Areas with high HIV prevalence: A spatial analysis of nationwide claims data in Germany.

OBJECTIVE: We aimed to identify spatial clusters of high HIV prevalence in Germany. METHODS: Using nationwide outpatient claims data comprising information of about 88% of the total German population (N = 72 041 683), we examined spatial variations and spatial clusters of high HIV prevalence at the district level (N = 401). People with HIV were identified using the International Statistical Classification of Diseases and Related Health Problems, Tenth Revision (ICD-10 codes) B20, B22, and B24 (HIV disease) documented as 'confirmed'. RESULTS: Among 72 041 683 people with statutory health insurance in Germany in 2021, 72 636 had diagnosed HIV, which corresponds to a prevalence of 101 per 100 000 individuals (0.10%). Of these, 56 895 were males (78%). At a district level, the HIV prevalence varied by a factor of 32 between 13 in a rural district in Bavaria and 417 per 100 000 individuals in the German capital, Berlin. The spatial autocorrelation coefficient was 0.24 (p < 0.0001, Global Moran's I). Several high-prevalence spatial clusters of different sizes were identified, mostly located in western Germany. The largest cluster comprised eight districts in the southern part of Hesse, including the city of Frankfurt and the city of Mainz in Rhineland-Palatinate. The second cluster consisted of four districts in North Rhine-Westphalia, including the cities of Cologne and Düsseldorf. Two districts in southern Germany (Mannheim and Ludwigshafen) formed the third cluster. Only urban districts were observed in spatial clusters of high HIV prevalence. CONCLUSIONS: The current study identified for the first time spatial clusters with high HIV prevalence in Germany. This understanding is of particular importance when planning the general and specialized medical care of patients with HIV and to support preventive measures.

Similar long-term efficacy of dual therapy containing raltegravir and a boosted protease inhibitor versus standard triple therapies in pretreated HIV-1-infected patients in a retrospective, real-life cohort of 14 years.

OBJECTIVES: Raltegravir is used in many antiretroviral combinations, but its use in treatment-experienced patients without knowledge of baseline resistance is discussed controversially as a number of comparative studies have shown a higher rate of virological failure. However, it has been used frequently for the management of treatment failure, as it was the first integrase inhibitor to become available, and thus offered new options for patients with multiple resistance. The strategic use of raltegravir in this setting is examined in this study. METHODS: In order to examine the efficacy of raltegravir in second and later lines of antiretroviral combinations, data for 740 patients from three clinical cohorts were analysed with a focus on the combinations that were used. These were stratified into the combination of two nonnucleoside reverse transcriptase inhibitors and raltegravir (2NRTIs + RAL), the combination of a boosted protease inhibitor and raltegravir (bPI + RAL), and other raltegravir-containing combinations. RESULTS: The overall rate of virological suppression to < 50 HIV-1 RNA copies/mL was 69.5%. Although the baseline rate of virological suppression was higher for 2NRTIs + RAL than for the other strata, the outcomes were similar for all three groups at weeks 24, 48, 72 and 96. CONCLUSIONS: These data indicate that, in a real-life setting, raltegravir can be used with a high virological success rate in treatment-experienced patients, and that the different combinations analysed (2NRTIs + RAL, bPI + RAL and others) show comparable rates of virological suppression.

[Malnutrition in Elderly Trauma Patients - Comparison of Two Assessment Tools]. / Die Erfassung des Ernährungsstatus alterstraumatologischer Patienten ­ ein Vergleich zweier etablierter Screeningmethoden.

Background: The prevalence of malnutrition in hospitalised patients is reported to be between 16 and 55 % across disciplines. Within hospital care, screening for malnutrition is required. However, in orthopaedics and trauma surgery, there is still no generally accepted recommendation for the methods for such a data survey. In the present study, the following aspects are to be investigated with the help of two established scores: (1) the prevalence of malnutrition in the patient population of geriatric trauma care, and (2) the correlation between methods of data survey. Material and Methods: Between June 2014 and June 2015, a consecutive series of hospitalised trauma patients were studied prospectively with two validated screening instruments to record nutritional status. The study was carried out at a municipal trauma surgery hospital, which is a first level interregional trauma centre as well as a university hospital. The Nutritional Risk Screening (NRS) and the Mini Nutritional Assessment (MNA Short and Long Form) were used. All patients were divided into three age groups: < 65 years, 65-80 years, and > 80 years. The prevalence of malnutrition in geriatric trauma patients and the correlation between the screening instruments were determined. For a better comparison, prescreening and main assessment were applied to all patients. For statistical evaluation, both quantitative and semi-quantitative parameters were used. Furthermore, the Kolmogorov-Smirnov test, Spearman's correlation analysis and the chi-square test were applied. These tests were two-sided and had a level of significance of 5 %. The present study was partially funded by the Oskar-Helene-Heim Foundation. Results: 521 patients (43.8 % women, 56.2 % men), with a mean age of 53.96 ± 18.13 years, were statistically evaluated within the present study. Depending on the method of the data survey, malnutrition (NRS≥3) in geriatric trauma patients varied from 31.3 % (65-80 years) to 60 % (> 80 years). With MNA, 28.8 and 54.3 % of patients were at risk of malnutrition (MNA 17-23.5), while the fractions of patients already suffering from malnutrition (MNA < 17) were 5.4 and 8.6 %, respectively. The correlation between the NRS and MNA total scores increases with the age of the patients. The correlation coefficient for patients under 65 years is r = - 0.380, while among patients aged between 65 and 80, it is r = - 0.481, and for patients over 80 years, there is a medium to strong correlation of r = - 0.638 (each with a Spearman correlation of p < 0.001). For the total population as well as the different age groups, statistically significant correlations were recorded between the categorised scores (chi-square test for linear trend, p < 0.001). Summary: The present study demonstrates high prevalence of malnutrition among the geriatric trauma patients. Because of its easy and rapid application, the NRS has an advantage in clinical use. It was shown that the two methods of data survey were highly correlated.

Improved virological and immunological efficacy of resistance-guided switch in antiretroviral therapy: a Frankfurt HIV cohort analysis.

To evaluate the treatment outcome of antiretroviral therapy, depending on the use and utility of a concept of resistance-guided switch, patients from the Frankfurt HIV cohort have been followed for 24 weeks. If available, prior resistance data have been evaluated and patients were grouped into their expected viral response. The data of 354 patients were thus analysed, taking into account the genotypic sensitivity score of the administered medication (> or ≤2). When looking at the proportion of patients who achieved a viral load of <50/ml, the response rates differed significantly better for patients with a favourable resistance scoring as compared to an unfavourable one (71.9 % as compared to 56.0 %, p = 0.008). Interestingly, patients with a favourable resistance score also showed a better immunological response, as measured by median CD4 cell count of 391/µl [interquartal range (IQR) 250-530/µl] against 287/µl (IQR 174-449/µl) and a larger total increase of 141/µl against 38/µl. A significant virological and immunological benefit could be demonstrated for patients of a cohort with resistance-guided antiretroviral therapy adjustments.

[Changing spectrum of renal disease in HIV infection]. / Veränderungen im Spektrum der Nierenerkrankungen bei HIV-Infektion.

BACKGROUND AND OBJECTIVE: Renal disease is a common complication in HIV-infected patients. The causes and spectrum of kidney disease among these patients is extensive, including HIV-related and HIV unrelated causes. Our objective was to assess the changes in distribution of renal disease under antiretroviral therapy (ART). PATIENTS AND METHODS: Retrospective analysis of all patients from the Frankfurt HIV Cohort (FHC) who underwent renal biopsy because of chronic, progressive renal disease between 1989 and 2012. Two time periods were defined: 1989-2001 (early period) and 2000-2012 (late period). RESULTS: 69 HIV-infected patients, mostly Caucasian and male, underwent renal biopsy (early period: 22 patients, late period: 47 patients). During the total observation time immuncomplex-mediated glomerulonephritis (26.1 %), hypertensive (20.3 %) and diabetic nephropathy (20.3 %) were the most frequent causes of chronic renal disease. HIV-associated renal diseases were predominant in the first period, whereas hypertensive and diabetic kidney disease accounted for almost 50 % of cases diagnosed in the late period. Other types of renal disease frequently encountered during the late period include renal AA-amyloidosis and tenofovir-related kidney disease. CONCLUSION: The underlying pathology of renal disease in HIV-infected patients is highly variable and evolving. Since the introduction of HAART, renal disease not directly related to HIV has become the predominant cause, reflecting the growing burden of co-morbidities in this aging population.

Acute kidney injury caused by tenofovir disoproxil fumarate and diclofenac co-administration.

OBJECTIVES: The renal elimination of tenofovir (TFV) may be subject to renal drug-drug interactions that may increase the risk of kidney injury. Case reports indicated that diclofenac might increase TFV-associated nephrotoxicity via a drug-drug interaction, leading to an increased intracellular TFV concentration in proximal tubular cells. METHODS: A retrospective analysis of data for all patients from the Frankfurt HIV Cohort (FHC) who had diclofenac prescriptions between January 2008 and June 2012 was carried out. RESULTS: Among 89 patients with diclofenac use, 61 patients (68.5%) were treated with tenofovir disoproxil fumarate (TDF) and 28 patients (31.5%) were treated with TDF-sparing combination antiretroviral therapy (cART). Thirteen patients (14.6%) developed acute kidney injury (AKI) shortly after initiating diclofenac treatment. AKI occurred exclusively in TDF-treated patients, although all had previously stable renal function. All cases were accompanied by new onset of at least two parameters indicating proximal tubular damage, such as normoglycaemic-glucosuria and hypophosphataemia. TFV-associated nephrotoxicity was demonstrated by renal biopsy in four cases. Additionally, 11.5% of patients on TDF treatment developed new-onset proximal tubular damage, while having a preserved glomerular filtration rate. In contrast, diclofenac did not affect renal function in patients with TDF-sparing cART, as only one case of isolated hypophataemia was observed in these patients. In univariate analysis, risk factors for AKI were TDF-containing cART (P = 0.0076) and pre-existing hypophosphataemia (P = 0.0086). CONCLUSIONS: Drug-drug interaction caused by diclofenac could exacerbate TFV-associated nephrotoxicity. Diclofenac should be used with caution in patients on TDF therapy, especially in those with hypophosphataemia. Our findings need to be confirmed in larger studies.

End-stage renal disease and dialysis in HIV-positive patients: observations from a long-term cohort study with a follow-up of 22 years.

OBJECTIVES: Renal disease is a common and serious complication in HIV-infected patients. METHODS: A retrospective cohort analysis for the period 1989-2010 was carried out to determine the prevalence, incidence and risk factors for end-stage renal disease (ESRD). ESRD was defined as initiation of renal replacement therapy. Three time periods were defined: 1989-1996 [pre-highly active antiretroviral therapy (HAART)], 1997-2003 (early HAART) and 2004-2010 (late HAART). RESULTS: Data for 9198 patients [78.2% male; 88.9% Caucasian; cumulative observation time 68 084 patient-years (PY)] were analysed. ESRD was newly diagnosed in 35 patients (0.38%). Risk factors for ESRD were Black ethnicity [relative risk (RR) 5.1; 95% confidence interval (CI) 2.3-10.3; P < 0.0001], injecting drug use (IDU) (RR 2.3; 95% CI 1.1-4.6; P = 0.02) and hepatitis C virus (HCV) coinfection (RR 2.2; 95% CI 1.1-4.2; P = 0.03). The incidence of ESRD decreased in Black patients over the three time periods [from 788.8 to 130.5 and 164.1 per 100 000 PY of follow-up (PYFU), respectively], but increased in Caucasian patients (from 29.9 to 41.0 and 43.4 per 100 000 PYFU, respectively). The prevalence of ESRD increased over time and reached 1.9 per 1000 patients in 2010. Mortality for patients with ESRD decreased nonsignificantly from period 1 to 2 (RR 0.72; P = 0.52), but significantly from period 1 to 3 (RR 0.24; P = 0.006), whereas for patients without ESRD mortality decreased significantly for all comparisons. ESRD was associated with a high overall mortality (RR 9.9; 95% CI 6.3-14.5; P < 0.0001). CONCLUSION: As a result of longer survival, the prevalence of ESRD is increasing but remains associated with a high mortality. The incidence of ESRD declined in Black but not in Caucasian patients. IDU and HCV were identified as additional risk factors for the development of ESRD.

"Trivalent influenza vaccination of healthy adults 3 years after the onset of swine-origin H1N1 pandemic: restricted immunogenicity of the new A/H1N1v constituent?".

Influenza vaccination is advised annually to reduce the burden of influenza disease. For sufficient vaccine campaigns also a continuous adoption of influenza vaccines are necessary, due to particularly high genetic variability of influenza A virus. Therefore, we evaluate the effectiveness of the trivalent influenza vaccine 2010/2011, against influenza A (H1N1, H3N2) and influenza B. Immune response was investigated in paired sera from 92 healthcare workers with the hemagglutination inhibition assay (HI). Protective antibody levels (HI titer ≥40) were found after vaccination for influenza A/California/07/2009(H1N1): 84.71 % [GMT: 115.34]; for influenza A/Perth/16/2009(H3N2): 94.94 % [GMT: 268.47] and for influenza B/Brisbane/60/2008: 96.20 % [GMT: 176.83]; matching with the currently circulating virus strains. However, the highest seroprevalence rate was found against influenza B; pre- and post-vaccination titers as well, which may be due to comparatively high virus preservation. Remarkable, lowest seropositivity was seen against H1N1. Despite the significant titer rise, sufficient H1N1 herd immunity was still not achieved. It can be assumed that a high influenza A herd immunity may be a requirement for a successful booster vaccination.

Tuberculosis skin test, but not interferon-γ-releasing assays is affected by BCG vaccination in HIV patients.

OBJECTIVE: Of this study was to compare the results of tuberculin skin test (TST) with two interferon-γ releasing-assays (IGRA) in a cohort of HIV positive patients, to analyze impact of prior Bacille-Calmette-Guérin (BCG)-vaccination. METHODS: Prospective cross sectional study, enrolling only asymptomatic adult HIV infected outpatients from a large German University hospital clinic. All participants were simultaneously tested for latent tuberculosis infection (LTBI) by QuantiFERON-TB Gold, T-SPOT.TB and TST. Only individuals with available definite results (positive/negative, indeterminates excluded) from all three test systems and recalling BCG-vaccination status by interview questionnaire were evaluated. RESULTS: From 286 study participants, 133 were evaluable; BCG-vaccination history was positive for 18 individuals, and negative for 115. The proportion of individuals with a positive TST was significantly higher for vaccinated (n = 6, 33.3%) than for unvaccinated individuals (n = 13, 11.3%, p = 0.013). There were no significant differences in the proportion of patients with CDC stage C, origin from a TB endemic country or in the CD4 count between the two groups. CONCLUSION: TST but not IGRAs interfered significantly with prior BCG vaccination in a cohort of HIV infected individuals from a low prevalence TB country. Therefore IGRA should preferentially be used for LTBI-testing in BCG-vaccinated adult HIV-patients.

Orthotopic liver transplantation in human-immunodeficiency-virus-positive patients in Germany.

Objectives. This summary evaluates the outcomes of orthotopic liver transplantation (OLT) of HIV-positive patients in Germany. Methods. Retrospective chart analysis of HIV-positive patients, who had been liver-transplanted in Germany between July 1997 and July 2011. Results. 38 transplantations were performed in 32 patients at 9 German transplant centres. The reasons for OLT were end-stage liver disease (ESLD) and/or liver failure due to hepatitis C (HCV) (n = 19), hepatitis B (HBV) (n = 10), multiple viral infections of the liver (n = 2) and Budd-Chiari-Syndrome. In July 2011 19/32 (60%) of the transplanted patients were still alive with a median survival of 61 months (IQR (interquartile range): 41-86 months). 6 patients had died in the early post-transplantation period from septicaemia (n = 4), primary graft dysfunction (n = 1), and intrathoracal hemorrhage (n = 1). Later on 7 patients had died from septicaemia (n = 2), delayed graft failure (n = 2), recurrent HCC (n = 2), and renal failure (n = 1). Recurrent HBV infection was efficiently prevented in 11/12 patients; HCV reinfection occurred in all patients and contributed considerably to the overall mortality. Conclusions. Overall OLT is a feasible approach in HIV-infected patients with acceptable survival rates in Germany. Reinfection with HCV still remains a major clinical challenge in HIV/HCV coinfection after OLT.

Intensification of a failing regimen with zidovudine may cause sustained virologic suppression in the presence of resensitising mutations including K65R.

OBJECTIVES: The reverse transcriptase (RT)-mutation K65R limits further therapeutic options and has been selected by unfavorable RT-combinations, e.g. tenofovir in combination with abacavir and/or didanosine. METHODS: We identified HIV-1 infected patients from a large treatment cohort who experienced virological failure (HIV-1 RNA >1000 copies/mL) with evidence of resistance mutations including the K65R, but without thymidine analogue mutations (TAMs) in genotypic resistance assay. Phenotype was performed from previously collected frozen plasma. The patients were followed for clinical and resistance outcome after treatment intensification with only zidovudine. RESULTS: Five patients had experienced antiretroviral treatment failure on various nucleoside analogue combinations, containing abacavir, didanosine, lamivudine, nevirapine, reverset and/or tenofovir. RT-sequence revealed mutations at position K65R in combination with other non-TAMs. The patients' median viral load prior to zidovudine intensification was 3.551 Log10 (range 3.053-4.681) and despite evidence for resistance to the failing drug regimen, all responded within 4 weeks to undetectable levels (<1.699 Log10 or <50 copies/mL) and remained virologically suppressed during follow-up (20 months through 6.5 years). CONCLUSIONS: In virologically failing patients due to K65R- and other non-thymidine-mutations, simple regimen intensification with zidovudine resulted in sustained HIV-1 suppression. The finding of re-sensitized HIV-1 in patients may be clinically relevant.

The influence of HAART on the efficacy and safety of pegylated interferon and ribavirin therapy for the treatment of chronic HCV infection in HIV-positive Individuals.

OBJECTIVE: This study was performed to investigate the impact of HAART versus no HAART and nucleoside free versus nucleoside containing HAART on the efficacy and safety of pegylated interferon and ribavirin therapy for the treatment of chronic HCV infection in HIV/HCV co-infected patients. In addition a control group of HCV mono-infected patients undergoing anti-HCV therapy was evaluated. METHODS: Multicenter, partially randomized, controlled clinical trial. HIV-negative and -positive patients with chronic HCV infection were treated with pegylated interferon alfa-2a and ribavirin (800 - 1200 mg/day) for 24 - 48 weeks in one of four treatment arms: HIV-negative (A), HIV-positive without HAART (B) and HIV-positive on HAART (C). Patients within arm C were randomized to receive open label either a nucleoside containing (C1) or a nucleoside free HAART (C2). RESULTS: 168 patients were available for analysis. By intent-to-treat analysis similar sustained virological response rates (SVR, negative HCV-RNA 24 weeks after the end of therapy) were observed comparing HIV-negative and -positive patients (54% vs. 54%, p = 1.000). Among HIV-positive patients SVR rates were similar between patients off and on HAART (57% vs. 52%, p = 0.708). Higher SVR rates were observed in patients on a nucleoside free HAART compared to patients on a nucleoside containing HAART, though confounding could not be ruled out and in the intent-to-treat analysis the difference was not statistically significant (64% vs. 46%, p = 0.209). CONCLUSIONS: Similar response rates for HCV therapy can be achieved in HIV-positive and -negative patients. Patients on nucleoside free HAART reached at least equal rates of sustained virological response compared to patients on standard HAART.

[Novel influenza H1N1/2009: virus transmission among health care worker]. / Neue Grippe H1N1/2009: Infektionsübertragung auf medizinisches Personal.

HISTORY AND ADMISSION FINDINGS: A 27-year-old female presented with fever (40 C) and infection of the upper respiratory tract in an emergency room (ER) department of our university hospital. Within the last days, she worked as a nurse in that ER, responsible for taking care of patients with novel influenza and also executing screening-examinations of suspicious cases. INVESTIGATIONS: Patient in a reduced condition of health. C-reactive protein was significantly elevated (6.6 mg/dl - norm < 0.5). A PCR carried out on the admission day revealed a highly positive reaction (CT:19.29). DIAGNOSIS, TREATMENT AND COURSE: Due to positive PCR laboratory report for H1N1/2009 and multiple occupational contacts with H1N1/2009 patients, therapy with neuraminidase inhibitor was started. After a five-day antiviral therapy and clinical signs of recovery, PCR was negative on the sixth treatment day. CONCLUSION: Health care workers (HCWs) are at risk of occupational exposure to influenza. Against the backdrop of the spread of H1N1 (2009) appropriate protective measures should be implemented to reduce the risk for transmission in health-care settings. The acquisition of epidemiologic data of occupational infections in Germany ought to be optimized. Required protective measures should be evaluated with regard to practicability and effectiveness.

Once-daily treatment with saquinavir mesylate (2000 mg) and ritonavir (100 mg) together with a fixed-dose combination of abacavir/lamivudine (600/300 mg) or tenofovir/emtricitabine (245/200 mg) in HIV-1-infected patients.

OBJECTIVES: To investigate the feasibility and pharmacokinetics of a once-daily regimen of 2000 mg saquinavir mesylate boosted with 100 mg ritonavir. PATIENTS AND METHODS: Patients successfully treated with 1000 mg saquinavir boosted with 100 mg ritonavir twice daily together with two nucleoside or nucleotide reverse transcriptase inhibitors [N(t)RTIs] who were switched to 2000 mg saquinavir with 100 mg ritonavir once daily with unchanged N(t)RTI therapy were analysed. CD4 cells, HIV-RNA PCR and metabolic parameters were compared between baseline and 3, 6, 9 and 12 months after the switch. Saquinavir and ritonavir drug levels were measured before and a median of 3 weeks after switching from twice to once daily at 0, 1, 2, 4, 6, 9, 12 and 24 h after intake of the medication. The area under the serum concentration-time curve from 0 to 24 h (AUC(0-24)) was calculated using the trapezoidal rule. RESULTS: Eighteen patients (16 males, median age of 41 years) with a median CD4 cell count of 464 cells/mm(3) were analysed. HIV-RNA PCR remained <500 copies/mL for all patients. After switching from 100 mg twice daily to 100 mg once daily, the AUC(0-24) for ritonavir decreased significantly [21 874 to 10 267 ng.h/mL, geometric mean ratio (GMR) = 0.47; P < 0.001], whereas the AUC(0-24) for saquinavir decreased only marginally from 35 000 to 34 490 ng.h/mL (GMR = 0.99; P = 0.426). The CD4 cell count and the fasting metabolic parameters remained unchanged. CONCLUSIONS: Once-daily treatment with ritonavir-boosted saquinavir was well tolerated and resulted in similar saquinavir drug exposure despite much lower ritonavir concentrations when compared with a twice-daily dosing schedule.

CAD/CAM to fabricate ceramic implant abutments and crowns: a preliminary in vitro study.

BACKGROUND: This study evaluated the feasibility of fabricating implant abutments and crowns from pre-sintered feldspathic porcelain blocks using the chair-side CAD/CAM, CEREC3D((R)) system. METHODS: Thirty-two implant analogues were divided into two groups. In the control group, prefabricated machined anatomical titanium (Ti) abutments were screw-retained to the analogues. In the test group, machined feldspathic porcelain abutments were cemented on prefabricated machined Ti links and screw-retained to the implant analogues. These feldspathic porcelain abutments were fabricated out of pre-sintered feldspathic porcelain blocks as duplicates of the abutments in the control group using the CAD/CAM, CEREC3D system. Thirty-two feldspathic porcelain crowns, also fabricated out of pre-sintered ceramic blocks, were then cemented with resin cement on all the abutments in both groups. All samples were subsequently subjected to fracture strength testing under static load. An unpaired t-test was used to compare fracture load values between the two groups. RESULTS: The test group using feldspathic porcelain abutments and crowns showed statistically significant higher mean fracture strength than the control group with the Ti abutments and feldspathic porcelain crowns. CONCLUSIONS: This preliminary study showed that the chair-side CAD/CAM technology can be utilized to fabricate customized ceramic abutments with their associated ceramic crowns using pre-sintered feldspathic porcelain blocks.

Both long-term HIV infection and highly active antiretroviral therapy are independent risk factors for early carotid atherosclerosis.

OBJECTIVE: There is controversy over whether or not chronic HIV infection contributes to atherosclerosis. We investigated the relationship between HIV infection, antiretroviral medication and ultrasound evidence of early atherosclerosis in the context of vascular risk factors. DESIGN: A case-control design with 292 HIV-positive subjects and 1168 age- and sex-matched controls. METHODS: We assessed vascular risk factors, blood pressure, serum lipids and carotid intima media thickness (IMT) in cases and controls. With multivariate regression models, we investigated the effects of HIV status and antiretroviral medication on IMT. RESULTS: The common carotid artery (CCA) IMT value was 5.70% (95% confidence interval [3.08-8.38%], p<0.0001) or 0.044 mm [0.021-0.066 mm] (p=0.0001) higher in HIV-positives, adjusted for multiple risk factors. In the carotid bifurcation (BIF), the IMT values were 24.4% [19.5-29.4%] or 0.250 mm [0.198-0.303 mm] higher in HIV patients (p<0.0001). An investigation of antiretroviral substances revealed higher CCA- and BIF-IMT values in patients receiving combination antiretroviral therapy (HAART). CONCLUSIONS: HIV infection and HAART are independent risk factors for early carotid atherosclerosis. Assuming a risk ratio similar to that in large population-based cohorts, the observed IMT elevation suggests that vascular risk is 4-14% greater and the "vascular age" 4-5 years higher in HIV-positive subjects. The underlying mechanisms remain to be clarified.

A standardized, comprehensive magnetic resonance imaging protocol for rapid and precise quantification of HIV-1-associated lipodystrophy.

OBJECTIVES: Although multiple methods have been proposed, there is no current gold standard for assessing HIV-1-associated lipodystrophy. METHODS: HIV-1-infected participants were randomly enrolled and surveyed about changes in the abdomen, thigh, cheek and neck areas. Magnetic resonance imaging (MRI) sequences of these sites were obtained. Participants were grouped according to survey results, and the MRI measurements were compared between groups. RESULTS: One hundred participants were included in the study, of whom 79% reported any body fat changes. Persons reporting increased abdominal girth had higher visceral ([mean+/-standard deviation] 142+/-75 vs. 59+/-48 cm2; P<0.0001) and total abdominal adipose tissue than those reporting no change (344+/-119 vs. 201+/-95 cm2; P<0.0001). The amount of localized fat was less for persons reporting sunken cheeks and reduced diameter of the legs compared with those who noted no changes (5.9+/-3.6 vs. 9.3+/-3.8 cm2; P<0.0001, and 35+/-28 vs. 112+/-56 cm2; P<0.0001). Participants reporting increased neck girth had a thicker fat layer in the dorsocervical region compared with those reporting no change (4.0+/-1.8 vs. 2.3+/-1.4 cm; P<0.0002). CONCLUSIONS: MRI is a precise method for rapidly surveying body regions affected by HIV-1-associated lipodystrophy. Our proposed protocol provides a rapid, comprehensive survey of these areas, without the need to combine multiple modalities or to expose subjects to radiation.

Interleukin 18 and periodontal disease.

Cytokines are of major importance in periodontal disease progression. It is generally agreed that control of the Th1/Th2 balance is central to the immunoregulation of periodontal disease. There is increasing evidence in humans that the stable periodontal lesion is mediated by Th1 cells, while the progressive lesion sees a shift toward Th2 cells. Equally, there is conflicting evidence, mainly in animal models, that bone loss is mediated by Th1 responses, and that Th2 responses are protective. In the presence of IL-12, IL-18 induces Th1 responses while, in the absence of IL-12, it promotes Th2 responses. It is clear, therefore, that since IL-18 has the ability to induce either Th1 or Th2 differentiation, it becomes important to consider its role in periodontal disease. This review endeavors to give an overview of this cytokine and its relevance for periodontal disease.

First case of successful allogeneic stem cell transplantation in an HIV-patient who acquired severe aplastic anemia.

We report on the first successful allogeneic stem cell transplantation (SCT) in an HIV-infected patient with severe aplastic anemia (SAA) per- formed at a tertiary care institution. Highly active antiretroviral therapy (HAART) was administered until transplantation and restarted 34 days later with sustained virological response. The patient did however develop a rapid rise in HIV load during the interruption of HAART associated with an acute febrile illness. Due to the extended period between the onset of SAA until SCT, the posttransplant course was complicated by bacterial infections. Stage two skin GvHD, but no AIDS-defining opportunistic diseases were experienced. Neutrophils recovered to >0.5/nL on day +18 and the CD4 count reached 250/microL on day +71 and >500/microL on day +182. The patient is in good condition with an ECOG score of 0 twelve months after transplantation. This report demonstrates the feasibility of allogeneic stem cell transplantation in the HIV setting.

A randomized, open-label study to compare the effects of two different doses of recombinant human growth hormone on fat reduction and fasting metabolic parameters in HIV-1-infected patients with lipodystrophy.

BACKGROUND: Several studies have shown beneficial effects of recombinant human growth hormone (r-hGH) in reducing visceral adipose tissue (VAT) in HIV-1-infected patients with lipodystrophy. METHODS: Patients were randomized to r-hGH 4 mg daily (group A) or three times per week (group B) over 12 weeks, followed by a 2 mg daily maintenance dose for 12 weeks. Magnetic resonance imaging (MRI) scans were performed to assess body composition. RESULTS: A total of 26 subjects were included in the study. VAT was reduced overall by 35.1 cm(2) (29.5%) at week 12 and by 49 cm(2) (39.9%) at week 24, respectively, compared with baseline (P<0.001 for both comparisons). By week 12, VAT was reduced by 27 and 29% (A vs B; P=0.47) while facial fat was reduced by 3.3 and 2.6 cm(2) in groups A and B, respectively (P=0.96). Over 24 weeks, VAT was reduced by 42 and 38% (P=0.35) and facial fat by 3.2 and 2.4 cm(2) in groups A and B, respectively (P=0.91), compared with baseline. There was a greater increase in high-density lipoprotein (HDL) in group A than in group B (4.9 vs 2.4 mg/dL in week 12 and 7.1 vs -0.4 mg/dL in week 24; P=0.03). Fasting insulin levels increased, whereas glucose and insulin measured in oral glucose tolerance tests remained unchanged. Drug-related side effects were transient and reversible, but more common in group A (67%) than in group B (29%). CONCLUSIONS: This study confirms reports that r-hGH effectively reduces VAT, with a relatively small reduction of facial and limb fat.