Cohort Profile: The Zurich Primary HIV Infection Study.

The Zurich Primary HIV Infection (ZPHI) study is a longitudinal cohort study established in 2002, aiming to study the clinical, epidemiological, and biological characteristics of primary HIV infection. The ZPHI enrolls individuals with documented primary HIV-1 infection. At the baseline and thereafter, the socio-demographic, clinical, and laboratory data are systematically collected, and regular blood sampling is performed for biobanking.

Late outcome after surgical and topical treatment for Aspergillus mediastinitis after heart transplantation.

The 7-year long-term survival after Aspergillus fumigatus mediastinitis after heart transplantation, an uncommonly described condition, is herein reported. A 66-year-old male developed an infection with A. fumigatus covering the entire thoracic cavity with a fungal turf after orthotopic heart transplantation.

Emergence of Resistance to Integrase Strand Transfer Inhibitors during Dolutegravir Containing Triple-Therapy in a Treatment-Experienced Patient with Pre-Existing M184V/I Mutation.

With the current widespread use of dolutegravir in low-income countries, the understanding of the impact of nucleoside reverse transcriptase inhibitor (NRTI-) associated mutations on the efficacy of dolutegravir-containing antiretroviral therapy (ART) is of utmost importance. We describe a rare case of a patient with pre-existing M184V/I mutation and virological failure on a dolutegravir/lamivudine/abacavir regimen with the emergence of integrase strand transfer inhibitor resistance mutations. Additional risk factors, which may have triggered the virological failure, included suboptimal adherence and low nadir CD4+ cell count.

A Treatment-as-Prevention Trial to Eliminate Hepatitis C Among Men Who Have Sex With Men Living With Human Immunodeficiency Virus (HIV) in the Swiss HIV Cohort Study.

Background: In 2016, the World Health Organization (WHO) introduced global targets for the elimination of hepatitis C virus (HCV) by 2030. We conducted a nationwide HCV micro-elimination program among men who have sex with men (MSM) living with human immunodeficiency virus (HIV) from the Swiss HIV Cohort Study (SHCS) to test whether the WHO goals are achievable in this population.

Methods: During phase A (10/2015-06/2016), we performed a population-based and systematic screening for HCV-RNA among MSM from the SHCS.

Noninferiority of Simplified Dolutegravir Monotherapy Compared to Continued Combination Antiretroviral Therapy That Was Initiated During Primary Human Immunodeficiency Virus Infection: A Randomized, Controlled, Multisite, Open-label, Noninferiority Trial.

Background: Patients who start combination antiretroviral therapy (cART) during primary human immunodeficiency virus type 1 (HIV-1) infection show a smaller HIV-1 latent reservoir, less immune activation, and less viral diversity compared to patients who start cART during chronic infection. We conducted a pilot study to determine whether these properties would allow sustained virological suppression after simplification of cART to dolutegravir monotherapy.

Methods: EARLY-SIMPLIFIED is a randomized, open-label, noninferiority trial.

High Number of Potential Transmitters Revealed in a Population-based Systematic Hepatitis C Virus RNA Screening Among Human Immunodeficiency Virus-infected Men Who Have Sex With Men.

Background: The proportion of undiagnosed hepatitis C virus (HCV) infections in high-risk populations, such as human immunodeficiency virus (HIV)-infected men who have sex with men (MSM) is unclear. Identification of potential HCV transmitters is important to reach World Health Organization HCV elimination targets.

Methods: Between October 2015 and May 2016, we performed a systematic HCV RNA-based screening among HIV-infected MSM participating in the Swiss HIV Cohort Study (SHCS).

High Cure Rates With Grazoprevir-Elbasvir With or Without Ribavirin Guided by Genotypic Resistance Testing Among Human Immunodeficiency Virus/Hepatitis C Virus-coinfected Men Who Have Sex With Men.

Background: This study was performed to investigate the efficacy and safety of grazoprevir-elbasvir guided by baseline resistance-associated substitutions (RASs) in the Swiss HCVree Trial.

Methods: We performed hepatitis C virus (HCV) RNA screening among all men who have sex with men (MSM) enrolled in the Swiss HIV Cohort Study. Individuals with replicating HCV genotype 1 or 4 infection were eligible for grazoprevir-elbasvir treatment.

Associations Between Antiretroviral Treatment and Avascular Bone Necrosis: The Swiss HIV Cohort Study.

Background: HIV-infected individuals have an increased risk of avascular bone necrosis (AVN). Antiretroviral therapy (ART) and particularly protease inhibitors (PI) have been implicated as a risk factor. We aimed to study the associations of ART with the occurrence of AVN among Swiss HIV Cohort Study participants (SHCS).

[Hoarsness after a trip to the United States of America].

A 52 year old Swiss presented with a sore throat and progressive hoarseness. The histology showed a granulomatous inflammation of the epiglottis. Microbiology revealed dimorphic fungi in the sputum which were identified as Histoplasma sp.

High prevalence of anorectal chlamydial infection in HIV-infected men who have sex with men in Switzerland.

Human immunodeficiency virus (HIV)-infected men who have sex with men (MSM) were enrolled in an anorectal Chlamydia trachomatis screening study. Anorectal Chlamydia DNA was detected in 16 (10.9%) of 147 men, mainly among asymptomatic patients and patients having >20 sexual partners.

Cellular immune responses and disease control in acute AIDS-associated Kaposi's sarcoma.

Kaposi's sarcoma-associated herpesvirus (KSHV) specific T cell responses and KSHV viremia were analyzed in seven HIV-infected patients with active Kaposi's sarcoma lesions who initiated highly active antiretroviral therapy, and were compared between patients with improved Kaposi's sarcoma and those with progressive Kaposi's sarcoma requiring further systemic chemotherapy. Patients with controlled Kaposi's sarcoma disease demonstrated undetectable Kaposi's sarcoma viremia together with KSHV-specific CD8 T cells secreting interferon-gamma and tumor necrosis factor-alpha, whereas progressors showed increasing viremia with weak or no T-cell responses. These data point toward a potential role of KSHV-specific immunity in the control of AIDS-associated Kaposi's sarcoma.

Association of noncirrhotic portal hypertension in HIV-infected persons and antiretroviral therapy with didanosine: a nested case-control study.

Background: Noncirrhotic portal hypertension (NCPH) is a newly described life-threatening liver disease of unknown cause in human immunodeficiency virus (HIV)-infected persons. Postulated pathogenesis includes prolonged exposure to antiretroviral therapy, particularly didanosine.

Methods: We performed a nested case-control study including 15 patients with NCPH and 75 matched control subjects of the Swiss HIV Cohort Study to investigate risk factors for the development of NCPH.

Partial deletion of CYP2B6 owing to unequal crossover with CYP2B7.

Objective: To evaluate the possibility of copy number variation (CNV) of CYP2B6.

Methods: We investigated CNV in 226 HIV-1-infected individuals by quantitative PCR. Identification of a candidate CNV prompted characterization of the size of deletion by assessment of absence of exons, mapping of the recombination site by sequencing, and by southern blot.

HIV replication elicits little cytopathic effects in vivo: analysis of surrogate markers for virus production, cytotoxic T cell response and infected cell death.

Several potential mechanisms for viral destruction of HIV-infected cells have been described. The hypothesis was examined that if HIV were cytopathic, a positive relation between the in vivo virus production or CTL activity and infected cell death should be observed. In a regression analysis no significant relation was found between surrogate markers for in vivo virus production or the virus-specific CTL response and death rates of productively infected cells.

Tenofovir-containing nucleoside/nucleotide-only antiretroviral maintenance therapy: decision making and virological outcome.

Objective: To assess the virological outcome of patients with undetectable human immunodeficiency (HI) viremia switched to tenofovir (TDF)-containing nucleosideonly (NUKE-only) treatments and to investigate the factors influencing the physicians' decision for application of a nonestablished therapy.

Method: Patients' characteristics and history were taken from the cohort database. To study the decision-making process, questionnaires were sent to all treating physicians.

Antiretroviral treatment and osteonecrosis in patients of the Swiss HIV Cohort Study: a nested case-control study.

We examined risk factors for avascular bone necrosis (AVN) particularly focusing o the question of whether antiretroviral treatment (ART) is associated with the emergence of osteonecrosis. After 11 years of following the entire cohort, 26 patients were found to have AVN. Compared to 260 concurrent HIV-infected controls, at risk when cases were diagnosed, patients with AVN had lower CD4 cell count nadirs (median 86.

Long-term safety of discontinuation of secondary prophylaxis against Pneumocystis pneumonia: prospective multicentre study.

Objectives: To assess the long-term safety of discontinuation of secondary anti-Pneumocystis prophylaxis in HIV-infected adults treated with antiretroviral combination therapy and who have a sustained increase in CD4 cell counts.

Design: Prospective observational multicentre study.

Patients And Methods: The incidence of P.

Quantification of infectious HIV-1 plasma viral load using a boosted in vitro infection protocol.

Methods currently used for HIV-1 viral load measurements are very sensitive, but cannot distinguish between infectious and noninfectious particles. Here we describe the development of a novel, sensitive, and highly reproducible method that allows rapid isolation and quantification of infectious particles from patient plasma. By immobilizing HIV-1 particles in human plasma to platelets using polybrene, we observed a 10- to 1000-fold increase in infectivity over infection protocols using free virus particles.

Infrequent transmission of HIV-1 drug-resistant variants.

Transmission of drug-resistant variants is influenced by several factors, including the prevalence of drug resistance in the population of HIV-1-infected patients, HIV-1 RNA levels and transmission by recently infected patients. In order to evaluate the impact of these factors on the transmission of drug-resistant variants, we have defined the population of potential transmitters and compared their resistance profiles to those of newly infected patients. Sequencing of pol gene was performed in 220 recently infected patients and in 373 chronically infected patients with HIV-1 RNA >1000 copies/ml.

The role of CFTR and SPINK-1 mutations in pancreatic disorders in HIV-positive patients: a case-control study.

Objective: Pancreatic disorders in HIV-positive patients are frequent. CFTR and SPINK-1 mutations have been reported to increase the risk of pancreatitis, but no data are available in HIV-positive patients. This study will evaluate the frequency of CFTR mutations and SPINK-1 polymorphisms in HIV-positive patients with clinical pancreatitis or asymptomatic elevation of serum pancreatic enzymes.

HIV-specific cellular immune response is inversely correlated with disease progression as defined by decline of CD4+ T cells in relation to HIV RNA load.

The average time between infection with human immunodeficiency virus (HIV) and development of acquired immune deficiency syndrome is approximately 8 years. However, progression rates vary widely, depending on several determinants, including HIV-specific immunity, host genetic factors, and virulence of the infecting strain. In untreated HIV-infected patients with different progression rates, we examined HIV-specific T cell responses in combination with host genetic markers, such as chemokine/chemokine-receptor (CCR) polymorphisms and human leukocyte antigen (HLA) genotypes.