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Introduction Treating the early phase of schizophrenia is crucial for preventing further episodes and improving quality of life, functioning, and social inclusion. Pharmacotherapies are first-line treatments, but have limitations. There is consensus on the need for non-pharmacological interventions for individuals in the early phase of schizophrenia. Several psychological interventions have shown promising effects; however, their comparative effectiveness remains largely unknown. To address this issue, a network meta-analysis will be performed. We aim to develop a hierarchy of existing psychological treatments concerning their efficacy and tolerability, which will inform treatment guidelines. Protocol Randomized controlled trials (RCTs) investigating psychological interventions for first-episode psychosis, first-episode schizophrenia, or early phase schizophrenia will be included. The primary outcome will be overall schizophrenia symptoms (measured up to 6 and 12 months, and at the longest follow-up) and relapse as a co-primary outcome. Secondary outcomes are premature discontinuation; change in positive, negative, and depressive symptoms of schizophrenia; response; quality of life; overall functioning; satisfaction with care; adherence; adverse events; and mortality. The study selection and data extraction are performed by two independent reviewers. We will assess the risk of bias of each study using the Cochrane Risk of Bias tool 2 and evaluate the confidence in the results using Confidence in Network Meta-Analysis (CINeMA). Subgroup and sensitivity analyses will be conducted to explore heterogeneity and assess the robustness of our findings. Discussion This systematic review and network meta-analysis aims to compare multiple existing psychological interventions, establishing which are best for symptom reduction, relapse prevention, and other important outcomes in early phase schizophrenia. Our results may provide practical guidance concerning the most effective psychological intervention to reduce symptom severity and the societal burden associated with the disorder.

Introduction Treating the early phase of schizophrenia is crucial for preventing further episodes and improving quality of life, functioning, and social inclusion. Pharmacotherapies are first-line treatments, but have limitations. There is consensus on the need for non-pharmacological interventions for individuals in the early phase of schizophrenia. Several psychological interventions have shown promising effects; however, their comparative effectiveness remains largely unknown. To address this issue, a network meta-analysis will be performed. We aim to develop a hierarchy of existing psychological treatments concerning their efficacy and tolerability, which will inform treatment guidelines. Protocol Randomized controlled trials (RCTs) investigating psychological interventions for first-episode psychosis, first-episode schizophrenia, or early phase schizophrenia will be included. The primary outcome will be overall schizophrenia symptoms (measured up to 6 and 12 months, and at the longest follow-up) and relapse as a co-primary outcome. Secondary outcomes are premature discontinuation; change in positive, negative, and depressive symptoms of schizophrenia; response; quality of life; overall functioning; satisfaction with care; adherence; adverse events; and mortality. The study selection and data extraction are performed by two independent reviewers. We will assess the risk of bias of each study using the Cochrane Risk of Bias tool 2 and evaluate the confidence in the results using Confidence in Network Meta-Analysis (CINeMA). Subgroup and sensitivity analyses will be conducted to explore heterogeneity and assess the robustness of our findings. Discussion This systematic review and network meta-analysis aims to compare multiple existing psychological interventions, establishing which are best for symptom reduction, relapse prevention, and other important outcomes in early phase schizophrenia. Our results may provide practical guidance concerning the most effective psychological intervention to reduce symptom severity and the societal burden associated with the disorder.

Abstract Background Early phase dose-finding (EPDF) trials are crucial for the development of a new intervention and influence whether it should be investigated in further trials. Guidance exists for clinical trial protocols and completed trial reports in the SPIRIT and CONSORT guidelines, respectively. However, both guidelines and their extensions do not adequately address the characteristics of EPDF trials. Building on the SPIRIT and CONSORT checklists, the DEFINE study aims to develop international consensus-driven guidelines for EPDF trial protocols (SPIRIT-DEFINE) and reports (CONSORT-DEFINE). Methods The initial generation of candidate items was informed by reviewing published EPDF trial reports. The early draft items were refined further through a review of the published and grey literature, analysis of real-world examples, citation and reference searches, and expert recommendations, followed by a two-round modified Delphi process. Patient and public involvement and engagement (PPIE) was pursued concurrently with the quantitative and thematic analysis of Delphi participants’ feedback. Results The Delphi survey included 79 new or modified SPIRIT-DEFINE (n = 36) and CONSORT-DEFINE (n = 43) extension candidate items. In Round One, 206 interdisciplinary stakeholders from 24 countries voted and 151 stakeholders voted in Round Two. Following Round One feedback, one item for CONSORT-DEFINE was added in Round Two. Of the 80 items, 60 met the threshold for inclusion (≥ 70% of respondents voted critical: 26 SPIRIT-DEFINE, 34 CONSORT-DEFINE), with the remaining 20 items to be further discussed at the consensus meeting. The parallel PPIE work resulted in the development of an EPDF lay summary toolkit consisting of a template with guidance notes and an exemplar. Conclusions By detailing the development journey of the DEFINE study and the decisions undertaken, we envision that this will enhance understanding and help researchers in the development of future guidelines. The SPIRIT-DEFINE and CONSORT-DEFINE guidelines will allow investigators to effectively address essential items that should be present in EPDF trial protocols and reports, thereby promoting transparency, comprehensiveness, and reproducibility. Trial registration SPIRIT-DEFINE and CONSORT-DEFINE are registered with the EQUATOR Network ( https://www.equator-network.org/ ).

Metastatic breast cancer (BC) remains an incurable disease. Besides endocrine and targeted agents, chemotherapy is still a relevant therapeutic option for this disease. Recently, antibody-drug conjugates (ADCs) have shown to overcome the lack of tumor specificity and systemic toxicity typically associated with traditional chemotherapies, thus improving the therapeutic index. To effectively exploit this technological breakthrough, identification of optimal target antigens (Ags) is of utmost importance. To make the ideal target, differential expression of target Ags between healthy and cancer tissues, as well as specific mechanisms of ADC internalization after Ag-antibody interaction are required.Therefore, several in silico strategies to identify and characterize new promising candidate Ags have been developed. If initial in vitro and in vivo positive data are documented, thus providing a biological rationale for further Ag investigation, early phase clinical trials are designed. In BC, these strategies have already led to the development of effective ADCs, namely trastuzumab emtansine (T-DM1), trastuzumab deruxtecan (T-DXd) and sacituzumab govitecan (SG), primarily targeting HER2 and TROP-2. However, promising new Ags are currently under investigation, with encouraging results especially coming from targeting HER3, FRα, Tissue Factor, LIV-1, ROR1-2, and B7–H4.In this review, we describe the landscape of emergent and future potential targets (i.e., other than HER2 and TROP-2) investigated in BC for ADC development. Predominant target expression, function, preclinical rationale, potential clinical implication, as well as preliminary clinical trial results are provided.

Abstract Background Our randomized controlled clinical trial will explore the potential of bazedoxifene plus conjugated estrogen to modulate breast tissue-based risk biomarkers as a surrogate for breast cancer risk reduction. This paper investigates the statistical design features of the trial and the rationale for the final choice of its design. Group sequential designs are a popular design approach to allow a trial to stop early for success or futility, potentially saving time and money over a fixed trial design. While Bayesian adaptive designs enjoy the same properties as group sequential designs, they have the added benefit of using prior information as well as inferential interpretation conditional on the data. Whether a frequentist or Bayesian trial, most adaptive designs have interim analyses that allow for early stopping, typically utilizing only the primary endpoint. A drawback to this approach is that the study may not have enough data for adequate comparisons of a single, key secondary endpoint. This can happen, for example, if the secondary endpoint has a smaller effect than the primary endpoint. Methods In this paper, we investigate a trial design called two-endpoint adaptive, which stops early only if a criterion is met for primary and secondary endpoints. The approach focuses the final analysis on the primary endpoint but ensures adequate data for the secondary analysis. Our study has two arms with a primary (change in mammographic fibroglandular volume) and secondary endpoint (change in mammary tissue Ki-67). Results We present operating characteristics including power, trial duration, and type I error rate and discuss the value and risks of modeling Bayesian group sequential designs with primary and secondary endpoints, comparing against alternative designs. The results indicate that the two-endpoint adaptive design has better operating characteristics than competing designs if one is concerned about having adequate information for a key secondary endpoint. Discussion Our approach balances trial speed and the need for information on the single, key secondary endpoint.

Abstract Background Fibroproliferative repair starts early in the inflammatory phase of acute respiratory distress syndrome (ARDS) and indicates a poor prognosis. Lumican, a small leucine-rich proteoglycan, is implicated in homeostasis and fibrogenesis, but its role in ARDS is unclear. Methods Bronchoalveolar lavage fluid (BALF) samples were obtained from ARDS patients (n = 55) enrolled within 24 h of diagnosis and mechanically ventilated (n = 20) and spontaneously breathing (n = 29) control subjects. Lipopolysaccharide (LPS)-induced acute lung injury (ALI) mouse models were intratracheally administered an adeno-associated virus (AAV) vector expressing lumican shRNA. Primary human lung fibroblasts (HLF) and small airway epithelial cells (SAECs) were cultured with tumour necrosis factor (TNF)-α or lumican. Luminex/ELISA, histochemistry/immunohistochemistry, immunofluorescence microscopy, quantitative real-time PCR, and western blotting were performed. Results Lumican levels were significantly higher in the BALF of ARDS patients than in that of ventilated or spontaneously breathing controls (both p

Abstract Background For decades there has been a continuous increase in the number of people receiving welfare benefits for being outside the work force due to mental illness. There is sufficient evidence for the efficacy of Individual Placement and Support (IPS) for gaining and maintaining competitive employment. Yet, IPS is still not implemented as routine practice in public community mental health services. Knowledge about implementation challenges as experienced by the practitioners is limited. This study seeks to explore the experiences of the front-line workers, known as employment specialists, in the early implementation phase. Methods Qualitative data were collected through field notes and five focus group interviews. The study participants were 45 IPS employment specialists located at 14 different sites in Northern Norway. Transcripts and field notes were analysed by thematic analyses. Results While employment specialists are key to the implementation process, implementing IPS requires more than creating and filling the role of the employment specialist. It requires adjustments in multiple organisations. The new employment specialist then is a pioneer of service development. Some employment specialists found this a difficult challenge, and one that did not correspond to their expectations going into this role. Others appreciated the pioneering role. IPS implementation also challenged the delegation of roles and responsibilities between sectors, and related legal frameworks related to confidentiality and access. The facilitating role of human relationships emphasised the importance of social support which is an important factor in a healthy work environment. Rural areas with long distances and close- knit societies may cause challenges for implementation. Conclusion The study provides increased understanding on what happens in the early implementation phase of IPS from the employment specialists’ perspective. Results from this study can contribute to increased focus on job satisfaction, turnover and recruitment of employment specialists, factors which have previously been shown to influence the success of IPS. The greatest challenge for making “IPS efficacy in trials” become “IPS effectiveness in the real world” is implementation, and this study has highlighted some of the implementation issues.

Abstract Background Mental burden due to the SARS-CoV-2 pandemic has been widely reported for the general public and specific risk groups like healthcare workers and different patient populations. We aimed to assess its impact on mental health during the early phase by comparing pandemic with prepandemic data and to identify potential risk and protective factors. Methods For this systematic review and meta-analyses, we systematically searched PubMed, PsycINFO, and Web of Science from January 1, 2019 to May 29, 2020, and screened reference lists of included studies. In addition, we searched PubMed and PsycINFO for prepandemic comparative data. Survey studies assessing mental burden by the SARS-CoV-2 pandemic in the general population, healthcare workers, or any patients (eg, COVID-19 patients), with a broad range of eligible mental health outcomes, and matching studies evaluating prepandemic comparative data in the same population (if available) were included. We used multilevel meta-analyses for main, subgroup, and sensitivity analyses, focusing on (perceived) stress, symptoms of anxiety and depression, and sleep-related symptoms as primary outcomes. Results Of 2429 records retrieved, 104 were included in the review (n = 208,261 participants), 43 in the meta-analysis (n = 71,613 participants). While symptoms of anxiety (standardized mean difference [SMD] 0.40; 95% CI 0.15–0.65) and depression (SMD 0.67; 95% CI 0.07–1.27) were increased in the general population during the early phase of the pandemic compared with prepandemic conditions, mental burden was not increased in patients as well as healthcare workers, irrespective of COVID-19 patient contact. Specific outcome measures (eg, Patient Health Questionnaire) and older comparative data (published ≥5 years ago) were associated with increased mental burden. Across the three population groups, existing mental disorders, female sex, and concerns about getting infected were repeatedly reported as risk factors, while older age, a good economic situation, and education were protective. Conclusions This meta-analysis paints a more differentiated picture of the mental health consequences in pandemic situations than previous reviews. High-quality, representative surveys, high granular longitudinal studies, and more research on protective factors are required to better understand the psychological impacts of the SARS-CoV-2 pandemic and to help design effective preventive measures and interventions that are tailored to the needs of specific population groups.

Abstract Pemigatinib is a potent inhibitor of the fibroblast growth factor receptor (FGFR) family of receptors that is approved for the treatment of cholangiocarcinoma with FGFR2 fusion or other rearrangements. Data from a first‐in‐human clinical study were used to assess the potential for pemigatinib to produce clinically significant effects on heart rate (HR) and cardiac repolarization (QTc). A central tendency analysis for electrocardiogram (ECG) outliers and a plasma concentration‐QTc analysis were conducted to assess cardiac safety in the first‐in‐human pemigatinib study (FIGHT‐101; NCT02393248). The study included 113 participants who received at least one dose of pemigatinib as monotherapy and had at least one pair of plasma pharmacokinetic (PK) and ECG data points collected. Timed 12‐lead ECGs were performed within 15 min of PK blood draws. The ECG parameters for each dose group in the study varied within expectations for patients with advanced malignancies. Categorical analysis of QT interval corrected for HR by Fridericia's method did not reveal dose dependence in the incidence of outliers, and the results of the central tendency and concentration‐QTc analyses did not suggest a dose‐ or concentration‐dependent drug effect. Least squares mean change from baseline in HR was small and did not indicate a clinically relevant effect on HR, and no effect was observed on cardiac conduction as assessed by PR and QRS intervals. In conclusion, pemigatinib does not exhibit any clinically significant prolongation of QTc or dose‐dependent changes in HR. Clinical trial registration: ClinicalTrials.gov NCT02393248.

Objective: The burden of suicidal behavior is anticipated to increase as a sequela of the COVID-19 pandemic. However, there is limited evidence on suicidal behavior among healthcare workers, an at-risk population. Our study aimed to investigate suicidal ideation in terms of the rate and associated factors in a sample of Malaysian healthcare workers during the early-phase of the COVID-19 pandemic.Methods: A subpopulation analysis (N = 171) was conducted within a larger, nation-wide cross-sectional study of Malaysian healthcare worker psychological distress from March 18–21, 2020. Current suicidal ideation was measured with item 9 of the Patient Health Questionnaire-9 (PHQ-9). The following independent variables were assessed: socio-demographic profile, occupation and service-related factors, health-anxiety (Health Anxiety Inventory, HAI), lifetime anxiety disorder and severity of depression (PHQ-9).Results: The proportion of healthcare workers with current suicidal ideation (19/171) and clinical depression (17/171) were 11.1 and 9.9%, respectively. Multivariable analysis showed that clinical depression was the most significant factor associated with current suicidal ideation (p < 0.001, OR = 55.983, 95% CI = 9.015–347.671) followed by mild (subthreshold) depression (p = 0.001, OR = 115.984, 95% CI = 2.977–85.804). Service duration of more than 10 years was associated with significantly less suicidal ideation (p = 0.049, OR = 0.072, 95% CI = 0.005–0.993).Conclusions: Depression (subthreshold and especially within the clinical range) and early-career status (

The Australian clinical trials sector has grown steadily over the past decade, particularly with respect to early phase trials where Australia's research capacity, capability and quality of research is revered. With an increase in the number of internationally sponsored clinical research projects being conducted in Australia, particularly in the early phase setting, there has been a corresponding growth in the number of clinical research sites conducting early phase clinical trials. Australian researchers are guided by a multitude of research codes, guidance and statements which govern the conduct of clinical trials. Although international guidance regarding the conduct of early phase clinical trials exists, there is currently no single source outlining best practice recommendations for the conduct of early phase clinical trials in Australia.In recognition of this Clinical Trials: Impact & Quality (CT:IQ), a collaborative of sector stakeholders, convened a project team with comprehensive knowledge of the Australian clinical trials sector and particularly early phase research, to evaluate and collate broadly applicable and implementable guidance for the conduct of early phase clinical trials. Although the initial intent was to create guidance specific to early phase, we recognize the project outcomes are more broadly implementable irrespective of the research phase and are intended to support all clinical research sites to conduct high-quality clinical trials in Australia.

The ability to accurately predict the early progression of hemorrhagic fever with renal syndrome (HFRS) is crucial for reducing morbidity and mortality rates in severely affected patients. However, the utility of biomarkers for predicting clinical outcomes remains elusive in HFRS. The aims of the current study were to analyze the serum levels of immune function-related proteins and identify novel biomarkers that may help ascertain clinical outcomes of HFRS. Enzyme-linked immunosorbent assay, Luminex, and bioanalyzer assays were used to quantitatively detect 15 biomarkers in 49 serum samples of 26 patients with HFRS. High hemoglobin (HGB) and low urine output (UO) levels were identified as potential biomarkers associated with the acute HFRS. The serum soluble urokinase plasminogen activator receptor (suPAR) and C-X-C motif chemokine ligand 10 (CXCL10) values increased in the early phase of diseases. Elevated suPAR, interleukin-10 (IL-10), CXCL10, and decreased transforming growth factor-beta 3 (TGF-β3) were representative predictors of the disease severity. Upregulation of the HGB showed a significant correlation with high levels of suPAR and CXCL10. Reduced UO positively correlated with increased suPAR, CXCL10, and TGF-β2, and decreased vascular endothelial growth factor and TGF-β3. The changing HGB and UO criteria, high suPAR, IL-10, CXCL10, and low TGF-β3 of HFRS raise significant awareness for physicians regarding prospective biomarkers for monitoring early warning signs of HFRS. This study provides critical insights into the clinical and immunological biomarkers for disease severity and progression in patients with HFRS to identify early predictions of fatal outcomes.

This article examines the understudied subjects of Lermontov life and work: his stay This article examines the understudied subjects of Lermontov life and work: his stay at the Moscow noble boarding school and his direct engagement in Cepheus, a literary annual run by the literary circle of Raich, where Lermontov’s first poem, “Thoughts, Ex tracts, and Reflections…” was published. The author proves the authorship of Lermontov’s “Thoughts…” that had been included in the sixth volume of the academic edition of his works under the category of “Dubia” but had been excluded from many later editions. Close reading of “Thoughts...” and a comparative study of selected fragments with Le rmontov’s letters to M. A. Shan-Girey demonstrate that even this early essay drawing on tological differences between the principles of classicism and Romanticism bears the im print of the Early Romantic aesthetics. The analysis reveals typological similarities between “Thoughts…” and the ideas of Jena school that were most fully manifested in the writings of brothers Schlegel brothers thoroughly studied in the literary circle of Raich. In a section devoted to aesthetic views of S. E. Raich, the author disagrees with those researchers who consider him to be either archaist or classicist and claims that he was an adept of Jena school rather than a “neopetrarchist.” Ideas discussed in the circle and during the lectures influenced the young poet as his future work testifies. Within the period of 1829-1831, he published a Byronic poem “June 11, 1831,” on the one hand, and a poem “Angel” that echoes the ideas of Wackenroder, on the other hand. If for Raich, a combination of these two conflicting Romantic schools was inconceivable, for young Lermontov, it was a natural outcome of his apprenticeship period since each school offered him the means to under stand the essence of Romantic method as such.

This article examines the understudied subjects of Lermontov life and work: his stay at the Moscow noble boarding school and his direct engagement in Cepheus, a literary annual run by the literary circle of Raich, where Lermontov’s first work, “Thoughts, Extracts, and Reflections…” was published. The author proves the authorship of Lermontov’s “Thoughts…” that was included in the sixth volume of the academic edition of his works under the category of “Dubia” but excluded from many later editions. Close reading of “Thoughts...” and a comparative study of selected fragments with Lermontov’s letters to M.A. Shan-Girey demonstrate that even this early essay drawing ontological differences between the principles of classicism and Romanticism bears the imprint of the Early Romantic aesthetics. The analysis reveals typological similarities between “Thoughts…” and the ideas of Jena school that were most fully manifested in the writings of Schlegel brothers thoroughly studied in the literary circle of Raich. In a section devoted to aesthetic views of S.E. Raich, the author disagrees with those researchers who consider him to be either archaist or classicist and claims that he was an adept of Jena school rather than a “neopetrarchist.” Ideas discussed in the circle and during the lectures influenced Lermontov as his future work testifies. Within the period of 1829–1831, he published a Byronic poem “June 11, 1831,” on the one hand, and a poem “Angel” that echoes the ideas of Wackenroder, on the other hand. If for Raich, a combination of these two conflicting Romantic schools was inconceivable, for young Lermontov, it was a natural outcome of his apprenticeship period since each school offered him the means to understand the essence of Romantic method as such.

Experimental therapeutic oncology agents are often combined to circumvent tumor resistance to individual agents. However, most combination trials fail to demonstrate sufficient safety and efficacy to advance to a later phase. This study collected survey data on phase 1 combination therapy trials identified from ClinicalTrials.gov between January 1, 2003 and November 30, 2017 to assess trial design and the progress of combinations toward regulatory approval. Online surveys (N = 289, 23 questions total) were emailed to Principal Investigators (PIs) of early-phase National Cancer Institute and/or industry trials; 263 emails (91%) were received and 113 surveys completed (43%). Among phase 1 combination trials, 24.9% (95%CI: 15.3%, 34.4%) progressed to phase 2 or further; 18.7% (95%CI: 5.90%, 31.4%) progressed to phase 3 or regulatory approval; and 12.4% (95%CI: 0.00%, 25.5%) achieved regulatory approval. Observations of “clinical promise” in phase 1 combination studies were associated with higher rates of advancement past each milestone toward regulatory approval (cumulative OR = 11.9; p = 0.0002). Phase 1 combination study designs were concordant with Clinical Trial Design Task Force (CTD-TF) Recommendations 79.6% of the time (95%CI: 72.2%, 87.1%). Most discordances occurred where no plausible pharmacokinetic or pharmacodynamic interactions were expected. Investigator-defined “clinical promise” of a combination is associated with progress toward regulatory approval. Although concordance between study designs of phase 1 combination trials and CTD-TF Recommendations was relatively high, it may be beneficial to raise awareness about the best study design to use when no plausible pharmacokinetic or pharmacodynamic interactions are expected.

Background: Mitochondrial dysfunction plays an important role in the pathogenesis of amyotrophic lateral sclerosis (ALS). We aimed to demonstrate mitochondrial dysfunction in ALS using a lactate stress test and to examine the relationship between mitochondrial dysfunction with motor deterioration. Methods: We enrolled 116 patients and observed clinical variables, including the survival state. Results: Patients with a rapid slope of revised ALS functional rating scales (ALSFRS-r) (>20 U/year) exhibited the slowest elimination rate (median −4.67 × 10−3 mmol·L−1·min−1 , coefficient of variation, 590.15%), the shortest duration (0.63 ± 0.28 years) and the worst ALSFRS-r (32.59 ± 4.93). Patients with a moderate slope of ALSFRS-r (10-20 U/year) showed a moderate elimination rate (median −11.33 × 10−3 mmol·L−1·min−1 , coefficient of variation, 309.89%), duration (1.16 ± 0.45 years), and ALSFRS-r (34.83 ± 6.11). The slower progressing (

Background: The outbreak of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and the related disease (COVID-19) has rapidly spread to a pandemic proportion, increasing the demands on health systems for the containment and management of COVID-19. Nowadays, one of the critical issues still to be pointed out regards COVID-19 treatment regimens and timing: which drug, in which phase, for how long? Methods: Our narrative review, developed using MEDLINE and EMBASE, summarizes the main evidences in favor or against the current proposed treatment regimens for COVID-19, with a particular focus on antiviral agents. Results: Although many agents have been proposed as possible treatment, to date, any of the potential drugs against SARS-CoV-2 has shown to be safe and effective for treating COVID-19. Despite the lack of definitive evidence, remdesivir remains the only antiviral with encouraging effects in hospitalized patients with COVID-19. Conclusions: In such a complex moment of global health emergency, it is hard to demand scientific evidence. Nevertheless, randomized clinical trials aiming to identify effective and safe drugs against SARS-CoV-2 infection are urgently needed in order to confirm or reject the currently available evidence.

Natural killer (NK) cells may be important in modulating HIV replication in early course of HIV infection. The effector function of NK cells is finely tuned by a balance between signals delivered by activating and inhibitory receptors. However the influence of expression of these receptors on the early course of HIV replication and subsequent disease progression is not explored in context of HIV-1 C infection. The expression pattern of activating (NKp46,NKp44, NKp30, NKG2D,NKG2C) and inhibitory (CD158b, NKG2A and ILT2) receptors was determined in 20 patients with recent HIV-1 C infection within 3-7 months of acquiring HIV infection and was compared with the expression pattern in individuals with progressive (N=12), non progressive HIV-1C infection (LTNPs, N=12) and healthy seronegative individuals (N=20). The association of the expression of these receptors on the rate of disease progression was assessed using viral load set point in recently infected individuals as a marker of disease progression. The study showed that higher cytotoxic potency of NK cells was associated with low viral load set point in recent HIV infection (r=-0.701; p=0.0006) and higher CD4 counts (r=0.720; p=0.001). The expression of activating receptors (NKp46, NKp30 and NKG2D) on cytotoxic NK cells but not on regulatory NK cells was significantly associated with low viral set point(p< 0.01) and viral load in LTNPs (p< 0.01).The study also indicated that cytotoxic NK cells might show the ability to specifically lyse HIV infected CD4 cells. This data collectively showed that early and sustained higher expression of activating receptors on cytotoxic NK cells could be responsible for increased cytotoxicity, reduced viral burden and thus delaying the disease progression. The study to identify the influence of HIV on the molecular mechanism of the expression of these receptors will be helpful in further understanding of NK cell mediated control in early HIV infection.