Post-transplant сyclophosphamide after matched donor hematopoietic stem cell transplantation in children with acute leukemia.

INTRODUCTION: The data on post-transplant cyclophosphamide (PTCy) in pediatric acute leukemia after matched allo-HSCT are limited to case series. The present study aimed to assess the results of PTCy-based GVHD prophylaxis in a large cohort of children with acute leukemia after matched allo-HSCT. METHODS: A retrospective analysis of 190 pediatric patients with acute leukemia who had a first allograft between 2008 and 2020 from a matched sibling donor (MSD) or matched unrelated donor (MUD) was carried out. In the MSD setting, GVHD prophylaxis consisted of PTCy alone (n = 28) for the study group, and calcineurin inhibitor (CNI) ± antimetabolite (n = 30) for the control group. In MUD setting, most patients in the study group received GVHD prophylaxis with PTCy+CNI+mycophenolate mofetil (n = 42, 66.7%) or PTCy+CNI+sirolimus (n = 12, 19%). All patients (n = 69) in the control group received ATG+CNI+antimetabolite. RESULTS: After MUD allo-HSCT, the incidences of acute GVHD grade III-IV and moderate/severe chronic GVHD were significantly lower in the PTCy group compared to control (6.6% vs. 35.0% and 12.7% vs. 47.1%, respectively, p < .0001). Five-year GVHD-free, relapse-free survival (GRFS) after MUD allo-HSCT was higher in the PTCy group compared to control (35.1% vs. 7.3%, p < .0001). At the same time, there was no significant difference between both groups after MSD allo-HSCT. CONCLUSIONS: In pediatric acute leukemia, PTCy-based GVHD prophylaxis for MUD allo-HSCT is a feasible and effective option that results in a low incidence of GVHD. Compared to the ATG-based approach, PTCy provides better control of GVHD in children. In pediatric allo-HSCT from MSD, PTCy demonstrates comparable effectiveness to conventional GVHD prophylaxis.

Comparison of protein profiles obtained by matrix-assisted laser desorption/ionization-Time-of-flight mass spectrometry in representatives of the family Mycobacteriaceae grown on various nutrient media.

Background: The nutrient medium effects on the quality of the matrix-assisted laser desorption/ionization-time-of-flight (MALDI-ToF) mass spectra. The standard library includes spectra of microorganisms of the family Mycobacteriaceae grown on the Lowenstein-Jensen and Middlebrook Media. There are new methods for culturing microorganisms from this group, including inoculation on chromogenic media. Methods: The study included 240 strains of NTM isolated from patients during tuberculosis examination. The inoculation of the biological material was carried out on solid culture media of Lowenstein-Jensen and universal chromogenic media. Identification of bacteria from both types of media was performed by MALDI-ToF mass spectrometry (Bruker Daltonik GmbH, Germany). Analysis of protein spectra was performed. Results: For all strains, the spectra revealed both coinciding peaks (regardless of the cultivation medium) and significant differences, including the complete absence of some peaks depending on the medium. The results of a greater divergence of peaks in mass and intensity were obtained for slow-growing species than for fast-growing species. For all analyzed cultures, the number of peaks in the mass spectra was significantly higher when cultivating on a universal chromogenic medium than on a Lowenstein-Jensen medium. Conclusions: The use for NTM cultivation of a universal chromogenic medium makes it possible to obtain acceptable identification results by MALDI-ToF mass spectrometry using a standard library.

Carcino-Evo-Devo, A Theory of the Evolutionary Role of Hereditary Tumors.

A theory of the evolutionary role of hereditary tumors, or the carcino-evo-devo theory, is being developed. The main hypothesis of the theory, the hypothesis of evolution by tumor neofunctionalization, posits that hereditary tumors provided additional cell masses during the evolution of multicellular organisms for the expression of evolutionarily novel genes. The carcino-evo-devo theory has formulated several nontrivial predictions that have been confirmed in the laboratory of the author. It also suggests several nontrivial explanations of biological phenomena previously unexplained by the existing theories or incompletely understood. By considering three major types of biological development-individual, evolutionary, and neoplastic development-within one theoretical framework, the carcino-evo-devo theory has the potential to become a unifying biological theory.

Bioinspired Stretchable Transducer for Wearable Continuous Monitoring of Respiratory Patterns in Humans and Animals.

A bio-inspired continuous wearable respiration sensor modeled after the lateral line system of fish is reported which is used for detecting mechanical disturbances in the water. Despite the clinical importance of monitoring respiratory activity in humans and animals, continuous measurements of breathing patterns and rates are rarely performed in or outside of clinics. This is largely because conventional sensors are too inconvenient or expensive for wearable sensing for most individuals and animals. The bio-inspired air-silicone composite transducer (ASiT) is placed on the chest and measures respiratory activity by continuously measuring the force applied to an air channel embedded inside a silicone-based elastomeric material. The force applied on the surface of the transducer during breathing changes the air pressure inside the channel, which is measured using a commercial pressure sensor and mixed-signal wireless electronics. The transducer produced in this work are extensively characterized and tested with humans, dogs, and laboratory rats. The bio-inspired ASiT may enable the early detection of a range of disorders that result in altered patterns of respiration. The technology reported can also be combined with artificial intelligence and cloud computing to algorithmically detect illness in humans and animals remotely, reducing unnecessary visits to clinics.

Immunohistochemistry localises myosin-7a to cochlear efferent boutons.

Background: Myosin 7a is an actin-binding motor protein involved in the formation of hair-cell stereocilia both in the cochlea and in the vestibular system. Mutations in myosin 7a are linked to congenital hearing loss and are present in 50% of Type-1 Usher syndrome patients who suffer from progressive hearing loss and vestibular system dysfunction. Methods: Myosin 7a is often used to visualise sensory hair cells due to its well characterised and localised expression profile. We thus conducted myosin-7a immunostaining across all three turns of the adult rat organ of Corti to visualise hair cells. Results: As expected, we observed myosin 7a staining in both inner and outer hair cells. Unexpectedly, we also observed strong myosin 7a staining in the medial olivocochlear efferent synaptic boutons contacting the outer hair cells. Efferent bouton myosin-7a staining was present across all three turns of the cochlea. We verified this localisation by co-staining with a known efferent bouton marker, the vesicular acetylcholine transporter. Conclusions: In addition to its role in stereocilia formation and maintenance, myosin 7a or certain myosin-7a expression variants might play a role in efferent synaptic transmission in the cochlea and thus ultimately influence cochlear gain regulation. Our immunohistochemistry results should be validated with other methods to confirm these serendipitous findings.

A photonic crystal material for the online detection of nonpolar hydrocarbon vapors.

A modern level of nanotechnology allows us to create conceptually new test systems for chemical analyses and to develop sensitive and compact sensors for various types of substances. However, at present, there are very few commercially available compact sensors for the determination of toxic and carcinogenic substances, such as organic solvents that are used in some construction materials. This article contains an overview of how 3D photonic crystals are used for the creation of a new test system for nonpolar organic solvents. The morphology and structural parameters of the photonic crystals, based upon a crystalline colloidal array with a sensing matrix of polydimethylsiloxane, have been determined by using scanning electron microscopy and by the results of specular reflectance spectroscopy based on the Bragg-Snell law. A new approach has been proposed for the application of this sensor in chemical analysis for the qualitative detection of saturated vapors of volatile organic compounds due to configuration changes of the photonic bandgap, recorded by diffuse reflectance spectroscopy. The exposure of the sensor to aromatic (benzene, toluene and p-xylene) and aliphatic (n-pentane, n-heptane, n-octane and n-decane) hydrocarbons has been analyzed. The reconstitution of spectral parameters of the sensor during the periodic detection of saturated vapors of toluene has been evaluated.

Fast adaptation of cooperative channels engenders Hopf bifurcations in auditory hair cells.

Since the pioneering work of Thomas Gold, published in 1948, it has been known that we owe our sensitive sense of hearing to a process in the inner ear that can amplify incident sounds on a cycle-by-cycle basis. Called the active process, it uses energy to counteract the viscous dissipation associated with sound-evoked vibrations of the ear's mechanotransduction apparatus. Despite its importance, the mechanism of the active process and the proximate source of energy that powers it have remained elusive, especially at the high frequencies characteristic of amniote hearing. This is partly due to our insufficient understanding of the mechanotransduction process in hair cells, the sensory receptors and amplifiers of the inner ear. It has been proposed previously that cyclical binding of Ca2+ ions to individual mechanotransduction channels could power the active process. That model, however, relied on tailored reaction rates that structurally forced the direction of the cycle. Here we ground our study on our previous model of hair-cell mechanotransduction, which relied on cooperative gating of pairs of channels, and incorporate into it the cyclical binding of Ca2+ ions. With a single binding site per channel and reaction rates drawn from thermodynamic principles, the current model shows that hair cells behave as nonlinear oscillators that exhibit Hopf bifurcations, dynamical instabilities long understood to be signatures of the active process. Using realistic parameter values, we find bifurcations at frequencies in the kilohertz range with physiological Ca2+ concentrations. The current model relies on the electrochemical gradient of Ca2+ as the only energy source for the active process and on the relative motion of cooperative channels within the stereociliary membrane as the sole mechanical driver. Equipped with these two mechanisms, a hair bundle proves capable of operating at frequencies in the kilohertz range, characteristic of amniote hearing.

Rapid mechanical stimulation of inner-ear hair cells by photonic pressure.

Hair cells, the receptors of the inner ear, detect sounds by transducing mechanical vibrations into electrical signals. From the top surface of each hair cell protrudes a mechanical antenna, the hair bundle, which the cell uses to detect and amplify auditory stimuli, thus sharpening frequency selectivity and providing a broad dynamic range. Current methods for mechanically stimulating hair bundles are too slow to encompass the frequency range of mammalian hearing and are plagued by inconsistencies. To overcome these challenges, we have developed a method to move individual hair bundles with photonic force. This technique uses an optical fiber whose tip is tapered to a diameter of a few micrometers and endowed with a ball lens to minimize divergence of the light beam. Here we describe the fabrication, characterization, and application of this optical system and demonstrate the rapid application of photonic force to vestibular and cochlear hair cells.

The sense of hearing relies on specialized sensory cells in the inner ear. Each of these hair cells converts sounds into electrical signals that the brain can interpret. The hair cell takes its name from the bundle of rod-like structures that protrude from its top surface, which resemble hairs under the microscope. The hair bundle acts as an antenna that bends in response to sound waves. When a hair bundle moves in a particular direction, it opens ion channels in the hair-cell membrane. The resulting flow of ions into the cell triggers a cascade of events that ends with an electrical signal traveling to the brain. Many experiments on hearing rely on being able to manipulate the movement of a hair bundle. Researchers typically use one of two methods to achieve this. In the first, a flexible glass fiber pushes against the hair bundle, whereas the second involves a jet of fluid directed against the cell. Neither of these techniques can move hair bundles fast enough for researchers to explore the vast range of sound frequencies that human ears can detect. What is more, both methods are prone to introducing errors into experiments. Abeytunge, Gianoli et al. have developed a new method for moving hair bundles, this time with the aid of light. When light interacts with objects it exerts a photonic force. Abeytunge, Gianoli et al. show that a tapered optical fiber with a miniscule rounded lens can focus a laser beam to deliver enough photonic force to move a hair bundle. The laser beam does not damage the hair bundle, but moves it fast enough to allow researchers to study a broader range of mammalian hearing, while avoiding the errors that have bedeviled previous methods.

The Development of Cooperative Channels Explains the Maturation of Hair Cell's Mechanotransduction.

Hearing relies on the conversion of mechanical stimuli into electrical signals. In vertebrates, this process of mechanoelectrical transduction (MET) is performed by specialized receptors of the inner ear, the hair cells. Each hair cell is crowned by a hair bundle, a cluster of microvilli that pivot in response to sound vibrations, causing the opening and closing of mechanosensitive ion channels. Mechanical forces are projected onto the channels by molecular springs called tip links. Each tip link is thought to connect to a small number of MET channels that gate cooperatively and operate as a single transduction unit. Pushing the hair bundle in the excitatory direction opens the channels, after which they rapidly reclose in a process called fast adaptation. It has been experimentally observed that the hair cell's biophysical properties mature gradually during postnatal development: the maximal transduction current increases, sensitivity sharpens, transduction occurs at smaller hair-bundle displacements, and adaptation becomes faster. Similar observations have been reported during tip-link regeneration after acoustic damage. Moreover, when measured at intermediate developmental stages, the kinetics of fast adaptation varies in a given cell, depending on the magnitude of the imposed displacement. The mechanisms underlying these seemingly disparate observations have so far remained elusive. Here, we show that these phenomena can all be explained by the progressive addition of MET channels of constant properties, which populate the hair bundle first as isolated entities and then progressively as clusters of more sensitive, cooperative MET channels. As the proposed mechanism relies on the difference in biophysical properties between isolated and clustered channels, this work highlights the importance of cooperative interactions between mechanosensitive ion channels for hearing.

The Increase of the Magnitude of Spontaneous Viral Blips in Some Participants of Phase II Clinical Trial of Therapeutic Optimized HIV DNA Vaccine Candidate.

We developed a candidate DNA vaccine called "DNA-4"consisting of 4 plasmid DNAs encoding Nef, Gag, Pol(rt), and gp140 HIV-1 proteins. The vaccine was found to be safe and immunogenic in a phase I clinical trial. Here we present the results of a phase II clinical trial of "DNA-4". This was a multicenter, double-blind, placebo-controlled clinical trial of safety, and dose selection of "DNA-4" in HIV-1 infected people receiving antiretroviral therapy (ART). Fifty-four patients were randomized into 3 groups (17 patients-group DNA-4 0.25 mg, 17 patients-group DNA-4 0.5 mg, 20 patients-the placebo group). All patients were immunized 4 times on days 0, 7, 11, and 15 followed by a 24-week follow-up period. "DNA-4" was found to be safe and well-tolerated at doses of 0.25 mg and 0.5 mg. We found that the amplitudes of the spontaneous viral load increases in three patients immunized with the candidate DNA vaccine were much higher than that in placebo group-2800, 180,000 and 709 copies/mL, suggesting a possible influence of therapeutic DNA vaccination on viral reservoirs in some patients on ART. We hypothesize that this influence was associated with the reactivation of proviral genomes.

Characterization of the Transmitted Virus in an Ongoing HIV-1 Epidemic Driven by Injecting Drug Use.

Understanding features of the HIV-1 transmission process has the potential to inform biological interventions for prevention. We have examined the transmitted virus in a cohort of people who inject drugs and who are at risk of HIV-1 infection through blood contamination when injecting in a group. This study focused on seven newly infected participants in St. Petersburg, Russia, who were in acute or early infection. We used end-point dilution polymerase chain reaction to amplify single viral genomes to assess the complexity of the transmitted virus. We also used deep sequencing to further assess the complexity of the virus. We interpret the results as indicating that a single viral variant was transmitted in each case, consistent with a model where the exposure to virus during transmission was limited. We also looked at phenotypic properties of the viral Env protein in isolates from acute and chronic infection. Although differences were noted, there was no consistent pattern that distinguished the transmitted variants. Similarly, despite the reduced genetic heterogeneity of the more recent subtype A HIV-1 epidemic in St. Petersburg, we did not see reduced variance in the neutralization properties compared to isolates from the more mature subtype C HIV-1 epidemic. Finally, in looking at members of injecting groups related to the acute HIV-1 infection/early subjects, we found examples of sequence linkage consistent with ongoing and rapid spread of HIV-1 in these groups. These studies emphasize the dynamic nature of this epidemic and reinforce the idea that improved prevention methods are needed.

A Cohort Approach to Real-Time Detection of Acute HIV Infections Among People Who Inject Drugs in St. Petersburg, Russia.

To detect acute HIV infections (AHIs) in real time among people who inject drugs (PWID) in St. Petersburg, Russia and to test the feasibility of this approach. Prospective cohort study. One hundred seronegative or acutely HIV-infected at screening PWID were enrolled and followed until the end of the 12-month pilot period. Each participant was evaluated, tested, and counseled for HIV monthly. Two HIV tests were used: HIV antibody and HIV RNA PCR. If diagnosed with AHI, participants were followed weekly for a month; then, monthly for 3 months; and then, quarterly for the duration of the follow-up period. HIV risk behavior was assessed at each study visit. Most enrolled PWID were 30-39 years old, male, completed high school or more, not employed full-time, heroin users, and frequently shared injection paraphernalia. AHI prevalence at screening was 1.8% [95% confidence interval (CI): 0.4, 5.5]. Three participants with AHI at enrollment represented 3% (95% CI: 0.6, 8.5) of the 100 participants who consented to enroll. Among the HIV-uninfected participants (n = 97), the AHI incidence over time was 9.3 per 100 person-years. Persons with AHI were more likely to report alcohol intoxication within the prior 30 days. This was the first study to detect AHI using a cohort approach. The approach proved to be feasible: recruitment, retention, AHI detection, and virological endpoints were successfully reached. A cost analysis in a real-world setting would be required to determine if this strategy could be brought to scale. The study revealed continued high HIV incidence rate among PWID in St. Petersburg, Russia and the importance of prevention and treatment programs for this group.

Lipid bilayer mediates ion-channel cooperativity in a model of hair-cell mechanotransduction.

Mechanoelectrical transduction in the inner ear is a biophysical process underlying the senses of hearing and balance. The key players involved in this process are mechanosensitive ion channels. They are located in the stereocilia of hair cells and opened by the tension in specialized molecular springs, the tip links, connecting adjacent stereocilia. When channels open, the tip links relax, reducing the hair-bundle stiffness. This gating compliance makes hair cells especially sensitive to small stimuli. The classical explanation for the gating compliance is that the conformational rearrangement of a single channel directly shortens the tip link. However, to reconcile theoretical models based on this mechanism with experimental data, an unrealistically large structural change of the channel is required. Experimental evidence indicates that each tip link is a dimeric molecule, associated on average with two channels at its lower end. It also indicates that the lipid bilayer modulates channel gating, although it is not clear how. Here, we design and analyze a model of mechanotransduction where each tip link attaches to two channels, mobile within the membrane. Their states and positions are coupled by membrane-mediated elastic forces arising from the interaction between the channels' hydrophobic cores and that of the lipid bilayer. This coupling induces cooperative opening and closing of the channels. The model reproduces the main properties of hair-cell mechanotransduction using only realistic parameters constrained by experimental evidence. This work provides an insight into the fundamental role that membrane-mediated ion-channel cooperativity can play in sensory physiology.

HIV incidence and behavioral correlates of HIV acquisition in a cohort of injection drug users in St Petersburg, Russia.

The aim of the project was to study human immunodeficiency virus (HIV) incidence, sociodemographic and behavioral correlates of HIV acquisition among injection drug users (IDUs).A total of 717 IDUs were recruited, tested, and counseled for HIV-1; 466 HIV-negative participants were enrolled and followed-up at 6 and 12 months. Sociodemographic and behavioral data were collected during each study visit. The association of sociodemographic and behavioral factors to HIV-1 incidence was assessed.During the 9-month recruitment period, 717 IDUs were screened and 466 participants were enrolled. HIV-1 prevalence at baseline was 35%. Most enrolled subjects were young (median age 30), male (75%), injected heroin in the previous 3 months (86%), about 50% had shared syringes and other paraphernalia, and 44% had unprotected sex in the last month. The retention rate at the 12-month follow-up was 72% and the adjusted retention rate was 88%. The HIV incidence rate was 7.2/100 person-years. HIV incidence was significantly associated with specific drug risk behaviors, including injecting the mixture of heroin and psychostimulants, the frequency of injecting in groups with other people, and having more drug dealers.The St Petersburg IDUs cohort demonstrates one of the highest HIV incidence rates in the world. In 2004 to 2006, the HIV incidence was 4.5, in 2005 to 2007-19.6, and in 2008 to 2009-7.2/100 person-years. The peak of HIV epidemic among IDUs in St Petersburg, as determined by 3 independent cohort studies, was in 2006 to 2007. Interventions targeting IDUs with long experience of heroin injection and high levels of injection risk behaviors are urgently needed.

Comparative Aspects of Hearing in Vertebrates and Insects with Antennal Ears.

The evolution of hearing in terrestrial animals has resulted in remarkable adaptations enabling exquisitely sensitive sound detection by the ear and sophisticated sound analysis by the brain. In this review, we examine several such characteristics, using examples from insects and vertebrates. We focus on two strong and interdependent forces that have been shaping the auditory systems across taxa: the physical environment of auditory transducers on the small, subcellular scale, and the sensory-ecological environment within which hearing happens, on a larger, evolutionary scale. We briefly discuss acoustical feature selectivity and invariance in the central auditory system, highlighting a major difference between insects and vertebrates as well as a major similarity. Through such comparisons within a sensory ecological framework, we aim to emphasize general principles underlying acute sensitivity to airborne sounds.

Central auditory neurons have composite receptive fields.

High-level neurons processing complex, behaviorally relevant signals are sensitive to conjunctions of features. Characterizing the receptive fields of such neurons is difficult with standard statistical tools, however, and the principles governing their organization remain poorly understood. Here, we demonstrate multiple distinct receptive-field features in individual high-level auditory neurons in a songbird, European starling, in response to natural vocal signals (songs). We then show that receptive fields with similar characteristics can be reproduced by an unsupervised neural network trained to represent starling songs with a single learning rule that enforces sparseness and divisive normalization. We conclude that central auditory neurons have composite receptive fields that can arise through a combination of sparseness and normalization in neural circuits. Our results, along with descriptions of random, discontinuous receptive fields in the central olfactory neurons in mammals and insects, suggest general principles of neural computation across sensory systems and animal classes.

Two Independent HIV Epidemics in Saint Petersburg, Russia Revealed by Molecular Epidemiology.

The HIV epidemic in Russia, one of the world's fastest growing, has been concentrated mostly among people who inject drugs (PWID). We sought to explore the epidemiology of the epidemic in St. Petersburg by sampling from the highest risk groups of PWID and men who have sex with men (MSM) and use viral sequencing data to better understand the nature of the city's epidemic. Serological testing confirmed an HIV prevalence among PWID in excess of 40%. All but 1 of 110 PWID whose blood samples were tested for genetic diversity were infected by subtype A virus, specifically by the AFSU strain. The remaining person was infected with a CRF-06cpx recombinant. Analysis of pairwise genetic distance among all PWID studied revealed an average of 3.1% sequence divergence, suggesting clonal introduction of the AFSU strain and/or constraints on sequence divergence. The HIV prevalence was less than 10% among MSM. All 17 sequences from HIV-infected MSM were found to be a clade B virus with a much higher average sequence diversity of 15.7%. These findings suggest two independent epidemics with little overlap between the two highest at-risk populations, which will require different HIV prevention approaches.

ELFN1-AS1: a novel primate gene with possible microRNA function expressed predominantly in human tumors.

Human gene LOC100505644 uncharacterized LOC100505644 [Homo sapiens] (Entrez Gene ID 100505644) is abundantly expressed in tumors but weakly expressed in few normal tissues. Till now the function of this gene remains unknown. Here we identified the chromosomal borders of the transcribed region and the major splice form of the LOC100505644-specific transcript. We characterised the major regulatory motifs of the gene and its splice sites. Analysis of the secondary structure of the major transcript variant revealed a hairpin-like structure characteristic for precursor microRNAs. Comparative genomic analysis of the locus showed that it originated in primates de novo. Taken together, our data indicate that human gene LOC100505644 encodes some non-protein coding RNA, likely a microRNA. It was assigned a gene symbol ELFN1-AS1 (ELFN1 antisense RNA 1 (non-protein coding)). This gene combines features of evolutionary novelty and predominant expression in tumors.

Central auditory neurons display flexible feature recombination functions.

Recognition of natural stimuli requires a combination of selectivity and invariance. Classical neurobiological models achieve selectivity and invariance, respectively, by assigning to each cortical neuron either a computation equivalent to the logical "AND" or a computation equivalent to the logical "OR." One powerful OR-like operation is the MAX function, which computes the maximum over input activities. The MAX function is frequently employed in computer vision to achieve invariance and considered a key operation in visual cortex. Here we explore the computations for selectivity and invariance in the auditory system of a songbird, using natural stimuli. We ask two related questions: does the MAX operation exist in auditory system? Is it implemented by specialized "MAX" neurons, as assumed in vision? By analyzing responses of individual neurons to combinations of stimuli we systematically sample the space of implemented feature recombination functions. Although we frequently observe the MAX function, we show that the same neurons that implement it also readily implement other operations, including the AND-like response. We then show that sensory adaptation, a ubiquitous property of neural circuits, causes transitions between these operations in individual neurons, violating the fixed neuron-to-computation mapping posited in the state-of-the-art object-recognition models. These transitions, however, accord with predictions of neural-circuit models incorporating divisive normalization and variable polynomial nonlinearities at the spike threshold. Because these biophysical properties are not tied to a particular sensory modality but are generic, the flexible neuron-to-computation mapping demonstrated in this study in the auditory system is likely a general property.

The feasibility of an intensive case management program for injection drug users on antiretroviral therapy in St. Petersburg, Russia.

BACKGROUND: The majority of HIV-infected individuals requiring antiretroviral therapy (ART) in Russia are Injection Drug Users (IDU). Substitution therapy used as part of a comprehensive harm reduction program is unavailable in Russia. Past data shows that only 16% of IDU receiving substance abuse treatment completed the course without relapse, and only 40% of IDU on ART remained on treatment at 6 months. Our goal was to determine if it was feasible to improve these historic outcomes by adding intensive case management (ICM) to the substance abuse and ART treatment programs for IDU. METHODS: IDU starting ART and able to involve a "supporter" who would assist in their treatment plan were enrolled. ICM included opiate detoxification, bi-monthly contact and counseling with the case, weekly group sessions, monthly contact with the "supporter" and home visits as needed. Full follow- up (FFU) was 8 months. Stata v10 (College Station, TX) was used for all analysis. Descriptive statistics were calculated for all baseline demographic variables, baseline and follow-up CD4 count, and viral load. Median baseline and follow-up CD4 counts and RNA levels were compared using the Kruskal-Wallis test. The proportion of participants with RNA < 1000 copies mL at baseline and follow-up was compared using Fisher's Exact test. McNemar's test for paired proportions was used to compare the change in proportion of participants with RNA < 1000 copies mL from baseline to follow-up. RESULTS: Between November 2007 and December 2008, 60 IDU were enrolled. 34 (56.7%) were male. 54/60 (90.0%) remained in FFU. Overall, 31/60 (52%) were active IDU at enrollment and 27 (45%) were active at their last follow-up visit. 40/60 (66.7%) attended all of their ART clinic visits, 13/60 (21.7%) missed one or more visit but remained on ART, and 7/60 (11.7%) stopped ART before the end of FFU. Overall, 39/53 (74%) had a final 6-8 month HIV RNA viral load (VL) < 1000 copies/mL. CONCLUSIONS: Despite no substitution therapy to assist IDU in substance abuse and ART treatment programs, ICM was feasible, and the retention and adherence of IDU on ART in St. Petersburg could be greatly enhanced by adding ICM to the existing treatment programs.