DORAVIR: a French national survey of people with HIV-1 treated with an antiretroviral regimen including doravirine.

BACKGROUND: Doravirine is the latest NNRTI to be approved for the treatment of HIV-1 and has a different resistance profile from first-generation NNRTIs. Our aim was to investigate the virological efficacy of antiretroviral treatment including doravirine in people living with HIV-1 (PLWHIV), the factors associated with virological failure (VF) and those associated with the emergence of reverse transcriptase (RT) mutations in the case of VF. METHODS: A retrospective national survey of PLWHIV who were either naive or experienced on antiretroviral treatment including doravirine was conducted. VF was defined as two consecutive plasma viral loads (VLs) of ≥50 copies/mL or one VL of ≥200 copies/mL. Genotypic resistance tests were interpreted using the Stanford (v9.4.1) and ANRS (v33) algorithms. RESULTS: Of the 589 PLWHIV treated with a doravirine-containing regimen, 8.5% were naive and 91.5% had prior antiretroviral experience; 56.9% were infected with HIV-1 B subtype. Overall, 88.3% and 85.1% of participants were virologically controlled at Month (M)3 and M6 of doravirine treatment, respectively. In multivariable analysis, CRF02_AG subtype, higher zenith plasma HIV-1 RNA VL, doravirine initiation in the context of failure and baseline V179D mutation presence were associated with VF. Among 88 PLWHIV who experienced virological failure at M6, 15.9% had a median of 2 (IQR 1-3) HIV RT mutations. In multivariable analysis, the only factor associated with the occurrence of mutations was a genotypic sensitivity score that was not fully sensitive. CONCLUSIONS: This study is one of the largest to characterize the virological efficacy of doravirine-containing regimens in clinical practice and to identify factors associated with VF or emergence of resistance mutations that should be considered in clinical management.

Hematological profiles of patients with tuberculosis and nontuberculous mycobacteria infections in Bamako, Mali.

Background: Pulmonary tuberculosis (TB) remains one of the main causes of morbidity and mortality in Mali. Nontuberculous mycobacteria (NTM) infections are very common but are often cofounded with TB because of the similarity of symptoms, which makes the diagnosis difficult. Hematological abnormalities associated with TB have been described, but not with NTM. Therefore, the goal of this study was to compare the hematological parameters of patients infected with TB and NTM infections. Methods: A cross-sectional study enrolling TB and NTM participants was conducted in 2018-2020. Five milliliters of venous blood and sputum samples were collected from each participant to determine the hematological parameters using the RUBY CELL-DYN Ruby Version 2.2 ML. A BACTEC MGIT 960 and multiplex reverse transcription-polymerase chain reaction were used to distinguish Mycobacterium tuberculosis from NTM, respectively. Results: Of the total 90 patients enrolled, there was a decrease in hemoglobin and hematocrit levels in both the groups (P = 0.05). In addition, we found that the percentages of basophil cells (P = 0.01) and mean values of platelets (P = 0.04) were significantly higher in TB patients than those of NTMs. Moreover, the mean of absolute values of eosinophil cells of TB patients was significantly lower than those of NTMs (P = 0.03). Conclusion: We found significant statistical differences in basophils, platelets, and eosinophils in differentiating TB and NTM in this pilot study. Future studies with patients at different clinical stages are needed to confirm the hematological profiles of TB and NTM patients.

Four days/week antiretroviral maintenance strategy (ANRS 170 QUATUOR): substudies of reservoirs and ultrasensitive drug resistance.

BACKGROUND: In a 4 days/week (4/7 days) maintenance strategy (ANRS-170 QUATUOR trial), the virological impact of an intermittent strategy was assessed by ultrasensitive virological analyses of reservoirs and resistance. METHODS: HIV-1 total DNA, ultra-sensitive plasma viral load (USpVL) and semen VL were measured in the first 121 participants. Sanger and ultra-deep sequencing (UDS) were performed on the HIV-1 genome (Illumina technology) according to the ANRS consensus. A generalized estimation equation with a Poisson distribution was used to compare changes in the proportion of residual viraemia, detectable semen HIV RNA and HIV DNA within and between the two groups over time. RESULTS: The proportion of participants with residual viraemia at Day 0 (D0) and Week 48 (W48) was 16.7% and 25.0% in the 4/7 days group and 22.4% and 29.7% in the 7/7 days group, respectively (+8.3% versus +7.3%, P = 0.971). The proportion of detectable DNA (>40 copies/106 cells) at D0 and W48 was 53.7% and 57.4% in the 4/7 days group and 56.1% and 51.8% in the 7/7 days group, respectively (+3.7% versus -4.3%, P = 0.358). Semen HIV RNA was detectable (≥100 copies/mL) in 2.2% of participants at D0 and 4.5% at W48 in the 4/7 days group versus 6.1% and 9.1% in the 7/7 days group, respectively (+2.3% versus +3.0%, P = 0.743). Emerging resistance at failure was more frequent in the 4/7 days group detected by Sanger sequencing: 3/6 participants versus 1/4 in the 7/7 days group, and similar with the UDS assay: 5/6 versus 4/4, respectively. CONCLUSIONS: These findings support the potency of a 4/7 days maintenance strategy on virological suppression at the reservoirs and emergent resistance level, including minority variants.

Hepatitis B Virus in West African Children: Systematic Review and Meta-Analysis of HIV and Other Factors Associated with Hepatitis B Infection.

While Hepatitis B virus (HBV) and the human immunodeficiency virus (HIV) are endemic in West Africa, the prevalence of HBV/HIV coinfection and their associated risk factors in children remains unclear. In this review, we sought to assess HBsAg seroprevalence among 0- to 16-year-olds with and without HIV in West African countries and the risk factors associated with HBV infection in this population. Research articles between 2000 and 2021 that reported the prevalence of HBV and associated risk factors in children in West Africa were retrieved from the literature using the Africa Journals Online (AJOL), PubMed, Google Scholar, and Web of Science databases as search tools. StatsDirect, a statistical software, was used to perform a meta-analysis of the retained studies. HBV prevalence and heterogeneity were then assessed with a 95% confidence interval (CI). Publication bias was evaluated using funnel plot asymmetry and Egger's test. Twenty-seven articles conducted across seven West African countries were included in this review. HBV prevalence among persons aged 0 to 16 years was 5%, based on the random analysis, given the great heterogeneity of the studies. By country, the highest prevalence was observed in Benin (10%), followed by Nigeria (7%), and Ivory Coast (5%), with Togo (1%) having the lowest. HBV prevalence in an HIV-infected population of children was (9%). Vaccinated children had lower HBV prevalence (2%) than unvaccinated children (6%). HBV prevalence with a defined risk factor such as HIV co-infection, maternal HBsAg positivity, undergoing surgery, scarification, or being unvaccinated ranged from 3-9%. The study highlights the need to reinforce vaccination of newborns, screening for HBV, and HBV prophylaxis among pregnant women in Africa, particularly in West Africa, to achieve the WHO goal of HBV elimination, particularly in children.

Prevalence of HIV-1 Natural Polymorphisms and Integrase-Resistance-Associated Mutations in African Children.

Integrase inhibitors (INIs) are a potent option for HIV treatment. Limited data exist on INI resistance in West Africa, particularly in children living with HIV/AIDS. We determined the prevalence of integrase gene polymorphisms and the frequency of naturally occurring amino acid (aa) substitutions at positions associated with INI resistance. Dried blood spot (DBS) samples were obtained from one hundred and seven (107) HIV-1-infected children aged less than 15 years old in two West African countries, Benin and Mali. All children were naïve to INI treatment, 56 were naïve to anti-retroviral therapy (ART), and 51 had received ART. Genetic sequencing of HIV integrase was successful in 75 samples. The aa changes at integrase positions associated with INI resistance were examined according to the Stanford HIV Genotypic Resistance database. The median ages were 2.6 and 10 years for ART-naïve and -treated children, respectively. The most common subtypes observed were CRF02_AG (74.7%) followed by CRF06_cpx (20%). No major INI-resistance mutations at positions 66, 92, 121, 143, 147, 148, 155, and 263 were detected. The most prevalent INI accessory resistance mutations were: L74I/M (14/75, 18.6%) followed by E157Q (8/75, 10.6%), G163E/N/T/Q (5/75, 6.6%), Q95A/H/P (2/75, 2.6%), and T97A (4/75, 5.3%). Other substitutions observed were M50I/L/P, H51E/P/S/Q, I72V, T112V, V201I, and T206S. Polymorphisms at positions which may influence the genetic barrier and/or drive the selection of specific INI-resistance pathways were detected. However, no transmitted drug resistance (TDR) to INI was detected among samples of INI-naïve patients. These findings support the use of this treatment class for children with HIV-1, particularly in West Africa.

Multidrug resistant bacteria isolated from nosocomial infections at University Teaching Hospital of Point-G, Bamako, Mali.

An infection is said to be nosocomial or hospital if it is absent when the patient enters the hospital and it appears and develops at least 48 h late. The objective of this study was to determine the resistance phenotypes of bacteria isolated from nosocomial infections at the University Teaching Hospital of Point G. Urine, blood, pus, skin and bronchoalveolar fluid samples were taken in different units, and bacteria isolations were performed on usual selective media such as Drigalski Colombia agar supplemented with nalidixic acid and colistin and 5% sheep blood and chocolate agar. Identifications of bacteria such as Enterobacteriaceae, Pseudomonas and acinetobacter, and Staphylococci were done using API20E gallery, API20NE gallery and catalase/oxidase tests, and the Pastorex Staph kit respectively. The antimicrobial susceptibility testing was performed on Mueller-Hinton agar using the diffusion method. A total of 463 patients were inpatients for at least 48 h in the different units, and a nosocomial infection was notified in at least 57 patients (12.3%). A total of 65 episodes of nosocomial infections were observed in these 57 patients. Of the bacteria isolated, multidrug-resistant bacteria (MDR) represented 63.7% (n=36). These were extended-spectrum beta-lactamase (ESBL)-secreting Enterobacteriaceae (n=21), high-level cephalosporinase (n=13) and methicillin-resistant coagulase-negative Staphylococci (n=2). Despite this high number of multi-resistant bacteria isolated in this study; colistin and amikacin had very good activity on enterobacteriaceae. The results show the need to strengthen hygiene in the intensive care units in order to fight against nosocomial infections at the UTH of Point G.

SARS-CoV-2 Neutralizing Responses in Various Populations, at the Time of SARS-CoV-2 Variant Virus Emergence: Evaluation of Two Surrogate Neutralization Assays in Front of Whole Virus Neutralization Test.

The SARS-CoV-2 neutralizing antibodies response is the best indicator of effective protection after infection and/or vaccination, but its evaluation requires tedious cell-based experiments using an infectious virus. We analyzed, in 105 patients with various histories of SARS-CoV-2 infection and/or vaccination, the neutralizing response using a virus neutralization test (VNT) against B.1, Alpha, Beta and Omicron variants, and compared the results with two surrogate assays based on antibody-mediated blockage of the ACE2-RBD interaction (Lateral Flow Boditech and ELISA Genscript). The strongest response was observed for recovered COVID-19 patients receiving one vaccine dose. Naïve patients receiving 2 doses of mRNA vaccine also demonstrate high neutralization titers against B.1, Alpha and Beta variants, but only 34.3% displayed a neutralization activity against the Omicron variant. On the other hand, non-infected patients with half vaccination schedules displayed a weak and inconstant activity against all isolates. Non-vaccinated COVID-19 patients kept a neutralizing activity against B.1 and Alpha up to 12 months after recovery but a decreased activity against Beta and Omicron. Both surrogate assays displayed a good correlation with the VNT. However, an adaptation of the cut-off positivity was necessary, especially for the most resistant Beta and Omicron variants. We validated two simple and reliable surrogate neutralization assays, which may favorably replace cell-based methods, allowing functional analysis on a larger scale.

Relationships between gut microbiota, red meat consumption and colorectal cancer.

Excessive consumption of red and processed meat has been associated with a higher risk of developing colorectal cancer. There are many attempts to explain the risk of colorectal cancer associated with the consumption of red and processed meat: The temperature cooking of meat such as grilling and smoking contribute to the formation of mutagenic compounds including heterocyclic amines and polycyclic aromatic hydrocarbons.Heme iron in red meat is involved in the formation of N-nitroso compounds and lipid peroxidation products in the digestive tract.Fatty red meat is involved in the production of secondary bile acids by the bacteria of the gut microbiota. Many of the products formed are genotoxic and can cause DNA damage and initiate carcinogenesis of colorectal cancer. Various mechanisms contributing to their genotoxic role have been established in human and animal studies. In addition, there is increasing evidence that compounds formed from red and processed meat interact with the gut microbiota in colorectal cancer pathways. Although several early studies in animals and humans suggest a direct causal role of the gut microbiota in the development of colorectal cancer, the links between diet, gut microbiota, and colonic carcinogenesis are largely associations rather than proven causal relationships. Various biological mechanisms, including inflammation and oxidative stress can lead to DNA damage, gut dysbiosis, and therefore increase the risk of colorectal cancer. Dysbiosis of the gut microbiota may increase the risk of colorectal cancer through dietary component promotion of colonic carcinogenesis. In this paper, we review and update current knowledge about the relationships between red meat consumption, gut microbiota, and colorectal cancer.

Weak immunogenicity of SARS-CoV-2 vaccine in patients with hematologic malignancies.

This study evaluated the safety and immunogenicity of BNT162b2 vaccine in patients with hematological malignancies. Antibodies blocking spike binding to immobilized ACE-2 (NAb) correlated with anti-Spike (S) IgG d42 titers (Spearman r = 0.865, p < 0.0001), and an anti-S IgG d42 level ≥3100 UA/mL was predictive of NAb ≥ 30%, the positivity cutoff for NAb (p < 0.0001). Only 47% of the patients achieved an anti-S IgG d42 level ≥3100 UA/mL after the two BNT162b2 inocula, compared to 87% of healthy controls. In multivariable analysis, male patients, use of B-cell targeting treatment within the last 12 months prior to vaccination, and CD19+ B-cell level <120/uL, were associated with a significantly decreased probability of achieving a protective anti-S IgG level after the second BNT162b2 inoculum. Finally, using the IFN-γ ELISPOT assay, we found a significant increase in T-cell response against the S protein, with 53% of patients having an anti-S IgG-positive ELISPOT after the second BNT162b2 inoculum. There was a correlation between the anti-S ELISPOT response and IgG d42 level (Spearman r = 0.3026, p = 0.012). These findings suggest that vaccination with two BNT162b2 inocula translates into a significant increase in humoral and cellular response in patients with hematological malignancies, but only around half of the patients can likely achieve effective immune protection against COVID-19.

Factors associated with the emergence of integrase resistance mutations in patients failing dual or triple integrase inhibitor-based regimens in a French national survey.

BACKGROUND: Successful 2-drug regimens (2DRs) for HIV were made possible by the availability of drugs combining potency and tolerability with a high genetic barrier to resistance. How these deal with resistance development/re-emergence, compared with 3DRs, is thus of paramount importance. MATERIALS AND METHODS: A national survey including patients who were either naive or experienced with any 2DR or 3DR but failing integrase strand transfer inhibitor (INSTI)-containing regimens [two consecutive plasma viral load (VL) values >50 copies/mL] was conducted between 2014 and 2019. Genotypic resistance tests were interpreted with the v28 ANRS algorithm. RESULTS: Overall, 1104 patients failing any INSTI-containing regimen (2DRs, n = 207; 3DRs, n = 897) were analysed. Five hundred and seventy-seven (52.3%) patients were infected with a B subtype and 527 (47.3%) with non-B subtypes. Overall, 644 (58%) patients showed no known integrase resistance mutations at failure. In multivariate analysis, factors associated with the emergence of at least one integrase mutation were: high VL at failure (OR = 1.24 per 1 log10 copies/mL increase); non-B versus B subtype (OR = 1.75); low genotypic sensitivity score (GSS) (OR = 0.10 for GSS = 2 versus GSS = 0-0.5); and dolutegravir versus raltegravir (OR = 0.46). Although 3DRs versus 2DRs reached statistical significance in univariate analysis (OR = 0.59, P = 0.007), the variable is not retained in the final model. CONCLUSIONS: This study is one of the largest studies characterizing integrase resistance in patients failing any INSTI-containing 2DR or 3DR in routine clinical care and reveals factors associated with emergence of integrase resistance that should be taken into consideration in clinical management. No difference was evidenced between patients receiving a 2DR or a 3DR.

Caution in interpretation of SARS-CoV-2 quantification based on RT-PCR cycle threshold value.

RT-PCR is the reference method for diagnosis of a Severe Acute Respiratory Syndrome-Coronavirus-2 (SARS-CoV-2) infection. During the setting up of 6 SARS-CoV-2 RT-PCR assays in our laboratory, comparative evaluations were systematically undertaken and allowed to evidence major discrepancies on cycle threshold RT-PCR results between techniques. These tendencies were confirmed in routine application when analyzing sequential samples from the same patients. Our aim was to examine the impact of the technique among factors influencing RT-PCR result, a far surrogate of 'viral load' in the heterogeneous environment of respiratory specimens.

Characterization of drug resistance and the defective HIV reservoir in virally suppressed vertically infected children in Mali.

BACKGROUND: In the perspective of ART-free HIV remission, vertically infected children treated with suppressive ART from early infancy represent an optimal population model to better understand the genetic complexity of the reservoir. OBJECTIVES: To evaluate the proportion of defective viral population and the genotypic resistance patterns in cell-associated HIV DNA. METHODS: In a cohort including 93 ART-treated vertically HIV-infected (VHIV) children in Mali with plasma HIV-1 RNA ≤50 copies/mL for at least 6 months, we studied total HIV DNA, percentage of defective genomes and resistance by reverse transcriptase and protease bulk sequencing from whole blood in dried blood spots. RESULTS: Children had a median age of 9.9 years at the time of inclusion (IQR = 7.6-13.4) and 3.3 years (IQR = 2-7) at ART initiation; median ART duration was 5.5 years (IQR = 3.7-7.3). The median level of total HIV DNA was 470 copies/106 cells with one patient presenting undetectable HIV DNA (<66 copies/106 cells). We observed the presence of at least one stop codon in viruses from 34 patients (37%). The presence of stop codons was not correlated with the level of HIV DNA or duration of ART. We showed a high prevalence of HIV-1 resistance in DNA with 26% of children harbouring virus resistant to at least one NRTI and 40% to at least one NNRTI. CONCLUSIONS: While these VHIV children were successfully treated for a long time, they showed high prevalence of resistance in HIV DNA and a moderate defective HIV reservoir.

Diagnostic Laboratories' Capacities and Preparedness for Emerging Viral Diseases in Guinea and Mali.

The 2014-2016 Ebola epidemic in Guinea highlighted the need for more extensive evaluation of laboratories diagnostic capacities and preparedness in anticipation of future emerging viral disease outbreaks. We developed a questionnaire to assess the diagnostic capacities and preparedness of the four major medical laboratories in Guinea and Mali that are responsible for the provision of Ebola, Lassa, and Dengue diagnostics. The questionnaire inquired about the current state and need for equipment and reagents and adequacy of equipment and training received. In Guinea, all three diagnostic laboratories have the capacity and are well-prepared to perform Ebola diagnostics, however, only two have the capacity and trained staff to diagnose Lassa and none are currently prepared to diagnose Dengue infection. In Mali, the University Clinical Research Center (UCRC) laboratory, which was in charge of Ebola diagnostics during the last epidemic, currently has the capacity and is prepared to diagnose Ebola, Lassa, and Dengue infections. Combined, Guinea and Mali appear to have complementary capacity and preparedness to diagnose these Category A Priority Pathogens. While, the equipment, reagents and training efforts should be maintained, the gap in Dengue diagnostic capability in Guinea should be addressed with further equipping and training of additional district laboratories to strengthen the public health response for all viral diseases in these high-risk, yet, low-resource settings.

Seroprevalence and risk factors for HIV, HCV, HBV and syphilis among blood donors in Mali.

BACKGROUND: HIV, HBV and HCV remain a global public health concern especially in Africa. Prevalence of these infections is changing and identification of risk factors associated with each infection in Mali is needed to improve medical care. METHODS: We conducted a cross-sectional study of all individuals donating blood (n = 8207) in 2018 to the blood bank at university hospital in Bamako, Mali, to assess prevalence and risks factors associated with HIV, HBV, HCV and syphilis infections. RESULTS: HIV-seroprevalence was 2.16% and significantly increased with age, being married and decreasing education level. In multivariate analysis, after adjustements with age, marital status and geographical setting, only education level was associated with HIV-infection (OR, 1.54 [95% CI, 1.15-2.07], p = 0.016). HBsAg prevalence was 14.78% and significantly increased with to be male gender. In multivariate analysis, adjusting for age, marital status and type of blood donation, education level (OR, 1.17 [95%CI, 1.05-1.31], p = 0.02) and male gender (OR, 1.37 [95%CI, 1.14-1.65], p = 0.005) were associated with HBV-infection. HCV-prevalence was 2.32% and significantly increased with living outside Bamako. In multivariate analysis, adjusting for gender, age and education level, living outside Bamako was associated with HCV-infection (OR, 1.83 [95% CI, 1.41-2.35], p < 0.001). Syphilis seroprevalence was very low (0.04%) with only 3 individuals infected. Contrary to a prior study, blood donation type was not, after adjustments, an independent risk factor for each infection. CONCLUSIONS: Overall, HIV and HBV infection was higher in individuals with a lower level of education, HBV infection was higher in men, and HCV infection was higher in people living outside of Bamako. Compared to studies performed in 1999, 2002 and 2007 in the same population, we found that HIV and HCV prevalence have decreased in the last two decades whereas HBV prevalence has remained stable. Our finding will help guide infection prevention and treatment programs in Mali.

INSTI-Based Triple Regimens in Treatment-Naïve HIV-Infected Patients Are Associated With HIV-RNA Viral Load Suppression at Ultralow Levels.

BACKGROUND: During antiretroviral therapy (ART), HIV-1-infected patients may present with ultralow (UL) HIV-RNA viral loads (VLs) below quantification levels of current assays. Reasons for UL-VL detection and its relation to virological rebound (VR) are unclear. METHODS: HIV-1-infected, ART-naïve patients followed at 2 university hospitals were included. All participants had an HIV-RNA >200 copies/mL at ART initiation and achieved a VL <50 copies/mL during ART. UL-VL was determined by the presence/absence of polymerase chain reaction signal detected using a commercially available assay (COBAS, TaqMan, Roche). Random-effects Poisson regression was used for assessing determinants of UL-VL not detected overtime and conditional risk set analysis for VR (1 VL > 200 copies/mL or 2 VL > 50 copies/mL) while accounting for frequency of VL measurements. RESULTS: Between 2009 and 2013, 717 patients initiated ART containing 2 nucleos(-t)ide reverse transcriptase inhibitors (NRTIs) plus a non-NRTI (29.4%), a protease inhibitor (58.4%), or an integrase-strand transfer inhibitor (INSTI; 12.1%). During a median (interquartile range) 3.4 (2.3-4.6) years, 676 (94.3%) patients achieved UL-VL not detected. In multivariable analysis, UL-VL not detected overtime was associated with younger age (P < .001), female gender (P = .04), lower baseline VL (P < .001), baseline CD4+ >500 vs <350/mm3 (P < .001), and INSTI-containing ART (P = .009). One hundred thirty-one (18.3%) patients had VR during follow-up, which was independently associated with a CD4/CD8 ratio <0.8 during follow-up (P = .01) and time spent with UL-VL not detected (P < .001). When UL-VL not detected occurred for ≥50% of the follow-up duration (n = 290), faster time to reach UL-VL not detected (P < .001), faster CD4+ T-cell count increase (P = .03), and faster CD4/CD8 ratio increase (P = .001) were observed. CONCLUSIONS: VL suppression at an ultralow level is associated with INSTI-class ART initiation. Extensive VL suppression below ultralow detection could improve immune reconstitution.

Resistance to integrase inhibitors: a national study in HIV-1-infected treatment-naive and -experienced patients.

OBJECTIVES: To describe integrase strand transfer inhibitor (INSTI) resistance profiles and factors associated with resistance in antiretroviral-naive and -experienced patients failing an INSTI-based regimen in clinical practice. METHODS: Data were collected from patients failing an INSTI-containing regimen in a multicentre French study between 2014 and 2017. Failure was defined as two consecutive plasma viral loads (VL) >50 copies/mL. Reverse transcriptase, protease and integrase coding regions were sequenced at baseline and failure. INSTI resistance-associated mutations (RAMs) included in the Agence Nationale de Recherches sur le SIDA genotypic algorithm were investigated. RESULTS: Among the 674 patients, 359 were failing on raltegravir, 154 on elvitegravir and 161 on dolutegravir therapy. Overall, 90% were experienced patients and 389 (58%) patients showed no INSTI RAMs at failure. The strongest factors associated with emergence of at least one INSTI mutation were high VL at failure (OR = 1.2 per 1 log10 copies/mL increase) and low genotypic sensitivity score (GSS) (OR = 0.08 for GSS ≥3 versus GSS = 0-0.5). Patients failing dolutegravir also had significantly fewer INSTI RAMs at failure than patients failing raltegravir (OR = 0.57, P = 0.02) or elvitegravir (OR = 0.45, P = 0.005). Among the 68 patients failing a first-line regimen, 11/41 (27%) patients on raltegravir, 7/18 (39%) on elvitegravir and 0/9 on dolutegravir had viruses with emergent INSTI RAMs at failure. CONCLUSIONS: These results confirmed the robustness of dolutegravir regarding resistance selection in integrase in the case of virological failure in routine clinical care.

Occult Hepatitis B Virus Infection: An Old Entity With Novel Clinical Involvements.

BACKGROUND: Occult hepatitis B infection (OBI) is recognized as a risk factor for cirrhosis and hepato-cellular carcinoma. However, OBI brings together a large spectrum of patients who might harbor different characteristics and prognosis. METHODS: We analyzed the databases of a university hospital in Paris to identify OBI among patients (n = 3966) concomitantly tested for hepatitis B virus (HBV) DNA and serology during a 7-year period. OBI patients were gathered into clinical entities according to their clinical records. RESULTS: Forty-seven OBIs were identified (1.2%). All patients had detectable anti-HBc, isolated (n = 26) or associated with anti-HBs (n = 21). The proportion of OBIs was 3.4% for patients with isolated anti-HBc and 4.2% for patients with both anti-HBc and anti-HBs. Four clinical categories of OBI patients were identified: patients with a passed HBV infection with HBs Ag clearance (group A, 23.4%); HBV-exposed patients receiving immunosuppressive therapy (group B, 29.8%); HIV/HBV-coinfected patients with therapy discontinuation (group C, 17%); HBV-exposed patients with severe liver conditions (group D, 29.8%). Significant follow-up was available for 32 patients, showing a more deleterious prognosis in group D patients, associated more with their underlying condition than the OBI status. CONCLUSIONS: OBI is a heterogeneous condition with various clinical implications.

Simultaneous diagnosis of tuberculous and non-tuberculous mycobacterial diseases: Time for a better patient management.

Tuberculosis (TB) is the deadliest infectious disease in the world which disproportionately affects low-and-middle-income countries (LMICs) where diagnostic resources and treatment options are limited. The incidence of pulmonary non-tuberculous mycobacteria (NTM) disease is also rapidly increasing in these regions traditionally dominated by TB infections. This poses significant diagnostic and treatment challenges, since these two diseases are often indistinguishable clinically or by sputum smear microscopy (SSM), the most commonly used TB diagnostic tool in LMICs. Consequently, NTM-infected patients usually receive unnecessary TB treatment for months. TB patients with NTM co-infections may also be treated incorrectly due to inaccurate SSM and Xpert™ MTB/RIF (M. tuberculosis./rifampin) results. These issues complicate the management of patients and contribute to the worsening of the current TB and NTM epidemiological features including development of drug resistant strains. It is therefore critical to develop improved diagnostic tools to accurately distinguish these two different pathogens that have many similar clinical and epidemiological features but have different treatment regimens. In this review, we will discuss limitations with current diagnostic tools and the need to develop novel techniques that can accurately and simultaneously diagnose TB and NTM disease._.

High Rates of Baseline Drug Resistance and Virologic Failure Among ART-naive HIV-infected Children in Mali.

BACKGROUND: Limited data exist on drug resistance and antiretroviral treatment (ART) outcomes in HIV-1-infected children in West Africa. We determined the prevalence of baseline resistance and correlates of virologic failure (VF) in a cohort of ART-naive HIV-1-infected children <10 years of age initiating ART in Mali. METHODS: Reverse transcriptase and protease genes were sequenced at baseline (before ART) and at 6 months. Resistance was defined according to the Stanford HIV Genotypic Resistance database. VF was defined as viral load ≥1000 copies/mL after 6 months of ART. Logistic regression was used to evaluate factors associated with VF or death >1 month after enrollment. Post hoc, antiretroviral concentrations were assayed on baseline samples of participants with baseline resistance. RESULTS: One-hundred twenty children with a median age 2.6 years (interquartile range: 1.6-5.0) were included. Eighty-eight percent reported no prevention of mother-to-child transmission exposure. At baseline, 27 (23%), 4 (3%) and none had non-nucleoside reverse transcriptase inhibitor (NNRTI), nucleoside reverse transcriptase inhibitor or protease inhibitor resistance, respectively. Thirty-nine (33%) developed VF and 4 died >1 month post-ART initiation. In multivariable analyses, poor adherence [odds ratio (OR): 6.1, P = 0.001], baseline NNRTI resistance among children receiving NNRTI-based ART (OR: 22.9, P < 0.001) and protease inhibitor-based ART initiation among children without baseline NNRTI resistance (OR: 5.8, P = 0.018) were significantly associated with VF/death. Ten (38%) with baseline resistance had detectable levels of nevirapine or efavirenz at baseline; 7 were currently breastfeeding, but only 2 reported maternal antiretroviral use. CONCLUSIONS: Baseline NNRTI resistance was common in children without reported NNRTI exposure and was associated with increased risk of treatment failure. Detectable NNRTI concentrations were present despite few reports of maternal/infant antiretroviral use.