bluuebunny/crossref_metadata_2025_split huggingface dataset:
AIDS defining opportunistic infections in patients with high CD4 counts in the combination antiretroviral therapy (cART) era: things ain't what they used to be
Authors: Gisler Valentin , Kraus David , Nemeth Johannes , Than Lecompte Marthe , Merz Laurent , Stoeckle Marcel , Schmid Patrick , Bernasconi Enos , Weber Rainer , Cavassini Matthias , Calmy Alexandra , Elzi Luigia , Furrer Hansjakob 
Published: November 2014

IntroductionAccording to reports from observational databases, classic AIDS‐defining opportunistic infections (ADOIs) occur in patients with CD4 counts above 500/µL on and off cART. Adjudication of these events is usually not performed. However, ADOIs are often used as endpoints, for example, in analyses on when to start cART.Materials and MethodsIn the database, Swiss HIV Cohort Study (SHCS) database, we identified 91 cases of ADOIs that occurred from 1996 onwards in patients with the nearest CD4 count >500/µL. Cases of tuberculosis and recurrent bacterial pneumonia were excluded as they also occur in non‐immunocompromised patients. Chart review was performed in 82 cases, and in 50 cases we identified CD4 counts within six months before until one month after ADOI and had chart review material to allow an in‐depth review. In these 50 cases, we assessed whether (1) the ADOI fulfilled the SHCS diagnostic criteria (www.shcs.ch), and (2) HIV infection with CD4 >500/µL was the main immune‐compromising condition to cause the ADOI. Adjudication of cases was done by two experienced clinicians who had to agree on the interpretation.ResultsMore than 13,000 participants were followed in SHCS in the period of interest. Twenty‐four (48%) of the chart‐reviewed 50 patients with ADOI and CD4 >500/µL had an HIV RNA <400 copies/mL at the time of ADOI. In the 50 cases, candida oesophagitis was the most frequent ADOI in 30 patients (60%) followed by pneumocystis pneumonia and chronic ulcerative HSV disease (Table 1). Overall chronic HIV infection with a CD4 count >500/µL was the likely explanation for the ADOI in only seven cases (14%). Other reasons (Table 1) were ADOIs occurring during primary HIV infection in 5 (10%) cases, unmasking IRIS in 1 (2%) case, chronic HIV infection with CD4 counts <500/µL near the ADOI in 13 (26%) cases, diagnosis not according to SHCS diagnostic criteria in 7 (14%) cases and most importantly other additional immune‐compromising conditions such as immunosuppressive drugs in 14 (34%).ConclusionsIn patients with CD4 counts >500/ µL, chronic HIV infection is the cause of ADOIs in only a minority of cases. Other immuno‐compromising conditions are more likely explanations in one‐third of the patients, especially in cases of candida oesophagitis. ADOIs in HIV patients with high CD4 counts should be used as endpoints only with much caution in studies based on observational databases.
Investigating barriers in HIV‐testing oncology patients. The IBITOP study: phase I
Authors: Merz Laurent , Peters Solange , Zimmermann Stefan , Cavassini Matthias , Darling Katharine 
Published: November 2014

BackgroundSince the advent of combined antiretroviral therapy (ART), the incidence of non‐AIDS‐defining cancers (non‐ADCs) among HIV‐positive patients is rising. We previously described HIV testing rates of <5% in our oncology centre, against a local HIV prevalence of 0.4% [1]. We have since worked with the Service of Oncology to identify, how HIV testing can be optimized, we have conducted a study on investigating barriers in HIV‐testing oncology patients (IBITOP) among treating oncologists and their patients.MethodsAfter an initial two‐month pilot study to examine feasibility [2], we conducted the first phase of the IBITOP study between 1st July and 31st October 2013. Patients of unknown HIV status, newly diagnosed with solid‐organ non‐AIDS‐defining cancer, and treated at Lausanne University Hospital were invited to participate. Patients were offered HIV testing as a part of their initial oncology work‐up. Oncologist testing proposals and patient acceptance were the primary endpoints.ResultsOf 235 patients with a new oncology diagnosis, 10 were excluded (7 with ADCs and 3 of known HIV‐positive status). Mean age was 62 years; 48% were men and 71% were Swiss. Of 225 patients, 75 (33%) were offered HIV testing. Of these, 56 (75%) accepted, of whom 52 (93%) were tested. A further ten patients were tested (without documentation of being offered a test), which gave a total testing rate of 28% (62/225). Among the 19 patients who declined testing, reasons cited included self‐perceived absence of HIV risk, previous testing and palliative care. Of the 140 patients not offered HIV testing and not tested, reasons were documented for 35 (25%), the most common being previous testing and follow‐up elsewhere. None of the 62 patients HIV tested had a reactive test.ConclusionsIn this study, one third of patients seen were offered testing and the HIV testing rate was fivefold higher than that of previously observed in this service. Most patients accepted testing when offered. As HIV‐positive status impacts on the medical management of cancer patients, we recommend that HIV screening should be performed in settings, where HIV prevalence is >0.1%. Phase II of the IBITOP study is now underway to explore barriers to HIV screening among oncologists and patients following the updated national HIV testing guidelines which recommend testing in non‐ADC patients undergoing chemotherapy.
Profile and mortality outcome of patients admitted with cryptococcal meningitis to an urban district hospital in KwaZulu‐Natal, South Africa
Authors: Adeyemi Benjamin , Ross Andrew 
Published: November 2014

IntroductionCryptococcal meningitis (CCM) is one of the leading causes of early mortality among HIV‐infected patients. This study was a part of clinical audit [1] aimed at improving care for patients with CCM at an urban district hospital in South Africa.MethodsClinical records of all patients (age>13 years) admitted to the hospital with a diagnosis of CCM (based on a positive India ink, positive cryptococcal latex agglutination test (CLAT) or a positive culture of Cryptococcus neoformans) between June 2011 and December 2012 were retrospectively reviewed. Descriptive statistics and Chi‐square analysis were generated with Epi Info 7.1.2.0. 95% confidence intervals were reported where appropriate.ResultsOf the 127 patients admitted with CCM, only 97 (76.4%) knew their HIV status. Only 44.8% (43/96) of those who knew they were HIV positive were on antiretroviral therapy (ART). Seventeen out of 25 patients (68%) previously treated for CCM had defaulted fluconazole and only 60% (15/25) were on ART. Acute mortality (death within 14 days of CCM diagnosis) was 55.9% (71/127). The median time to death from diagnosis was four days (IQR 2–9). The association between CSF WBC count<20cells/mL and increased risk of death within 14 days was statistically significant (OR 2.2; 95% CI 1.1–4.6, p=0.03). Patients with heavy cryptococcal burden (reported as numerous yeasts seen on microscopy) at diagnosis were three times more likely to die within 14 days of diagnosis of CCM (OR 3.2; 95% CI 0.9–10.7, p=0.06). Even though a CD4 count<100cells/mm3 was associated with a 1.6 times increased acute mortality risk, the association was not statistically significant (OR 1.6; 95% CI 0.6–4.6, p=0.3). The role of elevated CSF opening pressure at diagnosis was not assessed because only two (1.6%) patients had their baseline opening pressure measured.ConclusionsAcute CCM‐related mortality remains high. The number of patients who do not know their HIV status, the number of HIV positive patients not on ART, the high level of non‐adherence to fluconazole and the proportion of patients not on ART after at least one previous CCM episode all point to the need of developing comprehensive strategies aimed at encouraging HIV testing and improving patient's retention in HIV care and support.
Improved outcomes from HIV/TB co‐infection in Singapore following a switch to earlier anti‐retroviral therapy
Authors: Young Barnaby , Marimuthu Kalisvar , Suay Hong Gan , Yee Sin Leo 
Published: November 2014

IntroductionRecent clinical trials have provided clear evidence to support early anti‐retroviral therapy (ART) in patients with HIV/TB co‐infection and low CD4 counts. We investigated how this has changed treatment and outcomes in Singapore.Materials and MethodsA retrospective review was performed with inpatient and outpatient records for all subjects diagnosed with HIV/TB co‐infection from 2006 to 2011 attending the Tuberculosis Control Unit, Tan Tock Seng Hospital, Singapore. Data for subjects with a presenting CD4<200 cell/mm3 were extracted and split into two groups, “Delayed”: ART more than 8/52 after starting TB treatment, and “Early”: ART within 8/52 of starting TB treatment.ResultsOne hundred thirty‐four out of 180 subjects in the database met the inclusion criteria for this study, 89 in the delayed group and 45 in the early. No statistically significant differences in baseline demographics between the two groups were identified. Both groups presented with markedly low CD4 counts, with overall 60% <50cells/mm3. Median CD4 counts were lower in the delayed ART group (37 vs 50, p=0.015). Prevalence of other opportunistic infections at TB diagnosis was not significantly different (20%), but TB in the early ART group was more likely to include extra‐pulmonary disease (46% vs 57%, p=0.038). Four cases were culture negative, 2 multi‐drug resistant and 10 (7.8%) were isoniazid mono‐resistant. There was a significant trend to earlier ART with more recent TB diagnosis (p<0.001). In the first 365 days after TB diagnosis, 11 deaths occurred in the delayed ART group, and 0 in the early (p=0.033). A Kaplan‐Meier time‐to‐event analysis demonstrated a clear separation in the frequency of death or opportunistic infections at eight weeks (Figure 1, p<0.001). Immune reconstitution disease was significantly more likely in the early ART group, but did not result in death (9% vs 38%, p<0.001). Treatment interruptions due to adverse drug events (ADE) developed in a median of 25 days (IQR 15–43). Interestingly, early ART was associated with a significantly lower number of treatment interruptions attributed to ADEs, with a higher proportion of patients completing two months of pyrazinamide induction (66% vs 85%, p=0.054) and rifampicin consolidation (79% vs 95%, p=0.03) – after excluding resistance or death. A trend to longer duration TB treatment was observed with delayed ART.ConclusionsSignificant improvements in HIV/TB infection outcomes correlate with the switch to earlier ART.
Alarming increase in tuberculosis and hepatitis C virus (HCV) among HIV infected intravenous drug users
Authors: Oprea Cristiana , Ianache Irina , Radoi Roxana , Erscoiu Simona , Tardei Gratiela , Nicolaescu Olimpia , Nica Maria , Calistru Petre , Ruta Simona , Ceausu Emanoil 
Published: November 2014

IntroductionIn the last years, we observed an alarming increase in the number of newly diagnosed HIV infected intravenous drug users (IDUs) co‐infected with hepatitis viruses or with severe bacterial infections. The aim of our study was to assess the incidence, the demographic and clinical characteristics of IDUs diagnosed with HIV, HCV and tuberculosis (TB).Materials and MethodsProspective study on HIV infected IDUs with HCV and TB admitted in a single centre between January 2009 and April 2014. Data were compared to a group of HIV infected IDUs without TB. Statistical analysis was performed using Graphpad Prism 4.01.ResultsOut of 450 HIV infected IDUs, 134 (29.7%) were diagnosed with HIV, HCV and TB. TB incidence among IDUs increases from 0% in 2009 to 30.2% in 2013. The TB coinfected patients had a mean age at diagnosis of 30 [15–56] years; were in majority males, 106 (84.4%); from urban areas, 120 (89.5%); and had significantly lower education level (85% vs 68.3%, p<0.0001) and higher rates of unemployment (80% vs 55%, p<0.0001) than those without TB. The median CD4 cell count was lower in the TB versus non TB IDUs (143 vs 472/mm3, p<0.0001). TB infected IDUs tend to be more frequently late presenters (59.7 vs 24.6, p<0.0001) and to have advanced HIV disease (47.7 vs 7.59%, p<0.0001) than those without TB. TB cultures were positive in 64 (47.7%) patients, 3 (2.2%) had multidrug resistant TB and 2 (1.5%) had extended drug resistance. Disseminated and/or extrapulmonary TB was diagnosed in 51 patients (38%). The overall mortality rate was higher in TB compared to non TB IDUs (19.4% vs 8.2%, p=0.0007), disseminated TB being associated with the most severe immunosuppression (median CD4 cell count 42/mm3) and the highest mortality rate (27.4%).ConclusionsThe incidence of TB in HIV/HCV coinfected IDUs was high and rose over the time. TB infection was more frequent in patients with severe immunosuppression and the mortality rate was higher in IDUs with disseminated and/or extrapulmonary disease. IDUs are important candidates for acquiring and transmitting HIV infection, viral hepatitis and TB, being difficult to control due to their high‐risk behaviours. Strengthening of HIV transmission prevention strategies, particularly in identified risk groups, is mandatory.
Telaprevir combination therapy in HCV/HIV co‐infected patients (INSIGHT study): sustained virologic response at 12 weeks final analysis
Authors: Montes Marisa , Nelson Mark , Marie Girard Pierre , Sasadeusz Joe , Horban Andrzej , Grinsztejn Beatriz , Zakharova Natalia , Rivero Antonio , Lathouwers Erkki , Janssen Katrien , Ouwerkerk‐Mahadevan Sivi , Witek James 
Published: November 2014

IntroductionWe report the SVR12 final analysis of a phase 3 study of telaprevir in combination with peginterferon (P)/ribavirin (R) in HCV‐genotype 1, treatment‐naïve and ‐experienced patients with HCV/HIV co‐infection (INSIGHT).Materials and MethodsPatients receiving stable, suppressive HIV antiretroviral (ARV) therapy, containing atazanavir/ritonavir, efavirenz, darunavir/ritonavir, raltegravir, etravirine or rilpivirine, received telaprevir 750 mg q8h (1125 mg q8h if on efavirenz) plus P (180 µg once‐weekly) and R (800 mg/day) for 12 weeks, followed by an additional 12 weeks (non‐cirrhotic HCV treatment‐naïve and relapse patients with extended rapid viral response [eRVR]) or 36 weeks (all others) of PR alone. Analysis was performed when all patients had completed the follow‐up visit of 12 weeks after last planned dose.ResultsOne hundred sixty‐two patients were enrolled and treated (65 efavirenz, 59 atazanavir/ritonavir, 17 darunavir/ritonavir, 17 raltegravir, 4 etravirine). Mean age was 45 years, 78% were male, 92% were Caucasian; mean CD4 count was 687 cells/mm3. Sixty four patients (40%) were HCV treatment‐naïve and 98 (60%) were treatment experienced (29 relapsers, 18 partial responders and 51 null responders). 64% were subtype 1a. 30% had bridging fibrosis (17%) or cirrhosis (13%). 19% of patients discontinued telaprevir, including 9% due to an adverse event (AE), 8% reaching a virologic endpoint and 2% for other reasons (non compliance or not defined). Treatment responses are shown in Table 1. There were no HIV RNA breakthroughs. Most frequently reported (≥20% patients) AEs were pruritus 43%; fatigue 27%; rash 34%, anorectal events 30% and influenza‐like illness (25%). Anemia was reported in 15% of patients; grade ≥3 haemoglobin decrease occurred in 2.5% of patients. 6% of patients experienced serious AEs.ConclusionsIn this phase 3 study of HIV‐infected, HCV treatment‐naïve and ‐experienced patients, 49% achieved eRVR and 57% reached SVR12. In patients with an eRVR, SVR12 rates were >80%, irrespective of prior treatment history.
Evaluation of drug‐drug interaction between daclatasvir and methadone or buprenorphine/naloxone
Authors: Garimella Tushar , Wang Reena , Luo Wen‐Lin , Wastall Philip , Kandoussi Hamza , Demicco Michael , Bruce Douglas , Hwang Carey , Bertz Richard , Bifano Marc 
Published: November 2014

IntroductionDaclatasvir (DCV) is a potent hepatitis C virus (HCV) NS5A replication complex inhibitor with pangenotypic (1–6) activity in vitro. Methadone (MET) and buprenorphine (BUP) are opioid medications used to treat opioid addiction; patients on HCV therapy may require MET or BUP treatment. The effect of DCV on the pharmacokinetics (PK) of MET or BUP/naloxone (NLX) was assessed in subjects on stable MET or BUP.Materials and MethodsAn open‐label, two‐part study assessed the effect of steady‐state oral administration of DCV on the PK of MET (Part 1, P1) or BUP/NAL (Part 2, P2). Safety/tolerability and pharmacodynamics (PD, opioid withdrawal scales/overdose assessment) were also assessed. Subjects (P1, N=14; P2, N=11) received daily single‐dose oral MET (40–120mg) or BUP/NLX (8/2–24/6mg) based on their prescribed stable dose throughout, in addition to DCV (60mg QD) on Days 2–9. Serial PK sampling occurred predose and postdose till 24 hours on Day 1 (MET/BUP) and Day 10 (MET/BUP/DCV). Noncompartmental PK were derived. Geometric mean ratios (GMR) and 90% confidence intervals (90% CI) for MET/BUP/norBUP Cmax and AUCTAU were derived from linear mixed effects models.ResultsSubjects were aged 19–39 years, mostly white (P1, 93%; P2, 100%) and male (P1, 71%; P2, 91%). All subjects completed the study. No clinically meaningful effect was demonstrated as the GMR and 90% CIs fell within the prespecified interval (P1, 0.7–1.4; P2, 0.5–2.0: see Table 1). DCV coadministration was well‐tolerated: overall, six (43%) subjects had adverse events (AEs) (all mild and resolved without treatment). DCV had no clinically significant effect on the PD of MET or BUP/NLX.ConclusionsSteady‐state administration of DCV 60mg QD had no clinically meaningful effect on the PK of MET or BUP/NLX and was generally well‐tolerated, suggesting that no dose adjustments will be required.
Effect of HIV infection‐related factors on SVR rate in HCV treatment in HIV‐infected patients
Authors: Kravchenko Alexey , Kuimova Uliana 
Published: November 2014

IntroductionFactors that have an effect on the rate of sustained virological response (SVR) in chronic hepatitis C (CHC) patients include: genotype of hepatitis C virus (HCV); level of HCV RNA replication and rate of its reduction in the course of treatment; original hepatic fibrosis level; genotype of Interleukin‐28B (especially for Genotype 1 HCV – G1); daily ribavirin (RBV) dose. This study evaluated the effect of the HIV infection‐related factors on the SVR rate in HCV treatment in patients with concurrent infection (HIV/HCV).MethodsThe follow‐up included 232 HIV/HCV‐infected patients. Ninety‐nine of 232 patients with HIV/HCV‐infection received antiretroviral therapy (ART) for at least three months before the initiation of the CHC treatment. Before the HCV therapy, the median of CD4+cells was 406/mm3 (with ART) and 507/mm3 (without ART). Patients received HCV treatment with pegylated interferon (PEG‐IFN) and RBV (1000/12,000 mg/day) during 24–48 weeks.ResultsSVR was received in 50% of patients with G1 HCV, and 80.1% of patients with Genotypes 2/3 (G2/3; p<0.0001). The SVR rate in the group of patients without ART was reliably higher, 74.4% (with ART – 58.6%; p=0.0053). No significant differences in the SVR rate (62.3% and 69.6%, accordingly) were detected after the differentiation of patients based on the initial absolute values of CD4+cells count (<350 cells/mm3 and >350 cells/mm3). In 127 patients with the HIV/HCV‐infection, the percentage of CD4+cells before the CHC treatment was >25% and more (Group 1 [Gr. 1]), and in 105 patients ≤25% (Group 2 [Gr. 2]). The SVR rate for Gr. 1 patient was 74.6%, and for Gr. 2 patients –58.1% (p=0.0023). The SVR rate in patients with G1 HCV was 56.8% (Gr. 1) and 44.2% (Gr. 2; p=0.1095), whereas the rate for G2 and 3 was 85.5% and 71.7%, accordingly (p=0.0242). Forty patients in Gr. 1 and 59 patients in Gr. 2 received ART. The comparison of the SVR rate for these patients showed no significant differences: 60% and 57.6%, accordingly. SVR rate in the patients without ART demonstrated that for Gr.1 patients (CD4+>25%) was reliably higher, 82.8% (compared to Gr.2 with 58.7%; p=0.0012).ConclusionsAlong with factors related to HCV and the patient, the SVR rate in the HCV treatment with PEG‐IFN and RBV may be affected in patients with the concurrent infection by the use of ART and original relative content of CD4+cells. The maximum SVR rate was achieved in the patients without ART and with the CD4+cells >25% (baseline). When indicted, it is reasonable to provide HCV treatment to HIV‐infected patients as long as the percentage of CD4+cells remains high and there is no need of ART.
Liver Fibrosis progression using Fibroscan in HIV/HCV coinfected patients with undetectable HIV viral load
Authors: Perez‐Martinez Laura , Sanjoaquin Isabel , Rivero Maria , Gil‐Pérez Desiré , Letona Santiago , Irigoyen Olaiz Carmen , Arazo Piedad , Blanco Jose Ramón 
Published: November 2014

IntroductionSeveral factors such as duration of infection, age, male gender, consumption of alcohol, HIV infection and low CD4 count have been associated with fibrosis progression rate. However, it is relatively scarce, the knowledge about the liver fibrosis progression rate in HIV‐infected patients with undetectable HIV viral load (VL). For this reason, we performed the present study.Materials and MethodsObservational and multicenter study (2008–2012) conducted in four hospitals of the northern Spain. HIV/HCV (hepatitis c) virus coinfected patients ≥18 years on stable combination antiretroviral therapy (cART) (≥6 months) and with a HIV VL <50 copies/mL were selected to analyze their liver fibrosis progression. Fibrosis progression was assessed using a Fibroscan® (502 STEP 3 model) and measuring a basal test and a second one at least 12 months apart from baseline. This evolution was compared with different variables such as duration of HIV/HCV coinfection, gender, age, previous treatment for HCV, HCV genotype, CD4 lymphocyte counts and the cART employed at the basal test.ResultsA total of 608 patients were included (median age 29.4 years, 71.7% men). Of these, 463 patients met the inclusion criteria. In these patients, the liver fibrosis progression was nearly flat and the only variables related to a higher liver fibrosis progression were the increasing age of the patients (p=0.02) and the duration of the coinfection (p=0.001). CD4 lymphocyte counts showed a tendency to improved liver fibrosis (p=0.056).ConclusionsIn HIV/HCV coinfected patients on stable cART and HIV undetectable VL, the increase in liver fibrosis rate progression was nearly flat, although it was significantly associated with the duration of the coinfection and the age of the patient. The beneficial effects of the cART were independent of the antiretroviral drug employed. A tendency to a lower fibrosis progression was observed in those patients with a higher CD4 count.