The association between bacterial infections and the risk of coronary heart disease in type 1 diabetes.

BACKGROUND: Diabetes increases the risk of infections and coronary heart disease (CHD). Whether infections increase the risk of CHD and how this applies to individuals with diabetes is unclear. OBJECTIVES: To investigate the association between bacterial infections and the risk of CHD in type 1 diabetes. METHODS: Individuals with type 1 diabetes (n = 3781) were recruited from the Finnish Diabetic Nephropathy Study (FinnDiane), a prospective follow-up study. CHD was defined as incident events: fatal or nonfatal myocardial infarction, coronary artery bypass surgery or percutaneous coronary intervention, identified through national hospital discharge register data. Infections were identified through national register data on all antibiotic purchases from outpatient care. Register data were available from 1 January 1995 to 31 December 2015. Bacterial lipopolysaccharide (LPS) activity was measured from serum samples at baseline. Data on traditional risk factors for CHD were collected during baseline and consecutive visits. RESULTS: Individuals with an incident CHD event (n = 370) had a higher mean number of antibiotic purchases per follow-up year compared to those without incident CHD (1.34 [95% CI: 1.16-1.52], versus 0.79 [0.76-0.82], P < 0.001), as well as higher levels of LPS activity (0.64 [0.60-0.67], versus 0.58 EU mL-1 [0.57-0.59], P < 0.001). In multivariable-adjusted Cox proportional hazards models, the mean number of antibiotic purchases per follow-up year was an independent risk factor for incident CHD (HR 1.21, 95% CI: 1.14-1.29, P < 0.0001). High LPS activity was a risk factor for incident CHD (HR 1.93 [1.34-2.78], P < 0.001) after adjusting for static confounders. CONCLUSION: Bacterial infections are associated with an increased risk of incident CHD in individuals with type 1 diabetes.

Adipose-derived regenerative cells and fat grafting for treating breast cancer-related lymphedema: Lymphoscintigraphic evaluation with 1 year of follow-up.

BACKGROUND: Breast cancer-related lymphedema (BCRL) is a feared late complication. Treatment options are lacking at present. Recent studies have suggested that mesenchymal stromal cells can alleviate lymphedema. Herein, we report the results from the first human pilot study with adipose-derived regenerative cells (ADRCs) for treating BCRL with 1 year of follow-up. MATERIAL AND METHODS: We included 10 patients with BCRL. ADRCs were injected directly into the axillary region together with a scar-releasing fat grafting procedure. Primary endpoint was change in arm volume. Secondary endpoints were change in patient-reported outcomes, changes in lymph flow, and safety. RESULTS: During follow-up, no significant change in volume was noted. Patient-reported outcomes improved significantly with time. Five patients reduced their use of conservative management. Quantitative lymphoscintigraphy did not improve on the lymphedema-affected arms. ADRCs were well tolerated, and only minor transient adverse events related to liposuction were noted. CONCLUSIONS: In this pilot study, a single injection of ADRCs improved lymphedema based on patient-reported outcome measures, and there were no serious adverse events during the follow-up period. Lymphoscintigraphic evaluation showed no improvement after ADRC treatment. There was no change in excess arm volume. Results of this trial need to be confirmed in randomized clinical trials.

Improved survival for patients diagnosed with chronic lymphocytic leukemia in the era of chemo-immunotherapy: a Danish population-based study of 10455 patients.

The treatment of chronic lymphocytic leukemia (CLL) is in rapid transition, and during recent decades both combination chemotherapy and immunotherapy have been introduced. To evaluate the effects of this development, we identified all CLL patients registered in the nation-wide Danish Cancer Register between 1978 and 2013. We identified 10 455 CLL patients and 508 995 CLL-free control persons from the general population. Compared with the latter, the relative mortality rate between CLL patients and their controls decreased from 3.4 (95% CI 3.2-3.6) to 1.9 (95% CI 1.7-2.1) for patients diagnosed in 1978-1984 and 2006-2013, respectively. The improved survival corresponded to a decreasing risk of death from malignant hematological diseases, whereas the risk of death from infections was stable during the study period. These population-based data substantiate the improved survival for patients treated with chemo-immunotherapy demonstrated in clinical studies.

Endobronchial ultrasound-guided transbronchial needle aspiration: performance of biomedical scientists on rapid on-site evaluation and preliminary diagnosis.

OBJECTIVES: Rapid on-site evaluation (ROSE) of endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) followed by a subsequent preliminary adequacy assessment and a preliminary diagnosis, was performed at Aarhus University Hospital by biomedical scientists (BMS). The aim of this study was to evaluate the BMS accuracy of ROSE adequacy assessment, the preliminary adequacy assessment and the preliminary diagnosis as compared with the cytopathologist-rendered final adequacy assessment and final diagnosis. METHODS: The BMS-rendered assessments for 717 sites from 319 consecutive patients over a 4-month period were compared with the cytopathologist-rendered assessments. Comparisons of adequacy and preliminary diagnoses were based on inter-observer Cohen's Kappa coefficient with a 95% confidence interval (CI). RESULTS: Strong correlations between ROSE and final adequacy assessments [Kappa coefficient of 0.90 (CI: 0.85-0.96)] and between the preliminary and final adequacy assessments [Kappa coefficient of 0.93 (CI: 0.87-0.99)] were found. As for the correlation between the preliminary and final diagnoses, the Kappa coefficient was 0.99 (CI: 0.98-1). CONCLUSION: Both ROSE and preliminary adequacy assessments as well as preliminary diagnoses, all performed by BMS, were highly accurate when compared with the final assessment by the cytopathologist.

A liposome-based size calibration method for measuring microvesicles by flow cytometry.

UNLABELLED: ESSENTIALS: A gold standard to determine the sizes of microvesicles by flow cytometry is needed. We used fluorescently labeled liposomes to estimate the size of microvesicles with flow cytometry. We suggest that liposomes are more accurate size calibrators than the commonly used polystyrene beads. The liposome-based size calibrators improve the size assessment of microvesicle made with flow cytometry. BACKGROUND: During the past years, the need for a gold standard to determine the sizes of extracellular vesicles including microvesicles by flow cytometry has been emphasized. METHODS: This work suggests that artificial vesicles can be used as calibrators to estimate the size of microvesicles from the side scattering (SSC) measured with flow cytometry. We prepared fluorescently labeled liposomes with different maximum sizes defined by the pore size (200, 400, 800, and 1000 nm) of the membrane used for the extrusion. The fluorescence strengths from the largest liposomes pertaining to each pore size enabled us to verify the correlation between the SSC from a liposome and the corresponding size. CONCLUSIONS: This study indicates that artificial vesicles are more accurate size calibrators compared to the commonly used polystyrene calibrator beads illustrated by the SSC from 110 nm polystyrene beads corresponds to the scattering from ~400 nm vesicle-like particles. We also show that this method of size assessment based on SSC has a low resolution that is roughly estimated to be between 60 and 200 nm, dependent on the vesicle size.

Cardiac Abnormalities in Adult Patients With Polymyositis or Dermatomyositis as Assessed by Noninvasive Modalities.

OBJECTIVE: Cardiac events are a major cause of death in patients with idiopathic inflammatory myopathies. The study objective was in a controlled setting to describe cardiac abnormalities by noninvasive methods in a cohort of patients with polymyositis (PM) or dermatomyositis (DM) and to identify predictors for cardiac dysfunction. METHODS: In a cross-sectional study, 76 patients with PM/DM and 48 matched healthy controls (HCs) were assessed by serum levels of cardiac troponin I, electrocardiography, Holter monitoring, echocardiography with tissue Doppler imaging, and quantitative cardiac (99m) Tc-pyrophosphate ((99m) Tc-PYP) scintigraphy. RESULTS: Compared to HCs, patients with PM/DM more frequently had left ventricular diastolic dysfunction (LVDD) (12% versus 0%; P = 0.02) and longer QRS and QT intervals (P = 0.007 and P < 0.0001, respectively). In multivariate analysis, factors associated with LVDD were age (P = 0.001), disease duration (P = 0.004), presence of myositis-specific or -associated autoantibodies (P = 0.05), and high cardiac (99m) Tc-PYP uptake (P = 0.006). In multivariate analysis of the pooled data for patients and HCs, a diagnosis of PM/DM (P < 0.0001) was associated with LVDD. CONCLUSION: Patients with PM or DM had an increased prevalence of cardiac abnormalities compared to HCs. LVDD was a common occurrence in PM/DM patients and correlated to disease duration. In addition, the association of LVDD with myositis-specific or -associated autoantibodies and high cardiac (99m) Tc-PYP uptake supports the notion of underlying autoimmunity and myocardial inflammation in patients with PM/DM.

Seroincidence of non-typhoid Salmonella infections: convenience vs. random community-based sampling.

The incidence of reported infections of non-typhoid Salmonella is affected by biases inherent to passive laboratory surveillance, whereas analysis of blood sera may provide a less biased alternative to estimate the force of Salmonella transmission in humans. We developed a mathematical model that enabled a back-calculation of the annual seroincidence of Salmonella based on measurements of specific antibodies. The aim of the present study was to determine the seroincidence in two convenience samples from 2012 (Danish blood donors, n = 500, and pregnant women, n = 637) and a community-based sample of healthy individuals from 2006 to 2007 (n = 1780). The lowest antibody levels were measured in the samples from the community cohort and the highest in pregnant women. The annual Salmonella seroincidences were 319 infections/1000 pregnant women [90% credibility interval (CrI) 210-441], 182/1000 in blood donors (90% CrI 85-298) and 77/1000 in the community cohort (90% CrI 45-114). Although the differences between study populations decreased when accounting for different age distributions the estimates depend on the study population. It is important to be aware of this issue and define a certain population under surveillance in order to obtain consistent results in an application of serological measures for public health purposes.

History of antimicrobial use and the risk of Dientamoeba fragilis infection.

Associations between antimicrobial use and risk of enteric infection with intestinal protozoa are scarcely studied. The aim of this study was to quantify the risk of Dientamoeba fragilis infection conferred by exposure to antimicrobials. We conducted a registry-based retrospective cohort study of 9,945 Danish patients investigated for D. fragilis infection between 2008 and 2011, using data from the Danish Register of Medicinal Product Statistics, and calculating relative risks (RR) for D. fragilis infection by stratified binary regression. Furthermore, we conducted a population based case-control study using controls sampled from the Danish Civil Registration System, calculating hazard ratios (HR) for D. fragilis infection by conditional logistic regression. Exposure to metronidazole was found to confer decreased risk of D. fragilis infection; however, similar associations were found for antimicrobials not commonly used to treat D. fragilis, such as broad-spectrum penicillin, fluoroquinolones, and macrolides. In contrast, mebendazole exposure was associated with increased risk. The intake of antimicrobials influences the risk of D. fragilis.

Seroepidemiology of pertussis in a cross-sectional study of an adult general population in Denmark.

An increase in pertussis has been observed in several countries over the last decades, especially in adult populations. The seroprevalence of pertussis was determined in a cross-sectional study of the adult population in the Copenhagen area, Denmark, conducted between 2006 and 2008. Specific IgG antibodies against pertussis toxin (PT) were measured in 3440 persons resulting in an age-standardized seroprevalence of 3.0% (95% confidence interval 1.9-4.7) using an IgG anti-PT cut-off of 75 IU/ml. By using antibody decay profiles from longitudinal data the estimated seroincidence was 143/1000 person-years. In contrast, an incidence of 0.03/1000 person-years was estimated from the official data of notified cases during the same period. Of the investigated risk factors, only age and education were significantly associated with pertussis infection. This study indicates that pertussis is highly underestimated in the adult population in Denmark, which has implications for future prevention strategies, including raising the awareness of pertussis.

Dientamoeba fragilis in Denmark: epidemiological experience derived from four years of routine real-time PCR.

The intestinal protozoon Dientamoeba fragilis remains a clinical entity of dubious significance. While several previous studies address questions of epidemiology, only a handful have systematically employed and reported on the results from real-time polymerase chain reaction (qPCR), the best currently available diagnostic modality, and the comparison of results from different studies is, therefore, difficult. Since 2007, Statens Serum Institut (Denmark) has utilised qPCR for D. fragilis as routine diagnostic work-up for intestinal parasitosis, testing more than 22,000 samples from 2008 through 2011, and the aim of this study was to report on the results and experiences gained in the process. We demonstrate a staggeringly high proportion (43%) of investigated patients positive for D. fragilis, ranging from 12 to 71% depending on age group, showing a bimodal age distribution peaking in children and adults of parental age, as well as a clear association between exposure to children and risk of D. fragilis infection. We discuss these findings in light of the pinworm egg vector hypothesis and substantiate further our knowledge of risk factors pertaining to D. fragilis carriage.

Campylobacter seroconversion rates in selected countries in the European Union.

As a major foodborne pathogen, Campylobacter is frequently isolated from food sources of animal origin. In contrast, human Campylobacter illness is relatively rare, but has a considerable health burden due to acute enteric illness as well as severe sequelae. To study silent transmission, serum antibodies can be used as biomarkers to estimate seroconversion rates, as a proxy for infection pressure. This novel approach to serology shows that infections are much more common than disease, possibly because most infections remain asymptomatic. This study used antibody titres measured in serum samples collected from healthy subjects selected randomly in the general population from several countries in the European Union (EU). Estimates of seroconversion rates to Campylobacter were calculated for seven countries: Romania, Poland, Italy, France, Finland, Denmark and The Netherlands. Results indicate high infection pressures in all these countries, slightly increasing in Eastern EU countries. Of these countries, the differences in rates of notified illnesses are much greater, with low numbers in France and Poland, possibly indicating lower probability of detection due to differences in the notification systems, but in the latter case it cannot be excluded that more frequent exposure confers better protection due to acquired immunity.

Biomarker dynamics: estimating infection rates from serological data.

The marginal distribution of serum antibody titres in a cross-sectional population sample can be expressed as a function of the infection rate, taking into account heterogeneity in peak levels and decay rates. This marginal model allows estimation of incidences, as well as simple tests for homogeneity across age, gender or geographic strata, using likelihood ratio tests. An example is given using Campylobacter serum antibody data. Using a hierarchical dynamic model to analyse data from a follow-up study in patients with symptomatic Campylobacter infection, we show that the serum antibody response consists of a rapid increase to peak levels followed by a slow decline with a geometric mean halftime of 1.4, 0.6 and 0.3 years for IgG, IgM and IgA, respectively. Antibody peak levels and decay rates were highly variable among subjects. Incidence estimates are consistent among different antibody classes (IgG, IgM and IgA). High seroconversion rates indicate that Campylobacter infection is a frequent event, occurring approximately once every year in any adult person, in the Netherlands, supporting the conclusion that a small fraction of infections leads to symptoms severe enough for notification.

Elastic properties of thin poly(vinyl alcohol)-cellulose nanocrystal membranes.

In spite of extensive studies on the preparation and characterization of nanocomposite materials, the correlation of their properties at the nanoscale with those in bulk is a relatively unexplored area. This is of great importance, especially for materials with potential biomedical applications, where surface properties are as important in determining their applicability as bulk characteristics. In this study, the nanomechanical characteristics of thin poly(vinyl alcohol) (PVOH)-poly(acrylic acid) (PAA)-cellulose nanocrystal (CNC) membranes were studied using the nanoindentation module in an atomic force microscope (AFM) and the properties were compared with the macro-scale properties obtained by tensile tests. In general, the elastic properties measured by nanoindentation followed the same trend as macro-scale tensile tests except for the PVOH 85-PAA 0-CNC 15 sample. In comparison to the macro-scale elastic properties, the measured elastic moduli with AFM were higher. Macro-scale tensile test results indicated that, in the presence of PAA, incorporation of CNCs up to 20 wt% improved the elastic modulus of PVOH, but when no PAA was added, increasing the CNC content above 10 wt% resulted in their agglomeration and degradation in mechanical properties of PVOH. The discrepancy between macro-scale tensile tests and nanoindentation in the PVOH 85-PAA 0-CNC 15 sample was correlated to the high degree of inhomogeneity of CNC dispersion in the matrix. It was found that the composites reinforced with cellulose nanocrystals had smaller indentation imprints and the pile-up effect increased with the increase of cellulose nanocrystal content.

Clinical features of Clostridium difficile infection and molecular characterization of the isolated strains in a cohort of Danish hospitalized patients.

The purpose of this study was to compare clinical features of Clostridium difficile infection (CDI) to toxin gene profiles of the strains isolated from Danish hospitalized patients. C. difficile isolates were characterized by PCR based molecular typing methods including toxin gene profiling and analysis of deletions and truncating mutations in the toxin regulating gene tcdC. Clinical features were obtained by questionnaire. Thirty percent of the CDI cases were classified as community-acquired. Infection by C. difficile with genes encoding both toxin A, toxin B and the binary toxin was significantly associated with hospital-acquired/healthcare-associated CDI compared to community-acquired CDI. Significantly higher leukocyte counts and more severe clinical manifestations were observed in patients infected by C. difficile containing genes also encoding the binary toxin together with toxin A and B compared to patients infected by C. difficile harbouring only toxin A and B. In conclusion, infection by C. difficile harbouring genes encoding both toxin A, toxin B and the binary toxin were associated with hospital acquisition, higher leukocyte counts and severe clinical disease.

Usefulness of seroconversion rates for comparing infection pressures between countries.

Salmonella is a frequent cause of foodborne illness. However, since most symptomatic cases are not diagnosed, the true infection pressure is unknown. Furthermore, national surveillance systems have different sensitivities that limit inter-country comparisons. We have used recently developed methods for translating measurements of Salmonella antibodies into estimates of seroincidence: the frequency of infections including asymptomatic cases. This methodology was applied to cross-sectional collections of serum samples obtained from the general healthy population in three European countries. Denmark and The Netherlands had the lowest seroincidence (84,169 infections/1000 person-years), whereas Poland had the highest seroincidence (547/1000 person-years). A Bayesian method for obtaining incidence rate ratios was developed; this showed a 6·3 (95% credibility interval 3·3-12·5) higher incidence in Poland than in Denmark which demonstrates that this methodology has a wider applicability for studies of surveillance systems and evaluation of control programmes.

Enrichment of variations in KIR3DL1/S1 and KIR2DL2/L3 among H1N1/09 ICU patients: an exploratory study.

BACKGROUND: Infection by the pandemic influenza A (H1N1/09) virus resulted in significant pathology among specific ethnic groups worldwide. Natural Killer (NK) cells are important in early innate immune responses to viral infections. Activation of NK cells, in part, depend on killer-cell immunoglobulin-like receptors (KIR) and HLA class I ligand interactions. To study factors involved in NK cell dysfunction in overactive immune responses to H1N1 infection, KIR3DL1/S1 and KIR2DL2/L3 allotypes and cognate HLA ligands of H1N1/09 intensive-care unit (ICU) patients were determined. METHODOLOGY AND FINDINGS: KIR3DL1/S1, KIR2DL2/L3, and HLA -B and -C of 51 H1N1/09 ICU patients and 105 H1N1-negative subjects (St. Theresa Point, Manitoba) were characterized. We detected an increase of 3DL1 ligand-negative pairs (3DL1/S1(+) Bw6(+) Bw4(-)), and a lack of 2DL1 HLA-C2 ligands, among ICU patients. They were also significantly enriched for 2DL2/L3 ligand-positive pairs (P<0.001, Pc<0.001; Odds Ratio:6.3158, CI95%:2.481-16.078). Relative to St. Theresa aboriginals (STh) and Venezuelan Amerindians (VA), allotypes enriched among aboriginal ICU patients (Ab) were: 2DL3 (Ab>VA, P=0.024, Pc=0.047; Odds Ratio:2.563, CI95%:1.109-5.923), 3DL1*00101 (Ab>VA, P<0.001, Pc<0.001), 3DL1*01502 (Ab>STh, P=0.034, Pc=0.268), and 3DL1*029 (Ab>STh, P=0.039, Pc=0.301). Aboriginal patients ligand-positive for 3DL1/S1 and 2DL1 had the lowest probabilities of death (R(d)) (R(d)=28%), compared to patients that were 3DL1/S1 ligand-negative (R(d)=52%) or carried 3DL1*029 (R(d)=52%). Relative to Caucasoids (CA), two allotypes were enriched among non-aboriginal ICU patients (NAb): 3DL1*00401 (NAb>CA, P<0.001, Pc<0.001) and 3DL1*01502 (CA

Influenza pathogenesis: lessons learned from animal studies with H5N1, H1N1 Spanish, and pandemic H1N1 2009 influenza.

Because cases of highly pathogenic influenza are rare, no systematic clinical studies have evaluated different therapeutic approaches. Instead, treatment recommendations are aimed at the alleviation of clinical signs and symptoms, especially the restoration of respiratory function, and at the inhibition of virus replication, assuming viral load is responsible for disease phenotype. Studies of highly pathogenic influenza in different animal models, especially nonhuman primates and ferrets, reproduce many of the key observations from clinical cases. Host-response kinetics reveal a delayed but broad activation of genes involved in the innate and acquired immune responses (innate responses produce inflammatory responses), which continue after the virus has been cleared and may contribute importantly to the clinical signs observed. Experimental animal models point to an important role for immune dysregulation in the pathogenesis of highly pathogenic influenza. The use of these models to develop and validate therapeutic approaches is just beginning, but published studies reveal the importance of early treatment with antivirals and show the potential and limitations of approaches aimed at the host response.

Systemic nitric oxide clamping in normal humans guided by total peripheral resistance.

AIM: We wanted to stabilize the availability of nitric oxide (NO) at levels compatible with normal systemic haemodynamics to provide a model for studies of complex regulations in the absence of changes in NO levels. METHODS: Normal volunteers (23-28 years) were infused i.v. with the nitric oxide synthase (NOS) inhibitor N(G)-nitro-l-arginine methyl ester (l-NAME) at 0.5 mg kg(-1) h(-1). One hour later, the NO donor sodium nitroprusside (SNP) was co-infused in doses eliminating the haemodynamic effects of l-NAME. Haemodynamic measurements included blood pressure (MABP) and cardiac output (CO) by impedance cardiography. RESULTS: l-NAME increased MABP and total peripheral resistance (TPR, 1.02 + or - 0.05 to 1.36 + or - 0.07 mmHg s mL(-1), mean + or - SEM, P < 0.001). With SNP, TPR fell to a stable value slightly below control (0.92 + or - 0.05 mmHg s mL(-1), P < 0.05). CO decreased with l-NAME (5.8 + or - 0.3 to 4.7 + or - 0.3 L min(-1), P < 0.01) and returned to control when SNP was added (6.0 + or - 0.3 L min(-1)). A decrease in plasma noradrenaline (42%, P < 0.01) during l-NAME administration was completely reversed by SNP. Plasma renin activity decreased during l-NAME administration and returned towards normal after addition of SNP. In contrast, plasma aldosterone was increased by l-NAME and remained elevated. CONCLUSIONS: Concomitant NOS inhibition and NO donor administration can be adjusted to maintain TPR at control level for hours. This approach may be useful in protocols in which stabilization of the peripheral supply of NO is required. However, the dissociation between renin and aldosterone secretion needs further investigation.

Estimation of incidences of infectious diseases based on antibody measurements.

Owing to under-ascertainment it is difficult if not impossible to determine the incidence of a given disease based on cases notified to routine public health surveillance. This is especially true for diseases that are often present in mild forms as for example diarrhoea caused by foodborne bacterial infections. This study presents a Bayesian approach for obtaining incidence estimates by use of measurements of serum antibodies against Salmonella from a cross-sectional study. By comparing these measurements with antibody measurements from a follow-up study of infected individuals it was possible to estimate the time since last infection for each individual in the cross-sectional study. These time estimates were then converted into incidence estimates. Information about the incidence of Salmonella infections in Denmark was obtained by using blood samples from 1780 persons. The estimated incidence was about 0.094 infections per person year. This number corresponds to 325 infections per culture-confirmed case captured in the Danish national surveillance system. We present a novel approach, termed as seroincidence, that has potentials to compare the sensitivity of public health surveillance between different populations, countries and over time.

A common CD4 gene variant is associated with an increased risk of HIV-1 infection in Kenyan female commercial sex workers.

BACKGROUND: It has been predicted that CD4 C868T, a novel CD4 single-nucleotide polymorphism (SNP) that has been found to be highly prevalent among Africans, changes the tertiary structure of CD4, which may alter susceptibility to human immunodeficiency virus (HIV) infection. METHODS: Participants were from a Kenyan cohort and included 87 uninfected and 277 HIV-1-infected individuals. DNA sequencing was used to determine CD4 genotype. A2.01 cells expressing similar levels of either wild-type CD4 or CD4-Trp240 as well as peripheral blood mononuclear cells from uninfected donors were infected with HIV-1(IIIB) or a Kenyan primary HIV-1 isolate. HIV-1 p24 enzyme-linked immunosorbent assay was used to determine the outcome of infection. RESULTS: CD4 C868T was found to be significantly more prevalent among HIV-1-infected participants than among HIV-1-uninfected participants (P = .002), and C868T was associated with an increased incidence of HIV-1 infection as well (P = .005, log-rank test; P = .009, Wilcoxon test), with an odds ratio of 2.49 (P = .009). Both in vitro and ex vivo models demonstrated a significant association between CD4 C868T and susceptibility to HIV-1 infection (P < .001 and P = .003, respectively). CONCLUSION: Overall, the present study found a strong correlation between CD4 C868T and increased susceptibility to HIV-1 infection. Given the high prevalence of both HIV infection and CD4 C868T in African populations, the effect of this SNP on the epidemic in Africa could be dramatic.