Overall, subtype B was more prevalent in every region except for the southern, where subtype C prevails. CONCLUSIONS: To the best of our knowledge, this is the first TDR study conducted in Brazil with nationwide representative sampling. The TDR prevalence revealed a moderate rate in the five Brazilian geographical regions, although some cities presented higher TDR prevalence rates, reaching 14% in São Paulo, for example. These results further illustrate the importance of surveillance studies for designing future strategies in primary antiretroviral therapy, aiming to mitigate TDR, as well as for predicting future trends in other regions of the globe where mass antiretroviral (ARV) treatment was implemented.

Risk factors and drug-resistance patterns among pulmonary tuberculosis patients in northern Karnataka region, India.

BACKGROUND: India is one of the high tuberculosis (TB)-burden countries in the world. Resistance to anti-tuberculosis (anti-TB) drugs has already become an important and alarming threat in most of the regions worldwide. India ranks second in the world in harbouring multi-drug resistant cases (MDRTB). Prevalence of MDR-TB mirrors the functional state and efficacy of TB control programmes and realistic attitude of the community towards implementation of such programmes. The most important risk factor in the development of MDRTB is improper implementation in the guidelines in the management of TB, and high rate of defaults on the part of the patients. The study was carried out to evaluate the drug resistance pattern to first line anti-TB drugs in Northern Karnataka region, India. MATERIALS AND METHODS: A prospective study was conducted at J. N. Medical College and its associated Hospitals, Belgaum. Between January 2011 and December 2012, 150 sputum samples of suspected pulmonary TB patients based on the history were examined for the AFB culture by Lowenstein-Jensen (LJ) culture technique. A total of two early morning samples were collected for the smear [Ziehl-Neelsen (ZN) staining] and culture methods. It was observed that ZN staining for AFB was positive in 113 patients (75%), while AFB culture by LJ medium yielded growth in 66 cases (44%). Thus, a total of 66 AFB culture-positive samples by LJ medium were subjected for AFB drug-sensitivity testing (DST). DST was done for Isoniazid (INH), Rifampicin (RIF), Pyrazinamide (PZA), Ethambutol (EMB) and Streptomycin (SM) after isolation by using the resistance proportion method. RESULTS: A total of 66 AFB culture-positive specimens, 20 (30.3%) cases were sensitive to all the five drugs while 46 (69.7%) cases showed resistance to one or more drugs. Among these, the resistance to rifampicin was highest (80.4%), while resistance to isoniazid, pyrazinamide, ethambutol and streptomycin were observed to be 60%, 58.7%, 52.1% and 63%, respectively. It was also observed that, resistance to all five drugs was highest (39.18%). MDR isolates were obtained in 52.2% of the cases. Illiteracy, low socio-economic status, previous history of TB and alcoholism were found to have statistically significant association for the development of MDR. CONCLUSIONS: The prevalence of drug resistance in the present study was observed to be 69.7%. More than half of the cases were multi-drug resistant. The most common resistant pattern observed in this study was resistance to all the first-line drugs. Therefore, during initiation of new case proper explaining and completion of the treatment is very important to avoid the development of future drug resistance in the society.

Prevalence of and viral outcomes associated with primary HIV-1 drug resistance.

Primary, or transmitted, HIV antiretroviral resistance is an ongoing concern despite continuing development of new antiretroviral therapies. We examined HIV surveillance data, including both patient demographic characteristics and laboratory data, combined with HIV genotypic test results to evaluate the comprehensiveness of drug resistance surveillance, prevalence of primary drug resistance, and impact, if any, of primary resistance on population-based virological outcomes. The King County, WA Variant, Atypical, and Resistant HIV Surveillance (VARHS) system increased coverage of eligible genotypic testing - within three months of an HIV diagnosis among antiretroviral naïve individuals -- from - 15% in 2003 to 69% in 2010. VARHS under-represented females, Blacks, Native Americans, and injection drug users. Primary drug resistance was more common among males, individuals aged 20 - 29 years, men who had sex with men, and individuals with an initial CD4+ lymphocyte count of 200 cells/µL and higher. High level resistance to two or three antiretroviral classes declined over time. Over 90% of sequences were HIV-1 subtype B. The proportion of individuals with a most recent viral load (closest to April 2011) that was undetectable (<50 copies/mL) was not statistically significantly associated with primary drug resistance. This was true for both number and type of antiretroviral drug class; although small numbers of specimens with drug resistance may have limited our statistical power. In summary, although we found disparities in testing coverage and prevalence of drug resistance, we were unable to detect a significantly deleterious impact of primary drug resistance based on a most recent viral load.