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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.We identified HIV-1 infected patients from a large treatment cohort who experienced virological failure (HIV-1 RNA1000 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.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 or50 copies/mL) and remained virologically suppressed during follow-up (20 months through 6.5 years).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.

OBJECTIVE To determine rates of seroconversion after single vaccination with a novel split virion, inactivated, adjuvanted pandemic H1N1 influenza vaccine (A/California/7/2009) in HIV-1-infected patients (ClinicalTrials.gov Identifier: NCT01017172). DESIGN Single center diagnostic study. SETTING Institutional HIV outpatient department of an urban university clinic. PARTICIPANTS Adult HIV-1-infected individuals. INTERVENTION Serum samples were taken before and 21 days after vaccination. MAIN OUTCOME MEASURES Antibody titers determined by hemagglutination inhibition assay. Seroconversion to vaccination was defined by either an antibody titer of 1: 10 or less before and of at least 1: 40 after or at least 1: 10 before and at least four-fold increase in antibody titer 21 days after single vaccination. RESULTS One hundred and sixty patients (125 men/35 women) were analyzed. Before vaccination, 23 patients (14.4%) had a hemagglutination inhibition assay titer of at least 1: 40. A median of 22 +/- 3 days after vaccination, 110 (69%) patients seroconverted. Seroconverters were younger (45.1 +/- 10.0 vs. 48.8 +/- 11.3 years; P = 0.04), had a higher CD4 cell count (532 +/- 227 vs. 475 +/- 281 cells/microl; P = 0.03) and were more likely to have received a previous H5N1 vaccination in 2009 (25 vs. 8%; P = 0.02) when compared to nonresponders. No other significant differences were found comparing the two groups (prevaccination hemagglutination inhibition assay titer of > or =1: 40, AIDS, HAART, HIV RNA PCR

The number of HIV-infected patients receiving orthotopic liver transplantation (OLTX) is increasing. One major challenge is the severe drug-drug interactions between immunosuppressive drugs such as tacrolimus and ritonavir-boosted HIV-1 protease inhibitors (PIs). The introduction of raltegravir, which is not metabolized by the cytochrome system, may allow concomitant treatment without dose adaptation.We conducted a retrospective analysis of HIV-1-infected patients receiving tacrolimus concomitantly with different HIV therapies, including 12 h pharmacokinetic assessment of drug levels.Three OLTX patients received a ritonavir-boosted PI therapy when tacrolimus was added at very low doses of 0.06, 0.03 and 0.08 mg daily. Median tacrolimus blood levels were 6.6, 3.0 and 7.9 ng/mL over a follow-up period of 8, 22 and 33 months, respectively. In two other patients (one after OLTX and one with Crohn's disease), a raltegravir-based HIV therapy was started while patients received 1 or 2 mg of tacrolimus twice daily. No tacrolimus dose adjustment was necessary and drug levels remained unchanged.Decreasing the dose of tacrolimus to 0.03-0.08 mg daily in patients with concomitant boosted PI therapy resulted in stable tacrolimus blood levels without alteration of PI drug levels. Concomitant use of raltegravir and tacrolimus revealed no clinically relevant drug interaction.

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.

HIV-Patienten sind haufiger der Hospitalisation, Immunsuppression und Antibiotikaprophylaxen ausgesetzt. Daher ist bei HIV-positiven Patienten vermehrt mit resistenten Bakterienstammen zu rechnen. Zweck dieser Fall-Kontroll-Studie war es, die Empfindlichkeit von Pneumokokken erwachsener Patienten in Abhangigkeit von deren HIV-Status sowie die Patientenkollektive zu vergleichen. Zwischen Januar 2001 und Dezember 2005 wurden Proben internistischer Patienten eines universitaren Labors auf Streptococcus pneumoniae untersucht und im Fall eines Nachweises einer standardisierten Empfindlichkeitsprufung mittels Agardiffusionsmethode unterzogen. Bei allen Patienten mit kulturell nachgewiesener Pneumokokkeninfektion wurden retrospektiv nach Aktendurchsicht demographische und klinische Charakteristika einschlieslich HIV-Status erhoben. Insgesamt 135 Pneumokokkenisolate konnten 64 HIV-positiven (A) und 71 HIV-negativen Patienten (B) zugeordnet werden, Antibiogramme lagen von 134 Patienten vor. 44 (69,8% [A]) versus 42 (59,2% [B]) der Stamme waren voll empfindlich, reduzierte Empfindlichkeit („intermediar-E“) fand sich bei acht (12,7% [A]) versus 17 (23,9% [B]). Bei elf (17,5% [A]) respektive zwolf (16,9% [B]) der Isolate fand sich Resistenz gegen mindestens eines der untersuchten Antibiotika. Die wichtigste Resistenz zeigte sich gegen Erythromycin (11,1% [A] und 11,3% [B]). Gegen Penicillin war kein getesteter Stamm resistent. Die Unterschiede in der Antibiotikaempfindlichkeitstestung zwischen den Gruppen waren allesamt nicht signifikant. Die signifikanten Unterschiede der Gruppen zeigten die HIV-negativen Patienten alter, haufiger hospitalisiert und intensivmedizinisch versorgt sowie haufiger mit Nachweis von Pneumokokken aus primar sterilen Materialien (Liquor-/Blutkultur). Knapp nicht signifikant war der Unterschied im Parameter Tod innerhalb von 28 Tagen nach Kulturbefund, ebenso nicht signifikant war der Unterschied in der Immunsuppression. HIV-Patienten erlitten haufiger ein Rezidiv und waren ofter Raucher. Im Resistenzprofil fand sich kein signifikanter Unterschied zwischen Pneumokokkenisolaten HIV-positiver und HIV-negativer Erwachsener. Die fehlende Penicillinresistenz unterstreicht die Bedeutung der β-Lactame im Fall der typischen ambulant erworbenen Pneumonie, weshalb diese Antibiotikaklasse Mittel der Wahl auch bei HIV-Patienten sein sollte. Die HIV-negativen Kontrollpatienten dieser Studie waren alter, morbider, aber nicht weniger immunsupprimiert, Letzteres wohl als besondere Eigenschaft einer Universitatskliniks-Kontrollgruppe. Die HIV-Patienten stellten sich in einem weit weniger fortgeschrittenen Stadium ihrer Pneumokokkenerkrankung vor, wahrscheinlich als Folge eines ungehinderten Zugangs zur Spezialambulanz des Klinikums. Die hohere Zahl der Rezidive in der Gruppe der HIV-Patienten unterstreicht die Bedeutung der Pneumokokkenimpfung in diesem Kollektiv.

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.A case-control design with 292 HIV-positive subjects and 1168 age- and sex-matched controls.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.The common carotid artery (CCA) IMT value was 5.70% (95% confidence interval [3.08-8.38%], p0.0001) 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 (p0.0001). An investigation of antiretroviral substances revealed higher CCA- and BIF-IMT values in patients receiving combination antiretroviral therapy (HAART).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.

Several studies have shown reduction of visceral adipose tissue (VAT) using recombinant human growth hormone (r-hGH) in HIV-1+ patients, but whether these effects are maintained after the end of treatment is unknown. In a prospective, randomized study we previously studied the effects of r-hGH 4 mg daily vs 3 times/week over 12 weeks, followed by a 2 mg daily maintenance dose for an additional 12 weeks. T1 weighted MRI flash sequences were performed of the face, abdomen and at mid-thigh level (MTF) at baseline, week 12, week 24 and at follow-up. Of 20 subjects who completed the 24-week study, follow-up is available for 16 patients (15 male, mean age 44.8 y, mean duration of HIV infection 13.5 y). After a median time of follow-up of 9 months, VAT remained overall 18% below baseline level (p =0.005). MTF was significantly reduced by 12% compared to its baseline level (p =0.03). Fasting glucose levels significantly improved by 21% compared to baseline (p =0.006). These results suggest that the achieved reduction of VAT using r-hGH in lipodystrophic HIV+ patients is in part maintained after a median follow-up of 9 months.

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 cm2 (29.5%) at week 12 and by 49 cm2 (39.9%) at week 24, respectively, compared with baseline (P

Objectives The aim of the study was to evaluate the safety and efficacy of abacavir (ABC) and efavirenz (EFV) instead of a protease inhibitor (PI) in HIV-1-infected subjects treated with two nucleoside reverse transcriptase inhibitors (NRTIs) and one PI with undetectable viral loads (

This study evaluated 1433 human immunodeficiency virus (HIV)–infected patients starting highly active antiretroviral therapy (HAART), 409 (28%) of whom had prior nucleoside experience and achieved an HIV load of !400 copies/mL by 24 weeks of therapy. Three hundred seven patients experienced virus rebound during a total of 2773.3 person-years of follow-up. There was a higher rate of virus rebound among the patients with pre-HAART nucleoside experience (relative hazard [RH], 2.86; 95% confidence interval, 2.22–3.84; ) and a P ! .0001 decreasing rate of virus rebound with increasing duration of virus suppression (i.e., time since achieving a virus load of !400 HIV RNA copies/mL) among both the nucleoside-experienced and naive patients ( ), but the difference between the groups persisted into the third P ! .0001 year of follow-up ( ). Even patients who had experienced !2 months of nucleoside P p .0007 therapy before beginning HAART had an increased risk of virus rebound (RH, 1.95; P p ). It appears that only a small period of pre-HAART nucleoside therapy is sufficient to .009 confer a disadvantage, in terms of risk of virus rebound, that persists for several years.

To investigate if possible mitochondrial injury can be found in adipose tissue of nucleoside analogue reverse transcriptase inhibitor (NRTI)-treated patients, subcutaneous fat was taken from the buttocks of 24 HIV-positive patients and 8 HIV-negative controls. The content of mitochondrial DNA (mtDNA) was quantified using a Southern blot technique. Fat biopsies were examined by electron microscopy and screened by restriction fragment length polymorphism analysis for the presence of the nt 8344 and 3243 mtDNA point mutations. Age, sex, and body mass index did not differ between the HIV-negative controls, the HIV-positive patients currently treated with NRTIs (NRTI group, n = 19), and the HIV-positive patients without NRTIs (no-NRTI group, n = 5). The mean mtDNA content was 44% lower in the NRTI group compared with the no-NRTI group ( p =.01) but did not differ between the control group and the no-NRTI group. When the HIV-infected patients were stratified to a group with clinical signs of lipoatrophy at the biopsy site (LA group, n = 11) and a group without lipoatrophy (no-LA group, n = 13), the mean mtDNA content in the LA group was 39% lower than that in the no-LA group ( p =.02). No point mutations or deletions were observed. The adipocytes of patients with lipoatrophy contained multiple small lipid vacuoles, and the mitochondria harbored inclusions reminiscent of mtDNA cytopathies. mtDNA depletion and ultrastructural abnormalities of adipocytes suggest a link between mitochondrial damage, the use of NRTIs, and lipoatrophy in HIV-infected patients.

Introduction : HIV infection is accompanied by a variety of neurological disorders. Depression of cell-mediated immunity is followed by the development of central nervous system opportunistic infections/tumours, and frequently by the occurrence of the AIDS dementia complex (ADC). However, the pathophysiology of the emergence of neuro-AIDS is still unknown. Despite the development of cognitive impairments, the early diagnosis, objectification and quantification of the existence and extent of this impairment during infection are difficult to recognize in each individual case. To support the early diagnosis of ADC, there is a need for additional, non-invasive diagnostic methods. In this study, it is of interest to answer the clinically relevant question of whether magnetic resonance spectroscopy can detect changes in the cerebral metabolism of asymptomatic HIV-positive patients and is possibly suitable for the early diagnosis and prevention of HIV encephalopathy. Methods : A group of 13 asymptomatic, HIV-positive patients with combined antiretroviral therapy (cART) and 13 healthy controls were examined with 2D 1H-MRS and 3D 31P-MRS at 3T. The patients were treated with cART for at least 12 months. Changes in the absolute concentrations of phosphorylated metabolites (ATP), N-acetyl-aspartate, creatine, myo-Isonitol, glutamate/glutamine and choline-containing compounds were compared with that of control subjects. Results : Asymptomatic HIV-positive patients had significantly lower N-acetyl-aspartate in the white matter in a frontal and parietal target region. The other evaluated metabolites in the 1H MRS showed no significant difference between the HIV-positive patients and healthy controls. The 31P-MRS detected significant elevated values regarding the choline-containing compounds PEth, GPE and PCho. Conclusions : This spectroscopic study revealed a significantly lower N-acetyl-aspartate in the white matter in a frontal and parietal cerebral target region in asymptomatic, HIV-positive patients as an early sign of neuronal disintegration. The 31P-MRS detected significant elevated values regarding the choline-containing compounds PEth, GPE and PCho as an early sign of gliosis. Furthermore we could show that with the use of 1H-MRS and 31P-MRS cerebral metabolites can be reliably detected and measured in HIV-positive patients. The 1H-MRS and 31P-MRS is therefore suited as a diagnostic tool for early cerebral metabolic changes in HIV-positive patients. (Published: 2 November 2014) Citation : Abstracts of the HIV Drug Therapy Glasgow Congress 2014 Schuettfort G et al. Journal of the International AIDS Society 2014, 17(Suppl 3) :19577 http://www.jiasociety.org/index.php/jias/article/view/19577 | http://dx.doi.org/10.7448/IAS.17.4.19577

The immune response after influenza vaccination is impaired in HIV-infected individuals and can be enhanced by a second dose. The durability of the antibody protection and its clinical benefit is not known. We investigated clinical symptoms and antibody titres against H1N1 influenza A following no dose, 1 dose, or 2 doses of an ASO3-adjuvanted H1N1 vaccine in HIV-infected patients. Seroprotection was found in 7.9%, 52.2%, and 57.3% of patients who received no dose, 1 dose, and 2 doses of the vaccine, respectively (p-value for group comparison < 0.001), after a median of 8.2 ± 1.6 months. Clinical symptoms suggestive of an influenza-like illness were slightly more frequently reported in the unvaccinated group. Vaccinated HIV-infected patients were more likely to be seroprotected at follow-up, but there was no difference comparing those who had received 1 or 2 doses of the vaccine.

Background. Low 25-hydroxyvitamin D (25(OH)D) has been associated with inflammation, human immunodeficiency virus (HIV) disease progression, and death. We aimed to identify the prognostic value of 25(OH)D for AIDS, non-AIDS-defining events and death, and its association with immunological/inflammatory markers. Methods. Prospective 1-1 case-control study nested within the EuroSIDA cohort. Matched cases and controls for AIDS (n = 50 matched pairs), non-AIDS-defining (n = 63) events and death (n = 41), with plasma samples during follow-up were selected. Conditional logistic regression models investigated associations between 25(OH)D levels and annual 25(OH)D change and the probability of events. Mixed models investigated relationships between 25(OH)D levels and immunological/inflammatory markers. Results. In sum, 250 patients were included. Median time between first and last sample and last sample and event was 44.6(interquartile range [IQR]: 22.7-72.3) and 3.1(IQR: 1.4-6.4) months. Odds of death decreased by 46.0%(95% confidence interval [CI], 2.0-70.0, P =. 04) for a 2-fold increase in latest 25(OH)D level. There was no association between 25(OH)D and the occurrence of AIDS or non-AIDS-defining events (P >. 05). In patients with current 25(OH)D

Background Relatively little is known about the long-term durability of viral suppression in individuals initially achieving a viral load of less than 50 copies/ml within 24 weeks of starting antiretroviral therapy, nor the extent to which therapy interruption accounts for the loss of suppression. Methods We intensely followed all 336 antiretroviral-naive patients attending the Goethe Universitat Clinic who began multi-drug combination regimens and in whom a viral load of less than 50 copies/ml was achieved within 24 weeks, in order to assess the risk of viral load rebound. Inspection of case notes allowed the distinction of viral rebound according to whether there was an associated complete interruption of therapy. Results A total of 61 patients experienced viral rebound during 543.1 person-years of follow-up, giving a 25.3% risk of rebound by 3.3 years from first achieving viral suppression. However, for 47 of the patients with viral rebound there was an associated documented complete interruption of antiretroviral therapy, mostly as a result of co-morbidities, leaving 14 who appear to represent a failure of the virological efficacy of therapy (viral breakthrough; 5.2% risk by 3.3 years). The risk of viral breakthrough declined with the increased duration of suppression (P = 0.01). Conclusion The intrinsic virological effectiveness of multi-drug antiretroviral therapy in previously drug-naive individuals appears to be such that viral suppression, once achieved, can be maintained for several years in patients not interrupting therapy. The major challenge is to develop regimens that can be taken consistently and safely for such long periods of time.

Background Patients with human immunodeficiency virus (HIV) infection and a history of Pneumocystis carinii pneumonia are at high risk for relapse if they are not given secondary prophylaxis. Whether secondary prophylaxis against P. carinii pneumonia can be safely discontinued in patients who have a response to highly active antiretroviral therapy is not known. Methods We analyzed episodes of recurrent P. carinii pneumonia in 325 HIV-infected patients (275 men and 50 women) in eight prospective European cohorts. Between October 1996 and January 2000, these patients discontinued secondary prophylaxis during treatment with at least three anti-HIV drugs after they had at least one peripheral-blood CD4 cell count of more than 200 cells per cubic millimeter. Results Secondary prophylaxis was discontinued at a median CD4 cell count of 350 per cubic millimeter; the median nadir CD4 cell count had been 50 per cubic millimeter. The median duration of the increase in the CD4 cell count to more than 200 per cubic mi...

We report the case of a 25-year-old, hepatitis C-infected man, who presented with severe rhabdomyolysis and acute renal failure, and later developed posterior encephalopathy with cortical blindness after the ingestion of magic mushrooms. Conventional respiratory and cardiovascular support including mechanical ventilation, continuous veno-venous hemodialysis and corticosteroids led to improvement and the patient recovered completely over the following months. Magic mushrooms are becoming increasingly fashionable among drug users, as they are believed to be more harmless than other hallucinogenic designer drugs. So far, little is known about their possible severe side effects.

Background Illicit drug abuse is an independent risk factor for chronic kidney disease, but the pathogenic consequences of long-term exposure to illicit drugs and contaminants under unsterile conditions remains unclear. Study Design Case series. Setting & Participants All deceased persons (n=129) who underwent forensic autopsy because of suspected connection with illicit drug abuse between January 1, 2009, and April 30, 2011, in Frankfurt/Main, Germany. Predictor Clinical characteristics and patterns of drug abuse. Outcomes Histopathologic alterations of the kidney. Measurements Hematoxylin and eosin, periodic acid−Schiff, Sirius, and Congo Red stainings and immunoglobulin A immunohistochemistry of all cases; additional histochemical stainings or immunohistochemistry and electron microscopy in selected cases. Results Individuals were mostly white (99.2%), were male (82.2%), and had intravenous drug use (IVDU) (81.4%). Median age at death was 39 years and duration of drug abuse was 17 years. The majority (79.1%) took various drugs in parallel as assessed by toxicologic analysis. Despite a young age, the deceased had a high burden of comorbid conditions, especially cardiovascular disease, liver cirrhosis, and infections. Evaluation of the kidneys demonstrated a broad spectrum of pathologic alterations predominated by arteriosclerotic and ischemic damage, mild interstitial inflammation, calcification of renal parenchyma, and interstitial fibrosis and tubular atrophy, with hypertensive-ischemic nephropathy as the most common cause of nephropathy. Interstitial inflammation (OR, 16.59; 95% CI, 3.91-70.39) and renal calcification (OR, 2.43; 95% CI, 1.03-5.75) were associated with severe IVDU, whereas hypertensive and ischemic damage were associated with cocaine abuse (OR, 6.00; 95% CI, 1.27-28.44). Neither specific glomerular damage indicative for heroin- and hepatitis C virus−related disease nor signs of analgesic nephropathy were found. Limitations White population, lack of a comparable control group, incomplete clinical data, and absence of routine immunohistochemistry and electron microscopy. Conclusions Illicit drug abuse is associated with a broad but unspecific spectrum of pathologic alterations of the kidneys. Cocaine abuse has a deleterious role in this setting by promoting hypertensive and ischemic damage.

Immune response rates following influenza vaccination are often lower in HIV-infected individuals. Low vitamin D levels were correlated with weak immune response in cancer patients and are known to be lower in HIV-infected patients.Diagnostic study to determine immune response against the H1N1v component after a single, intramuscular dose of the 2010/11 seasonal, trivalent influenza vaccine (TIV) in adult HIV-infected and healthy controls scheduled for influenza vaccination (ClinicalTrials.gov Identifier: NCT01017172). Influenza A/H1N1 antibody titers (AB) were determined before and 21 days after vaccination by hemagglutination inhibition assay.Immune response was not different between HIV-infected patients (n = 36) and healthy controls (n = 42) who were previously naïve to the H1N1v component of the TIV. Comparing HIV-infected patients (n = 55) and healthy controls (n = 63) who had received 1 or 2 doses of an AS03 adjuvanted H1N1 vaccine in the previous winter season (2009/10), seroconversion rate and the geometric mean AB titer after TIV of the HIV-infected patients were more than twice as high compared to healthy controls. This difference was mainly driven by the 2-dose schedule for HIV patients in 2009/10. Vitamin D levels were lower in HIV patients but did not correlate with immune response.HIV-infected patients who had received 1 or 2 doses of an adjuvanted H1N1 vaccine in the previous year (2009/10) had a significant higher seroconversion rate following TIV as compared to healthy controls, indicating a stronger memory cell response due to the 2-dose schedule.

Background Chronic renal disease is a serious complication of long-term intravenous drug use (IVDU). Recent reports have postulated a changing pattern of underlying nephropathy over the last decades. Methods Retrospective investigation including all patients with prior or present IVDU that underwent renal biopsy because of chronic kidney disease between 01.04.2002 and 31.03.2012 in the city of Frankfurt/Main, Germany. Results Twenty four patients with IVDU underwent renal biopsy because of progressive chronic kidney disease or proteinuria. Renal AA-amyloidosis was the predominant cause of renal failure in 50% of patients. Membranoproliferative glomerulonephritis (GN) was the second most common cause found in 21%. Patients with AA-amyloidosis were more likely to be HIV infected (67 vs.17%; p=0.036) and tended to have a higher rate of repeated systemic infections (92 vs. 50%; p=0.069). Patients with AA-amyloidosis presented with progressive renal disease and nephrotic-range proteinuria but most patients had no peripheral edema or systemic hypertension. Development of proteinuria preceded the decline of GFR for approximately 1–2 years. Conclusions AA-amyloidosis was the predominant cause of progressive renal disease in the last 10 years in patients with IVDU. The highest rate of AA-amyloidosis observed was seen in HIV infected patients with IVDU. We speculate that chronic HIV-infection as well as the associated immunosuppression might promote development of AA-amyloidosis by increasing frequency and duration of infections acquired by IVDU.

Summary 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–Guerin (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.

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) (), hepatitis B (HBV) (), multiple viral infections of the liver () 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 (), primary graft dysfunction (), and intrathoracal hemorrhage (). Later on 7 patients had died from septicaemia (), delayed graft failure (), recurrent HCC (), and renal failure (). 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.

Chronic kidney disease (CKD) is an important cause of morbidity and mortality in HIV-positive individuals. Hepatitis C (HCV) co-infection has been associated with increased risk of CKD, but prior studies lack information on potential mechanisms. We evaluated the association between HCV or hepatitis B (HBV) co-infection and progressive CKD among 3,441 antiretroviral-treated clinical trial participants. Progressive CKD was defined as the composite of end-stage renal disease, renal death, or significant glomerular filtration rate (eGFR) decline (25% decline to eGFR 800,000 IU/ml had increased odds (OR 3.07; 95% CI 1.60–5.90). Interleukin-6, hyaluronic acid, and the FIB-4 hepatic fibrosis index were higher among participants who developed progressive CKD, but were no longer associated with progressive CKD after adjustment. Future studies should validate the relationship between HCV viremia and CKD. Trial Registration ClinicalTrials.gov NCT00027352; NCT00004978

Genotypes of samples from protease inhibitor-naïve patients in Frankfurt's HIV Cohort were analyzed with five tipranavir resistance prediction algorithms. Mean scores were higher in non-B than in B subtypes. The proportion of non-B subtypes increased with increasing scores, except in weighted algorithms. Virtual and in vitro phenotype analyses of samples with increased scores showed no reduced tipranavir susceptibility. Current algorithms appear suboptimal for interpretation of resistance to tipranavir in non-B subtypes; increased scores might reflect algorithm bias rather than “natural resistance.”

The human immundeficiency virus (HIV) protease inhibitor atazanavir is often used in once-daily observed therapy of methadone substituted former opiate drug users. We performed a matched-pairs analysis on 24 patients (12 men/women) taking atazanavir/ritonavir 300/100 mg daily plus reverse transcriptase inhibitors, with (n = 12) or without (n = 12) methadone co-administration.Twenty-four-hour pharmacokinetic profiles of atazanavir/ritonavir were assessed at steady-state and measured by liquid chromatography-tandem mass spectrometry. The geometric mean (GM, t test) minimum and maximum plasma drug concentrations (C(min), C(max)), area under the concentration-time curve (AUC), and total clearance (CL(total)) were compared between the groups of pairs, which were matched for age, sex, weight, and ethnicity.The GM [90% confidence interval (CI)] of the atazanavir C(min), C(max), and AUC of patients taking the methadone oral solution at doses of 20-175 mg/day simultaneously with antiretroviral therapy were impaired compared to patients not taking methadone oral solution: C(min) = 315 (range 197-448) vs. 519 (279-793) ng/mL [GM ratio (GMR) = 0.61, p = 0.229]; C(max) = 1714 (1238-2262) vs. 3190 (2412-4076) ng/mL (GMR = 0.54, p = 0.018); AUC = 21,987 (15,870-29,327) vs. 35,572 (26,211-46,728) ng h/mL (GMR = 0.62, p = 0.074). Methadone dose, which is proportional to the amount of methadone oral solution (10 mg/mL), was significantly correlated to atazanavir C(max) (r (2) = 0.40, p = 0.001) and AUC (r (2) = 0.32, p = 0.006). Ritonavir pharmacokinetics was similar between the groups with C(min), C(max), and AUC GMR of 1.01, 0.80, and 0.96, respectively.The partial decrease in atazanavir plasma concentrations in patients concomitantly taking racemic methadone oral solution in this daily observed therapy setting deserves further attention, and therapeutic drug monitoring should be considered.

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

HIV patients are overexposed to hospital environment, immune suppression, and antibiotic prophylaxes. Therefore, with HIV positive patients an increased risk for resistant bacterial rods is to be expected. The purpose of this case-control study was to determine the susceptibility patterns of pneumococci from adult patients in relation to their HIV status and to compare both patient groups.Between January 2001 and December 2005, samples from internal medicine patients of one university hospital laboratory were investigated on culture of Streptococcus pneumoniae and in case of a positive vial, a resistance test was done by agar diffusion method. All patients with culture-confirmed infection due to pneumococci underwent a standardized retrospective evaluation in regard to demographic and clinical characteristics including HIV status.A total amount of 135 Streptococcus pneumoniae cultures could be assigned to 64 HIV-positive (A) and 71 HIV-negative patients (B), with susceptibility results for 134 isolates. Full susceptibility was seen in 44 (69.8% [A]) versus 42 (59.2% [B]) samples, reduced susceptibility ("intermediate-susceptible") was found in eight (12.7% [A]) versus 17 (23.9% [B]). Eleven (17.5% [A]) and twelve (16.9% [B]), respectively, out of all pneumococci were tested resistant to at least one antibiotic. Among these, resistance to erythromycin was most relevant (11.1% [A] and 11.3% [B]). None of the tested rods was resistant to penicillin. All differences between groups for susceptibility testing were not found significant. HIV-negative patients were significantly older, needed more often hospitalization and intensive care, and cultures for pneumococci were more frequently positive in primary sterile materials, such as cerebrospinal fluid and blood. The difference concerning death within 28 days following positive sample was just not significant as well as in immune suppression status of patients. HIV patients experienced more frequently an infection relapse and were more frequently smokers.No obvious difference in pneumococci resistance patterns was observed between HIV-positive and HIV-negative adult patients. The absence of resistance to penicillin underscores the importance of beta-lactams in case of typical community-acquired pneumonia; therefore, this class of antibiotics should be included in treatment guidelines as first-line drugs also for HIV patients. HIV-negative controls of this study were more aged and suffered from a higher morbidity, however, the fact that they were not significantly less immune suppressed may be special character of a university hospital control patient group. HIV patients presented in an earlier stage of their pneumococcal disease, probably due to a direct access to tertiary hospital medical supply. A higher relapse rate underscores the importance of pneumococcal vaccination for HIV patients.

We studied the impact of tenofovir disoproxil fumarate, given as an antiretroviral medication, on patients with chronic hepatitis B virus (HBV) co-infection.The polymerase gene-sequence evolution and quantitative HBV loads (HBVL) were observed for 48 weeks in patients taking tenofovir-containing antiretroviral therapy. The patients were grouped according to baseline strata: high-replicative virus (6 log copies/mL), low-replicative virus at detectable virus loads (6 log) and HBs-antigen-positive, HBV-DNA-negative individuals.Thirty-one patients were evaluated. The median decline in 20 patients with high-replicative HBV infection was -5.37 log (range: 3.57-7); 11 out of 20 decreased to undetectable levels (lower limit of detection =200 copies/mL) and another three were below 400 copies/mL. Out of six patients with detectable HBV-DNA at week 48 (HBVL result: range 3.36-4.32 log(10)), we were able to carry out a re-sequence in four patients. We did not observe relevant emerging resistance mutations, or a relevant virus load re-increase from nadir (+0.5 log). The patients with low-replicative virus (n = 9) and the baseline DNA-negative patients (n = 2) had an undetectable HBV-DNA at week 48. Two patients became HBeAg-negative; one DNA-negative patient became HBsAg-negative.Tenofovir is effective in treating HBV infection in HIV patients. Patients with high-replicative virus may benefit from this treatment strategy by a reduction in replicative status, a precondition for improved hepatic function. A few patients showed low-level HBV replication. Indicators for clinical HBV-resistance to tenofovir were not observed.

It is important to identify the optimal dosage and best method of infusion of parenteral vancomycin to be used over a several week period for the treatment of osteomyelitis. A retrospective study was undertaken to compare a high dose vancomycin treatment (HD: 40 mg/kg/d) with a standard dose treatment (SD: 20 mg/kg/d), and also to compare the modality of infusion using either intermittent vancomycin infusion (IVI) or continuous vancomycin infusion (CVI). 89 patients with Gram-positive cocci osteomyelitis requiring vancomycin treatment were followed, and the outcome and therapeutic safety were compared. There were significantly more adverse drug reactions (acute renal failure) in the IVI subgroup (HD-IVI vs SD-IVI, p-value 0.007). No cases of renal failure were found in the HD-CVI subgroup. The best outcome was found in the subgroup of patients who received HD-CVI (HD-CVI vs SD-IVI, overall log rank p-value 0.02). HD-CVI treatment appears to provide an improved outcome with fewer adverse drug reactions.

Background. With increasing life spans of HIVinfected individuals under highly active antiretroviral therapy, long-term consequences of the chronic infection and antiretroviral treatment are becoming more prevalent. Data on prevalence and consequences of hypertension are limited, but recent studies suggest that HIV-infected individuals are at a higher risk of developing hypertension. Methods. In this prospective study, HIV-1-infected patients from the Frankfurt AIDS Cohort Study (FACS) were followed for 1 year to determine the frequency of systemic hypertension and to assess the associated clinical and demographic factors. Results. A total 214 HIV-1-infected patients, predominantly Caucasian males, participated in the study. Prevalence of systemic hypertension was 29%. The groups of hypertensive and normotensive individuals were comparable in terms of ethnic background and duration of infection. As in the general population, hypertensive subjects were older (49.1±11.1 vs 39.0± 8.1 years; P

CMV-colitis is rare in HIV positive patients with CD4 counts higher than 100 microl(-1). We report a patient who was suffering from extensive CMV-colitis despite modest immune defect. The diagnosis was confirmed by repeated biopsies. The patient experienced an unusually long recovery which was only achieved after initiation of HAART.

Postmortem neuropathologic reports for a consecutive series of 436 HIV-seropositive patients who died between 1985 and 1999 were matched with clinical data for 371 of them. Cases were divided into four groups depending on the date of death. The chosen time periods reflected the type of antiretroviral therapy available: before 1987 (before zidovudine); 1987-1992, the period of monotherapy (nucleoside analog reverse transcriptase inhibitors [NRTIs]); 1993-1995, the era of the use of dual NRTI combinations; and 1996-1999, the era of highly active antiretroviral therapy (HAART) containing protease inhibitors. Fifty-seven percent of our cases in this group had been prescribed HAART. In our study population, accessibility to the latest antiretroviral therapy was widespread. The total number of HIV autopsies declined after the advent of combination therapy. The prevalence of opportunistic infections-cytomegalovirus, toxoplasmosis, cryptococcosis, and central nervous system lymphoma-decreased over time. Cerebral tuberculosis, aspergillosis, herpes, and progressive multifocal leukoencephalopathy showed a downward trend, but the numbers were too low for statistical analyses. The incidence of HIV encephalopathy increased over time (p =.014). The rising prevalence of HIV encephalopathy at time of death may reflect a longer survival time after initial HIV infection in the HAART era. Although combination therapies decrease overall mortality and prevalence of CNS opportunistic infections, these therapies may be less active in preventing direct HIV-1 effects on the brain.

Poster presentation: Background In the past years, once-daily (QD) dosing of antiretroviral combination therapy has become an increasingly available treatment option for HIV-1+ patients. Methods Open label study in which HIV-1+ patients treated with SAQ/RTV (1000/100 mg BID) and two NRTIs with HIV-RNA-PCR < 50 copies/ml were switched to SAQ/RTV(2000/100 mg QD) with unchanged NRTI-backbone. CD4-cells, HIV-RNA-PCR, SAQ and RTV drug-levels and metabolic parameters were compared. Summary of results 17 patients (15 male, 42 years), median CD4 456 ± 139/micro l were included so far. The median follow-up time is 4 months. The HIV-RNA-PCR remained

Background: The combination of stavudine (d4T), 3TC and NVP was the WHO recommended first-line regimen for the treatment of naïve HIV-1 infected patients in resource-limited settings. But peripheral polyneuropathy, lipoatrophy and symptomatic hyperlactatemia are frequent and treatment-limiting adverse events associated with stavudine, especially when combined with antituberculous drugs. Tenofovir combined with lamivudine and efavirenz has proven excellent efficacy, but there is little experience when given with NVP. Methods: Retrospective analysis of all patients receiving TDF, NVP and 3TC or FTC as first-line treatment in the Frankfurt HIV cohort. Summary of results: 70 patients (15 female) with a median CD4 cell count of 210/μl (47–949) and HIV-RNA PCR of 140,000 copies/ml (2,500–2,000,000) at baseline received TDF, NVP and 3TC/FTC, and were treated for a median of 68 weeks (16–278). CD4 cells rose up to cells/μl 322 (119–1075) and 75% of the patients remained on treatment. All patients on treatment at week 48 were 100,000 c/m. Reasons for discontinuation (24%) were mainly adverse events (13%), with rash (7%) and liver toxicity (6%) being the two most common, whereas virologic failure, drug interaction and non-adherence were all relatively rare (each 3%). Conclusion: The combination of NVP, TDF and 3TC or FTC is effective and well tolerated in previously naïve HIV-1 infected patients even when started with low CD4 cell counts (100,000 c/ml). In the latest amendment of the WHO guidelines TDF, instead of d4T, is the recommended first-line treatment in resource-limited settings.

of results Median baseline characteristics were a patient age of 42 years, male gender (n = 139; 80.4%) and 10.1 years from first HIV-positive test. 158 patients were ART-experienced and received a boosted double PI regimen due to previous RTI-resistance and/or toxicity. Among these, 68 patients previously had a structured treatment interruption and 90 patients have been treated with a PI-sparing ART regimen; 15 patients were ART-naive. Differences for metabolic parameters between groups were not significant. Fiftyeight out of 173 patients received a lipid-lowering agent (LLA) (LOPSAQ n = 42, ATSAQ n = 11, FOSAQ n = 5) and seven (4%) were initiated on a new LLA during the study. Total cholesterol significantly increased over 48 weeks for all groups: 166 mg/dL to 213 mg/dL (LOPSAQ), 168 mg/ dL to 216 mg/dL (ATSAQ) and 161 mg/dl to 235 mg/dl (FOSAQ) after 48 weeks (for all, p < 0.01; ITT-analysis), whereas median triglyceride levels significantly increased only for the LOPSAQ-group (195 mg/dl to 283 mg/dl; p < 0.01), but not for the other two groups (ATSAQ: 161 mg/ dL to 202 mg/dL, p = 0.2; FOSAQ: 130 mg/dl to 220 mg/ dl, p = 0.6). HDLand LDL-cholesterol increased non-significantly in all groups. See Figure 1.

BACKGROUND: The safety of interrupting maintenance therapy for previous opportunistic infections other than Pneumocystis carinii pneumonia among patients with HIV infection who respond to potent antiretroviral therapy has not been well documented. OBJECTIVE: To assess the safety of interrupting maintenance therapy for cytomegalovirus (CMV) end-organ disease, disseminated Mycobacterium avium complex (MAC) infection, cerebral toxoplasmosis, and extrapulmonary cryptococcosis in patients receiving antiretroviral therapy. DESIGN: Observational study. SETTING: Seven European HIV cohorts. PATIENTS: 358 patients taking potent antiretroviral therapy (> or =3 drugs) who interrupted maintenance therapy at a CD4 lymphocyte count greater than 50 x 10(6) cells/L. MEASUREMENTS: Recurrence of opportunistic infection after interruption of maintenance therapy. RESULTS: 379 interruptions of maintenance therapy were identified: 162 for CMV disease, 103 for MAC infection, 75 for toxoplasmosis, and 39 for cryptococcosis. During 781 person-years of follow-up, five patients had relapse. Two relapses (one of CMV disease and one of MAC infection) were diagnosed after maintenance therapy was interrupted when the CD4 lymphocyte count was less than 100 x 10(6) cells/L or when only one recent measurement exceeded this value. Two relapses (one of CMV disease and one of MAC infection) were diagnosed after maintenance therapy was interrupted once CD4 counts were greater than 100 x 10(6) cells/L for 10 and 8 months, respectively. One relapse (toxoplasmosis) was diagnosed after maintenance therapy interruption at a CD4 lymphocyte count greater than 200 x 10(6) cells/L for 15 months. The overall incidences of recurrent CMV disease, MAC infection, toxoplasmosis, and cryptococcosis were 0.54 per 100 person-years (95% CI, 0.07 to 1.95 per 100 person-years), 0.90 per 100 person-years (CI, 0.11 to 3.25 per 100 person-years), 0.84 per 100 person-years (CI, 0.02 to 4.68 per 100 person-years), and 0.00 per 100 person-years (CI, 0.00 to 5.27 per 100 person-years), respectively. CONCLUSION: Maintenance therapy against previous infection with CMV, MAC, Toxoplasma gondii, or Cryptococcus neoformans in patients with HIV infection can be interrupted after sustained CD4 count increases to greater than 200 (or possibly 100 to 200) x 10(6) cells/L for at least 6 months after the start of potent antiretroviral therapy

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.