COVID-19 omicron variant outbreak in a hematopoietic stem cell transplant unit.

Recommendations and guidelines for management of SARS-COV-2 infection in hematologic patients were developed in the very difficult context of dealing with novel viral variants from one pandemic wave to another, with different susceptibility to available drugs and vaccines. Moreover, the largest SARS-COV-2 case series in patients treated for hematologic malignancies, including stem cell transplant recipients, was published before the Omicron surge, and refers mainly to Alpha and Delta viral variants. These infections had very high mortality, in a period when antivirals and monoclonal antibodies were mostly unavailable. Here, we report for the first time a SARS-COV-2 Omicron variant outbreak inside a Bone Marrow Transplant (BMT) Unit, describing the characteristics, clinical course, and infection outcomes shortly before and shortly after myeloablative transplantation. We detail how infections were treated off-label and managed inside the BMT ward, to guarantee the best possible outcomes while avoiding risks for non-infected inpatients. The positive outcomes observed suggest that it may not be absolutely necessary to obtain SARS-CoV-2 PCR negativity before BMT in hematologic patients after treated infection, in cases with long-term PCR positivity and high-risk hematologic disease.

Long-Term SARS-CoV-2 Antibody Seroprevalence in Blood Donors, Italy.

We evaluated SARS-CoV-2 antibody response in voluntary blood donors in Italy at different timepoints. Immediately after lockdown easing, 908/25,657 donors (3.5%) had low IgG titers against nucleocapsid. In the next 2 years, titers increased despite few COVID-19 symptoms. On multivariate analysis, allergic rhinitis was associated with reduced risk for symptomatic COVID-19.

Persistent SARS-CoV-2 infection with multiple clinical relapses in two patients with follicular lymphoma treated with bendamustine and obinutuzumab or rituximab.

PURPOSE: People with hematologic malignancies have a significantly higher risk of developing severe and protracted forms of SARS-CoV-2 infection compared to immunocompetent patients, regardless of vaccination status. RESULTS: We describe two cases of prolonged SARS-CoV-2 infection with multiple relapses of COVID-19 pneumonia in patients with follicular lymphoma treated with bendamustine and obinutuzumab or rituximab. The aim is to highlight the complexity of SARS-CoV-2 infection in this fragile group of patients and the necessity of evidence-based strategies to treat them properly. CONCLUSIONS: Patients with hematological malignancies treated with bendamustine and anti-CD20 antibodies had a significant risk of prolonged and relapsing course of COVID-19. Specific preventive and therapeutic strategies should be developed for this group of patients.

Weekly Rapid Antigen Test Screening for COVID-19 in Patients on Hemodialysis.

BACKGROUND/AIM: COVID-19 is a concerning issue among in-center hemodialysis (HD) patients. To prevent COVID-19 diffusion in our HD facility, weekly rapid nasal antigen test screening was performed for all asymptomatic patients on chronic HD. This study aimed to assess the performance of weekly rapid antigen test in detecting SARS-CoV-2 infection among asymptomatic patients receiving HD. PATIENTS AND METHODS: A retrospective analysis was conducted in HD patients who underwent rapid antigen test screening from December 2021 to March 2022. The diagnosis of COVID-19 with rapid antigen test was always confirmed by reverse transcriptase-polymerase chain reaction (RT-PCR). RESULTS: During the observational period, 1,748 rapid antigen tests were performed in 220 HD patients. Mean age was 68.4±14.6 years. Fifteen (8.5%) patients resulted positive for SARS-CoV-2 infection using rapid antigen tests. The diagnosis was subsequently confirmed in 14 (93.3%) patients by RT-PCR. During the same period, 12 (5.4%) symptomatic patients, regularly screened with weekly rapid antigen test, resulted positive for SARS-CoV-2 infection using RT-PCR. Overall, weekly rapid antigen test screening identified 14 out of 26 (53.8%) COVID-19 cases and showed a positive predictive value of 93%. CONCLUSION: Weekly antigen test screening of asymptomatic patients on chronic HD detected around half of the COVID-19 cases in our population.

COVID-19 Rapid Antigen Test Screening in Patients on Hemodialysis.

Introduction: Patients receiving in-center hemodialysis are extremely vulnerable to COVID-19. It is unclear if routine screening of asymptomatic hemodialysis patients is an effective strategy to prevent COVID-19 outbreaks within the dialysis unit. Methods: We conducted a retrospective analysis of in-center hemodialysis patients who underwent bimonthly COVID-19 rapid antigen test screening from February 15th to December 26th, 2021. Nasal rapid antigen testing was performed in all asymptomatic patients. All rapid antigen-positive tests were confirmed by RT-PCR nasopharyngeal swab. Besides universal rapid antigen screening, RT-PCR testing was conducted in all symptomatic patients and contacts of COVID-19 subjects. Results: Overall, 4079 rapid antigen tests were performed in 277 hemodialysis patients on chronic hemodialysis with a mean age of 68.4 ± 14.6 years. Thirty-eight (0.9%) rapid antigen tests resulted positive. Only five (13.8%) positive-rapid antigen tests were also positive by RT-PCR testing. During the same period, 219 patients regularly screened by rapid antigen tests bimonthly underwent 442 RT-PCR nasopharyngeal swabs for clinical reasons. RT-PCR testing yielded a positive result in 13 (5.9%) patients. The time elapsed between PCR and the negative-rapid antigen test was 7.7 ± 4.6 days (range 1.8-13.9 days). At the end of the follow-up, 6.4% of the population on in-center hemodialysis contracted COVID-19, and routine rapid antigen tests detected only 5 out of 18 (27.7%) COVID-19 cases. No outbreaks of COVID-19 were identified within the dialysis unit. Conclusion: Bimonthly rapid antigen screening led to the early diagnosis of COVID-19 in less than one-third of cases. The short incubation period of the new SARS-CoV-2 variants makes bimonthly test screening inadequate for an early diagnosis of COVID-19. More frequent tests are probably necessary to improve the utility of COVID-19 nasal rapid antigen test in patients on hemodialysis.

Cytomegalovirus blood reactivation in COVID-19 critically ill patients: risk factors and impact on mortality.

PURPOSE: Cytomegalovirus (CMV) reactivation in immunocompetent critically ill patients is common and relates to a worsening outcome. In this large observational study, we evaluated the incidence and the risk factors associated with CMV reactivation and its effects on mortality in a large cohort of patients affected by coronavirus disease 2019 (COVID-19) admitted to the intensive care unit (ICU). METHODS: Consecutive patients with confirmed SARS-CoV-2 infection and acute respiratory distress syndrome admitted to three ICUs from February 2020 to July 2021 were included. The patients were screened at ICU admission and once or twice per week for quantitative CMV-DNAemia in the blood. The risk factors associated with CMV blood reactivation and its association with mortality were estimated by adjusted Cox proportional hazards regression models. RESULTS: CMV blood reactivation was observed in 88 patients (20.4%) of the 431 patients studied. Simplified Acute Physiology Score (SAPS) II score (HR 1031, 95% CI 1010-1053, p = 0.006), platelet count (HR 0.0996, 95% CI 0.993-0.999, p = 0.004), invasive mechanical ventilation (HR 2611, 95% CI 1223-5571, p = 0.013) and secondary bacterial infection (HR 5041; 95% CI 2852-8911, p < 0.0001) during ICU stay were related to CMV reactivation. Hospital mortality was higher in patients with (67.0%) than in patients without (24.5%) CMV reactivation but the adjusted analysis did not confirm this association (HR 1141, 95% CI 0.757-1721, p = 0.528). CONCLUSION: The severity of illness and the occurrence of secondary bacterial infections were associated with an increased risk of CMV blood reactivation, which, however, does not seem to influence the outcome of COVID-19 ICU patients independently.

Impact of resistance mutations on efficacy of dolutegravir plus rilpivirine or plus lamivudine as maintenance regimens: a cohort study.

OBJECTIVES: The aim of this study was to evaluate the impact of resistance mutations on efficacy of dolutegravir-based two-drug regimens (2DR). METHODS: Virologically suppressed patients with HIV-1 switching to dolutegravir + lamivudine or rilpivirine or to a dolutegravir-based three-drug regimen (3DR) with pre-baseline genotype were selected. Virological failure (VF) was defined as one HIV-RNA viral load (VL) >200 cps/mL or two consecutive VL >50 cps/mL; treatment failure (TF) was defined as VF or treatment discontinuation (TD). Resistance was defined as at least low-level resistance to at least one drug of the current regimen. Propensity score matching was used to conduct adjusted analyses within a competing risks framework. RESULTS: A total of 971 dolutegravir-based regimens were selected: 339 (34.9%) 2DR and 632 (65.1%) 3DR. The adjusted cumulative 48-week incidence of VF was 4.2% (90% CI 3.1%-5.3%) with 2DR and 4.7% (90% CI 3.5%-5.8%) with 3DR. The cumulative 48-week incidence of TF was 15.8% (90% CI 13.9%-17.9%) with 2DR and 24.5% (90% CI 22.2%-27.0%) with 3DR. For VF, the estimated hazard ratio (HR) for 2DR vs. 3DR was 1.02 (90% CI: 0.78-1.34), with evidence of effect modification by low-level resistance (HR 3.96, 90% CI: 2.10-7.46). The estimated HR of TF for 2DR vs. 3DR was 0.54 (90% CI: 0.48-0.60). The 48-week cumulative incidence of TD was 11.7% (8.7%, 14.6%) in 2DR and 19.6% (16.9%, 22.4%) in 3DR. CONCLUSIONS: Dolutegravir-based 2DR showed high virological efficacy and durability; however, past resistance increased the risk of VF, but not of TD or TF.

Herpes Simplex Virus Re-Activation in Patients with SARS-CoV-2 Pneumonia: A Prospective, Observational Study.

BACKGROUND: Herpes simplex 1 co-infections in patients with COVID-19 are considered relatively uncommon; some reports on re-activations in patients in intensive-care units were published. The aim of the study was to analyze herpetic re-activations and their clinical manifestations in hospitalized COVID-19 patients, performing HSV-1 PCR on plasma twice a week. METHODS: we conducted a prospective, observational, single-center study involving 70 consecutive patients with severe/critical SARS-CoV-2 pneumonia tested for HSV-1 hospitalized at Azienda Ospedaliero-Universitaria of Modena. RESULTS: of these 70 patients, 21 (30.0%) showed detectable viremia and 13 (62%) had clinically relevant manifestations of HSV-1 infection corresponding to 15 events (4 pneumonia, 5 herpes labialis, 3 gingivostomatitis, one encephalitis and two hepatitis). HSV-1 positive patients were more frequently treated with steroids than HSV-1 negative patients (76.2% vs. 49.0%, p = 0.036) and more often underwent mechanical ventilation (IMV) (57.1% vs. 22.4%, p = 0.005). In the unadjusted logistic regression analysis, steroid treatment, IMV, and higher LDH were significantly associated with an increased risk of HSV1 re-activation (odds ratio 3.33, 4.61, and 16.9, respectively). The association with the use of steroids was even stronger after controlling for previous use of both tocilizumab and IMV (OR = 5.13, 95% CI:1.36-19.32, p = 0.016). The effect size was larger when restricting to participants who were treated with high doses of steroids while there was no evidence to support an association with the use of tocilizumab Conclusions: our study shows a high incidence of HSV-1 re-activation both virologically and clinically in patients with SARS-CoV-2 severe pneumonia, especially in those treated with steroids.

A five-component infection control bundle to permanently eliminate a carbapenem-resistant Acinetobacter baumannii spreading in an intensive care unit.

BACKGROUND: Carbapenem-resistant Acinetobacter baumannii (CRAB) infection outbreaks are difficult to control and sometimes require cohorting of CRAB-positive patients or temporary ward closure for environmental cleaning. We aimed at controlling the deadly 2018 CRAB outbreak in a 12 bed- intensive care unit (ICU) including 9 beds in a 220 m2 open space. We implemented a new multimodal approach without ward closure, cohorting or temporarily limiting admissions. METHODS: A five-component bundle was introduced in 2018 including reinforcement of hand hygiene and sample extension of screening, application of contact precautions to all patients, enhanced environmental sampling and the one-time application of a cycling radical environmental cleaning and disinfection procedure of the entire ICU. The ICU-CRAB incidence density (ID), ICU alcohol-based hand rub consumption and antibiotic use were calculated over a period of 6 years and intervention time series analysis was performed. Whole genome sequencing analysis (WGS) was done on clinical and environmental isolates in the study period. RESULTS: From January 2013, nosocomial ICU-CRAB ID decreased from 30.4 CRAB cases per 1000 patients-days to zero cases per 1000 patients-days. Our intervention showed a significant impact (-2.9 nosocomial ICU-CRAB cases per 1000 bed-days), while no influence was observed for antibiotic and alcohol-based hand rub (AHR) consumption. WGS demonstrated that CRAB strains were clonally related to an environmental reservoir which confirms the primary role of the environment in CRAB ICU spreading. CONCLUSION: A five-component bundle of continuous hand hygiene improvement, extended sampling at screening including the environment, universal contact precautions and a novel cycling radical environmental cleaning and disinfection procedure proved to be effective for permanently eliminating CRAB spreading within the ICU. Cohorting, admission restriction or ICU closure were avoided.

Accuracy of the serological detection of IgG and IgM to SARS-Cov-2: a prospective, cross-sectional study.

In response to the rapidly evolving of SARS-CoV-2 infection, numerous serological tests have been developed but their sensitivity and specificity are unclear. We collected serum samples of patients and health-care professionals to assess the accuracy of chemiluminescent (CLIA) and two lateral flow immunochromatographic assays (LFIA) to determine IgG and IgM antibodies to SARS-CoV-2 virus. We calculated the φ correlation for qualitative results and test accuracy, adopting the following case definition: either real-time-PCR positivity or serological positivity with at least two different tests. We analyzed 259 samples, obtaining strong correlation between CLIA and both LFIA for IgG (φ=0.9), and moderate correlation for IgM (φ=0.6). For patients, the sensitivity was suboptimal for all methods (CLIA 81%, LFIA A 85%, LFIA B 78%), while it was poor in asymptomatic health-care workers (CLIA 50%, LFIA A 50%, LFIA B 33%). Overall, CLIA is more sensitive and specific for the determination of both IgG and IgM, whilst both LFIA methods reported good sensitivity and specificity for IgG, but scarce sensitivity for the IgM determination. The determination of SARS-CoV-2-specific IgG is useful to detect infection 6 days from symptom onset.

Cytomegalovirus reactivation after hematopoietic stem cell transplant with CMV-IG prophylaxis: A monocentric retrospective analysis.

Human cytomegalovirus (CMV) represents the most common viral infection after hematopoietic stem cell transplant (HSCT), mainly occurring as reactivation from latency in seropositive patients, with a different prevalence based on the extent and timing of seroconversion in a specific population. Here, we retrospectively analyzed a cohort of patients who underwent HSCT at our Institution between 2013 and 2018, all of whom were prophylactically treated with CMV-IG (Megalotect Biotest®), to define the incidence and clinical outcomes of CMV reactivation and clinically significant infection. CMV infection occurred in 69% of our patient series, mainly resulting from reactivation, and CMV clinically significant infection (CS-CMVi) occurred in 48% of prophylactically treated patients. CMV infection and CS-CMVi impacted neither on relapse incidence nor on overall survival nor on relapse-free survival. Moreover, a very low incidence of CMV end-organ disease was documented. CMV-IG used alone as prophylactic therapy after HSCT does not effectively prevent CMV reactivation.

Long-term maintenance of virologic suppression in native and migrant HIV-1 naïve patients: an Italian cohort study.

Little is known about long-term maintenance of virologic suppression in HIV migrants in Italy. The study aims to compare virologic failure rates and associated factors among antiretroviral therapy (ART)-naïve migrants and natives enrolled in the ARCA database since 2007 who achieved virologic suppression within 18 months from the beginning of the ART. Kaplan-Meier method assessed the probability of virologic suppression and failure. Cox regression model was used for multivariate analysis. Of 2515 patients, 2020 (80.3%) were Italian, 286 (10.6%) migrants from low-income countries, of whom 201 (75.0%) from Africa, and 227 (9.0%) from high-income-countries. The median follow-up was 4.5 years (IQR 2.5-7). No difference was observed in the time of achievement of virological suppression in the three groups (log-rank: p = 0.5687). Higher probability of virologic failure was observed in Africans compared to Italians, to patients from high-income-countries and from low-income-countries other than Africans (Log-rank = p < 0.001). In the adjusted analysis, a higher virologic failure risk was found in Africans only compared to Italians. [HR 4.01; 95% CI 2.44-6.56, p < 0.001]. In Italy, African migrants are less likely to maintain virologic suppression compared to natives and other migrants. Targeted interventions could be needed for foreigners, especially for Africans.

A Retrospective Whole-Genome Sequencing Analysis of Carbapenem and Colistin-Resistant Klebsiella Pneumoniae Nosocomial Strains Isolated during an MDR Surveillance Program.

Multidrug-resistant Klebsiella pneumoniae (MDR Kp), in particular carbapenem-resistant Kp (CR-Kp), has become endemic in Italy, where alarming data have been reported on the spread of colistin-resistant CR-Kp (CRCR-Kp). During the period 2013-2014, 27 CRCR-Kp nosocomial strains were isolated within the Modena University Hospital Policlinico (MUHP) multidrug resistance surveillance program. We retrospectively investigated these isolates by whole-genome sequencing (WGS) analysis of the resistome, virulome, plasmid content, and core single nucleotide polymorphisms (cSNPs) in order to gain insights into their molecular epidemiology. The in silico WGS analysis of the resistome revealed the presence of genes, such as blaKPC, related to the phenotypically detected resistances to carbapenems. Concerning colistin resistance, the plasmidic genes mcr 1-9 were not detected, while known and new genetic variations in mgrB, phoQ, and pmrB were found. The virulome profile revealed the presence of type-3 fimbriae, capsular polysaccharide, and iron acquisition system genes. The detected plasmid replicons were classified as IncFIB(pQil), IncFIB(K), ColRNAI, IncX3, and IncFII(K) types. The cSNPs genotyping was consistent with the multi locus sequence typing (MLST) and with the distribution of mutations related to colistin resistance genes. In a nosocomial drug resistance surveillance program, WGS proved to be a useful tool for elucidating the spread dynamics of CRCR-Kp nosocomial strains and could help to limit their diffusion.

Pretreatment HIV drug resistance and treatment failure in non-Italian HIV-1-infected patients enrolled in ARCA.

BACKGROUND: An increase in pretreatment drug resistance (PDR) to first-line antiretroviral therapy (ART) in low-income countries has been recently described. Herein we analyse the prevalence of PDR and risk of virological failure (VF) over time among migrants to Italy enrolled in ARCA. METHODS: HIV-1 sequences from ART-naive patients of non-Italian nationality were retrieved from ARCA database from 1998 to 2017. PDR was defined by at least one mutation from the reference 2009 WHO surveillance list. RESULTS: Protease/reverse transcriptase sequences from 1,155 patients, mainly migrants from sub-Saharan Africa (SSA; 42%), followed by Latin America (LA; 25%) and Western countries (WE; 21%), were included. PDR was detected in 8.6% of sequences (13.1% versus 5.8% for B and non-B strains, respectively; P<0.001). 2.1% of patients carried a PDR for protease inhibitors (PIs; 2.1% versus 2.3%; P=0.893), 3.9% for nucleoside/nucleotide reverse transcriptase inhibitors (NRTIs; 6.8% versus 2.1%; P<0.001) and 4.3% for non-nucleoside/nucleotide reverse transcriptase inhibitors (NNRTIs; 6.3% versus 3.1%; P=0.013). Overall, prevalence of PDR over the years remained stable, while it decreased for PIs in LA (P=0.021) and for NRTIs (P=0.020) among migrants from WE. Having more than one class of PDR (P=0.015 versus absence of PDR), higher viral load at diagnosis (P=0.008) and being migrants from SSA (P=0.001 versus WE) were predictive of VF, while a recent calendar year of diagnosis (P<0.001) was protective for VF. CONCLUSIONS: PDR appeared to be stable over the years in migrants to Italy enrolled in ARCA; however, it still remains an important cause of VF together with viral load at diagnosis.

No impact of previous NRTIs resistance in HIV positive patients switched to DTG+2NRTIs under virological control: Time of viral suppression makes the difference.

The accumulation of drug-resistance mutations on combined antiretroviral regimens (ART) backbone could affect the virological efficacy of the regimen. Our aim was to assess the impact of previous drug resistance to nucleoside reverse transcriptase inhibitors (NRTIs) on the probability of virological failure (VF) in patients, under virological control, who switched to dolutegravir (DTG)+2NRTIs regimens. All HIV-1 positive drug-experienced patients who started a regimen composed by DTG+2NRTIs [abacavir/lamivudine or tenofovir disoproxil fumarate (TDF) or tenofovir alafenamide (TAF)/emtricitabine (FTC)] in the ARCA collaborative group with HIV-RNA <50 cp/mL were included in the analysis. Patients with a previous VF to integrase inhibitors were excluded. The impact of single and combined NRTIs mutations on the probability of VF (defined as 2 consecutive HIV-RNA >50 copies/mL or one HIV-RNA >1000 copies/mL) was assessed by Kaplan Meier curves. A multivariable Cox regression analysis was constructed to assess factors potentially related to VF. Five hundred and eighty-eight patients were included in the analysis with a median time of viral suppression before the switch of 37 months (IQR 12-78), of whom 148 (25.2%) had at least one previous NRTIs resistance mutation. In the multivariable model no association was observed between NRTIs mutations and VF. Conversely, the duration of viral suppression before switch resulted associated with a lower risk of VF (for 1 month increase, adjusted Hazard Ratio 0.98, 95%CI 0.96-0.99; p=0.024). Previous NRTIs mutations appeared to have no impact on the risk of VF in patients switched to DTG+2NRTIs, whereas a longer interval on a controlled viremia decreased significantly the risk of VF.

Genome-based taxonomic revision detects a number of synonymous taxa in the genus Mycobacterium.

The aim of this study was to clarify the taxonomic status of named species within the genus Mycobacterium. The analysis of genomes belonging to 174 taxa (species or subspecies) of the genus Mycobacterium was conducted using both the Average Nucleotide Identity and the Genome to Genome Distance. A number of synonymous taxa were detected. The list of synonyms includes: two subspecies of M. chelonae (M. chelonae subsp. bovis and M. chelonae subsp. gwanakae), two subspecies of M. fortuitum (M. fortuitum subsp. fortuitum and M. fortuitum subsp. acetamidolyticum), four subspecies of M. avium (M. avium subsp. avium, M. avium subsp. silvaticum, M. avium subsp. paratuberculosis and "M. avium subsp. hominissuis"), two couples of subspecies of M. intracellulare (M. intracellulare subsp. intracellulare/M. intracellulare subsp. paraintracellulare and M. intracellulare subsp. chimaera/M. intracellulare subsp. yongonense), the species M. austroafricanum and M. vanbaalenii, the species M. senegalense and M. conceptionense, the species M. talmoniae and M. eburneum and the species M. marinum, M. ulcerans and M. pseudoshottsii. Furthermore one species were reclassified as subspecies of another mycobacterium: M. lepraemurium was reclassified as a subspecies of M. avium (M. avium subsp. lepraemurium). The updates to nomenclature are proposed basing on the priority of names according the Code of nomenclature of prokaryotes. For two species (M. bouchedurhonense and M. marseillense) the loss of standing in nomenclature is proposed because of unavailability of respective type strains in culture collections.

Pneumocystosis as a Complication of H1N1 Influenza A Infection in an HIV-Positive Patient on Effective cART.

H1N1 influenza A virus can affect the immune system, causing lymphopenia. This might be of great concern for HIV individuals undergoing effective antireroviral therapy (cART). We report the first confirmed case of H1N1-induced AIDS and Pneumocystis jiroveci pneumonia in an HIV-positive woman on effective cART since 2006.

Improvement of Legionnaires' disease diagnosis using real-time PCR assay: a retrospective analysis, Italy, 2010 to 2015.

AimTo evaluate real-time PCR as a diagnostic method for Legionnaires' disease (LD). Detection of Legionella DNA is among the laboratory criteria of a probable LD case, according to the European Centre for Disease Prevention and Control, although the utility and advantages, as compared to culture, are widely recognised.MethodsTwo independent laboratories, one using an in-house and the other a commercial real-time PCR assay, analysed 354 respiratory samples from 311 patients hospitalised with pneumonia between 2010-15. The real-time PCR reliability was compared with that of culture and urinary antigen tests (UAT). Concordance, specificity, sensitivity and positive and negative predictive values (PPV and NPV, respectively) were calculated.ResultsOverall PCR detected eight additional LD cases, six of which were due to Legionella pneumophila (Lp) non-serogroup 1. The two real-time PCR assays were concordant in 99.4% of the samples. Considering in-house real-time PCR as the reference method, specificity of culture and UAT was 100% and 97.9% (95% CI: 96.2-99.6), while the sensitivity was 63.6% (95%CI: 58.6-68.6) and 77.8% (95% CI: 72.9-82.7). PPV and NPV for culture were 100% and 93.7% (95% CI: 91.2-96.3). PPV and NPV for UAT were 87.5% (95% CI: 83.6-91.4) and 95.8% (95% CI: 93.5-98.2).ConclusionRegardless of the real-time PCR assay used, it was possible to diagnose LD cases with higher sensitivity than using culture or UAT. These data encourage the adoption of PCR as routine laboratory testing to diagnose LD and such methods should be eligible to define a confirmed LD case.

Impact of the M184V Resistance Mutation on Virological Efficacy and Durability of Lamivudine-Based Dual Antiretroviral Regimens as Maintenance Therapy in Individuals With Suppressed HIV-1 RNA: A Cohort Study.

BACKGROUND: Dual therapy (DT) with boosted protease inhibitors (bPIs) plus lamivudine has been shown to be superior to bPI monotherapy in virologically suppressed patients despite previous selection of the lamivudine resistance M184V mutation. We compared the virological efficacy of lamivudine-based DT in patients with and without a history of M184V detection. METHODS: We retrospectively analyzed patients with HIV-RNA ≤50 copies/mL switching to DT with at least 1 previous resistance genotype in the ARCA database. Time to virological failure (VF; HIV-RNA ≥200 copies/mL or 2 consecutive HIV-RNA >50 copies/mL) and to treatment discontinuation (TD) was analyzed by survival analysis. RESULTS: Four hundred thirty-six patients switching to lamivudine plus bPIs (70%) or integrase inhibitors (30%) were included. Patients with M184V (n = 87) were older, had lower nadir CD4+ cell count, longer duration of antiretroviral therapy and of virologic suppression, and higher rate of hepatitis C virus infection compared with patients without M184V. The 3-year probability of remaining free from VF was 91.9% (95% confidence interval [CI], 86.6-97.2) without M184V and 87.8% (95% CI, 78.4-97.2) with M184V (P = .323). The time to TD did not differ between groups. Multivariate analysis adjusting for baseline variables differing between groups also did not detect M184V as being associated with VF or TD; however, the 3-year probability of remaining free of viral blips (isolated HIV-RNA 51-199 copies/mL) was 79.8% (95% CI, 67.8%-91.8%) with M184V vs 90.1% (95% CI, 84.0%-96.2%) without M184V (P = .016). CONCLUSIONS: Previous selection of M184V did not increase the risk of VF or TD with lamivudine-based DT but was associated with a higher probability of viral blips.