Lymphocytes Proliferate in Blood and Lymph Nodes Following Interleukin-2 Therapy in Addition to Highly Active Antiretroviral Therapy

AIDS (London, England). Jan, 2002  |  Pubmed ID: 11807298

Substantial redistribution of lymphocytes occurs upon the initiation of highly active antiretroviral therapy (HAART) and immune-based HIV therapies.

Double-blind, Randomized, Placebo-controlled Phase III Trial of Oxymetholone for the Treatment of HIV Wasting

AIDS (London, England). Mar, 2003  |  Pubmed ID: 12646793

Despite highly active antiretroviral therapy (HAART), chronic involuntary weight loss still remains a serious problem in the care of HIV patients. Various alterations in energy metabolism and endocrine regulation have been found to cause loss of lean body mass (LBM) and body cell mass (BCM). Previous studies in HIV-positive men undergoing androgen replacement therapy or treatment with recombinant growth hormone (rGH) have shown partial restoration of LBM, but these treatments have largely been ineffective in eugonadal individuals.

Progressive Multifocal Leukencephalopathy in Patients on Highly Active Antiretroviral Therapy: Survival and Risk Factors of Death

Journal of Acquired Immune Deficiency Syndromes (1999). Oct, 2004  |  Pubmed ID: 15385733

To describe the clinical course and risk factors of death in highly active antiretroviral therapy (HAART)-treated patients with progressive multifocal leukencephalopathy (PML); to evaluate the efficacy of cidofovir in addition to HAART.

[Syphilis with HIV Coinfection]

Journal Der Deutschen Dermatologischen Gesellschaft = Journal of the German Society of Dermatology : JDDG. Oct, 2004  |  Pubmed ID: 16281586

In recent years a rising incidence of syphilis has been observed, especially in the population of homosexual men. Because of altered sexual behavior in terms of increased promiscuity paralleled by decreased use of condoms and the fact that a syphilis infection increases the susceptibility to HIV coinfection, the incidence of HIV is also rising once again in this population. In patients with HIV coinfection, the course of syphilis is often atypical or dramatic. Stage-specific features suggesting coinfection include prolonged primary ulcers persisting well into the secondary stage, numerous atypical cutaneous findings in the second stage and a rapid progression from stage to stage. The diagnosis of syphilis may be more difficult because of false positive or false negative serological findings in patients with HIV coinfection. Whether or not the CNS is more often involved is this patient group has not been established by prospective studies and remains controversial. However, WHO and CDC recommendations include evaluation of the CSF in HIV-infected patients with either late syphilis or when the time course is unknown period. There is worldwide agreement on the therapy of syphilis in patients with HIV coinfection. Patients with early syphilis should be treated with 2.4 benzathine penicillin i.m. once or twice; patients with late syphilis, twice or three times. Patients presenting with clinical or serological signs of neurosyphilis require 18-24 million IU penicillin i.v. daily for at least 2 weeks.

Liposomal Pegylated Doxorubicin Versus Low-dose Recombinant Interferon Alfa-2a in the Treatment of Advanced Classic Kaposi's Sarcoma; Retrospective Analysis of Three German Centers

Cancer Investigation. 2005  |  Pubmed ID: 16377582

Classic Kaposi's sarcoma (KS) is a rare neoplasm, predominantly occurring in older subjects of Eastern Europe or Mediterranean descent. While single lesions may be treated by simple excision, laser therapy, cryotherapy, or intralesional therapy, advanced or disseminated disease requires systemic treatment. Several studies reported the effectiveness of pegylated liposomal doxorubicin (PLD) and low-dose recombinant interferon alfa-2a (IFNalpha) in the treatment of AIDS-associated KS.

The Steady-state Pharmacokinetics of Nelfinavir in Combination with Tenofovir in HIV-infected Patients

Antiviral Therapy. 2005  |  Pubmed ID: 15865230

The nucleotide analogue, tenofovir, has been shown to lower plasma atazanavir levels in pharmacokinetic trials, an interaction that may be partly reversed by the addition of ritonavir, whereas plasma tenofovir levels are themselves raised when the drug is combined with lopinavir/ritonavir.

Switching to Atazanavir Improves Metabolic Disorders in Antiretroviral-experienced Patients with Severe Hyperlipidemia

Journal of Acquired Immune Deficiency Syndromes (1999). Jun, 2005  |  Pubmed ID: 15905733

To describe the efficacy and change in lipid profile in patients with severe hyperlipidemia after switch to an atazanavir-containing highly active antiretroviral therapy regimen.

[Coronary Heart Disease Associated with the Use of Highly Active Antiretroviral Therapy (HAART). A Case Report and Review]

Herz. Sep, 2005  |  Pubmed ID: 16170681

The use of highly antiretroviral therapy (HAART) significantly reduced morbidity and mortality by inhibition of virus replication. Even though long-term side effects are not fully known, this antiviral strategy has revolutionized the care of HIV-infected patients and is widely used in industrial countries. Until now, a variety of metabolic side effects, such as hyperlipidemia and insulin resistance, have been described. These metabolic alterations of antiretroviral therapy increase the cardiovascular risk profile of HIV-infected patients. It could be expected, that the increased cardiovascular risk profile in combination with long-term survival of this patient population, will increase the diagnostics and therapy of coronary diseases of HIVinfected patients in the next years. The present article (1) contains the case report of a 39-year-old HIV-infected male with an acute myocardial infarction, and (2) gives an overview about arteriosclerosis and coronary events in HIV-infected patients and the impact of antiretroviral therapy.

[Staphylococcal Infections of the Skin and Mucous Membranes. Guideline of the German Dermatologic Society, Study Group of Dermatologic Infectiology]

Journal Der Deutschen Dermatologischen Gesellschaft = Journal of the German Society of Dermatology : JDDG. Sep, 2005  |  Pubmed ID: 16189866

Carotid Intima-media Thickness in HIV-infected Individuals: Relationship of Premature Atherosclerosis to Neuropsychological Deficits?

European Neurology. 2006  |  Pubmed ID: 16733357

Intima-media thickness (IMT) measured by extracranial duplex sonography is a surrogate marker for atherosclerosis. It is well known that IMT is greater in HIV patients than in age-matched healthy controls due to HIV- induced endothelial damage and metabolic side-effects of antiretroviral therapy. However, it remains unclear whether atherosclerosis has an additional impact on cognitive function in HIV patients. Therefore, the objective of this study was to investigate the correlation between IMT and neuropsychological deficits in HIV patients.

Transcranial Sonography of the Third Ventricle and Cognitive Dysfunction in HIV Patients

Journal of Neurology. Sep, 2006  |  Pubmed ID: 16990993

Although the incidence and prevalence of dementia associated with human immunodeficiency virus (HIV) infection has decreased since the introduction of highly active antiretroviral therapy, cognitive dysfunction remains one of the most prevalent factors severely affecting quality of life in patients with HIV. Previous magnetic resonance imaging (MRI) studies showed a correlation between brain atrophy, enlargement of the ventricles and cognitive impairment in HIV patients.

Phase II Trial of a Toll-like Receptor 9-activating Oligonucleotide in Patients with Metastatic Melanoma

Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology. Dec, 2006  |  Pubmed ID: 17179105

The recent identification of toll-like receptors (TLRs) and respective ligands allows the evaluation of novel dendritic cell (DC) -activating strategies. Stimulation of TLR9 directly activates human plasmacytoid DCs (PDCs) and indirectly induces potent innate immune responses in preclinical tumor models. We performed an open-label, multicenter, single-arm, phase II pilot trial with a TLR9-stimulating oligodeoxynucleotide in melanoma patients.

Prevalence and Natural History of Heart Failure in Outpatient HIV-infected Subjects: Rationale and Design of the HIV-HEART Study

European Journal of Medical Research. Jun, 2007  |  Pubmed ID: 17666313

HIV infection is a global public health issue that is frequently associated with cardiac involvement. However, myocardial dysfunction and heart failure are often clinically occult or attributed incorrectly to other non-cardiac disease processes even a heightened awareness and knowledge for these cardiac diseases in HIV-infected patients may lead to earlier detection and a reduction in morbidity and mortality. The present study evaluates the frequency and clinical course of myocardial dysfunction and heart failure in a HIV-infected population.

Side Effects of HIV Therapy

Journal Der Deutschen Dermatologischen Gesellschaft = Journal of the German Society of Dermatology : JDDG. Sep, 2007  |  Pubmed ID: 17760894

The use of highly active effective antiretroviral therapies (ART) has dramatically decreased the morbidity and mortality of the HIV infection. Over 20 anti-retroviral substances are available in four different classes. Side effects of HIV therapy are common and may influence the prognosis, as the medications are required lifelong for the still incurable infection. ART-associated allergic reactions, lipodystrophy syndrome and immune reconstitution syndrome are side effects frequently seen by dermatologists. Exanthems are challenging as drug reactions must be separated from immune reconstitution, syphilis and viral exanthems and then the causative agent must be identified from a long list of medications. Non-nucleoside reverse transcriptase inhibitors typically cause allergic exanthems. Mitochondrial toxicity caused by nucleoside reverse transcriptase inhibitors is responsible for lipoatrophy and fatty changes in the liver. Protease inhibitors cause diarrhea, abnormalities of glucose and fat metabolism and lipohypertrophy. Before other medications or surgical measures are undertaken to address side effects of ART, the regimen should be adjusted to include alternative but equally effective agents.

Correlation of Epidermal Nerve Fiber Density with Pain-related Evoked Potentials in HIV Neuropathy

Pain. Aug, 2008  |  Pubmed ID: 18096318

HIV associated sensory neuropathy is a common neurological disorder with reported prevalence of 53%. When only small fibers are involved, the diagnosis of neuropathy remains difficult since standard nerve conduction studies generally are unremarkable. We assessed a method to identify small-fiber neuropathy using electrically evoked pain-related potentials and correlated the electrophysiological results with intraepidermal nerve fiber density in patients with HIV associated sensory neuropathy. Nineteen HIV positive patients were investigated for clinically diagnosed peripheral neuropathy with Neuropathy Symptoms Score (NSS)3 and Neuropathy Disability Score (NDS)5. Nine healthy HIV negative control subjects were recruited. We performed standard nerve conduction testing, electrically evoked pain-related potentials and skin biopsy in all participants. Pain-related evoked potentials revealed abnormalities in all HIV positive neuropathy patients, while standard nerve conduction testing was abnormal in eight patients only. Pain-related evoked potential latencies and amplitudes strongly correlated with intraepidermal nerve fiber density. The method of pain-related evoked potential conduction appears to be a sensitive, fast, non-invasive technique for the detection of small-fiber neuropathy and may prove to become a valuable diagnostic asset.

Impact of CYP2B6 983T>C Polymorphism on Non-nucleoside Reverse Transcriptase Inhibitor Plasma Concentrations in HIV-infected Patients

The Journal of Antimicrobial Chemotherapy. Apr, 2008  |  Pubmed ID: 18281305

The aim of this study was to investigate the frequency of CYP2B6 polymorphisms (according to ethnicity) and the influence of heterozygosity and homozygosity on plasma concentrations of efavirenz and nevirapine.

[Side Effects of Antiretroviral Therapy--skin Manifestations]

MMW Fortschritte Der Medizin. Apr, 2008  |  Pubmed ID: 19024907

Evolution of Raltegravir Resistance During Therapy

The Journal of Antimicrobial Chemotherapy. Jul, 2009  |  Pubmed ID: 19447792

We investigated the prevalence of raltegravir resistance-associated mutations at baseline and their evolution during raltegravir therapy in patients infected with different HIV-1 subtypes.

[BNP in HIV-infected Patients]

Herz. Dec, 2009  |  Pubmed ID: 20024643

HIV-infected patients exhibit an increased rate of cardiac diseases, due to an elevated rate of cardiac risk factors and side effects of antiretroviral therapy. The aim of the present study was to analyze the impact of B-type natriuretic peptide (BNP) in this patient population.

An Epidemiologic Study to Determine the Prevalence of the HLA-B*5701 Allele Among HIV-positive Patients in Europe

Pharmacogenetics and Genomics. May, 2010  |  Pubmed ID: 20375757

HLA-B*5701 is a major histocompatibility complex class I allele associated with an immunologically-mediated hypersensitivity reaction to abacavir. The objectives of this study were to evaluate HLA-B*5701 prevalence among European, HIV-1-infected patients and to compare the local and central laboratory screening results.

Prevalence of Cardiac Diastolic Dysfunction in HIV-infected Patients: Results of the HIV-HEART Study

HIV Clinical Trials. May-Jun, 2010  |  Pubmed ID: 20739268

Antiretroviral therapy has improved the prognosis for many individuals with HIV infection. Consequently, HIV infection has become a chronic and manageable disease with increased risk of cardiovascular disease. Isolated diastolic dysfunction (DD) may be the first indication of underlying cardiac disease and an early marker of coronary artery disease. Our aim was to assess the prevalence of DD in HIV-infected patients.

Lipodystrophy - a Sign for Metabolic Syndrome in Patients of the HIV-HEART Study

Journal Der Deutschen Dermatologischen Gesellschaft = Journal of the German Society of Dermatology : JDDG. Feb, 2010  |  Pubmed ID: 20002869

After the introduction of antiretroviral therapy, the life expectancy of HIV patients has increased to more than 30 years after initial diagnosis. Cardiovascular disease now is an important cause of death in HIV-infected patients.

Echocardiographic Findings and Abnormalities in HIV-infected Patients: Results from a Large, Prospective, Multicenter HIV-heart Study

American Journal of Cardiovascular Disease. 2011  |  Pubmed ID: 22254197

The aim of the current study was to assess cardiac structure and function as well as cardiac abnormalities in a large patient-population based multicenter study of HIV-infected subjects.

Are HIV Patients Undertreated? Cardiovascular Risk Factors in HIV: Results of the HIV-HEART Study

European Journal of Cardiovascular Prevention and Rehabilitation : Official Journal of the European Society of Cardiology, Working Groups on Epidemiology & Prevention and Cardiac Rehabilitation and Exercise Physiology. Feb, 2011  |  Pubmed ID: 21450595

Background: Antiretroviral therapy improved the survival of patients with human immunodeficiency virus (HIV) infection. With increased life expectancy, HIV-infected patients increasingly are experiencing comorbidities, most notably cardiovascular risk factors (CRFs) and coronary heart disease (CHD). Design: This study utilized a prospective, cross-sectional multicentre long-term design. Methods: In 803 patients (82% male; mean age 44.2 ± 10.3 years) we evaluated the prevalence of CRFs and 10-year risk of CHD using the Framingham risk model. The presence of a risk factor was determined based on the guidelines of the National Cholesterol Education Program (NCEP ATP III), the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC7), and the German Society of Cardiology. Results: The most common CRFs were smoking (51.2%), high triglycerides (39.0%), low high-density lipoprotein cholesterol (27.5 %) and high blood pressure (21.4%). In total, 60.3%, 21.6%, and 18.1% of patients were categorized as being at low (<10%), moderate (10-20%), and high (>20%) 10-year risk for CHD, respectively. In patients with hypertension, at least one antihypertensive drug was given in 91/163 (55.8%) patients. The percentage of patients on treatment with diabetes mellitus was 23/41 (56.1%). Anti-platelet therapy was prescribed to 42/102 (41.2%) patients with known CHD or CHD equivalent. In patients of moderate or high CHD risk there were more than 50% and 30% for LDL cholesterol and more than 60% and 40% for total cholesterol untreated. Conclusions: The prevalence of CRFs remains high in an HIV-infected population. CRF management of HIV-infected patients deserves further improvement.

HIV Prevalence and Route of Transmission in Turkish Immigrants Living in North-Rhine Westphalia, Germany

Medical Microbiology and Immunology. Nov, 2011  |  Pubmed ID: 21461764

The high number of Turkish immigrants in the German state North-Rhine Westphalia (NRW) compelled us to look for HIV-infected patients with Turkish nationality. In the AREVIR database, we found 127 (107 men, 20 women) Turkish HIV patients living in NRW. In order to investigate transmission clusters and their correlation to gender, nationality and self-reported transmission mode, a phylogenetic analysis including pol gene sequences was performed. Subtype distribution and the number of HIV drug resistance mutations in the Turkish patient group were found to be similar to the proportion in the non-Turkish patients. Great differences were observed in self-reported mode of transmission in the heterosexual Turkish male subgroup. Neighbour-joining tree of pol gene sequences gave indication that 59% of these reported heterosexual transmissions cluster with those of men having sex with men in the database. This is the first study analysing HIV type distribution, drug resistance mutations and transmission mode in a Turkish immigrant population.

The SnoB Study: Frequency of Baseline Raltegravir Resistance Mutations Prevalence in Different Non-B Subtypes

Medical Microbiology and Immunology. Nov, 2011  |  Pubmed ID: 21475993

The SnoB study analysed the variability of the integrase (IN) gene of non-B viruses from treatment-naïve patients to determine whether non-B subtypes carry natural resistance mutations to raltegravir (RAL). Plasma viral RNA from 427 patients was gained, and IN sequences were subtyped and screened for subtype-specific highly-variable residues. Seven viruses of different subtypes were phenotypically tested for RAL susceptibility; 359/427 samples could be sequenced. One hundred and seventy samples (47%) were classified as non-B subtypes. No primary RAL resistance-associated mutations (RRAMs) were detected. Certain secondary mutations were found, mostly related to specific non-B subtypes. L74 M was significantly more prevalent in subtype 02_AG, T97A in A and 06_cpx, V151I in 06_cpx, and G163R in 12_BF. Various additional mutations were also detected and could be associated with the subtype too. While K156 N and S230 N were correlated with B subtype, V72I, L74I, T112I, T125A, V201I and T206S were more frequent in certain non-B subtypes. The resistance factors (RF) of 7 viral strains of different subtypes ranged from 1.0 to 1.9. No primary or secondary but subtype-associated additional RRAMs were present. No correlation between RF and additional RRAMs was found. The prevalence of RRAMs was higher in non-B samples. However, the RFs for the analysed non-B subtypes showed lower values to those reported relevant to clinical failure. As the role of baseline secondary and additional mutations on RAL therapy failure is actually not known, baseline IN screening is necessary.

Cytochrome P450 2B6 (CYP2B6) and Constitutive Androstane Receptor (CAR) Polymorphisms Are Associated with Early Discontinuation of Efavirenz-containing Regimens

The Journal of Antimicrobial Chemotherapy. Sep, 2011  |  Pubmed ID: 21715435

Cytochrome P450 2B6 (CYP2B6) is responsible for the metabolic clearance of efavirenz and single nucleotide polymorphisms (SNPs) in the CYP2B6 gene are associated with efavirenz pharmacokinetics. Since the constitutive androstane receptor (CAR) and the pregnane X receptor (PXR) correlate with CYP2B6 in liver, and a CAR polymorphism (rs2307424) and smoking correlate with efavirenz plasma concentrations, we investigated their association with early (<3 months) discontinuation of efavirenz therapy.

Oral Health and the Heart - Does HIV Infection Open a Pathophysiological Gateway?

International Journal of Cardiology. Sep, 2011  |  Pubmed ID: 21764468

Improved Outcome with Rituximab in Patients with HIV-associated Multicentric Castleman Disease

Blood. Sep, 2011  |  Pubmed ID: 21778341

Although HIV-associated multicentric Castleman disease (HIV-MCD) is not classified as an AIDS-defining illness, mortality is high and progression to lymphoma occurs frequently. At present, there is no widely accepted recommendation for the treatment of HIV-MCD. In this retrospective (1998-2010), multicentric analysis of 52 histologically proven cases, outcome was analyzed with respect to the use of different MCD therapies and potential prognostic factors. After a mean follow-up of 2.26 years, 19 of 52 patients died. Median estimated overall survival (OS) was 6.2 years. Potential risk factors, such as older age, previous AIDS, or lower CD4 T cells had no impact on OS. Treatment was heterogeneous, consisting of cytostatic and/or antiviral agents, rituximab, or combinations of these modalities. There were marked differences in the outcome when patients were grouped according to MCD treatment. Patients receiving rituximab-based regimens had higher complete remission rates than patients receiving chemotherapy only. The mean estimated OS in patients receiving rituximab alone or in combination with cytostatic agents was not reached, compared with 5.1 years (P = .03). Clinical outcome and overall survival of HIV-MCD have markedly improved with rituximab-based therapies, considering rituximab-based therapies (with or without cytostatic agents) to be among the preferred first-line options in patients with HIV-MCD.

"One-stop-shop" Staging: Should We Prefer FDG-PET/CT or MRI for the Detection of Bone Metastases?

European Journal of Radiology. Jun, 2011  |  Pubmed ID: 19945240

The aim of this study was to compare the diagnostic accuracy of fully diagnostic, contrast-enhanced whole-body FDG-PET/CT and whole-body MRI for detection of bone metastases in patients suffering from newly diagnosed non-small cell lung cancer and malignant melanoma.

Treatment of AIDS-related Lymphomas: Rituximab is Beneficial Even in Severely Immunosuppressed Patients

AIDS (London, England). Feb, 2012  |  Pubmed ID: 22112600

OBJECTIVE:: AIDS-related lymphomas (ARLs) significantly contribute to mortality in HIV-infected patients. Optimal chemotherapy treatment and the use of rituximab remain controversial. The aim of the present cohort study was to analyze the outcome of HIV-infected patients diagnosed with ARL, with regard to the use of rituximab, clinical characteristics and histopathological markers. METHODS AND DESIGN:: This observational uncontrolled multicenter cohort study included 163 HIV-infected patients with ARL diagnosed between January 2005 and December 2008 in Germany. RESULTS:: Patients with CD20-positive ARL had a significantly better overall survival (OS) and progression-free survival (PFS) than patients with CD20-negative ARL [hazard ratio 0.28, 95% confidence interval (CI) 0.15-0.53 and hazard ratio 0.29, 95% CI 0.16-0.53]. In CD20-positive cases, the use of rituximab was associated with better OS and PFS (n = 128, hazard ratio 0.48, 95% CI 0.25-0.93 and hazard ratio 0.47, 95% CI 0.26-0.86), even in patients with severe immune deficiency at ARL diagnosis (CD4 T-cell count<100 cells/μl, n = 33; OS: hazard ratio 0.25, 95% CI 0.07-0.90). In multivariate analysis, CD4 T-cell counts more than 100 cells/μl and the use of rituximab were associated with better OS and PFS. In total, there were 12 polychemotherapy-associated deaths, which were not related to specific therapy regimens or to the use of rituximab. CONCLUSION:: In patients with CD20-positive ARL, CD4 T-cell count at ARL diagnosis and the use of rituximab had strong impact on survival. Rituximab was beneficial in ARL even in the setting of severe immune deficiency and was not associated with an increased risk of fatal infections.

How Individual Can Personalized Antiretroviral Treatment Be? Deep Salvage in an HIV-1-Infected Patient

Intervirology. 2012  |  Pubmed ID: 22286888

We present an HIV-1-infected male (who is now 52 years old) with a multi-drug-resistant virus and discuss the considerations finally leading to an antiretroviral regimen resulting in long-term viral suppression and excellent immunological response in a deep salvage situation. Even in a desperate situation with high-level multi-class resistance, highly individual, personalized antiretroviral regimes can be tailor-made to achieve unexpected improvements in the health status of a patient.

Detection of Abacavir Hypersensitivity by ELISpot Method

Inflammation & Allergy Drug Targets. Feb, 2012  |  Pubmed ID: 22338581

The antiretroviral agent abacavir can cause hypersensitivity reaction (HSR) and the presence of HLA-B*57:01 is predictive of abacavir-HSR in Caucasian HIV-infected patients. However, abacavir-HSR also occurs in HLA-B*57:01 negative patients. In these patients, a safe diagnostic tool to dissect clinically suspected HSR against abacavir from adverse reactions against co-administered drugs is mandatory, and abacavir-ELISpot was evaluated. Peripheral blood mononuclear cells from 87 HIV patients were stimulated by abacavir and the production of interferon-g to the ELISpot was determined. Abacavir treated patients with HSR [confirmed (n=5) or suspected (n=12)] vs. without HSR (n=42) displayed significantly higher numbers of abacavir-specific cells (82.3±23.0 or 10.5±4.5 vs. -0.5±1.0 spot forming cells per million PBMC, p<.005 each). In conclusion, we established the first abacavir-specific ELISpot. According to our preliminary data, a negative abacavir-ELISpot nearly excludes HSR against abacavir. Thereby the ELISpot may facilitate the decision to continue or withdraw abacavir treatment.